'T ' Indicate Tables. 3PPP, 380F 5HIAA (5-Hydro

Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information

Index

Page numbers followed by ‘f ’ indicate ﬁgures; page numbers followed by ‘t ’ indicate tables.

3PPP, 380f acetylcholine neurotransmitter, 128t 5HIAA (5-hydroxy-indole acetic acid), 483 as psychotropic drug target, 115, 117 in cerebrospinal ﬂuid, 488 acetylcholine receptors, TCA and, 602f acetylcholine transporters, 94t,99f AAADC (aromatic amino acid decarboxylase), acetylcholinesterase (AChE), 112, 170, 915, 343, 344f 915f AAB-001, 937 donepezil to inhibit, 925f “able stabilizers”, 717, 717f galantamine to inhibit, 930f ABT089, 449 rivastigmine to inhibit, 928f abuse, 945 ACh. See acetylcholine (ACh) acamprosate, 769 ACP 103, 446 actions, in ventral tegmental area (VTA), ACP-104, 375, 380f 978f ACR16, 380f for alcohol dependency, 976 ACTH (adrenocorticotropic hormone), 752, in combos for bipolar disorder, 715 753f icon, 976f actin, 36, 42f ACC-001, 937 action potential, 145, 159, 160f acetyl coenzyme A (AcCoA), as acetylcholine control over ﬁring, 217 precursor, 914 encoding of, 162f acetylcholine (ACh), 139, 902 ionic components of, 147f in arousal pathways, 396, 398f activity-dependent nociception, 795 and arousal spectrum, 817, 817f acute pain, 796f and blocked dopamine receptors, 339f neuropathic pain, 797f overactivity, 341 activity-dependent spine formation, by production, 914, 914f estradiol, 614f projections, 206, 207f acute pain, 774, 775, 796f via basal forebrain, 208f vs. chronic, 775t psychotropic drugs and, 53, 99, 128, 129 acute stress reaction, 193 reciprocal relationship with dopamine, 338f Adapin. See doxepin (Sinequan, Adapin) and reward, 946, 947f adaptive states, 138 termination of action, 915f adatanserin, 574 for treating nicotine dependence, 960 addiction, 945, 953f. See also substance abuse vesicular transporter for, 102 nicotine and, 955–959 acetylcholine-linked mechanisms, 448 overvalued reward in, 951

1057

© Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information

adenosine, 820, 859 agonists adenylate cyclase, binding to G protein, 70 absence of, 108, 112f ADHD. See attention deficit hyperactivity actions on ion channel, 133f disorder (ADHD) antagonist acting in presence of, 135f adhesion molecules, 31 and G protein-linked receptor, 110–112 and neuronal migration, 30f impact on ligand-gated ion channels, adipose tissue, insulin resistance in, 387, 390f 143f adolescence spectrum, 111f aggressiveness in, 425 and receptor conformation, 378f antidepressants for, 519f agoraphobia, in children, 713 brain restructuring in, 22, 22f,44 agranulocytosis, clozapine and, 410 mania in, 712 akathisia removal of synaptic connections, 42, 314 from aripiprazole, 421 risperidone for treating psychotic disorders, nigrostrial pathway dopamine deficiencies 412 and, 277 adrenocorticotropic hormone (ACTH), 752, from paroxetine withdrawal, 537 753f from SSRIs, 531 affective blunting, 251 alanine-serine-cysteine transporter (ASC-T), affective disorders, 454. See also mood disorders glial, 280 stress-induced, novel treatments, 754f alcohol, affective flattening, as SSRI side effect, 356 actions affective spectrum disorders, 556, 776t on reward circuits, 971f norepinephrine and, 546 in ventral tegmental area (VTA), 972f pain in, 802 consumption, vs. sleepiness, 851t “affective storms”, in children, 712 dependency/abuse affective symptoms by ADHD patients, 870 dorsal vs. ventral regulation, 322f social anxiety and, 769 mesolimbic dopamine pathway role in, 274 treatment, 973–977 multiple disorders impacting, 261f GABA-A receptor binding to, 737 pharmacy, 428, 430f heavy drinking in schizophrenia, shared with other disorders, vs. reduced-risk, 973 260 will power to reduce, 975f afferent neurons, peripheral, neuropathic pain icon, 970f and, 785 probability of dependence, 968t age. See also adolescence; children; elderly reduced-risk drinking, 975t synapse formation by, 49f and reward, 970 aggressive symptom pharmacy, 425, 427f alcoholics, smoking by, 970 aggressiveness, 256, 704f aldehyde dehydrogenase, 977 in dementia patients, 935 alertness, 650 multiple disorders impacting, 261f loss in schizophrenic patients, 259 bupropion for, 556 Agilect/Azilect (rasaligine), 579t as SSRI side effect, 530 for Parkinson’s disease, 582 allodynia, 775, 786, 795, 799f aging. See also elderly allosteric modulation, 140, 737, 738 erectile dysfunction and, 1000f alogia, 251, 252t hippocampus sensitivity to, 24, 24f alpha 1 adrenergic receptors normal, 908 atypical antipsychotic agents and, 385f and synapse loss, 25f and sedation, 397f agitation, 547 TCA and, 599, 603f benzodiazepines for, 434 alpha 1 antagonist, for posttraumatic stress in dementia patients, 935 disorder, 770 agnosia, 900 alpha-1 receptor, antagonism, 340f agomelatine (Valdoxan), 574, 658, 844f alpha 1 selective hypnotics, 840f icon, 661f alpha-1 unit, 153, 154f

1058 Index

alpha-2 adrenergic receptors, atypical Aβ42 oligomer interference with synaptic antipsychotic agents and, 385f function, 906, 906f alpha 2 antagonists, 414 Aβ42 production, 905f icon, 559f inflammation from plaque formation, and norepinephrine, 560f 907f and serotonin, 560f neuronal dysfunction and loss, 909f as serotonin norepinephrine disinhibitors, tangle formation, 908f 558, 562f amyloid plaques in, 901 alpha 2 delta ligands, 156, 158f Apo-E protein and, 907, 910f for anxiety disorders, 755 cholinergic deficiency, 920 binding of, 798f cholinesterase inhibitors for chronic pain, 801f best responders, 922, 922f in dorsal horn, 800f donepezil, 923, 924f for fibromyalgia, 808 galantamine, 926 and pain gate, 795 palliative responders, 924f potential therapeutic effects, 756f rivastigmine, 924, 926f alpha-2 delta protein, 153 tacrine, 923 gabapentin and pregabalin binding to, treatment outcomes, 921 158 usual responders, 923f alpha-2 delta unit, 155f clinical features, 901t alpha 2 receptors cognitive symptoms, 259 on axon terminal, 478f excitotoxicity and, 48f, 302, 303f blockade of, 559f expected exponential increase, 901 somatodendritic, 475, 479f familial cases early onset, 906 alpha 2A agonists, 891 folate for depression, 935 mechanism of action, 895f glutamate hypothesis of cognitive deficiency, alpha-4 beta-2 nicotinic acetylcholine receptor, 926–930 449 identifying at presymptomatic/prodromal alpha 4 beta 2 nicotinic receptors, 959, 960f stage, 911f reinforcement and, 958f neurofibrillary tangles in, 901 alpha-7-nicotinic cholinergic agonists, 448 problems with studies of, 912 alpha 7 nicotinic cholinergic receptors, 918 symptom pattern onset, 913f alpha amino-3-hydroxy-5-methyl-4- symptomatic treatments in development, 940 isoxazolepropionic acid (AMPA) symptoms shared with schizophrenia, 258, receptors, 286, 286f 259, 259f synapses with, 313f treatment, 128, 129 alpha APP, 903 untreated time course, 921f alpha heliz, 109f amantadine, 440 alpha-L-glutamyl transferace, 627 for bipolar disorder, 695 alpha pore icon, 696f of voltage-sensitive calcium channels, 154f mechanism of action of voltage-sensitive sodium channels, 151f on GABA, glutamate, sigma, and anticonvulsant binding, 151 dopamine, 676t alpha secretase, 902 VSSCs, synaptic vesicles, and carbonic alpha subunit, 147, 148f anhydrase, 675t alprazolam (Xanax), 53 possible actions in bipolar disorder, 698f and CYP 450 3A4, 608 putative clinical actions, 673t and sedation, 609 amenorrhea, 278, 336 alprostadil, 1004 American College of Rheumatology, criteria for ALS (amyotrophic lateral sclerosis) fibromyalgia, 805t excitotoxicity and, 48f American Psychiatric Association, 178 riluzole for, 685f amibegron, 662 Alzheimer’s disease, 426, 900 amines, 52t amyloid cascade hypothesis, 902 d-amino acid oxidase (DAO), 284f

Index 1059

amino acid transporters, 94t manic episode symptoms linked to, 506 inhibitory, 94t noradrenergic receptor simulation in, 547 amino acids, 52t overactive circuits, 745f to close VSSC, 148 regulating anxiety in, 241 for ligand-gated ion channels, 126 response to emotional input, 324 regulation of calcium channels, 153 and schizophrenia symptoms, 262f in voltage-gated ion channels, 147 serotonin and fear processing by, 234 amisulpride, 376, 380f amylin, 450 and cardiometabolic risk, 386t amyloid, and glutamate steady leak, 928 clinical actions of, 371 amyloid cascade hypothesis for Alzheimer’s and diabetes, 417 disease, 902, 905f for negative symptoms in schizophrenia, neuronal dysfunction and loss, 909f 428f amyloid plaques, 903 pharmacological icon, 423f in Alzheimer’s disease, 901 and QTc prolongation, 417 and glutamate excitotoxicity, 932f amitriptyline (Elavil, Endep, Tryptizol, and glutamate release, 927 Loroxyl), 53, 572, 597t treatment development to act on, 937 amnesia, 900 amyloid precursor protein (APP), 902 amotivational syndrome, 986 processing into Aβ peptides, amoxapine (Asendin), 419, 420f processing into soluble peptides, 904f AMPA (alpha-amino-3-hydroxy-5-methyl-4- amyotrophic lateral sclerosis (ALS) isoxazole-priopionic acid) glutamate excitotoxicity and, 48f receptors, 130, 164f riluzole for, 685f glutamate at, 147f Anafranil. See clomipramine (Anafranil) and synaptogenesis, 308 analgesics, 775 AMPA-kines, 445 probability of dependence, 968t amphetamines, 99t, 290, 576, 579t anandamide, 53, 946, 947f action anatomic G protein-linked receptors, 110t in ADHD, 885 anatomically addressed nervous system, 21 MAO inhibitors with, 579t neurodevelopment in, 22 and dopamine displacement, 107f “angel dust”, 144 and dopamine release, 272 anhedonia, 251, 252t dopamine transporter (DAT) and, 94, 103, anorexia, ﬂuoxetine for, 533 105f antagonists, 112–115 icon, 984f acting alone, 134f with MAOIs, and hypertension, 593t acting in presence of inverse agonist, 140f pharmacological actions, 889 acting in presence of partial agonist, 138f VMAT transport fo, 106f action in presence of agonists, 135f for wakefulness, 857, 858 vs. inverse agonist, 351 amygdala, 199f inverse agonist action reversed by, 141f activation, 234 for ligand-gated ion channels, 130 by VMPFC, 760 vs. partial agonists, 378f and anxiety/fear, 704f presynaptic, 445f and avoidance, 728f anterior cingulate cortex (ACC), 198, 199f beta-3 receptors in, 662 anterograde motor, 8f connection with locus coeruleus, 731 localization of, 9f and depressed mood, 490 anterograde transport, 14 and emotional learning, 949 fast, 16f and fear neurobiology, 729 antiaptotic receptors (TrkA), 29t and fearful faces, 236f anticholinergic agents impact on suicidal ideation, 493 D2 antagonism and, 339f information processing side effects, 341 and depressed mood, 492f anticholinergic effects, from diphenhydramine serotonin and, 744 (Benadryl), 847f

1060 Index

anticonvulsants, 129, 149. See also speciﬁc agents monoamine transporters as targets, 99t carbamazepine (Equetro), 678 and neurogenesis in hippocampus, 24f as mood stabilizers, 672 norepinephrine and dopamine reuptake gabapentin, 687 inhibitors (NDRIs), 99t, 552–556. See lamotrigine, 682–686 also norepinephrine dopamine reuptake levetiracetam, 689 inhibitors (NDRIs) oxcarbazepine/eslicarbazepine, 681 over life cycle, 519, 519f pregabalin, 687 pharmacokinetics, 603 riluzole, 686 prior responses to, and bipolar diagnosis, 470 topiramate, 686 putative mechanisms, 533t zonisamide, 687 response rates, 514f sodium channels as action site, 150 risks of use or avoidance during pregnancy, valproic acid, 672 618t antidepressant “poop out”, 461 risks to fetus, 618 antidepressants. See also heroic combos; role in bipolar disorder, 699 serotonin norepinephrine reuptake serotonin norepinephrine reuptake inhibitors inhibitors (SNRIs) (SNRIs), 541. See also serotonin allosteric site for binding, 97 norepinephrine reuptake inhibitors bipolar depression response to, 472f (SNRIs) brain MAO-A inhibition for efﬁcacy, 579 sites on transporter for, 95 in clinical practice, 639 suicidality in adolescent females, 617 cost-based algorithm, 642, 642f symptoms persisting after treatment with, evidence-based algorithm, 641f 516 evidence-based selections, 641 time course of effects, 521f reduced positive affect vs. increased trimonoaminergic modulators (TMMs) and, negative affect, 643 610 selection process, 639 triple-action combo, 657 symptom-based algorithm, 645f two mechanisms vs. one, 542, 542f symptom-based selection, 643, 644f antihistamines, 328 clinical trials, 514 sedation by, 846 combinations for major depressive disorder, side effects of, 846 651 antipsychotic agents combinations for unipolar depression, 652f as antidepressants, 658 continuation, 515f atypical, 342 CYP450 2D6 impact on plasma levels, 607 administration frequency, 368 delay in relief from depression, 528f cardiometabolic risk and, 386t in development, 658t cardiometabolic risk management, 391 targeting neurokinins, 660t hit-and-run receptor binding properties, targeting novel sites of action, 660t 370f effectiveness in clinical practice, 514 hypothetical action over time, 371f enhancement of serotonin and/or to improve schizophrenia symptoms, 355 norepinephrine, 98 pharmacological properties, 385f general principles, 512–520 and prolactin, 364f impact on mixed states of depression and properties, 365, 381f mania, 467 and weight gain risk, 386t increase in monoamines, 520f avoiding sedation and enhancing long-term interaction with MAOIs, 595t outcome, 401f interference with slow-wave sleep, 848 benzodiazepines to lead in or top off, 434f “intramolecular polypharmacy” of, 542 best practices for monitoring and managing, manic or hypmanic episode on, 463 395f L-5-methyltetrahydrofolate (MTHF) and, cardiometabolic risk and, 383–396 631f combining two, 437 monoamine oxidase inhibitors (MAOIs), conventional, 337f 574–597 vs. atypical, 358f

Index 1061

antipsychotic agents (Contd.) fear extinction, 760 D2 binding of, 369f fluvoxamine for, 537 D2-receptor antagonist, 329 GABA-A allosteric modulatory sites, hypothetical action over time, 369f hypothetical shift in set point, 740 muscarinic cholinergic blocking properties, GABA and, 241, 732–741 337–341 generalized anxiety disorder (GAD), 723f pharmacological properties, 328–342 pharmacy, 767f and prolactin, 364f treatment, 765 risk and benefits of long-term, 341 inability to extinguish maladaptive fear in use, 331t responses, 761 as D2 dopamine receptor blockers, 273 linking symptoms to circuits, 727f first-generation, 329f MAO inhibitors for, 575 high doses, 437f NET inhibition and, 558 links between binding properties and clinical noradrenergic hyperactivity in, 755 actions, 382 blocking, 758f low-potency, and dissociation, 370 obsessive compulsive disorder, 725f “off-label” uses, 328 pharmacy, 771f patient toleration of, 409 treatment, 770 pharmacokinetics, 402–408 overlap with depression, 722f pharmacological properties, 408–425 pain linked to, 802, 803f prescribing information, 328 painful somatic symptoms in, 791f prophylactic, 438 panic disorder, 723f receptor interactions for, 380 pharmacy, 768f sedation as short-term tool, 398f treatment, 768 side effects and compliance, 399f paroxetine for patients with, 536 switching, 431, 433f phenotype, 725f process to avoid, 433f posttraumatic stress disorder, 724f from sedating to nonsedating, 435f pharmacy, 770f antisocial personality disorder, 259 treatment, 770 anxiety preemptive or prophylactic treatments, 762 5HT1A partial agonist actions in, 746f with beta blockers, 763f amygdala and, 704f prevalence of, 757 GABA and, 732–741 quetiapine for, 414f gabapentin for, 688 serotonin for regulating in amygdala, 241 linking symptoms to circuits, 731f serotonin projections regulation of, 205, memories and, 730f 206f noradrenergic hyperactivity in, 755, 757f social anxiety disorder, 724f blocking, 758f pharmacy, 769f pregabalin for, 688 treatment, 769 reduced, 649 stress progression to, treatment, 754 serotonin, stress and, 741–749 symptom dimensions, 722–728 anxiety disorders symptom overlap in subtypes, 726 5HT1A receptors and, 349f symptom overlap with depression, 726 alpha 2 delta ligands for, 755 treating insomnia in, 843 amygdala and fear neurobiology, 729 venlafaxine for, 549 brain component regulating, 200 anxiolytics in children, 713 benzodiazepines as, 741 comorbid with fibromyalgia, 807t GABA, 741 CSTC loops and worry neurobiology, 764 probability of dependence, 968t diabolical learning hypothesis and, 230 anxious misery, 764 drug treatment action at ionotrophic anxious mood, 260 receptors, 124 anxious self-punishment, 249 fear conditioning, vs. fear extinction, 756, apathetic recovery, 530, 546 759f apathetic temperament, 460f

1062 Index

apathy, 249 deficit arousal, 871f circuits, 493f excessive arousal, 876f in depression, 491 arousal combos, 658 aphasia, 900 arousal spectrum, 816, 817f apical dendrites, 2, 219f ascending reticular activating system, 817 in pyramidal cell, 3f asenapine, 368f apnea, obstructive sleep, 855 Asendin (amoxapine), 419, 420f symptoms shared with other disorders, 869t asociality, 251, 252t Apo-E protein, and Alzheimer’s disease, 907, Asperger’s syndrome, 771 910f assaultiveness, 256 apoptosis, 27, 750f astrocytes, and Alzheimer’s disease, 906 from gene expression, 78 atherosclerosis, from repetitive autonomic and necrosis, 28f responses, 731 programmed into genome, 28 atomoxetine, 99t, 557, 604, 606f APP. See amyloid precursor protein (APP) for ADHD, 885, 889 appetite mechanism of action, 892f changes in, 493 with stress and comorbidity, 894f circuits, 498f CYP450 2D6 impact on plasma levels, 607 histamine-1 with 5HT2C antagonism, 387f for fibromyalgia, 810 reduced, 1010 for weight loss, 1011 appetite suppressants, interaction with MAOIs, atorvastatin 595t and CYP 450 3A4, 608 apprehensive expectations, 764 risk of muscle damage, 609 apraxia, 900 ATPase, 170f arborization, of neurons, 35f attention arcuate nucleus, 977 in ADHD patients, 873 aripiprazole, 375, 376, 380f CSTC loop to regulate, 213f actions as mood stabilizer, 693f impaired, in schizophrenia, 257 and cardiometabolic risk, 386t provoking circuits for, 235 in combos for bipolar disorder, 713, 717, 717f attention deficit hyperactivity disorder as CYP 2D6 substrate, 404, 405f (ADHD), 103, 235, 426, 863 and diabetes, 417 adults with, 880 dosage with carbamazepine, 407f vs. children, 881, 882t pharmacological actions, 693f prevalence of, 882 pharmacological icon, 422f treatment, 880, 897 raising levels of, 406f arousal spectrum of cognitive dysfunction and sedation, 430, 432f ADHD treatment, 872 switching from sedating agent to, 435 deficit arousal, 871f testing for cocaine abuse treatment, 986 excessive arousal, 876f and weight gain risk, 386t atomoxetine for, 557, 558 armodafinil (Nuvigil), for wakefulness, 857 mechanism of action, 892f aromatic amino acid decarboxylase (AAADC), brain restructuring and, 44 343, 344f causes, 870t arousal and comorbidity, priority for treatment, deficient daytime, 819f 880 desensitization in prefrontal cortext, 878f deficit arousal and, 870 and dopamine, 856f desensitizing arousal in prefrontal cortext, excessive, and ADHD, 873–877 878f mechanisms, 870 dopamine signals in prefrontal cortext, 886f norepinephrine projections regulation of, 205 how not to treat, 888f simultaneous deficient and excessive, in impact of development, 884f ADHD, 879f from improper neuronal migration, 29 spectrum of cognitive dysfunction in ADHD information processing, 874f ADHD treatment, 872 mania vs., 712, 713

Index 1063

attention deficit hyperactivity disorder AV965, 941 (ADHD) (Contd.) Aventyl. See nortriptyline (Pamelor, Endep, noradrenergic treatment, 889–897 Aventyl) atomoxetine, 889 avoidance, 728f norepinephrine signals in prefrontal cortext, avolution, 251, 252t 886f “awakening”, 410, 437 pharmacy, 896f axoaxonic synapses, 5, 6f, 36, 37f selective attention circuit, 866f axodendritic synapses, 36, 37f simultaneous deficient and excessive arousal, Axokine, 1011 879f axon hillock, 7f,8 stimulants for, 884, 885–889 of pyramidal neuron, 217 mechanism of action, 887f axon terminals. See also presynaptic axon stress terminals comorbidities and arousal levels, 877 alpha 2 receptors on, 478f and comorbidity, 893f axonal growth cone, 31, 32f sustained attention circuit, 867f docking, 32f symptoms and circuits, 864–870 axons, 1, 2, 2f DSM-IV, 864f in basket neurons, 4f matching, 865f in double bouquet cells, 4f symptoms shared with schizophrenia, 260 growth of, 31 timing of onset, 882 in mature brain, 31 tuning cortical pyramidal neurons, 875f myelination of fibers, 22 attention deficit, vs. attention deficit disorder, neurotrophins control of growth, 31 866 in pyramidal cell, 3f attitudes, hostile, 249 for transport function, 10 atypical antipsychotic agents, 342 axosomatic synapses, 36, 37f for ADHD, with stimulants, 879 Azilect. See rasaligine (Agilect/Azilect) administration frequency, 368 Azilect/Agilect (rasaligine), 579t in bipolar depression, 692f for Parkinson’s disease, 582 pharmacological actions, 693f cardiometabolic risk and, 386t bapineuzumab, AN1792(QS21), 937 cardiometabolic risk management, 391 barbiturates clozapine as, 409 and anxiety, 767 vs. conventional, 358f dependency/addiction, 986 hit-and-run receptor binding properties, as hypnotics, 840 370f basal dendrites, 2 hypothetical action over time, 371f in pyramidal cell, 3f for mania, actions, 691f basal forebrain, 203f for mania and bipolar depression, mechanism acetylcholine projections via, 208f of action, 690 cholinergic cell bodies in, 206 as mood stabilizers, 694f inefficient information processing, and sleep for nonpsychotic mania symptoms, 689 disturbances, 503f properties, 365, 385f nerve destruction, 902 and weight gain risk, 386t and sleep disturbances, 491, 494f auditory association cortex, 196f basal nucleus, 206 auditory hallucinations, 251 basilar dendrites, 219f Aurorix. See moclobemide (Aurorix, Manerix) basket neurons, 2, 4f autism, 426, 771 icon drawing, 4f cognitive symptoms, 259 realistic drawing, 4f irritability in children with, 427 BDNF. See brain-derived neurotrophic factor risperidone for irritability, 412 (BDNF) autonomic nervous system, 731 behavior autoreceptors, 475 in dementia, 934 autosomal dominant pattern, classic, 178f genes impact on, 88

1064 Index

hypothetical path from gene to, 182f in metabolic pharmacy, 429 linked to key brain regions, 203f metabolized by CYP 3A4, 404 repetition, and brain restructuring, 32 for obesity, 448 Benadryl (diphenhydramine), 846, 847f pharmacological icon, 424f half-life of, 836f and sedation, 432f benzamide antipsychotics, clinical actions of, sedation risk with, 430 371 binary neurotransmitter receptor complex, benzodiazepines, 244f binding to G protein, 69f actions on reward circuits, 987f binge eating, 1009 for aggression management, 427f biological endophenotype, 182, 182f for agitation, 434 for executive dysfunction, 233f agonist spectrum in panic disorder, 742f in path between gene and mental illness, 185 as anxiolytics, 741 vs. symptom endophenotype, 229 for bipolar disorder, 694 bipolar 1/2 disorder, 461, 462f in combos for bipolar disorder, 715 bipolar 1/4 disorder, 461, 462f for enhancing GABA actions, 732 bipolar disorder. See also mood stabilizers for fibromyalgia, 811 bifeprunox for treating, 424 GABA-A receptors and, 736f in children, 712 for generalized anxiety disorder, 765, 767 common comorbidities, 711f injectable, 425 comorbid conditions and, 709 for insomnia, 837f depressed phase of, 415 restrictions, 837 atypical antipsychotic agents in, 692f to lead in or top off antipsychotics, 434f bullet combos for, 716f long-term effects, 838f history, 471f nonselective, 841f lamotrigine as first-line treatment, 682 as PAMs, 142 response to antidepressants, 472f for panic disorder, 768 symptoms, 471f as positive allosteric modulators, 146f vs. unipolar depression, 468, 469t for posttraumatic stress disorder, 770 impact of antidepressant treatment on for social anxiety disorder, 769 unrecognized, 468 when switching antipsychotics, 435f olanzapine and, 411 beta 3 agonists, as antidepressants, 658, 662, pharmacological mechanisms to achieve 663f remission, 705 beta 3 receptors, 662f postpartum, 619 beta amyloid antagonists, 937, 938f progressive nature of, 473f beta amyloid, Apo-E protein ineffective binding rapid cycling, 458f to, 908 residual symptoms after first-line treatment, beta amyloid immunizations, 938f 702–710 beta amyloid plaques, 901 risperidone effectiveness for, 413 beta blockers spectrum, 461, 461f and CYP450 2D6 inhibitors, 608 symptoms shared with schizophrenia, 258, preemptive treatments, 763f 259, 259f for social anxiety disorder, 769 treating insomnia in, 843 beta endorphin, 53 treatment, 454, 455f beta secretase, 903 amantadine for, 695 inhibitors, 940f benzodiazepines for, 694 beta units, 155f calcium channel blockers for, 697 of voltage-sensitive sodium channels, 149, inositol for, 699 152f ketamine for, 695 BH4. See tetrahydrobiopterin (BH4) memantine for, 695 bicifidine, 552, 552f L-methylfolate (Deplin) for, 699 bifeprunox (DU 127090), 375, 376, 380f with mood stabilizer, 668 and cardiometabolic risk, 386t omega-3 fatty acids for, 698 and diabetes, 417 thyroid hormones for, 699

Index 1065

bipolar disorder (Contd.) deep brain stimulation, 638, 638f unstable and excessive neurotransmission, development process, 23f 706f development time course, 22, 22f and women, 710 dopamine pathways in, 268, 272f ziprasidone for, 416 fetal Bipolar I disorder, 456, 457f excitotoxicity in early development, 308f bipolar I 1/2 disorder, 463f insult and schizophrenia, 303 Bipolar II disorder, 456, 459f survival of wrong neurons, 305 bipolar II 1/2 disorder, 463, 464f focus on malfunctioning areas, 262 bipolar III disorder, 463, 464f functional areas, 197–201 Bipolar III 1/2 disorder, 463, 465f within left hemisphere, 202f Bipolar IV disorder, 465, 466f glutamate pathways in, 287, 289f bipolar mania, neurons mediating, 151 imaging, 223 “bipolar storm”, 704, 706f inefﬁcient information processing, and Bipolar V disorder, 465, 466f psychiatric disorders, 201 Bipolar VI disorder, 467, 467f key regions, 196f birth mapping mania symptoms onto circuits, 505 “apoptotic suicide” before, 27 neuroimaging of activation in depression, neuronal migration before, 22 507f blame, 249 neurons in, 1 blonanserin, 368f neurotransmitters in, 52t blood oxygenation, measuring with fMRI scan, neurotrophins and growth factors in, 174t 232f nociceptive pathways from spinal cord to, 782 blood pressure nucleus accumbens as pleasure center, 329 L channel and, 155 planes for visualizing, 200f monitoring, 392, 396f restructuring through lifetime, 22, 22f,44 noradrenergic receptor simulation and, 547 symptom localization in, 241 tyramine and, 582, 589 three-dimensional perspective, 201 blunted affect, 252t brain atrophy blurred vision, from conventional from chronic pain, 809 antipsychotics, 337, 338f reversing stress-related, 891 BMI. See body mass index (BMI) from stress, 748 BMS181, 101, 574 brain circuits, and schizophrenia symptoms, BMY-14802, 446 260 body dysmorphic disorder, 771 brain damage, 426 body mass index (BMI), 388f brain-derived neurotrophic factor (BDNF), 29t, baseline measurement, 395f 304, 612 monitoring, 396f 5HT6 receptors and, 447 bone marrow, carbamazepine impact, 679 genes coding for, 309f borderline personality disorder, 259, 426, 1011 and long-term memory formation, 345 Boston bipolar brew, 715, 716f serotonin signaling and release of, 751f bouquet cells, double, 2 stress and, 748 icon drawing, 4f suppression of production, 750f realistic drawing, 4f and synapse formation, 308, 311f BP987, testing for cocaine abuse treatment, 986 target gene for, 489 bradykinin, 779f brain imaging, 195 brain. See also circuits brain MAO-A, 579 activity in depression, 490 brain stimulation, of depressed patients, 633 areas impacting sleep, 491 brainstem areas regulating functions, 213 5HT3 receptor stimulation, and nausea or axonal growth in matrue, 31 vomiting, 531 behaviors linked to key regions, 203f cell bodies for acetylcholine in, 206 as “chemical soup”, 58 dopamine projections originating in, 204f damage, and mental illness, 228 monoamine centers, 202f

1066 Index

brainstem neurotransmitter centers, 203f calcium/calmodulin kinase (CaMK), 66f breast-feeding calcium-calmodulin–dependent protein kinases, depression and treatment during, 619 74 lithium and, 712 calcium channel blockers breathing, output during fear response, dihydropyridine, 155 729f L-type, 697, 698f bremelanotide, 1006, 1011 mechanism of action Brief Psychiatric Rating Scale, 253t on GABA, glutamate, sigma, and Brodmann areas, 197, 198f dopamine, 676t Buckeye bipolar bullets, 715, 716f VSSCs, synaptic vesicles, and carbonic bulimia, fluoxetine (Prozac) for, 533, 1011 anhydrase, 675t buprenorphine, 981 putative clinical actions, 673t icon, 981f calcium channels, 61, 145 bupropion, 99t, 103, 105, 244f glutamate to open, 47f action at dopamine transporter, 105f overexcitation and dangerous opening of, for adult ADHD, 885 301 for fibromyalgia, 810 voltage-sensitive (VSCCs), 60, 148 mechanism of action, in smoking cessation, ionic filter of, 150f 969f calcium ions, 124f metabolites, 553, 554f calcyon, genes for, 319f potency for CYP450 2D6 inhibition, 605 California careful cocktail, 715, 716f to reduce nicotine craving, 965 California rocket fuel, 656f with sertraline, 536 California sunshine, 717f burnout calmodulin, 74 of neuronal systems, 274 CaMK (calcium/calmodulin kinase), 66f in schizophrenic patients, 300, 301f cAMP response-element binding protein, stimulants and, 985, 985f 74 buspirone, 447, 651, 657 CAMs (cellular adhesion molecules), 36, 41f and anxiety disorders, 743 cannabinoid 1 receptor (CB1), 57 and CYP 450 3A4, 608 cannabinoid antagonists, 449 for generalized anxiety disorder, 765 cannabinoid receptors, 989 mechanism of action augmentation, 653f cannabis, 986 for treating nicotine dependence, 967–968, probability of dependence, 968t 977 capsaicin, 779 butyrylcholinesterase (BuChE), 915, 915f carbamazepine (Equetro), 153f rivastigmine to inhibit, 928f actions as mood stabilizer, 683f binding site of, 682f CAD106, 937 and CYP 450 3A4, 608 cadherins, 32 CYP450 3A4 and discontinuation, 408f caffeine, 821, 854, 859, 860f CYP450 3A4 induced by, 407f formulations, 859t for fibromyalgia, 811 interactions with fluvoxamine, 604 icon, 680f calcineurin interaction with MAOIs, 595t activation, 72 for manic phase of bipolar disorder, 672 calcium binding to, 74f mechanism of action calcium on GABA, glutamate, sigma, and activation of kinases and phosphatases, 74 dopamine, 676t activation of phosphatase, 64 VSSCs, synaptic vesicles, and carbonic excessive anhydrase, 675t and cell death, 48f putative clinical actions, 673t and excitotoxicity, 304f and sedation, 609 flux through NMDA ligand-gated ion vs. valproate, 679 channels, 144 and VSSCs, 707f influx through NMDA receptors, 164f carbonic anhydrase, topiramate and, 687

Index 1067

cardiac arrhythmias cGMP (cyclic guanosine monophosphate), 57 from combining 3A4 substrates with chandelier neurons, 3, 5, 6f inhibitors, 609 “cheese reaction”, tyramine and, 585 as tricyclic antidepressant side effect, 604f cheese, tyramine content of, 587f cardiac ischemia, from repetitive autonomic chemical integrator, somatic zone as, 6 responses, 731 chemical messengers cardiometabolic risk activation in signal transduction cascade, antipsychotic agents and, 389f 66f atypical antipsychotic agents and, 385, 386t conversion of electrical impulse to, 161f clozapine and, 410 chemical neurotransmission, 51 low risk antipscychotic agents, 386t principles, 51–61 olanzapine and, 411 chemical neurotransmitters, 38f, 51–54 receptors mediating, 385f chemical signals cardiovascular disease cascades of incoming, 7 atypical antipsychotic agents and, 383 and electrical signals, in neurotransmission, risk of, 388f 61 cardiovascular side effects, of antipsychotic genome encoding of, 7f drugs, 341 for neuronal migration, 29 catabolic enzymes, 36 “chemical soup”, brain as, 58 for prehemisynapse, 43f chest pain, noncardiac, triggers for, 800 cataplexy, gamma hydroxybutyrate for, 859 child abuse, 749, 751 catastrophic thinking, 764 chronic stress from, 752f catechol-O-methyl transferase (COMT), 221f childbearing years, depression during, 616 and dopamine breakdown, 267, 267f childhood, benefits of mild stress, 750 and dorsolateral prefrontal cortex, 265f children. See also autism genes for, 233, 319f “affective storms” in, 712 CATIE (Clinical Antipsychotic Trials of aggressiveness in, 425 Intervention Effectiveness), 399f antidepressants for, 519f CATIE-AD (Clinical Antipsychotic Trials of bipolar disorder and mood stabilizers, 712 Intervention Effectiveness in brain restructuring in, 22, 22f,44 Alzheimer’s Disease), 935 negative experiences, and synaptogenesis, 34 caudate, 202f psychotic illness, symptoms shared with CBT. See cognitive behavioral therapy (CBT) schizophrenia, 258, 259, 259f CCK. See cholecystokinin (CCK) risperidone for, 412 cell body. See soma tics in, 877 cell nucleus, transcription factor in, 75 chloride cellular adhesion molecules (CAMs), 36, 41f cotransport of, 95 central growth plates, neuron formation in, 30f reduced conductance, inverse agonists and, central nervous system, 21 142 sensitization process in, 795 chloride channel, in GABA-A receptor, 735f central sensitization syndromes chloride ions, 124f affective spectrum disorders, 800 chlorpromazine (Thorazine), 328, 331t fibromyalgia as, 806 cholecystokinin (CCK), 450 segmental, 795, 799f cholecystolinin agonists, 1011 “suprasegmental”, 798, 801f choline, as acetylcholine precursor, 914 central sulcus, 196f choline acetyl transferase (CAT), 914, 920 cerebellum, 203f choline transporters, 99, 99f Purkinje cells from, 3, 5f cholinergic deficiency hypothesis, for dementia, cerebral cortex, 196 918 antipsychotic agent binding to postsynaptic cholinergic neurons, 206 5HT2A receptors, 360f and memory formation, 920 neurons in, 3f cholinergic projections, and prefrontal cortex cerebrospinal fluid, 5HIAA in, 488 activity, 210f cFos gene, 81f, 83, 83f cholinergic receptors, nicotine action on, 955

1068 Index

cholinesterase inhibitors matching neurotransmitters to, 243f and Alzheimer’s disease, 920–926 matching symptoms to, 242f best responders, 922, 922f matching to neurotransmitters, 243f palliative responders, 924f psychomotor symptoms, 497f treatment outcomes, 921 sleep, 494f usual responders, 923f suicide, 498f chorea, dopamine hyperactivity in nigrostriatal treatment based on, 244f pathway and, 277 weight, 498f CHRNA (alpha-7 nicotinic cholinergic worry/obsessions, 764f receptor), 318f worthlessness, 499f chromosomes, and Alzheimer’s disease, 906 circulating hormones, 52t chronic insomnia, 831–839 citalopram, 99t, 538 chronic pain, 151, 774, 775, 795 icon, 538f vs. acute, 775t potency for CYP450 2D6 inhibition, 605 and brain atrophy, 809 cJun gene, 81f, 83, 83f diabolical learning hypothesis and, 229 Cl1007, 380f hypothesis for pain perception, 792 classic autosomal dominant pattern, 178f peripheral vs. central, 776t classic neurotransmission, 54, 55f cigarettes. See nicotine Clinical Antipsychotic Trials of Intervention ciliary neurotrophic factor (CNTF), 29t Effectiveness (CATIE), 399f and weight loss, 1011 clinical practice CIND (cognitive impairment nodementia), antidepressants in, 639 911 vs. clinical trials, 424 circadian rhythms symptom treatment, vs. disease treatment, 5HT7 receptors and, 349f 425 disturbance in, 823 clomipramine (Anafranil), 597t input to sleep/wake switch, 820 inhibition of serotonin reuptake pump, 598 melatonin to regulate, 844, 844f for obsessive compulsive disorder, 770 phase advanced, 827f clonidine, 621 phase delayed, 826f for ADHD, 895f wake drive, 823f for opiate detoxiﬁcation, 980 circuits, 195 for treating nicotine dependence, 967–968, and anxiety disorders, 727f 977 apathy, 493f Clopixol (zuclopenthixol), 331t appetite, 498f closed state, of voltage-sensitive sodium for attention, 235 channels, 152f depressed mood, 492f clozapine, 382f in depression, 489–496 5HT6-antagonist properties of, 447 elevated/irritable mood, 501f for affective symptoms in schizophrenia, 429 for executive functioning, genetic inﬂuence for aggression management, 426, 427f on, 235f and antagonism of muscarinic cholinergic fatigue, 495f receptor, 392f functioning, 56f augmenting, 437 goal-directed activity, 505f binding properties, 409f guilt, 499f and cardiometabolic risk, 386t linking worry symptoms to, 764f in combos for bipolar disorder, 713 malfunctioning, 224–231 as CYP 2D6 substrate, 404, 405f and depression symptoms, 643 dosage with carbamazepine, 407f imaging of, 231–237 M3 receptors blocked by, 392f psychiatric symptoms and, 229 for negative symptoms in schizophrenia, for mania, 496–507 428f mania symptom, 502f pharmacological icon, 409f mapping mania symptoms onto, 505 pharmacological properties, 409 matching mania symptoms to, 500f potency, and dissociation, 370

Index 1069

clozapine (contd.) cognitive impairment no dementia (CIND), 911 raising levels of, 406f cognitive symptom pharmacy, 428, 429f rebound psychosis from discontinued, 431 cold turkey, 980 for sedation, 431 collapsins, 31 for suicide reduction, 410, 430f colony stimulating factors, 174 for symptom reduction in psychosis, 425 coma, from opiates, 979 and weight gain risk, 386t combat, stress vulnerability, 193, 194f club drugs, 993 “combos” (combination of medications) actions on reward circuits, 994f for bipolar disorder treatment, 713 CNTF (ciliary neurotrophic factor), 29t for schizophrenia, 436, 450 Coaxil (tianeptine, Stablon), 597t for symptom reduction in psychosis, 425 cocaine, 99t, 103, 982 communication DAT blocking by, 103 dysfunction of, 251 and dopamine release, 272 between neurons, 55f,57f icon, 983f competitive elimination, 22, 22f, 41–49, 49f probability of dependence, 968t “complex genetics”, 180 undesirable effects, 984 complex regional pain syndromes (CRPSs), 786 vaccines for, 985 compulsions, 198 codeine, 977 CSTC loop to regulate, 213, 215f and CYP450 2D6 inhibitors, 608 compulsive sexual behavior, 1007 coding region of DNA, 79f,80 compulsive shopping, 1011 cognitive behavioral therapy (CBT), 639, 761 compulsive use of drugs, 953f cognitive blunting COMT (catechol-O-methyl transferase), 221f as antipsychotic side effect, 341 and dopamine degradation, 544 from conventional antipsychotics, 337, 338f genetics, 233 as SSRI side effect, 356 and life stressors, 766f cognitive circuits, provoking, 233 genotypes regulating dopamine, 765 cognitive functioning, 804 inhibitors, 448 5HT1A receptors and, 349f Met variant, 765 5HT2C receptors and, 349f and norepinephrine, 474 arousal spectrum in ADHD, deﬁcit arousal, subtle molecular abnormalities and, 235f 871f concentration, 646 constant synaptic revision and, 45 and malfunctioning circuits, 645f in depression, 552 treatment options for difﬁculties, 244f dopamine for regulating, 241 conceptual disorganization, 249 dorsolateral prefontal cortex (DLPFC) and, conduct disorder, 425 264f in children and adolescents, 877 enhancers, 921 mania vs., 712, 713 histamine for regulating, 241 connectivity, genes affecting, 304 impaired, 399 constipation in depressed elderly, 913 from conventional antipsychotics, 337, 338f mild in predementia, 908 from NET inhibition, 547 NMDA glutamate hyperactivity “constitutive activity”, 108, 112f hypothesis, 930 coping skills, 191f sedation and somnolence and, 400 coronal plane, for brain visualization, 200f slowing progression, 912 coronary artery disease, from cortisol in fear mesocortical prefrontal cortex and, 263f response, 730 neurons regulating, 204 cortex. See also dorsolateral prefontal cortex norepinephrine projections regulation of, 205 (DLPFC); orbitofrontal cortex; quantifying, 257 prefrontal cortex; ventromedial in schizophrenia, shared with other disorders, prefrontal cortex 259, 260f basket neurons in, 4f serotonin receptors and, 345 dorsal anterior cingulate, 198 sleepiness and, 854 Stroop task and, 238f

1070 Index

inhibitory interneurons in, 4f,6f cortisol, 172, 172f interneurons in, 2 in fear response, 730 limbic, noradrenergic receptor stimulation in, impact on cytoplasmic receptors, 75 547 cost-based selection of antidepressants, 642, mesocortical prefrontal 642f and emotion and cognitive symptoms, cotransmitters, 143 263f pairs, 53t and schizophrenia symptoms, 261, 262f at synapses, 54 somatosensory, 775 craving nicotine, 959 somatosensory association, 196f treatment, 962 spiny neuron input from, 3 with bupropion, 965, 969f visual association, 196f CREB (cyclic AMP response element–binding cortex-to-cortex circuit, 207 protein), 66f cortical arousal, neurotransmitters of, 398f Creutzfeldt-Jakob disease, 901t cortical brainstem glutamate projection, 289f CRF. See corticotrophin releasing factor cortical circuits (CRF) malfunctioning, 224–231 cross-dependence, 945 normal cross titration, 432, 433f stress and, 224f getting caught in, 434f stress sensitization, 225, 225f cross-tolerance, 945 normal, stress and, 224 CRPSs (complex regional pain syndromes), 786 and pyramidal cells, 214–221 “CSTC loop”. See cortical pyramidal neurons cortico-striatal-thalamic-cortical inhibition by 5HT1A receptors, 349f (CSTC) loops interneuron input to, 218f CX516, 445 tuning, in ADHD, 875f CX546, 446 cortico-cortical interactions, 210f CX619/Org 24448, 446 cortico-striatal-thalamic-cortical (CSTC) cyamemazine (Tercian), 331t loops, 209, 211f pharmacological icon, 421f for arousal regulation, 818 cyclic AMP (adenosine monophosphate), 66f attention, 213f disruptions in, 316f emotion, 214f synthesis, 70 executive functioning, 212f cyclic AMP response element–binding protein for hyperactivity, 868f (CREB), 66f impulses, 215f cyclic guanosine monophosphate (cGMP), 57, motor activity, 216f 997, 998f and reward, 949 cyclobenzapine and selective attention, 866f for ﬁbromyalgia, 810 and worry, 726, 727f interaction with MAOIs, 595t corticoaccumbens projections, NMDA d-cycloserine, 441, 443f glutamate receptor hypofunction in, 297f and cognitive behavioral therapy, 761 corticobrainstem glutamate pathways cyclothymic temperament, 456, 459f neurons, 291 with major depressive episodes, 463, 464f and NMDA receptor hypofunction Cymbalta. See duloxetine (Cymbalta, Xeristar) hypothesis of schizophrenia, 288–291 cystic ﬁbrosis, 178 corticocortical circuits, 207–209 cytisine, 960 corticocortical glutamate pathways, 289f cytochrome P450 (CYP450) enzyme systems, NMDA receptor regulation of, 299f 402, 402f corticostriatal glutamate pathways, 289f CYP450 1A2 substrates, 403, 403f corticothalamic glutamate pathways, 289f inhibition, 605f corticotrophin release factor 1 (CRF1) inhibition consequences, 606f antagonists, 663 and smoking, 404, 404f corticotrophin releasing factor (CRF), 754 CYP450 2C9, 404 in stress response of HPA axis, 752, 753f CYP450 2C19, 403

Index 1071

cytochrome P450 (CYP450) enzyme systems delta sleep, 848 (Contd.) delusions, 248, 250 CYP450 2D6, 403, 404, 405f antipsychotic action to reduce, 425 antidepressants as inhibitors, 406f diabolical learning hypothesis and, 230 genetic polymorphism for, 403, 403f link to nucleus accumbens, 704f inhibition, 539, 607f mesolimbic dopamine pathway role in, 272 inhibition consequences, 607f reduction with mesolimbic D2 receptor paroxetine as substrate and inhibitor, 537 block, 336 in risperidone conversion to paliperidone, dementia. See also Alzheimer’s disease 405f behavioral disturbances, 427 substrates, 606f bipolarity in, 467, 467f and venlafaxine conversion, 548, 548f causes, pathology and clinical features, 900 CYP450 3 A/3, 4, 406f cholinergic deﬁciency hypothesis, 918 inhibitors, 407f clinical features, 901t CYP450 3A4, 404, 608 depression as predecessor, 912 combining inhibitors with substrates, 609 future treatments, 935 substrates and inhibitors, 608f with Lewy bodies, 901t inducers, 406, 609 mild cognitive impairment preceding, 908 pharmacokinetic actions, 603 mixed, 902f types, 402 nondegenerative, 903t cytokines, 32, 174 pharmacy, 941f and Alzheimer’s disease, 906 poststroke, cognitive symptoms, 259 cytoplasmic proteins, 13f psychosis with, 412 transport of, 12 selective degenerative, pathological features, cytoskeleton, 8f 900t localization of, 9f symptoms shared with schizophrenia, 258, and slow transport of proteins, 13f 259f support proteins, 10 treatment, 914 acetylcholine increase, 914 d-amino acid oxidase activator (DAOA), 315f for psychiatric and behavioral symptoms, and NMDA receptor regulation, 314, 314f 934 d-amino acid oxidase (DAO), 314, 315f demethylation, 605f Darwin, Charles, 811 dendrites, 1, 2f DAT. See dopamine transporter (DAT) apical, 2, 219f “date rape” drug, 859 in pyramidal cell, 3f daytime sleepiness, 816. See also basal, 2, 219f sleepiness/hypersomnia in daytime in pyramidal cell, 3f excessive, 819f in basket neurons, 4f DBH (dopamine beta hydroxylase), 474 death from excessive neurotransmission, DDC (DOPA decarboxylase), 266, 266f 48f death. See also neurons, cell death in double bouquet cells, 4f premature loss of, sustained symptoms and, 230 atypical antipsychotic agents and, 383 protein synthesis in, 12f risk of, 388f and soma, 6 decongestants spine formation, estrogen and trophic actions and blood pressure, 593 on, 612 interaction with MAOIs, 594f for transport function, 10 interactions with drugs boosting dendritic spines, 2f sympathomimetic amines, 591 dendritic tree, 2f DED (depression-executive dysfunction) branch growth, 34f syndrome, 912 in double bouquet cells, 4f deep brain stimulation, 638, 638f excitotoxicity for pruning, 302 deﬁcit arousal, in ADHD, 870 normal pruning, 46f delta opiate receptors, 977 out of control pruning, 46f

1072 Index

of Purkinje cells, 3 relapse rates, 518f in pyramidal cell, 3f remission rates, 517f Depakote. See divalproex (Depakote) symptom-based algorithm, 645f dependence, 945 with mixed hypomania, 465 dephosphorylation, 73, 149 mixed states of mania and, 467t Depixol (ﬂupenthixol), 331t monoamine hypothesis, 520 Deplin (L-methylfolate), 629 normal monoamine neurotransmitter for bipolar disorder, 699 activity, 487f depressed mood, 260 reduced monoamine neurotransmitter circuits, 492f activity, 487f thyroid hormones and, 633f monoamine receptor hypothesis, 488f depression on mood chart, 454, 454f 5HT1A receptors and, 349f mood stabilizers for treating, 669f anxiety disorder symptom overlap with, 726 neuroimaging of brain activation in, 507f in bipolar disorder neuronal response to sadness vs. happiness, history, 471f 508f response to antidepressants, 472f neurotransmitter receptor hypothesis, 488 sleep disturbances in, 503f overlap with mania, 507 symptoms, 471f pain in, 779, 804 vs. unipolar depression, 468, 469t painful somatic symptoms in, 791f bipolar vs. unipolar, treatment, 701 risk across female life cycle, 615f chronic pain with stress progression to, treatment, 754 duloxetine for, 551 subtle molecular abnormalities and, 193f as suprasegmental central sensitization symptoms, 489, 490f syndrome, 798 matching to circuits, 491f comorbid psychiatric illness with, 647 residual, 517f CSTC loop to regulate, 212 and synapse loss, 25f as dementia predecessor, 912 treating insomnia in, 843 diabolical learning hypothesis and, 230 treatment disease progression in, 519 combination of medications, 652f and erectile dysfunction prevalence, 1001, MTHF vs. folic acid, 627 1001f residual symptoms after, 643 estrogen interaction with monoamines, 621f unipolar, distinguishing from bipolar in females depression, 468, 469t during childbearing years and pregnancy, depression-executive dysfunction syndrome 616 (DED), 912 during menopause, 620f depression pharmacy, 639, 640f over life cycle, estrogen and, 614 depressive psychosis, 249 during perimenopause, 619, 620f depressive temperament, 460f during postpartum period, 619 Deprimyl (Llofrepramine, Gamanil), 597t SNRIs for, 623f descending inhibition, and endogenous opioid SSRIs for, 622f peptides, folate for, in Alzheimer’s disease, 935 descending noradrenergic inhibition, hippocampus sensitivity to, 24, 24f enhancement of, 792f hypotheses for etiology, 488–489 descending serotonergic neurons, and pain, 793f hypothesis for pain perception, 792 desensitization incidence across female life cycle, 615f of ligand-gated ion channel, 138, 143f incidence across male life cycle, 616f of somatodendritic 5HT1A autoreceptors, major, 455f 526, 527f antidepressant combinations as standard, “designer drugs”, 990 651 desipramine (Norpramin, Pertofran), 597t common comorbidities, 650f inhibition of serotonin reuptake pump, 598 genes for, 192 NRI actions, 890 progressive nature of, 472f desmethylclomipramine, 605f

Index 1073

desvenlafaxine, 549, 621 3-[(2, 4-dimethoxy) benzylidene] anabaseine for fibrofog, 810 (DMXB-A), 449 for fibromyalgia, 808 dimethyltryptamine (DMT), 990 icon, 549f diphenhydramine (Benadryl), 846, 847f for neuropathic pain, 792 half-life of, 836f venlafaxine conversion to, 548, 548f direct-acting agonists, 112 desvenlafaxine XR (Pristiq), 541t “dirty drugs”, 542, 542f detoxification, 980, 981f DISC-1 (disrupted in schizophrenia-1), 305, detumescence, 1002 307, 310f dextromethorphan, 593, 718 genes for, 309f interaction with MAOIs, 595, 595t and glutamate synapses strengthening, 308, DHA (docosahexanoic acid), as mood stabilizer, 312f 698 and NMDA receptor regulation, 314f DHF (dihydrofolate), 627, 627f and NMDA regulation, 317 diabetes mellitus, 180 and synapse formation, 308, 311f atypical antipsychotic agents and, 383 and synaptic vesicle transport, 317 from cortisol in fear response, 730 discriminatory pathway, 782f neuropathy with, 550, 795 disease progression, in depression, 519 zotepine and, 418 disinhibition, 346, 612 diabetic ketoacidosis (DKA), 389, 393f disorganized/excited psychosis, 249 clozapine and, 410 disorientation, 249 olanzapine and, 411 distractibility, 506 risperidone and, 413 distractibility circuit, 504f diabolical learning, 229–231, 473 disulfiram, for alcoholism, 977 central sensitization as, 800 divalproex (Depakote), 157t circuit breakdown and worsening symptoms, for schizophrenia, 436 231f adding to antipsychotic, 437f circuit changes, new symptoms and treatment divine mission, 249 resistance, 232f dizziness, from paroxetine withdrawal, 537 psychiatric symptom persistence and circuit DKA. See diabetic ketoacidosis (DKA) breakdown, 230f DLPFC. See dorsolateral prefontal cortex substance abuse and, 948, 951, 953, 959 (DLPFC) diagnosis, categorical approach to constructing, DMT (dimethyltryptamine), 990 240f DMXB-A {3-[(2, 4-dimethoxy) benzylidene] Diagnostic and Statistical Manual of Mental anabaseine}, 449 Disorders (DSM), 178, 645f DNA, 78 bipolar spectrum, 461f regulation of synthesis rate of on depression symptoms, 490f neurotransmitter receptors, 86, 86f on mania symptoms, 500f regulatory regions of, 79f,83 diamine oxidase, and histamine termination, DNA of neuron, 8 828 damage from virus or toxin, 28 dianicline (SSR-591813), 960 docosahexanoic acid (DHA), as mood stabilizer, diarrhea, for serotonin receptor stimulation, 698 531 Dolmatil (sulpiride), 331t diazepam (Valium), 53 clinical actions of, 371 diet, tyramine modifications for MAO pharmacological icon, 423f inhibitors, 584t donepezil, 923 dihydrofolate (DHF), 627, 627f actions, 925f dihydrofolate reductase (DHFR), 627f icon, 924f dihydropyridine “calcium channel blockers”, dopa, 474, 475f 155, 158 dopa decarboxylase (DDC), 266, 266f binding to calcium channel, 159f dopamine, 103, 220, 264, 318f dimebon (Medivation), 941 5HT2A antagonists stimulation of release, dimerization, 611f 351

1074 Index

5HT2A receptors regulation of, 484f psychotropic drugs and, 53 5HT2A regulation of, 563 reciprocal relationship with acetylcholine, 5HT2C receptors regulation of, 486f 338f and acetylcholine activity, 339f reducing hyperactivity with lithium, 709f acetylcholine release inhibition, 340 release agonist actions at 5HT1A receptors and, 377 5HT1A and 5HT2A receptor regulation, amphetamine displacement of, 107f 345, 346 antidepressants impact on synaptic action, 5HT2C receptors and, 349f 520 nicotine and, 964f antipsychotic agents and, 691, 692f nicotinic partial agonists and, 965f and arousal, 856f presynaptic nicotinic heteroreceptors and, in arousal pathways, 396 918f and arousal spectrum, 817, 817f serotonin inhibition of, 352f brain pathways, 268, 272f serotonin receptors influence on, 351f and cognition regulation, 241 serotonin regulation of, 354f for cognitive function improvement, 854 reuptake, 104f COMT gene and, 235f and sexual motivation, 994 deficit in mesocortical projections to synthesis, 266f dorsolateral prefrontal cortex, 274 termination of action, 267f depression from deficiency, 520f and thalamic filter, 294f disinhibition, 578f tuning output with serotonin 2A/dopamine-2 at sertonin 1A receptors, 571–574 antagonists, 365 diverse levels in brain subsections, 275 volume neurotransmission and, 59f dopa conversion to, 474, 475f dopamine agonists, for bipolar disorder, 718 dorsolateral prefontal cortex regulation by, dopamine beta hydroxylase (DBH), 474 265f dopamine D1-selective agonists, 448 fluoxetine and release of, 534f dopamine D2 partial agonists, 342, 374f genes influencing, 265f aripiprazole as, 421 hit-and-run theory, 373f dopamine D2 receptor agonists, 374f increase in prefrontal cortex, NET and, 544 dopamine D2 receptors, 267 and information processing in prefrontal antagonists, 329, 329f cortex, 233 and anticholinergic agents, 339f interaction with serotonin, in nigrostriatal integrated theory of schizophrenia and, dopamine pathway, 353f 334f levels in untreated schizophrenia, 373f mesocortical dopamine pathway and, major projections, 204f 331f massive intracellular amount, consequences, nigrostrial dopamine pathway and, 332f 104 rapid dissociation of, 368f mesolimbic pathway to release, 946 tuberoinfundibular dopamine pathway and, and mood disorders, 474 334f neuronal tuning, 275 blockade in nucleus accumbens, 353 neurotransmission, in prefrontal cortex, 59 continuous occupancy, 415 neurotransmission spectrum, 374f conventional antipsychotic binding to, 365 norepinephrine transporter (NET) and, 94 dilemma of blocking in all dopamine output pathways, 336 untreated schizophrenia and after pure D2 output, 375f antagonist, presynaptic, 267, 269f untreated schizophrenia and after rapid dissociation from, 365, 367 serotonin dopamine antagonist, 366f side effects of unwanted blockade, 382 pharmacologic mechanisms influencing, 265f somatodendritic, 271f as pleasure neurotransmitter, 945 dopamine D3 antagonists, 448 in prefrontal cortex, NET and, 545f “dopamine deficiency syndrome”, 546 projections, 202 bupropion for, 556 prolactin inhibition by, 363f “dopamine hypothesis of schizophrenia”, 273

Index 1075

dopamine neurons, 351 cognitive symptoms and, 264f normal rate of tonic firing, 873 connections, 208 phasic firing of, 875 dopamine deficit in mesocortical projections dopamine neurotransmitter to, 274 as psychotropic drug indirect target, 116 dopaminergic regulation of cognition, 808 as psychotropic drug target, 114 executive dysfunction localization in, 491 dopamine partial agonists (DPAs), 371, 373f and executive function, 212f for aggression management, 427f genes influencing, 265f for cognitive function improvement, 428f inefficient information processing, and in development, 380f distractibility, 504f development of new, 448 information processing involving, 319 for first-line treatment of schizophrenia interactions with ACC, 210f positive symptoms, 425 mesocortical dopamine pathway, 275f integrated theory of schizophrenia and, mesolimbic dopamine pathways in 378f schizophrenia, 331f on market, 380f and n-back test, 234f in mesolimbic pathway, 376f regulation by dopamine and serotonin, for negative symptoms in schizophrenia, 265f 428f and schizophrenia symptoms, 261, 262f and nigrostriatal pathway, 377f and situation analysis of reward, 949 spectrum, 381f dothiepin (Prothiaden), 597t switching from SDA to, 436f double bouquet cells, 2, 4f dopamine receptors, 267, 268f icon drawing, 4f dopamine transporter (DAT), 93, 94, 95f, 266, realistic drawing, 4f 267f double depression, 456, 457f and amphetamines transport, 94, 105f downregulation, 87 blocking, 103 Down’s syndrome, 906 cocaine inhibition of, 983 doxepin (Sinequan, Adapin), 572, 597t and dorsolateral prefrontal cortex, 265f half-life of, 836f excessive occupancy, 554 as hypnotic, 847, 847f modafinil and, 857, 858f doxylamine, 846 reversal of, 108f DPAs. See dopamine partial agonists (DPAs) sertaline for inhibiting, 535 drowsiness. See also sleepiness/hypersomnia in dopaminergic combo, 652f daytime dopaminergic neurons, 266–268 from histamine-1 receptor blockade, 341 MAO subtypes in, 577 drug abuse, 425 dopaminergic projections, and prefrontal cortex by schizophrenic patients, 336 activity, 210f symptoms shared with schizophrenia, 259 dorsal anterior cingulate cortex, 198 drug-induced parkinsonism, 332 and Stroop task, 238f drug-induced psychoses, symptoms shared with dorsal anterior cingulate gyrus, 211 schizophrenia, 258 dorsal horn drug-induced reward, 946 alpha 2 delta ligands in, 800f drug interactions, 408 descending spinal synapses, 789 dry mouth dorsal horn projection neurons, 782 from conventional antipsychotics, 337, 338f classes, 784 from NET inhibition, 547 dorsal raphe, 205 DSM. See Diagnostic and Statistical Manual of dorsal root ganglion (DRG), 775 Mental Disorders (DSM) primary afferent neuron cell bodies in, 782 DU 127090. See bifeprunox (DU 127090) dorsolateral prefrontal cortex (DLPFC), 198, “dual action” serotonin-norepinephrine agents, 202f 544 activation by executive function tests, 865 duloxetine (Cymbalta, Xeristar), 99t, 541t activation of kinases and phosphatases, 233 CYP450 2D6 impact on plasma levels, 607 cognition regulation by, 273, 854 as CYP450 2D6 inhibitor, 607f

1076 Index

for fibrofog, 810 depression, 912 for fibromyalgia, 808 citalopram for, 539 icon, 550f treatment, 913 interactions with fluvoxamine, 604 risperidone for, 412 for neuropathic pain, 792 electrical integrator, axon hillock as, 7f,8 potency for CYP450 2D6 inhibition, 605 electrical signals dynorphins, 789 axon for propagating, 7f,8 dysbindin, 305 and chemical signals, in neurotransmission, genes coding for, 309f 61 and glutamate synapses strengthening, 308, conversion to chemical message, 161f 312f electroconvulsive therapy (ECT), 633 and NMDA receptor regulation, 314f elevated mood circuits, 501f and NMDA regulation, 317 EMD128130 (sarizotan), 380f and synapse formation, 308, 311f emotion vGluT regulated by, 317 amygdala response to input, 324 dysconnectivity, 305 brain component regulating, 200, 262 dyskinesias, dopamine hyperactivity in CSTC loop to regulate, 212, 214f nigrostriatal pathway and, 277, 278f depressed patient neuronal response, 508f dyslipidemia, 385 mesocortical prefrontal cortex and, 263f aripiprazole and, 422 mesolimbic dopamine pathway role in, 274 atypical antipsychotic agents and, 383 processing, 199f blood pressure monitoring, 392 brain areas impacting, 321 ziprasidone and, 417 emotional abuse, and synaptogenesis, 34 zotepine and, 418 emotional learning, amygdala and, 949 dysphoria, in withdrawal syndrome, 980 emotional maturity, constant synaptic revision dysphoric mania, 465 and, 45 dysthymia, 456, 456f emotional/motivation pathway, 784 on mood chart, 454, 454f emotional symptoms, of dementia, 934 unremitting, 457f emotional trauma, circuit response to, 224 dystonia, nigrostriatal pathway dopamine en passant presynaptic axon terminals, 2f deficiencies and, 277 enantiomers, for citalopram, 538 dystrobrevin-binding protein 1, 305 Endep (amitriptyline, Elavil, Tryptizol, Loroxyl), 53, 572, 597t. See also EAAT. See excitatory amino acid transporters nortriptyline (Pamelor, Endep, Aventyl) (EAAT) endocannabinoids (ECs), 57, 57f eating disorders, 771, 1008–1011 endocrine reactions, to fear, 730 and reward circuits, 1010f endogenous growth factors SSRIs for, 522 and neurogenesis in hippocampus, 24, 24f “ecstacy”, 990 promoting production, 24, 26f SERT transport of, 95 “endogenous marijuana”, 57 ECT (electroconvulsive therapy), 633 endogenous opiate neurotransmitters, 980f ectopic sites, hypersensitivity to stimuli, 786 endogenous opioid peptides, and descending Effexor XR. See venlafaxine XR (Effexor XR; inhibition, Efexor XR) endokinins, 664 efficacy, path to, 401f endophenotypes, 181, 182f efficacy profile, 400f endorphins, 789, 946, 947f EGF (epidermal growth factor), 29t energy eicosapentanoic acid (EPA), as mood stabilizer, loss 698 bupropion for, 556 Elavil (amitriptyline, Endep, Tryptizol, as SSRI side effect, 530 Loroxyl), 53, 572, 597t for neurotransmission, 38f elderly enhancer element, of gene regulatory region, 83 antidepressants for, 519, 519f enkephalins, 789, 977 circadian rhythms of, 824, 827f enteric nervous system, 811

Index 1077

enthusiasm, loss estradiol bupropion for, 556 activity-dependent spine formation by, 614f as SSRI side effect, 530 receptors for, 611f environment, 185 estrogen, 66f, 610 factors in ADHD, 870 for Alzheimer’s disease, 937 environmental stress, 187f as GABA inhibitor, 612 genetic abnormalities and, 192–193 as glutamate activator, 612 enzymes impact on cytoplasmic receptors, 75 activation in signal transduction cascade, 64 interaction with monoamines binding to G protein, 70 and depressed mood, 621f fast transport of, 15f vasomotor symptoms from, 524f function of, 170f and nuclear hormone receptors, 610, 611f inhibitors of, 167 regulation and major depression, over female as possible indirect target by psychotropic life cycle, 614 drugs, 171t and sexual motivation, 994 as psychopharmacological drug action site, and trophic actions, on dendritic spine 167–170 formation, 612 substrate binding to, 168f tropic properties, 613f targeted by psychotropic drugs, 170t estrogen receptors, 610 EPA (eicosapentanoic acid), as mood stabilizer, estrogen replacement therapy (ERT), 619, 620, 698 623 ephaptic cross-talk, 786, 787f estrogen response elements, 610, 611f ephedrine, 593 eszopiclone, 839, 839f with MAOIs, and hypertension, 593t and R zopiclone, 842t epidermal growth factor (EGF), 29t, 174 euphoria, from opiates, 977 epilepsy, from improper neuronal migration, euthymia, on mood chart, 454, 454f 29 evidence-based selection of antidepressants, epileptic neurons, 151 algorithm, 641, 641f eplivanserin (SR 46349), 447 excitation-secretion coupling, 60–61, 156, 159, EPS. See extrapyramidal symptoms (EPS) 161f Epworth Sleepiness Scale, 851, 852t excitatory amino acid transporters (EAAT), 94t, ERB signaling system, neuregulin activation of, 100, 101f 317 for glutamate takeup, 281f erectile dysfunction, 999, 1003f excitatory neurotransmission, 42 age and, 1000f “excitotoxic hypothesis of schizophrenia”, 300 pharmacology, 1002 excitotoxicity, 42, 46f,48f, 298, 303f prevalence of, 1000f in ALS, depression and, 1001, 1001f cellular events during, 304f treatment, 1003f in early fetal brain development, 308f erectile function, 1002f and glutamate systems, 301, 440 ERK (extracellular signal-regulated kinase), 76 and neuronal insult, 303 ERT (estrogen replacement therapy), 619, 620, executive dysfunction, 257, 496f 623 in ADHD, 864 erythromycin, and CYP 450 3A4, 609 biological endophenotype for, 233f escitalopram, 99t, 539 localization in dorsolateral prefrontal cortex, icon, 541f 491 eslicarbazepine, 681, 718 symptoms of, 241 actions as mood stabilizer, 683f executive functioning, 198, 650 essential amino acids, 285 in ADHD patients, 873 Essential Psychopharmacology: The Prescriber’s genetic inﬂuence on circuits regulating, 235f Guide (Stahl), 408, 409 impaired estazolam in dementia, 900 half-life of, 835f in schizophrenia, 257 for insomnia, 837f prefrontal cortex synaptogenesis and, 883f

1078 Index

regulation fear conditioning, vs. fear extinction, 756, 759f by CSTC loop, 212f fear extinction, 760 by mesocortical dopamine pathway, 273 fearful faces tests of, 865 and amygdala, 236f exercise serotonin transporter and, 745 and endogenous growth factors, 26f processing, 236f and neurogenesis in hippocampus, 24, 24f females. See women “exercising” the brain, 912 fetus extracellular portion of receptor, 109f brain extrapyramidal symptoms (EPS), 367, 369f excitotoxicity in early development, 308f 5HT2A antagonist to reduce, 351–353 insult and schizophrenia, 303 absence with atypical antipsychotics, 371f survival of wrong neurons, 305 D2 receptor blockage and, 332 insults in neurodegenerative theories of dopamine partial agonism and, 378f schizophrenia, 300f risperidone and, 412 risks of antidepressants to, 618 SDAs and, risks of mood stabilizers and lithium to, 712 from unwanted D2 receptor blockade, 382 valproic acid toxicity, 677 extroversion, in hyperthymic temperament, 460f fibro pharmacy, 810f exuberance, in hyperthymic temperament, 460f fibroblast growth factor (FGF), 29t, 174 “fibrofog”, 552, 808 facilitation pathways, serotonin as transmitter, improving symptoms of, 810 789 fibromyalgia, 777, 784, 805–811 family history, and bipolar diagnosis, 469f American College of Rheumatology criteria, fast transport, 13–15 805t anterograde, 16f comorbid mood and anxiety disorders, 807t low-molecular-weight neurotransmitter desvenlafaxine for, 550 machinery, 18f duloxetine for, 551 of materials, 15f functional somatic syndromes in, 807t neuropeptide machinery, 19f gabapentin for, 688 retrograde, 17f hypothesis for, 806 fasting triglycerides hypothesis for pain perception, 792 antipsychotic agents and, 391f milnacipran for, 551 baseline measurement, 391, 395f pain in muscles, 779 monitoring, 396f pain triggers, 800 quetiapine and, 415 painful somatic symptoms in, 791f rapid elevation of, 387 pregabalin for, 688 risperidone and, 413 as suprasegmental central sensitization ziprasidone and, 417 syndrome, 798 fatigue, 804 symptom-based algorithm, 809f circuits, 495f symptoms, 808f link to prefrontal cortex, 491 tender points for diagnosis, 806f and malfunctioning circuits, 645f treatment, 808 slow-wave sleep deficiency and, 848 “fight or flight”, 722, 731 fear. See also anxiety disorders first-generation antipsychotic agents, 329f affect of, 728f flashbacks, from hallucinogens, 991 autonomic output, 730f flibanserin (Ectris), 574, 1006 CSTC loop to regulate, 212 flight of ideas, 506 endocrine output of, 729f flumazenil, 740, 740f neurobiology, and amygdala, 729 fluoxetine (Prozac), 53, 99t, 532–536, 604 processing, 201 for bulimia, 1011 processing by amygdala, 323f and CYP 450 3A4, 608 serotonin and, 234 as CYP450 2D6 inhibitor, 607f processing response, 731 half-life of, 534 fear circuits, provoking, 234 icon, 533f

Index 1079

fluoxetine (Prozac) (Contd.) G protein-linked receptors, 92f, 105, 109f impact on norepinephrine and dopamine chemical neurotransmission, 70 release, 534f psychotropic drug action on, 107 metabolite of, 405 as psychotropic drug indirect target, 116t olanzapine and, 411 as psychotropic drug target, 107, 114t SERT and serotonin binding prevention by, with agonists, 110–112 97, 98f with antagonists, flupenthixol (Depixol), 331t inverse agonists, 121 fluphenazine (Prolixin), 331t light and dark as analogy for partial flurazepam agonists, 120 half-life of, 835f with no agonist, 108 for insomnia, 837f with partial agonists, 115–119 flurizan, 939 structure and function, 105–107 fluvastatin, 609 superfamily, 110f and CYP 450 3A4, 608 G protein-linked signal-transduction cascades, fluvoxamine, 99t, 405, 446, 537 65, 66f and CYP 450 3A4, 608 binary neurotransmitter receptor complex and CYP450 1A2 inhibition, 603, 605f binding to G protein, 69f icon, 538f elements of, 69f potency for CYP450 2D6 inhibition, 605 first messengers, 67, 69f fMRI (functional magnetic resonance imaging), functional outcome of neurotransmission, 231 68f Stroop task for, 235 later messengers, 71 folate, 627f second messenger, 65, 67 deficiency and monoamines, 630f key elements, 70 for depression, in Alzheimer’s disease, 935 release, 70f folic acid, 627f GABA (gamma-aminobutyric acid), 93, 94t, vs. MTHF, for depression, 627 290f folinic acid (Leucovorin), 626 alcohol actions at synapses, 971 food addiction, treatment, 1009 anxiety and, 732–741 Fos-Jun combination protein, 81f,83f and anxiety disorders, 732–741 Fos protein, 81f,83f, 85–87 and anxiety regulation in amygdala, 241 “Foxy” (5-methoxy-diisopropyltryptamine), 990 anxiolytics, 741 free polysomes, 10f,11 binding sites, 142 free radicals, 306f estrogen and, 610 and Alzheimer’s disease, 906 production, 732, 732f and neuron death, 302, 934 as psychotropic drug indirect target, 117 scavengers for excitotoxicity, 442f as psychotropic drug target, 114, 128, 129 Freud, Sigmund, 983 psychotropic drugs and, 53 frontal lobe, 197 sleep/wake switch regulation, 821, 822f frontotemporal dementia, 901t in thalamus, and insomnia, 820f full agonists, 110, 113f topiramate and, 687 for ligand-gated ion channels, 130 transporters, 100f function, topographical representation of, 211 valproate and, 674 functional G protein-linked receptors, 110t GABA-A allosteric modulatory sites, functional magnetic resonance imaging (fMRI), hypothetical shift in set point, 740 184, 231 GABA-A PAMs, and psychiatric insomnia, 842 blood oxygenation measurement with, 232 GABA agonist site, 737 Stroop task for, 235 GABA-ergic agents, potential therapeutic functional somatic syndromes, 777t effects, 743f functioning circuits, 56f GABA (gamma-aminobutyric acid) possible valproate sites of action, 678f G protein, binding to receptor-neurotransmitter GABA (gamma-aminobutyric acid) A complex, 70 receptors, pentameric structure, 126

1080 Index

GABA (gamma-aminobutyric acid) inhibitor, gamma secretase, 903 estrogen as, 612 inhibitors and modulators, 939, 939f GABA (gamma-aminobutyric acid) gamma units, 153, 155f interneurons, estrogen and, 614f gases, as neurotransmitters, 52t GABA (gamma-aminobutyric acid) neurons, gastrointestinal cramps, for serotonin receptor 292, 293f stimulation, 531 for connecting serotonin and dopamine gastrointestinal upset, from paroxetine neurons, 351 withdrawal, 537 dopamine impact on, 294f GAT, transporters for, 100 release, 351f “gate theory” of pain, 795 and sleepiness circuits, 821f GC (guanylyl cyclase), 997, 998f GABA neurotransmitter, 128t GDNF (glial cell line–derived neurotrophic GABA receptors factors), 29, 29t GABA-A subtypes, 734–741 gene expression mediation of tonic and phasic inhibition, enzymes regulating, 170f 736f messenger triggering of, 64 positive allosteric modulation, 739f neurotransmission regulation of, 78 subtypes, 733, 734f signal-transduction cascades influence, GABA reuptake pump, 732 73–88 GABA transaminase (GABA-T), 733, 733f generalized anxiety disorder (GAD), 723f GABA transporter (GAT), 732 insomnia with, 843 GABA vesicular transporter, 102 pharmacy, 767f GABAergic inhibitory interneurons, 216, symptoms shared with other disorders, 218f 869t gabapentin, 156, 157t treatment, 765 for anxiety disorders, 767 genes binding to alpha-2 delta protein, 158 5HT2A antagonists and expression, 570 channel blocking by, 798f activation in combos for bipolar disorder, 715 early, impact on late, 81f for fibromyalgia, 808 factors affecting, 85 icon, 688f with gene turned on, 79f mechanism of action late, 82f,83f on GABA, glutamate, sigma, and products, 80f dopamine, 676t when gene is off, 79f VSSCs, synaptic vesicles, and carbonic encoding of proteins, 179, 181f anhydrase, 675t hypothetic regulation of mood networks, for panic disorder, 768 506f putative clinical actions, 673t hypothetical path to behavior, 182f for social anxiety disorder, 769 hypothetical path to mental illness, 183f gaboxadol, 842 immediate-early, 80f,83 GAD (glutamic acid decarboxylase), 612, 732 monoamine hypothesis of antidepressant galactorrhea, 278, 336 action on expression, 523f galantamine, 926 in mood disorders, 507–509 actions, 930f quantitative methods measuring abnormal, icon, 929f 185 Gamanil. See Llofrepramine (Deprimyl, regulation by neurotransmitters, 82f Gamanil) as signal-transduction target, 71, 76, 77 gambling, 771 susceptibility, 304 compulsive, 1011 for schizophrenia, 309t gamma-aminobutyric acid (GABA). See GABA genetic abnormalities, degrees, and (gamma-aminobutyric acid) environmental stressors, 192–193 gamma hydroxybutyrate (GHB), 861f genetic G protein-linked receptors, 110t for fibromyalgia, 811 genetic programming, in neurodegenerative for wakefulness, 859 theories of schizophrenia, 300f

Index 1081

genetics in psychiatry, 177 NMDA receptor excitation spectrum by, classic theory, 178, 178f 303f imaging, 223, 233 for open calcium channel, 47f new paradigm, 179 pharmacology, 440 and prefrontal cortex abnormalities in preventing release, 445f ADHD, 870 psychotropic drugs and, 53, 128, 129 genomes, 7 recycled and regnerated, 281f apoptosis programmed into, 28 conversion to glutamine, 282f decoding of incoming signals, 7f glutamine release from glial cells, 282f neurotransmitter signaling between, 61, 63f reducing hyperactivity, with atypical protein orders from, 11 antipsychotics, 710f gepirone, 651, 657 release and anxiety disorders, 743 5HT1A and 5HT2A receptor effect, 361f GHB (gamma hydroxybutyrate), for amyloid plaques and, 927 ﬁbromyalgia, 811 of excessive, 47f ginko biloba, for Alzheimer’s disease, 936 lamotrigine impact on, 683 glial alanine-serine-cysteine transporter from presynaptic neuron, 164 (ASC-T), 280 presynaptic nicotinic heteroreceptors and, glial cell line–derived neurotrophic factor 918f (GDNF), 29, 29t regulation with 5HT1A, 359, 362 glial cells, 31 riluzole to prevent, glutamine release from, 282f serotonin inhibition of, 576f glycine from, 284 serotonin stimulation of, 575f and neuronal migration, 30f role in schizophrenia pathophysiology, 279 glial d-serine transporter, 284f signal transduction of, 163f glial derived neurotrophic factor, 174 susceptibility gene effect on, 317 glial SNAT, 280, 282f synapses, convergence of susceptibility genes glucocorticoid antagonists, 171, 172f for schizophrenia on, 314 potential for clinical use, 172 synthesis, 279 glucocorticoid receptors, 172 topiramate and, 687 glucocorticoids, release as stress response, 753, glutamate receptors, 285, 286f 753f metabotropic, 285, 288f glucose signal propagation, 164f monitoring fasting, 392 types, 287t PET scan to measure uptake, 232 glutamate transporters, 94t, 100, 101f glutamate, 42, 167 structure, 101f 5HT2A antagonists and inhibitory action of as trimers, 101 HT1A on release, 571 glutamatergic corticostriatal projections, agonist actions at 5HT1A receptors and, 377 NMDA glutamate receptor at AMPA and kainite receptors, 147f hypofunction in, 297f antipsychotic agents and, 691 glutamatergic excitatory projections, from binding to NMDA complex, 143 thalamus, 219f calcium channels associated with, 154 glutamic acid decarboxylase (GAD), 612, 732 conversion to glutamine, 100, 280, 281f glutaminase, 280, 282f as cortical pyramidal neuron output, 217f glutamine estrogen as activator, 612 glutamate conversion to, 100, 280, 281f excitotoxicity release from glial cells, 282f amyloid plaques and, 932f glutamine synthetase, 280 system overactivity, 274, 301 glycine, 93, 167, 443f GABA synthesis from, 732 binding to NMDA complex, 143 key pathways in brain, 287, 289f from glial cells, 284 NMDA hypofunction hypothesis of from l-serine, 285 schizophrenia and, 288–291 production, 283 mood stabilizers action on, 708f glycine agonists, 441

1082 Index

glycine receptors, 128t reduction with mesolimbic D2 receptor pentameric structure, 126 block, 336 glycine transporters (GlyT1), 94t, 100, 442 serotonin receptors and, 345 inhibitors, 444f voices in, 248 glycogen synthetase kinase 3 (GSK3), 66f, 173, hallucinogens, 990–993 173f actions, 992f glycogen synthetase kinase (GSK) actions on reward circuits, 991f inhibitors for Alzheimer’s disease, 937 icons, 992f lithium and, 632 haloperidol (Haldol), 331t goal-directed activity happiness circuit, 505f depressed patient neuronal response, 508f turning reward into, 950, 951f loss “God’s pharmacopeia”, 53 bupropion for, 556 “Goldilocks” solution, 118, 133 as SSRI side effect, 530 Golgi apparatus, 8f,84f HDC (histidine decarboxylase), 828f localization of, 9f heat-shock protein 90 (HSP90), 172f protein modification, 11f,12 heavy drinking, 973 grandiose expansiveness, 249 will power to reduce, 975f grandiosity, 506 hemipostsynapse, 39f in hyperthymic temperament, 460f hemipresynapse, 39f inefficient information processing and, hemisynapse, 36, 39f 502f heroic combos, growth cone, axonal, 31, 32f California rocket fuel, 656f docking, 32f SNRI plus modafinil, 657, 657f growth factor SNRI plus NDRI, 656f in brain, 174t SNRI plus stimulant, 656f fast transport of, 15f SSRI plus NDRI, 652f restoration of neurons by, 26f heroin, probability of dependence, 968t transport to soma, 15, 17f HHS. See hyperglycemic hyperosmolar GSI 953, 939 syndrome (HHS) GSK. See glycogen synthetase kinase (GSK) hippocampal dentate gyrus, 24 GSK-3 (glycogen synthase kinase 3), 66f, 173, hippocampus, 199f 173f adult neurogenesis in dentate region, 23f,24f guanfacine, for ADHD, 873, 895f atrophy from excessive glucocorticoid release, guanosine monophosphate (cGMP), 997, 998f 753f guanylyl cyclase (GC), 997, 998f blockade of beta receptors in, 763f guilt, 260 fear extinction and, 760 circuits, 499f and input to lateral amygdala, 760 serotonin and, 493 neurons in, and BDNF, 489 gut, 811 orbital frontal cortex interactions with, 210f CYP450 enzymes in wall, 402 and stress, 759f gut hormones, 52t volume reduction with stress, 748f GW742457, 447 histamine, 828–831 in arousal pathways, 396, 398f H1 histamine receptor, and weight gain, 383 and arousal spectrum, 817, 817f hair loss, as valproic acid side effect, 677 and cognition regulation, 241 Haldol. See haloperidol (Haldol) modafinil for promoting release, 823 hallucinations, 248, 251, 990 neurotransmitter pathways for, 207 5HT2A receptors and, 349f production, 828f 5HT2A receptors effect on glutamate release projections, 209f and, 359 release, 779f antipsychotic action to reduce, 425 sleep/wake switch regulation, 821, 822f link to nucleus accumbens, 704f termination of action, 828, 829f mesolimbic dopamine pathway role in, 272 transporters, 102

Index 1083

histamine 1 receptors, 830f hydroxy-methyl-glutaryl coenzyme A antagonism, 340f (HMG-CoA) reductase inhibitors, for atypical antipsychotic agents and, 385f Alzheimer’s disease, 936 blockade of, 341 hydroxy-pyruvate (OH-pyruvate), 284f and sedation, 397f 9-hydroxy-risperidone, 413. See also and sedation, drowsiness or sleep, 830 paliperidone TCA blockade of, 599 hydroxylation, 606f histamine-1, with serotonin-2C antagonist, and 5-hydroxytryptamine. See serotonin (5HT) appetite stimulation, 387f 5-hydroxytryptophan (5HTP), 343, 344f histamine 2 receptors, 830, 831f hydroxyzine, for anxiety disorders, 767 histamine 3 receptors, 830, 832f hypchondriasis, 771 histamine 4 receptors, 831 hyperactivity, 882 histamine H1 antagonists, as hypnotics, in ADHD, 864, 865f 846–848 circuit, 868f histamine N-methyl-transferase, 828, 829f CSTC loop to regulate, 213, 216f histamine neurotransmitter, as psychotropic of mesolimbic dopamine pathway, 273 drug target, 115 hyperalgesia, 775, 786, 799f histamine receptors, 829f inflammatory process in, 786 TCA antihistamine portion in, 602f hyperarousal, 876f histidine, 828, 828f hyperglycemic hyperosmolar syndrome (HHS), histidine decarboxylase (HDC), 828, 828f 389, 393f “hit and run” binding, 367 clozapine and, 410 homeostatic sleep drive, 820, 823f olanzapine and, 411 horizontal plane, for brain visualization, risperidone and, 413 200f hyperinsulinemia, 383 hormone-linked signal-transduction cascades, hyperprolactinemia, 336 65, 66f 5HT2A antagonists and reduction of, 362 first messengers, 67 from unwanted D2 receptor blockade, 382 second messenger, 65, 67 hypersexuality, 704f later messengers, 71 hypersomnia, 650 hormone nuclear receptor complex, 75 hypertension, 180 hormone response elements (HREs), 66f,75 agents combined with MAOIs causing, 593t hormone–nuclear receptor complex, 66 from repetitive autonomic responses, 731 hostile belligerence, 249 hypertensive crisis, 582, 584, 586t hostility. See aggressiveness reducing risk, 586 HPA axis. See hypothalamic-pituitary-adrenal hyperthermia, 595, 597 (HPA) axis hyperthermia/serotonin syndrome, from HSDD (hypoactive sexual desire disorder), MAOIs and other agents, 595t 1004, 1005f hyperthymic temperament, 460f dopamine and, 1007f with depressive episode, 466f matching to circuits, 1006f hypervigilance, 816 treatment, 1008f hypnotics human brains. See brain alpha 1 selective, 840f human genome, 78 benzodiazepines, 839 human sexual response. See also sexual doxepin as, 847, 847f dysfunction for fibromyalgia, 811 phases, 993–1007 half-lives, 833, 835f arousal, 995 histamine H1 antagonists as, 846–848 libido, 993 long-term effects, 838f orgasm, 999 pharmacy, 849f hunger, and reward circuits, 1010f serotonergic, 845 Huntington’s disease, 178, 901t hypoactive sexual desire disorder (HSDD), 5-hydroxy-indole acetic acid (5HIAA), 483 1004, 1005f in cerebrospinal fluid, 488 dopamine and, 1007f

1084 Index

matching to circuits, 1006f indolealkylamines, 990 treatment, 1008f inflammatory pain, 786, 788f hypoarousal, 871f inflammatory response, in necrotic cell death, hypocretin, and narcolepsy, 820 28f,29 hypomania, 454 information processing on antidepressant, 463 in ADHD, 874f mixed, depression with, 465 in amygdala on mood chart, 454, 454f and depressed mood, 492f protracted or recurrent, 461 serotonin and, 744 hypotension, MAO inhibitors and, 593 by brain, and psychiatric disorders, 201 hypothalamic nuclei, 204 improving, 239 dopamine pathway from, 272f in ADHD, 872, 872f hypothalamic-pituitary-adrenal (HPA) axis, inefficient 752, 753f in ADHD, 864, 865f hypothalamic releasing hormones, 52t in mania, 502f hypothalamus, 202f and sleep disturbances, 503f 5HT3 receptor stimulation, and nausea or in narcolepsy, 855f vomiting, 531 NMDA receptor hypofunction affect, 292 inefficient information processing, and sleep in prefrontal cortex, dopamine and, 233 disturbances, 503f schizophrenia and, 257, 319, 320f orexin-containing neurons in, 820 information transfer, abnormal, 33f and sleep disturbances, 491, 494f inhalants, 993 tuberomammillary nucleus (TMN) of, 819, probability of dependence, 968t 822f inherited disease, classic autosomal dominant ventrolateral preoptic (VLPO) nucleus of, pattern, 178f 819, 822f inhibitors, of enzymes, 167 hypthalamic thermoregulatory centers, 620 inhibitory amino acid transporters, 94t inhibitory interneurons, 2 icon drawing, ligand-gated, 126f chandelier neurons as, 3 structure and function, 125 double bouquet cells as, 4f ILGF (insulinlike growth factors), 29t inhibitory pathways, 789 iloperidone, 368f inositol, for bipolar disorder, 699 imaging genetics, 223, 233 in combos, 714 future, 236 insomnia, 816, 818f “seeing” ancestors in brain, 236 benzodiazepines for, 837f serotonin role in fear processing by amygdala, causes, 833t 234 chronic, 831–839 imaging, of malfunctioning circuits, 231–237 circuits, 820f imipramine (Tofranil), 597t defined, 833t immediate-early gene, 80f,83 diabolical learning hypothesis and, 230 impulsivity, 198, 259, 882 drug treatment action at ionotrophic in ADHD, 864 receptors, 124 circuit, 869f and malfunctioning circuits, 645f CSTC loop to regulate, 213, 215f and medical illnesses, 834t diabolical learning hypothesis and, 230 psychiatric in hyperthymic temperament, 460f and GABA-A PAMs, 842 regulating, 949 treatment, 843f in sexual behavior, 1007 and psychiatric disorders, 834t inactivated state, of voltage-sensitive sodium quetiapine for treating, 415 channels, 152f rebound, 837 inactivation, 138, 139 sleep/wake switch and, 825f inattention, 882 and sleepiness, 853f incertohypothalamic pathway, 204 trazodone for, 566 indiplon, 842 treatment, 128, 646, 823

Index 1085

insomnia/anxiety combo, 652f as psychotropic drug target, 128t insulin, blocking M3-cholinergic recepters to structure and function, 127f reduce, 392f tetrameric structure, 131f insulin family, 174 tetrameric subunit, 129f insulin resistance, 385 tetrameric subunit, top view, 130f atypical antipsychotic agents and, 390f and neurotransmission, 158–167 psychopharmacologist options for, 397f opening, 64 quetiapine and, 415 for prehemisynapse, 43f risperidone and, 413 third messenger opening, 77f ziprasidone and, 417 voltage-sensitive, 92f, 145–158 zotepine and, 418 ionic components, of action potential, 147f insulinlike growth factors (ILGF), 29t ionic filter, 149f integral proteins, 11f,12 of voltage-sensitive calcium channels, 150f integrated dopamine hypothesis of ionotrophic glutamate receptors, 130 schizophrenia, 279, 281f ionotrophic receptors, 123–125, 154, 286, 733 integrins, 32 glutamate, structure, 128 interest, loss ions, 123 bupropion for, 556 iproniazid, 574 as SSRI side effect, 530 IPT (interpersonal therapy), 639 interferons, 174 irreversible enzyme inhibitors, 167, 168f interleukins, 174 irritability, 260 “intermediate phenotypes”, 182, 182f irritable bowel syndrome, 779, 784, 811 International Association of the Study of Pain, diagnostic criteria, 812t 777 pain triggers, 800 International Classification of Diseases (ICD), 178 painful somatic symptoms in, 791f interneurons, 775 irritable mood circuits, 501f in cortex, 2 isocarboxazid (Marplan), 575, 579t inhibitory, 2 isoforms, in GABA-A receptor, 735f GABAergic, 216, 218f ispronicline (TC1734), 941 interpersonal functioning, impaired, in Ixel. See milnacipran (Ixel, Toledomin) schizophrenia, 324 interpersonal therapy (IPT), 639 joy, loss intracellular portion of receptor, 109f bupropion for, 556 intracellular scaffolding proteins, 36, 42f as SSRI side effect, 530 intracellular synaptic vesicle transporters, 93 judgment, distortions in schizophrenia, inverse agonists, 111f 324 actions of, 139f Jun proteins, 81f,83f, 85–87 antagonist to reverse actions of, 141f “junk” DNA, 78 vs. antagonists, 351 antagonists acting in presence of, 140f kainate glutamate receptors, 130 reversal by antagonist, 115 kainite receptors, 286, 286f ion channel-linked receptors, 123–125, 286 glutamate at, 147f CREB activation by, 74 kappa opiate receptors, 977 ion channel-linked signal-transduction ketamine, 144, 993 cascades, 65, 66f for bipolar disorder, 695 first messengers, 67 icon, 696f second messenger, 65, 67 mechanism of action later messengers, 71 on GABA, glutamate, sigma, and ion channels, 36 dopamine, 676t activation, 64f VSSCs, synaptic vesicles, and carbonic fast transport of, 15f anhydrase, 675t ligand-gated, 92f, 123–144 and NMDA receptor regulation, 708f different states, 137 possible actions in bipolar disorder, 698f pentameric subtypes, 126 putative clinical actions, 673t

1086 Index

and schizophrenia symptoms, 289, 440 learning model, and circuit inefﬁciency, 230 site of action, 697f lecozotan, 941 ketoconazole, 405 leptin, 174 and CYP 450 3A4, 609 leucine zipper transcription factor, 81f, 83, 83f, kinase enzymes, 66f 85–87 kinases Leucovorin (folinic acid), 626 activation by receptor activation, 87 levetiracetam, 156, 157f activation in signal transduction cascade, 64, icon, 689f 65f,72 mechanism of action calcium activation of, 74 on GABA, glutamate, sigma, and clash with phosphatase, 73 dopamine, 676t kleptomania, 771, 1011 at SV2A symaptic vesicle sites, 690f VSSCs, synaptic vesicles, and carbonic l-alpha-acetylmethodol acetate (LAAM), 981 anhydrase, 675t L channel, 154, 155t putative clinical actions, 673t la-do (lamotrigine-Depakote), 714, 714f and seizure reduction, 102 la-li-do (lamotrigine-lithium-Depakote), 714, levodopa, for Parkinson’s disease, MAO-B 714f inhibition and, 579 la-li (lamotrigine-lithium), 713, 714f Lewy bodies lactation, 278 damage to cholinergic neurons, 920 Lami-quel, 715, 716f dementia with, 901t lamotrigine, 153f li-do (lithium-Depakote/divalproex/valproate), actions as mood stabilizer, 685f 713, 714f binding site of, 684f libido, decreased, 1004 for bipolar disorder, 701 licarbazepine, 681 with depression, 700 binding site of, 682f combination of medications with, 715, 716f mechanism of action and glutamate reduction, 708f on GABA, glutamate, sigma, and icon, 684f dopamine, 676t mechanism of action VSSCs, synaptic vesicles, and carbonic on GABA, glutamate, sigma, and anhydrase, 675t dopamine, 676t oxcarbazepine conversion to, 681f VSSCs, synaptic vesicles, and carbonic putative clinical actions, 673t anhydrase, 675t lidocaine putative clinical actions, 673t anatomic site of action, 780f rashes from, 683 molecular site of action, 781f for schizophrenia, 436 and VSSC block, 778 adding to antipsychotic, 437f life cycle, antidepressants over, 519, 519f sites of action, on glutamate release, 685f life expectancy, of schizophrenic patients, 250 and VSSCs, 707f lifestyle, and stress, 191f language, odd use of, 257 ligand-gated ion channels, 92f, 123, 126f late gene, 81f agonists impact on, 143f lateral ﬁssure, 196f different states, 137 lateral parabrachial nucleus, 204 GABA receptors as, 733 lazaroids, as free radical scavenger, 442f pentameric subtypes, 126 learning as psychotropic drug target, 128t and brain restructuring, 32 states, 142f constant synaptic revision and, 45 structure and function, 125, 127f and endogenous growth factors, 26f subunit of tetrameric, 129f gene expression and, 78 top view, 130f long-term, 167 tetrameric structure, 131f and neurogenesis in hippocampus, 24, 24f limbic cortex, noradrenergic receptor simulation learning disabilities, from improper neuronal in, 547 migration, 29 limbic CSTC circuit, 868

Index 1087

lipid neurotransmitter, 52t LY450139, 939 lithium, 173, 173f d-lysergic acid diethylamide (LSD), 990 for affective symptoms in schizophrenia, 429 actions, 992f for Alzheimer’s disease, 937 lysosomes, 8f,84f for bipolar disorder, 701 localization of, 9f in combos organelle and protein destruction by, 15, 17f for bipolar disorder, 713 for depression, 562f macrolide antibiotics, and CYP 450 3A4, 609 for depression, 635f magnesium, 142 in bipolar disorder, 700 as negative allosteric modulators, 146f for dopamine hyperactivity reduction, 709f removing block, 167 and fetal toxicity risk, 712 removing from calcium channel, 164f GSK-3 inhibition by, 173 magnetic resonance imaging, functional mechanism of action, 670f (fMRI), 184 as mood stabilizer, 671f Maintenance of Wakefulness Test (MWT), side effects of, 671 852t for suicide reduction, 429, 430f major depressive disorder (MDD), 455f. See also liver depression CYP450 enzymes in, 402 antidepressant combinations as standard, 651 insulin resistance in, 387, 390f common comorbidities, 650f riluzole impact, genes for, 192 valproic acid toxicity, 677 overlap with anxiety disorders, 722f local anesthesia, 775, 780f progressive nature of, 472f and VSSC block, 778 relapse rates, 518f locus coeruleus (LC), 202f remission rates, 517f connection with amygdala, 731 symptom-based algorithm, 645f excessive noradrenergic output from, 755 symptoms shared with other disorders, lofepramine (Deprimyl, Gamanil), 597t 869t long-term outcomes, symptom exacerbation malingering, 784 and, 230 Manerix (moclobemide, Aurorix), 579t long-term potentiation (LTP), 144, 308, 312f mania, 499f Loroxyl (amitriptyline, Elavil, Endep, on antidepressant, 463 Tryptizol), 53, 572, 597t cognitive symptoms, 504f Lou Gehrig’s disease. See amyotrophic lateral core symptoms of episode, 506 sclerosis (ALS) excess neurotransmission and, 47f lovastatin mapping symptoms to circuits, 500f and CYP 450 3A4, 608 mixed states of depression and, 467t risk of muscle damage, 609 on mood chart, 454, 454f low-potency antipsychotic agents, and mood stabilizers for treating, 669f dissociation, 370 neurotransmission instabililty and, 704 loxapine (Loxitane), 331t overlap with depression, 507 5HT6-antagonist properties of, 447 patient response to no-go task, 509f pharmacological icon, 420f prepubertal and adolescent, 712 Loxitane. See loxapine (Loxitane) residual symptoms after ﬁrst-line treatment, LSD (d-lysergic acid diethylamide), 990 703 actions, 992f sleep disturbances in, 503f LTP. See long-term potentiation (LTP) symptoms and circuits, 496, 502f LuAA34893, 552, 552f treatment Ludiomil (maprotiline), 597t with atypical antipsychotic agents, 689, inhibition of serotonin reuptake pump, 598 691f luxapine, 419 with mood stabilizer, 668 LY 293558, 446 MAOIs. See monoamine oxidase inhibitors LY354740, 443 (MAOIs) LY379268, 443 MAPK (MAP kinase), 66f,76

1088 Index

maprotiline (Ludiomil), 597t in dementia, 900 inhibition of serotonin reuptake pump, electroconvulsive therapy and, 634 598 men, depression incidence across life cycle, 616f marijuana, 986 menopause, depression and treatment during, actions on reward circuits, 989f 620f Marplan (isocarboxazid), 575, 579t menstrual cycle, reproductive hormones and “master switch”, 287 synaptogenesis, 613f MDL 100907, 447 “menstrual magnification”, 616 MDMA (3, 4-methylene- “mental exercise”, 45 dioxymethamphetamine), 990 mental illness actions, 992f and brain damage, 228 medial preoptic area (MPOA), and sexual drive, genes and risk for, 177 994 hypothetical path from gene to, 183f medial raphe, 205 model of remission from episode, 228f “medical food”, 629 and smoking, 955 medical illnesses, and insomnia, 834t mental retardation, 426 Medivation (dimebon), 941 from improper neuronal migration, 29 mefipristone, 172 neuron wiring and, 33f MEK (mitogen-activated protein mental stimulation, value of, 49 kinase/extracellular signal–regulated meperidine, interaction with MAOIs, 595, 595t kinase), 66f meprobamate, and anxiety, 767 melanocortin, and sexual desire, 995 mescaline DOM, 990 melanocyte inhibitory factor (MIF-1), 663, actions, 992f 664f mesocortical dopamine neurons, 291 melatonergic agents, 844, 844f mesocortical dopamine pathway, 272f melatonin, 844f and D2 antagonists, 331f half-life of, 836f dopamine output and, 366f melatonin neurotransmitter, as psychotropic secondary dopamine deficiency in, 356 drug target, 114 and serotonin-dopamine antagonism, 359f melatonin-sensitive neurons, in suprachiasmatic to ventromedial prefrontal cortex, 276f nucleus (SCN), 820 mesocortical prefrontal cortex Mellaril (thioridazine), 331t and emotion and cognitive symptoms, 263f and CYP450 2D6 inhibitors, 608 and schizophrenia symptoms, 261, 262f Mem 1003, 940 mesolimbic circuits MEM3454, 449 malfunctioning, and positive symptoms of memantine, 440, 926–934 schizophrenia, 261, 262, 262f for bipolar disorder, 695 and positive symptoms of schizophrenia, 263f possible actions, 698f mesolimbic dopamine hypothesis, 274f mechanism of action, 930, 933f mesolimbic dopamine pathway, 272, 272f on GABA, glutamate, sigma, and blockade of D2 receptor antagonists, 330, dopamine, 676t 330f VSSCs, synaptic vesicles, and carbonic blockade of D2 receptors, 329 anhydrase, 675t dopamine output and, 366f and NMDA receptor regulation, 708f hyperactivity of, 281f putative clinical actions, 673t and thalamus, 297f memory, 201 neurotransmitter regulation, 947f cholinergic fibers and, 206 as pleasure center, 945, 946f formation process, cholinergic neurons and, mesolimbic pathway, dopamine partial agonist 920 in, 376f gene expression and, 78 mesoridazine (Serentil), 331t long-term formation, 144 messenger RNA, 84f BDNF and, 345 met-met carriers, 233 loss metabolic highway, 388f age and, 908 monitoring on, 395f

Index 1089

metabolic pharmacy, 429, 431f for fibromyalgia, 810 metabotropic glutamate receptors (mGluRs), H1 antihistamine actions, 564, 565f 285, 288f half-life of, 835f metformin, 1011 hypnotic actions, 848 methadone, 981 icon, 563f icon, 981f for panic disorder, 768 interaction with MAOIs, 595, 595t SNRI plus, 656f methamphetamine, 983 for social anxiety disorder, 769 icon, 984f mitochondria, 8f, 307f undesirable effects, 984 energy for neurotransmission from, 38f methionine, 233 fast transport of, 14, 15f 5-methoxy-diisopropyltryptamine (“Foxy”), 990 localization of, 9f 6-(S)-5-methyl-tetrahydrofolate (MTHF), 699 mixed hypomania, depression with, 465 methylation, MTHF regulation of, 630 mixed mood state, 454 3, 4-methylene-dioxymethamphetamine MK0752, 939 (MDMA), 990 Moban. See perphenazine (Trilafon) actions, 992f moclobemide (Aurorix, Manerix), 579t methylene tetrahydrofolate reductase (THF-R), for treating nicotine dependence, 967 627f modafinil, 99t, 244f L-methylfolate (Deplin), 629 for ADHD, 873 for bipolar disorder, 699 in adults, 885 in combos, 714 combining with lamotrigine, 715, 716f methylphenidate, 99t, 103, 105 for fibromyalgia, 810 action at dopamine transporter, 105f mechanism of action, 858f action in ADHD, 885 for promoting histamine release, 823 and blood pressure, 593 SNRI plus, 657f vs. cocaine, 983 testing for cocaine abuse treatment, 985 DAT blocking by, 103 for wakefulness, 857 with MAOIs, and hypertension, 593t molecular cascades, neurotransmitter-induced, for wakefulness, 857, 858 impact on postsynaptic proteins, 88 L-5-methyltetrahydrofolate (MTHF), 625, molecular components, for synapse formation, 627f 36, 40f and antidepressants, 631f molecular G protein-linked receptors, 110t vs. folic acid, for depression, 627 molecular memories, and addiction, 959 and methylation reactions, 630 molecules trimonoamine modulation of, 632f conversion by enzyme activity, 167 mGluRs (metabotropic glutamate receptors), subtle abnormalities 285, 288f and depression, 193f mianserin, 559f and schizophrenia, 192f microglia, and Alzheimer’s disease, 906 and SERT, 237f microtubules, 8f,10 variable impact of abnormalities, 185 localization of, 9f molindone (Moban), 331t slow transport of, 14f monoamine autoreceptors, 60 transport of, 13 volume neurotransmission and, 60f mild cognitive impairment, 908 monoamine neurotransmitters, 453 milnacipran (Ixel, Toledomin), 99t, 541t monoamine oxidase inhibitors (MAOIs), for fibrofog, 810 574–597 for fibromyalgia, 808 with amphetamine actions, 579t icon, 551f currently approved, 579t for neuropathic pain, 792 drug interactions, 591 mirtazapine, 446, 559f interaction with decongestants, 594f actions at serotonin synapses, 564f interaction with SRIs, 596f actions overview, 566f irreversible, dangerous tyramine levels with, for anxiety disorders, 767 592f

1090 Index

new developments, 585 mood networks, genes hypothetically for panic disorder, 768 regulating, 506f tyramine dietary modifications for, 584t mood stabilizers, 406, 426, 668. See also lithium monoamine oxidase (MAO), 112, 170, 221f for aggression management, 427f and dopamine breakdown, 267, 267f anticonvulsants, 672. See also specific agents enzymes, 579t atypical antipsychotic agents, 689, 694f and norepinephrine, 474, 476f in clinical practice, 700–718 subtype A inhibition, 580f pharmacy, 700, 701f combined with subtype B inhibition, 583f residual symptoms after first-line and dietary tyramine management, 582 treatment, 702–710 and tyramine, 586f selection process, 700 subtype A, norepinephrine destruction by, symptom-based algorithm for sequential 584f treatment, 700 subtype B inhibition, 581f combinations for bipolar disorder, 713 transdermal delivery, 588–591 definition, 668 subtypes, 577 and fetal toxicity risk, 712 monoamine transporters, 15, 94, 94t,95f, 99, future options, 718 219f gender differences, 712 binding sites, 96f,97f and glutamate, 708f presynaptic, 93t mechanism of action as targets of antidepressants and stimulants, on GABA, glutamate, sigma, and 99t dopamine, 676t monoamines, 15 VSSCs, synaptic vesicles, and carbonic coupled with neuropeptide, 54 anhydrase, 675t estrogen interaction with, and depressed putative clinical actions, 673t mood, 621f for schizophrenia, 436 “fine-tuning” action on pyramid cells, 220 adding to antipsychotic, 437f folate deficiency and, 630f symptom-based algorithm input to enhance signal, 220f deconstructing mania/bipolar spectrum interaction with estrogen, vasomotor disorder symptoms, 703f symptoms from, 524f deconstructing mania diagnostic molecular sites for regulating, 221f symptoms, 702f regulating “tuners”, 221 symptom matching to circuits, 704f monohydroxyderivative, 681 targeting neurotransmitters, 705f mood for treating depression, 669f 5HT2C receptors and, 349f for treating mania, 669f norepinephrine projections regulation of, and VSSCs, 707f 205 morphine, 977 serotonin projections regulation of, 205, 206f brain production of, 53 serotonin receptors and, 345 motivation mood chart, 454f mesolimbic dopamine pathway role in, 272 mood disorders reduction in, 251, 276 comorbid with fibromyalgia, 807t motor activity description, 454 as antipsychotic side effect, 341 future treatments for, 659–664 CSTC loop to regulate, 216f genes and neuroimaging in, 507–509 disturbances, 248 mapping, 454f dopamine and prevention of side effects, 370 neurotransmitters and circuits in, 474–480 in fear, 730 with pain, 802, 803f nigrostrial dopamine pathway to control, pain linked to, 804, 804f 277 prevalence of, 468f motor behavior, CSTC loop to regulate, 213 progressive nature of, 470–473 motor skills, constant synaptic revision and, 45 treatment-resistant, 473 movement, neurons regulating, 204 mood episodes, 455f mRNA, and peptide production, 11f

Index 1091

MTHF. See L-5-methyltetrahydrofolate formulations, 975f (MTHF) icon, 973f mu opioid receptors, 789, 977 for reversing opiate action, 979 alcohol actions on, 973 testing for cocaine abuse treatment, 986 Multiple Sleep Latency Test (MSLT), 852t for treating nicotine dependence, 967 muscarinic-1 agonists, 449 NAMs (negative allosteric modulators), 145f muscarinic-1 receptors narcolepsy, 820, 873 atypical antipsychotic agents and, 385f gamma hydroxybutyrate for, 859 and sedation, 397f information processing in, 855f muscarinic 3 (M3) antagonism, and symptoms shared with other disorders, 869t antipsychotic agents, 393f Nardil (phenelzine), 575, 579t muscarinic cholinergic receptors, 547, 916f natural disaster, stress vulnerability, 193, 194f antagonism of, 390 “natural highs”, 945, 947f blockade from conventional antipsychotics, nausea 337, 338f from 5HT3 receptor stimulation, 531 blocking to reduce insulin release, 392f bifeprunox and, 424 subtypes, 917 from venlafaxine, 549 TCA blockade of, 599 Navane (thiothixene), 331t myelination, of axon fibers, 22 NCAMs (neuronal cell adhesion molecules), myocardial infarction 31t,32 antipsychotic agents and, 417 NDDIs (norepinephrine dopamine from repetitive autonomic responses, 731 disinhibitors), 658 myocarditis, clozapine and, 410 NDRIs. See norepinephrine and dopamine myoclonus, from SSRIs, 531 reuptake inhibitors (NDRIs) NE. See norepinephrine (NE) N-acetyl cysteine, 986 NE reuptake pump, 474 n-back test, 233, 233f NE transporter (NET). See norepinephrine and dorsolateral prefrontal cortex, 234f transporter (NET) by narcolepsy patients, 855f necrosis, and apoptosis, 28f in schizophrenia, 321f nefazodone, 405, 572, 639 N channels, 154, 155t and CYP 450 3A4, 608 inhibitors of, 158f icon, 567f and neurotransmitter release, 156 negative affect, 499f neurotransmitter release regulation, 155, 156f increased, 495 N-methyl-d-aspartate (NMDA) glutamate vs. reduced positive affect, 643 receptors, 130, 142, 164f negative allosteric modulators (NAMs), 141, cotransmitter binding to, 143 145f N-methyl-d-aspartate (NMDA) glutamate magnesium as, 146f system, development abnormalities, 274 negative feedback regulatory signal, 476 N-methyl-glycine, 442 Negative Symptom Assessment, 253t N-methyl -histamine, 829f negative symptom pharmacy, 427, 428f N-methyl indole acetic acid (N-MIA), 828, nemifitide, 663, 664f 829f nemonapride, 368f N-methyl loxapine, 419 nerve growth factor (NGF), 29, 29t,57f N-MIA (N-methyl indole acetic acid), 828, nerve impulse propagation, in presynaptic 829f neuron, 160f nalmefene, for alcohol dependency, 976 nerves, normal, and severed, 785f naloxone NET. See norepinephrine transporter (NET) in detoxification process, 981 net agonists, 134 for reversing opiate action, 979 net antagonists, 134 naltrexone, 769 netrins, 32 actions, in ventral tegmental area (VTA), 974f neurasthenia, 805 for blocking mu opiate receptors, 973 neuregulin, 305, 310f in combos for bipolar disorder, 715 genes coding for, 309f

1092 Index

and glutamate synapses strengthening, 312f neurotransmission and, 48f and NMDA receptor regulation, 314f preventing in schizophrenia, 440 and NMDA regulation, 317 chandelier, 3 and synapse formation, 308, 311f communication between, 55f,57f neuroanatomy, 196 components, 8, 8f neurodegeneration, 34f fast transport of, 16f and synapse loss, 25f localization of, 9f neurodegenerative disorders, 35 cyclical activation, estrogen and, 612 neurodevelopment, 34f damage from virus or toxin, 28 disorders, 34 dopaminergic, 266–268 neuron wiring and, 33f double bouquet cells, 2 and neuronal selection, 27f electrical impulse in, 145 process, 23f formation during prenatal gestation, 22 time course of, 22, 22f generic structure, 2f neurofibrillary tangles, in Alzheimer’s disease, internal operations, subcellular organelles, 901 6–10 formation process, 906, 927 loss of, sustained symptoms and, 230, 232f neurofilaments, 8f,10 noradrenergic, 474–476 localization of, 9f postsynaptic, signal propagation, 163f slow transport of, 14f presynaptic, nerve impulse propagation in, transport of, 13 160f neurogenesis, 24 restoration by growth factor, 26f adult, in hippocampus dentate region, 23f,24f sensitivity to calcium, 305f from gene expression, 78 spiny, 2–3 neuroimaging structural and regulatory molecules of, 10f in depression, 507f structure of unique, 1–6 in mood disorders, 507–509 pyramidal cells, 2–6 neurokinin antagonists, 449, 664 varieties of, 1–6 neurokinin receptors, 665t wiring of neurokinins, 52t correct, 33f targeting with antidepressants in wrong, 33f development, 660t neuropathic pain, 775, 784, 797f neurolepsis, 276, 329, 396 peripheral mechanisms, 785 neuroleptic-induced deficit syndrome, 330 and sympathetic nervous system, 786 neuroleptic-induced tardive dyskinesia, 277 neuropeptides neuroleptic malignant syndrome, 342 coupled with monoamines, 54 neuroleptics, 329 fast transport of machinery for, 19f neuromas, 785 function in neurotransmission, 15 neuronal cell adhesion molecules (NCAMs), transporters, 102 31t,32 neuropoietic cytokines, 174 neuronal circuitry, and psychiatric disorders, 223 neuropsychological assessment batteries, neuronal migration, 29, 30f 257 neuronal presynaptic reuptake pump, 285 neurosteroids, targeting neuronal selection, 27–29 benzodiasepine-insensitive GABA-A and neurodevelopment, 27f receptors, 737 neuronal transport, 12–20 neurotensin antagonists, 450 neurons, 21 neurotransmission. See also chemical anatomic zones of, 7f neurotransmission arborization, 35f anatomical basis, 21 basket, 2 and cell death, 48f branching or arborization of, 22 chemical basis, 21 cell death, 29 classic, 54, 55f excitotoxic mechanism and, 304f energy for, 38f glutamate activity and, 301 excess, 47f

Index 1093

neurotransmission (Contd.) neurotrophic factors, 29, 29t,57f functional outcome in G protein-linked 5HT6 receptors and, 349f system, 68f and axonal traffic direction, 32f and ion channels, 158–167 constant synaptic revision and, 45 nonsynaptic diffusion, 58 neurotrophin-linked signal-transduction preventing, 156 cascades, 65, 66f retrograde, 57f,61 first messengers, 67 sensitivity of, 88 later messengers, 71 unstable and excessive in bipolar disorder, 706f second messenger, 67 volume, 58, 58f neurotrophins (NT), 29t,75 neurotransmitter-induced molecular cascades, and axon sprouting, 32f impact on postsynaptic proteins, 88 in brain, 174t neurotransmitter nodes, 201–207 control of axon growth, 31 neurotransmitter receptor hypothesis of second messenger, 66 depression, 488 NGB2904, testing for cocaine abuse treatment, neurotransmitter receptors 986 binding to, 70 NGF (nerve growth factor), 29, 29t,57f change in number of pre- and postsynaptic, nicotine, 955, 960f 38 abuse by ADHD patients, 870, 880 regulation of, 85f actions, 957f subtypes, 111f dependence/addiction, 955–959 neurotransmitters, 8f, 36, 51–54 alternate delivery to treat, 960 activation of signal-transduction cascades, probability of developing, 964 66f treatment, 959–968 and arousal spectrum, 817, 817f dependency/addiction, properties, 918 changes in receptor sensitivity, 521 and dopamine release, 964f for circuit regulation, 241 probability of dependence, 968t of cortical arousal, 398f response to administration, 966f in depression treatment, 652f nicotinic full agonists, 960 in dorsal horn, 782, 783f nicotinic partial agonists (NPA), 449 fast transport for, 14, 15, 15f and dopamine release, 965f fast transport of machinery for, 18f molecular actions, 961f gene regulation by, 82f response to, 967f glutamate as, 279 nicotinic receptors influence on CTSC loops, 210 acetylcholine, 917, 917f ion channels opened by, 124 allosteric modulation, 919f linking symptoms to circuits to, 731f alpha 4 beta 2, 959, 960f linking worry symptoms to circuits to, 764f reinforcement and, 958f listing, 52t cholinergic, 139, 955 matching to circuits, 243f calcium channels associated with, 154 naturally occurring, 53 pentameric structure, 126 and orgasm, 999f desensitization, 956 for prehemisynapse, 43f presynaptic, 918f presynaptic release of, 161f nigrostriatal dopamine pathway, 272f reception of released, 164 antipsychotic agent binding to postsynaptic receptor hypothesis of antidepressant action, D2 receptors, 358f 522f and D2 antagonists, 332f sexual arousal and, 997f dopamine output and, 366f slow-onset signaling and dopamine partial agonists (DPAs), 377f AtoB,62f serotonin 2A antagonists in, BtoA,63f serotonin-dopamine interaction, 353f transporters, 93f serotonin regulation of dopamine release, classification and structure, 92, 93 354f vesicular, 94t “Nissl substance”, 11

1094 Index

nitric oxide (NO), 57, 57f node, 197 psychopharmacology, 996 nodes of Ranvier, 785, 786f and sexual arousal, 998f nondegenerative dementias, 903t nitric oxide synthetase, inhibiting, 537 nonsteroidal anti-inflammatory drug (NSAID) nitric oxide synthetase (NOS), 997 cyclooxygenase (COX-2) inhibitors, 787 NK1 antagonists (substance P antagonists), 665 nonsteroidal anti-inflammatory drugs NK3 antagonists, 665 (NSAIDs), for Alzheimer’s disease, 937 NMDA glutamate hyperactivity hypothesis, 930 nonsynaptic diffusion neurotransmission, 58 NMDA (N-methyl-d-aspartate) antagonists, noradrenaline. See norepinephrine (NE) 440, 441f noradrenergic and specific serotonergic NMDA (N-methyl-d-aspartate) receptors, 286, antidepressant (NaSSA), mirtazapine as, 286f 563f blocking glutamate actions at, 708f noradrenergic inhibition, descending, enhancement of activity, 444f enhancement of, 792f excitation spectrum by glutamate, 303f noradrenergic neurons, 474–476 genes affecting, 304 descending, and pain, 791f and glutamate systems, 283, 284f MAO subtypes in, 577 histamine action at, 831 norepinephrine and dopamine reuptake hypofunction, 446 inhibitors (NDRIs), 99t, 552–556 hypofunction hypothesis of schizophrenia, action, 553f 290f actions in prefrontal cortex and striatum, 555f and corticobrainstem glutamate pathways, icon, 553f 288–291 SNRI plus, 656f hypofunction in glutamatergic corticostriatal SSRIs plus, and corticoaccumbens projections, 297f “norepinephrine deficiency syndrome”, 546 ketamine binding to, 697f norepinephrine dopamine disinhibitors long-term potentiation (LTP) triggered by, (NDDIs), 658 312f mirtazapine as, 563 normal excitatory neurotransmission of, 302f norepinephrine dopamine inhibitors (NDRIs), production, 283 for fibromyalgia, 810 regulation of corticocortical glutamate norepinephrine (NE), 220, 453. See also pathways, 299f serotonin norepinephrine reuptake requirements for active, 443f inhibitors (SNRIs) susceptibility gene regulation of, 317 5HT2A receptors regulation of, 484f synapses with, 313f and alpha 2 antagonists, 560f and synaptogenesis, 308 antidepressants’ enhancement of, 98 NNDI. See norepinephrine and dopamine antidepressants impact on synaptic action, disinhibitors (NDDI) 520 nociception, 775, 777 antipsychotic agents and, 691, 692f activity-dependent, 795 in arousal pathways, 396, 398f acute pain, 796f and arousal spectrum, 817, 817f neuropathic pain, 797f autoreceptors as gatekeepers, 478f pathway to pain, 782f depression from deficiency, 520f nociceptive nerve fibers and depression symptoms, 546 activation, 778f disinhibition, 562f normal pain and, 778 at sertonin 1A receptors, 571–574 nociceptive pain fluoxetine and release of, 534f acute, and opiates, 790f hyperactivity in anxiety, 755, 757f peripheral blockade of acute, 780f blocking, 758f nociceptive pathways and mood disorders, 474 to spinal cord, 778 normal destruction by MAO-A, 584f from spinal cord to brain, 782 projections, 204, 205f nociceptive transduction, 779f psychotropic drugs and, 53 nociceptor, 775 regulation of seretonin release, 476, 480, 480f

Index 1095

norepinephrine (NE) (Contd.) with interpersonal psychotherapy, 639 as accelerator, 482f NRI actions, 890 bidirectional control, 483f “not otherwise specified” (NOS), 461 as brake, 481f novel peptides, 664f release noxious stimulus, 775 5HT2C receptors and, 349f NRA0562, 368f presynaptic alpha 2 receptor regulation, NRI. See norepinephrine selective reuptake 475 inhibitors (NRIs) serotonin regulation of, 477 NSAIDs (nonsteroidal anti-inflammatory tyramine and, 585f drugs), for Alzheimer’s disease, 937 synthesis, 474, 475f NT (neurotrophins), 29t termination of action, 474, 476f nuclear hormone receptors, 67, 171, 172f transport pump, 474 and estrogen, 610, 611f tricyclic antidepressant to block reuptake as possible target by psychotropic drugs, 171t pump, 598 nuclear ligand–activated transcription factors, turning off its own release, 558 610, 611f norepinephrine neurons nucleus raphe magnus, 789 normal rate of tonic firing, 873 nucleus, 8, 8f phasic firing of, 875 localization of, 9f norepinephrine neurotransmitter nucleus accumbens, 202f as psychotropic drug indirect target, 116 5HT2C receptors regulation of dopamine, as psychotropic drug target, 114 486f norepinephrine receptors, 477f D2 receptor blockade in, 353 norepinephrine reuptake inhibition (NRI), 420f and delusions and hallucinations, 704f to desensitize excessive arousal systems, 877 as pleasure center, 329 norepinephrine reuptake pump, 544 rewarding input to, 948f norepinephrine selective reuptake inhibitors and schizophrenia symptoms, 262, 262f (NRIs), 99t, 448 nucleus basalis (of Meynert), 206, 920 actions, 558f nucleus linearis, 205 for fibromyalgia, 810 “number needed to harm”, 333, 417 icon, 557f plus mirtazapine, 656f obesity, 1008 plus modafinil, 657f 5HT2C receptors and, 349f plus NDRI, 656f atypical antipsychotic agents and, 383 plus stimulant, 656f blood pressure monitoring, 392 norepinephrine transporter (NET), 93, 94, 95f, peptide treatments for, 450 474, 475, 476f serotonin receptors and, 345 cocaine ability to inhibit, 983 treatment, 1009 inhibition, 557 observation, for negative symptom identification and dopamine in prefrontal cortex, 544, in schizophrenia, 252, 254f 545f obsessions, 764 high degrees of, and sedation, 558 diabolical learning hypothesis and, 230 by norquetiapine, 415 obsessive compulsive disorder, 725f potential side effects, 546 fluvoxamine for, 537, 538 therapeutic actions of, 546 pharmacy, 771f norfluoxetine, 405 treatment, 770 Norpramin. See desipramine (Norpramin, obstructive sleep apnea, 855 Pertofran) symptoms shared with other disorders, 869t norquetiapine, 414, 414f occipital lobe, 196f actions as mood stabilizer, 693f OH-pyruvate. See hydroxy-pyruvate pharmacological actions, 693f (OH-pyruvate) nortriptyline, 572 olanzapine, 403, 403f nortriptyline (Pamelor, Endep, Aventyl), 597t 5HT6-antagonist properties of, 447 inhibition of serotonin reuptake pump, 598 actions as mood stabilizer, 693f

1096 Index

for alcohol dependency, 977 Org 25501, 446 and antagonism of muscarinic cholinergic Org 25573, 446 receptor, 392f organelles. See also subcellular organelles and cardiometabolic risk, 386t destruction of discarded, 15 in combos for bipolar disorder, 713 retrograde transport of discarded, 17f as CYP 2D6 substrate, 404, 405f orgasm, 999 and diabetes, 417 and neurotransmitters, 999f fluoxetine with, 533 orlistat, 1010 half-life of, 835f osanetant (SR142801), 450 M3 receptors blocked by, 392f overconfidence, in hyperthymic temperament, pharmacological actions, 693f 460f pharmacological icon, 411f oxcarbazepine, 153f potency, and dissociation, 371 actions as mood stabilizer, 683f raising levels of, 406f binding site of, 682f for sedation, 431 converion to licarbazepine, 681f testing for cocaine abuse treatment, 986 for fibromyalgia, 811 and weight gain risk, 386t mechanism of action olfactory bulb, 23f,24 on GABA, glutamate, sigma, and omega-3 fatty acids dopamine, 676t for Alzheimer’s disease, 937 VSSCs, synaptic vesicles, and carbonic for bipolar disorder, 698 anhydrase, 675t in combos for bipolar disorder, 714 putative clinical actions, 673t ondansetron, 977 and VSSCs, 707f OPC 4293, 375 open state, of voltage-sensitive sodium P/Q channels, 154, 155t channels, 152f inhibitors of, 158f opiate receptors, 980f and neurotransmitter release, 155, 156, 156f opiates, 977–981 P75 (proaptotic receptors), 29t actions on reward circuits, 979f pain, 775. See also chronic pain; fibromyalgia acute nociceptive pain and, 790f acute vs. chronic, 775t dependency/addiction, treatment, 980 in affective spectrum disorders, 802 for fibromyalgia, 811 definitions, 775 interaction with MAOIs, 595, 595t from Internaional Association of the Study reward and, 977 of Pain, 777 withdrawal, 979 in depression, 650 opioid peptides, 52t descending noradrenergic neurons and, 791f oppositional defiant disorder, 425 diabolical learning hypothesis and, 229 in children and adolescents, 877 in disorder diagnosis, depression and anxiety optimism, in hyperthymic temperament, 460f with, 803 Orap. See pimozide (Orap) evaluating, 812t orbitofrontal cortex, 198, 199f excessive excitatory neurotransmission and, CSTC loop from, 212 43 and impulsivity, 869f explained, 774 interactions with ACC, 210f gabapentin for, 687 manic episode symptoms linked to, 506 “gate theory”, 795 prefrontal projections from, 949 link to mood and anxiety, 804, 804f risk taking and, 502f nociception to, 782f and schizophrenia symptoms, 261, 262f numerical rating scale for monitoring, 813t orexin, and narcolepsy, 820 opening gate from inside, 800 orexin-containing neurons pregabalin for, 687 in hypothalamus, 820 preventing permanent syndromes, 802 sleep/wake switch regulation, 822f preventing progression to chronic persistent, Org 24292, 446 802 Org 25271, 446 psychopharmacologists view of, 777

Index 1097

pain diaries, 813t partial agonists, 111f pain relievers, opiates as, 977 actions on ion channel, 136f paliperidone, 404, 405f antagonist acting in presence of, 138f actions as mood stabilizer, 693f vs. antagonists, 378f in combos for bipolar disorder, 713 light and dark as analogy for, 120 pharmacological actions, 693f net effect, 137f pharmacological icon, 413f reversal by antagonist, 115 and sedation, 432f PBN. See parabrachial nucleus (PBN) sedation risk with, 430 PCP. See phencyclidine (PCP) Pamelor. See nortriptyline (Pamelor, Endep, peptides, 8f, 12, 52t Aventyl) novel, 664f pancreas, valproic acid toxicity, 677 synthesis, 11f panic attacks, 731 perceptual distortions, 248 excess neurotransmission and, 47f periaqueductal gray matter, 204, 789 from hallucinogens, 990 and avoidance, 728f panic disorder, 723f dopamine pathway from, 272f benzodiazepine agonist spectrum in, 742f and motor responses to fear, 730 in children, 713 perimenopause MAO inhibitors for, 575 depression and treatment during, 619, 620f pharmacy, 768f depression risk during, 615f treatment, 768 desvenlafaxine for reducing symptoms, 550 panic, excessive excitatory neurotransmission periodic limb movement disorder (PLMD), and, 43 834t parabrachial nucleus (PBN) peripheral afferent neurons dopamine pathway from, 272f incoming synapses from, 787 lateral, 204 neuropathic pain and, 785 and respiratory changes, 729f peripheral pain, 774 paranoia, 324 vs. central pain, 776t paranoid projection, 249 peripheral proteins, 12 paranoid psychosis, 249 perospirone, 419, 559f from stimulants, 985 pharmacological icon, 419f paraphilias, 771 peroxisome proliferator activated receptor paraventricular nucleus, and sexual drive, 994 (PPAR) gamma agonists, for paresthesias, 786 Alzheimer’s disease, 936 parietal lobe, 196f perphenazine (Trilafon), 331t parkinsonism personality drug-induced, 332 change in dementia, 900 from SSRIs, 531 and stress, 191f Parkinson’s disease, 638 as stress buffer or ampliﬁer, 190–191 dementia, 920 Pertofran. See desipramine (Norpramin, dopamine agonists for treatment, 267 Pertofran) excitotoxicity and, 48f PET (positron emission tomography), 231 levodopa for, MAO-B inhibition and, 579 to measure glucose uptake, 232 nigrostriatal pathway dopamine deﬁciencies phantom pain, 795 and, 277, 278f pharmacodynamics, 402 protoxins and, 582 pharmacokinetics, 402 quetiapine for, 415 pharmacologic G protein-linked receptors, transplantation of fetal substantia nigra cells 110t for, phase advanced circadian rhythms, 827f Parnate. See tranylcypromine (Parnate) phase delayed circadian rhythms, 826f paroxetine, 99t, 536, 604, 606f phencyclidine (PCP), 144, 696, 993 CYP450 2D6 impact on plasma levels, 607 and schizophrenia symptoms, 289, 290, 440 as CYP450 2D6 inhibitor, 607f phenelzine (Nardil), 575, 579t icon, 537f phenethylamine, 577

1098 Index

phentermine, with MAOIs, and hypertension, mesolimbic dopamine pathway as, 945, 946f 593t nucleus accumbens as, 329 phenylalkylamines, 990 PLG (L-prolyl-L-leucy-L-glycinamide), 663 phenylephrine, 592 PLMD (periodic limb movement disorder), with MAOIs, and hypertension, 593t 834t phenylpropanolamine, 593 PMDD (premenstrual dysphoric disorder), 616 with MAOIs, and hypertension, 593t SSRIs for, 522 phosphatase, 170f PMS (premenstrual syndrome), 616 activation in signal transduction cascade, 65f, PNU 9639/OSU 6162, 380f 74f polyamine site, 831 calcium activation of, 74 polypharmacy, 436, 438f clash with kinase, 73 polysialic acid–neuronal cell adhesion molecules as messenger in cascade, 64 (PSA-NCAM), 31t removal of phosphates from proteins, 76f polysomes, 8f phosphates in dendrites, 12 kinase activation to add to phosphoproteins, free, 10f,11 75f localization of, 9f removal from proteins, 76f POMC (pro-opiomelanocortin), 977, 980f phosphodiesterases (PDE), 997, 1002 pore, for VSCCs, 153 phosphoproteins, 64f, 149, 173f positive affect, 499f creation, 64, 65f reduced, 495 phosphates added to, 75f vs. increased negative affect, 643 removing phosphatase from, 64, 65f positive allosteric modulators (PAMs), 130, as signal-transduction target, 71 141, 144f phosphorylation, 73–78, 149, 795 benzodiazepines as, 146f abnormal, and neuroﬁbrillary tangles, for insomnia, 838f 902 Positive and Negative Syndrome Scale, 253t physical abuse, and synaptogenesis, 34 positron emission tomography (PET), 231 Pick’s disease, cognitive symptoms, 259 to measure glucose uptake, 232 piloerection, opiate withdrawal and, 980 posthemisynapse, required elements for, 43f pimozide (Orap), 331t postpartum period combining 3A4 inhibitor with, 609 and bipolar mood episodes, 711 and CYP 450 3A4, 608 depression and treatment during, 619 pindolol, 651 depression risk during, 615f pineal gland, melatonin secretion from, 844 postpartum psychosis, 619 pipothiazine (Piportil), 331t poststroke dementia, cognitive pituitary symptoms, 259 regulation of prolactin secretion, 362 postsynaptic dendrites, 37f SPA action in, 377 incoming signals from, 7, 7f pituitary peptides, 52t postsynaptic density proteins, 10 pizza, tyramine content of commercial-chain, postsynaptic elements, 36 588f postsynaptic neurons placebo, 514 nerve impulse propagation, 165f response rates, 515f presynaptic neuron genome communication substitution, 516f to genome, 61 plasma membrane transporters, 93 signal propagation, 166f pleasure “talk back” to presynaptic neurons, 54, 57f loss postsynaptic receptors bupropion for, 556 and norepinephrine, 475 as SSRI side effect, 530 for posthemisynapse, 43f mesolimbic dopamine pathway role in, 272, for synaptic formation, 36 276 postsynaptic response, increasing, 41 reduce ability to experience, 251 postsynaptic serotonin receptors, excessive pleasure center stimulation of, 597

Index 1099

postsynaptic site, formation of separate and on GABA, glutamate, sigma, and adjacent, 45f dopamine, 676t posttraumatic stress disorder, 193, 194f VSSCs, synaptic vesicles, and carbonic pharmacy, 770f anhydrase, 675t reexperiencing in, 730f for panic disorder, 768 treatment, 770 putative clinical actions, 673t potassium, 146 for social anxiety disorder, 769 countertransport of, 95 pregnancy glutamate transport and, 100 antidepressant risks or avoidance during, 618t potassium ions, 124f and bipolar mood episodes, 711 potentiation, long-term, 167 depression during, 616 calcium inﬂux through NMDA receptors estrogen levels during, 617 and, 164f prehemisynapse, required elements for, 43f pramipexole, 718 premenstrual dysphoric disorder (PMDD), 616 pramlintide, 450, 1011 SSRIs for, 522 pravastatin, 609 premenstrual phase, bipolar disorder during, 711 and CYP 450 3A4, 608 premenstrual syndrome (PMS), 616 precursor stem cell prenatal gestation, neuron formation, 22 potential for transplant, 27 preschool ADHD, 882 transplantation of, presenilin 1, 907 prefrontal cortex, 2, 196f presenilin 2, 907 5HT2A receptor activation, in schizophrenia, presynaptic 5HT1A receptors, 348f 360 presynaptic 5HT1B/D receptors, 347f and ADHD, 864–870 presynaptic antagonists, 445f areas within, 197–200 presynaptic axon terminals, 2f,5f, 524 and CSTC loop, 211f in basket neurons, 4f desensitizing arousal in, 878f in double bouquet cells, 4f dopamine increase from NET inhibition, in pyramidal cell, 3f 544, 545f presynaptic D2 receptors, 268, 269f dopamine neurotransmission in, 59 presynaptic density proteins, 10 dopaminergic projections and, 210f presynaptic elements, 36 fatigue and, 491 presynaptic monoamine transporters, 93t fetal development, and schizophrenia, 303 antidepressants that block, 98 impact on suicidal ideation, 493 presynaptic nerve, sodium in, 61 information processing in, dopamine and, presynaptic neurons 233 genome communication to postsynaptic NDRI actions in, 555f neuron genome, 61 regulatory importance of dopamine, 544 nerve impulse propagation in, 160f and schizophrenia symptoms, 261, 262f postsynaptic neurons “talk back” to, 54, 57f and sleep disturbances, 491, 494f signal propagation, 166f SPA action in, 377 stimulation of, 55f synaptogenesis, and executive function presynaptic transporters, for monoamines, 95f development, 883f presynaptic voltage-sensitive calcium channels prefrontal motor cortex, supplemental motor (VSCCs), 154 area, 213 presynaptic zone, 7f prefrontal pyramidal neurons, in ADHD, 873 primary afferent neurons (PANs), 775 pregabalin, 156, 157t cell bodies in dorsal root ganglia, 782 for anxiety disorders, 767 demyelination of, 786 binding to alpha-2 delta protein, 158 response characteristics, 779 channel blocking by, 798f types, 779 in combos for bipolar disorder, 715 primary auditory cortex, 196f for ﬁbromyalgia, 808 primary insomnia, 831 icon, 688f primary motor cortex, 196f mechanism of action primary somatosensory cortex, 196f

1100 Index

Pristiq. See desvenlafaxine XR (Pristiq) gene encoding of, 179, 181f proapoptotic receptors (P75), 29t glutamate for biosynthesis, 279 pro-opiomelanocortin (POMC), 977, 980f intracellular scaffolding, 42f problem solving, 198 ion channel subunits, 126 procognitive agents, D1-selective agonists as, peripheral, 12 448 phosphates removal from, 76f prodrome postsynaptic density, 10 negative symptoms, 252, 256f presynaptic density, 10 preventing progression to, 227 retrograde transport of discarded, 17f prodynorphin, 977, 980f roles of, 11 proenkephalin, 977, 980f slow transport, 13f progesterone, 612 synthesis, 10f, 11–12, 78 projection neurons, 775 in dendrites, 12f prolactin Prothiaden (dothiepin), 597t amisulpride and, 423 “proton pump”, 102 atypical antipsychotic agents and, 364f protoxins, and Parkinson’s disease, 582 clozapine and, 409 protriptyline (Vivactil), 597t conventional antipsychotic agents and, 364f inhibition of serotonin reuptake pump, elevation, 336 598 inhibiting release, 278 Prozac (fluoxetine). See fluoxetine (Prozac) inhibition by dopamine, 363f PSA-NCAM (polysialic acid–neuronal cell olanzapine and, 411 adhesion molecules), 31t quetiapine and, 415 “pseudo anticholinergic” syndrome, 547 rise in levels, 334f pseudocholinesterase, 915 risperidone and, 413 pseudodementia, 912 secretion regulation, 362 pseudoephedrine, 593 serotonin stimulation of, 363f with MAOIs, and hypertension, 593t and sexual desire, 995 psilocybin, 990 zotepine and, 418 actions, 992f Prolixin (fluphenazine), 331t psychedelic, 990 L-prolyl-L-leucy-L-glycinamide (PLG), 663, psychiatric disorders 664f abnormal neuronal migration and, 30f promotor element, of gene regulatory region, chronic pain link to pathophysiology, 774 83 gene expression factors and, 78 propoxyphene, interaction with MAOIs, 595, and insomnia, 834t 595t remission of, risk for relapse, 229 prostaglandins, 1004 reward and, 943 protease inhibitors, 405 stress diathesis hypothesis, 749 and CYP 450 3A4, 609 psychiatric insomnia protein kinase A, G protein-linked receptor and GABA-A PAMs, 842 activation of, 74 treatment, 843f protein kinases, 170f psychiatric symptoms activation in signal transduction cascade, 73f and malfunctioning circuits, 229 and gene activation, 79f progression from stress sensitization to, 226, inactive, 72 226f protein phosphatase, formation, 72 sustained and neuron loss, 232f proteins, 8f psychomotor agitation, CSTC loop to regulate, and alpha-1 pore-forming unit of VSCC, 213 153 psychomotor retardation cytoplasmic, 13f CSTC loop to regulate, 213 transport of, 12 from SSRIs, 531 cytoskeletal support, 10 psychomotor symptoms destruction of discarded, 15 circuits, 497f functional changes due to activation, 64f in depression, 491

Index 1101

psychopharmacological agents purines, 52t, 859 and endogenous growth factors, 26f Purkinje cells, 5f gene expression factors and, 78 from cerebellum, 3 major targets, 92f pyramidal cells, 2, 3f,6 psychopharmacologic agents, and neurogenesis axon hillock of, 217 in hippocampus, 24 concept of optimal tuning, 765 psychopharmacologist, symptoms and circuits and cortical circuits, 214–221 for, 239–245 excitatory inputs, 219 psychopharmacology, 943 excitatory outputs, 215 psychosis, 247 fine tuning, 220 acute, ziprasidone for, 416 inhibitory contacts close to axons of, 3 antipsychotic action to reduce symptoms, 425 inhibitory inputs, 216 as associated feature in disorders, 249t interneuron input to, 218f disorders requiring presence as defining malfunctioning glutamate input into, 298 feature, 248, 248t output and input, 295 excess neurotransmission and, 47f output from, 217f extreme arousal in, 818 pyramidal neurons from improper neuronal migration, 29 cortical, tuning, in ADHD, 875f mesolimbic dopamine pathway role in, 272 prefrontal, in ADHD, 873 neurons regulating, 204 pyromania, 1011 positive symptoms, 251t postpartum, 619 QTc prolongation, ziprasidone and, 417 quetiapine for, 415 quazepam rebound, from discontinued clozapine, 431 half-life of, 835f psychotherapy, 49, 639 for insomnia, 837f and brain restructuring, 32 Quel kit, 715, 716f and endogenous growth factors, 26f questioning, for negative symptom and neurogenesis in hippocampus, 24, 24f identification in schizophrenia, 254f psychotic depression, symptoms shared with quetiapine, 382f schizophrenia, 258, 259f 5HT6-antagonist properties of, 447 psychotic episode, 250 actions as mood stabilizer, 693f psychotic illness binding properties, 414f combination chemotherapies for, 450 and cardiometabolic risk, 386t misconceptions, 247 in combos for bipolar disorder, 715, 716f psychotomimetic, 990 and diabetes, 417 psychotropic drugs dosage with carbamazepine, 407f enzymes as possible indirect targets, 171t half-life of, 836f G protein-linked receptors as target, 107, 114t hypnotic actions, 848 with agonists, 110–112 pharmacological actions, 693f with antagonists, pharmacological icon, 414f inverse agonists, 121 potency, and dissociation, 370 light and dark as analogy for partial for sedation, 431 agonists, 120 switching to nonsedating agent, 435 with no agonist, 108 and weight gain risk, 386t with partial agonists, 115–119 quinidine, 718 neurotransmitter transporters as targets, 99 quinone oxidoreductase 2, 844 nuclear hormone receptors as potential target, 171t R channels, 155, 155t selecting based on topographic location of R enantiomer function, 241 for citalopram, 538 sites of action, 91, 149 at serotonin transporter, 540f molecular, 91 R zopiclone, and eszopiclone, 842t transduction cascade as target, 65 racemic citalopram, 538 voltage-sensitive ion channels as target, 157t racemic zopiclone, 839, 839f

1102 Index

racing thoughts, 506 relapse, 516, 945 inefﬁcient information processing and, 502f after antipsychotic treatment, vs. side effects, radafaxine, 554, 556f 341 RAGS (repulsive axon guidance signals), 31 after psychiatric disorder remission ramelteon, 839, 844f preventing, 230 half-life of, 836f risk for, 229 rape, stress vulnerability, 193, 194f of depression, 513f raphe magnus, 205 frequency with drug continuation, 515f raphe obscurus, 205 rates in major depressive disorders, 518f raphe pallidus, 205 remission raphe pontis, 205 antidepressant combinations for, 651 rapid cycling, 454, 456, 458f of psychiatric disorders, risk for relapse, 229 switches, 458f rates for SNRIs vs. SSRIs, 543 rapid dissociation, 365, 367, 368f rates in major depressive disorders, 517f rapid “off” time, 365 by schizophrenic patient, 300 rapid “poop out”, 462f of symptoms, 513f Ras, kinase cascade activation by, 76 as treatment goal, 512 rasaligine (Agilect/Azilect), 579t renewal forgetting, 959 for Parkinson’s disease, 582 reproductive hormones, across menstrual cycle, rashes 613f from lamotrigine, 683 repulsive axon guidance signals (RAGS), 31 from zonisamide, 687 “rescue analgesia”, 802 reasoning. See also cognitive functioning resentment, 249 distortions in schizophrenia, 324 residual symptoms, in depression, 517f rebound, 945 resilience rebound insomnia, 837 from exposure to mild stress, 751 rebound psychosis, from discontinued loss from stress overload, 225 clozapine, 431 response, to depression treatment, 512, 512f reboxeine, 99t restless leg syndrome (RLS), 834t reboxetine, 557, 889 restlessness, from paroxetine withdrawal, 537 and CYP 450 3A4, 608 retardation, 249 potency for CYP450 2D6 inhibition, 605 retrograde motor, 8f recapture, of neurotransmitter, 92 localization of, 9f receptor-ion channel complex, other molecules retrograde neurotransmission, 57f,61 binding to, 140 retrograde transport, 14–15 receptor tyrosine kinases, 67, 171, 171t fast, 17f receptors retrograde vesicle, 8f downregulation, 86f localization of, 9f life cycle, 84f,87 reuptake, of neurotransmitter, 92 optimal amount of stimulation, 221f reuptake pumps, 15 synthesis, 85f absence, and dopamine diffusion, 59f upregulation, 87f,88 fast transport of, 15f recognition molecules, 31, 31t,32f reuptake transporters, 36 for synapse repair and regeneration, 32 for prehemisynapse, 43f recovery, 513f reversal, of dopamine transporter (DAT), 108f recurrence of depression, 513f reverse signaling, 61 recurrent collateral, in pyramidal cell, 3f reversible enzyme inhibitors, 167, 168, 169f reduced-risk drinking, 973, 975t reversible inhibitor of MAO-A (RIMA), 587, reexperiencing, 730f 590f regulatory proteins reward of voltage-sensitive sodium channels, 149 alcohol and, 970 for VSCCs, 155f blocking mechanisms, 330 regulatory regions of DNA, 79f, 80, 83 in mesolimbic dopamine system, 336 reinforcement, 945 conditioning to cues, 952f

Index 1103

reward (Contd.) and cardiometabolic risk, 386t mesolimbic dopamine pathway role in, 272, in combos for bipolar disorder, 713 276 conversion to paliperidone, 405f neurons regulating, 204 as CYP 2D6 substrate, 404, 405f nicotine and, 955 and diabetes, 417 opiates and, 977 pharmacological actions, 693f output, 950, 951f pharmacological icon, 412f overvalued in addiction, 951 potency, and dissociation, 370 reactive bottom-up system, 946, 948f raising levels of, 406f exposure to drugs, 948 and sedation, 430, 432f reﬂective top-down system, 949, 950f for treating irritability, 427 will power vs. temptation, 952, 954f and weight gain risk, 386t reward circuits, 945–953 rivastigmine, 924 alcohol and, 971f actions, 928f disorders of, treatment, 944 icon, 926f eating disorders and, 1008 RLS (restless leg syndrome), 834t eating, food and, 1010f RNA, 10f hallucinogen action on, 991f RNA polymerase, 80, 170f mesolimbic dopamine pathway for, 945, 946f and gene activation, 79f nicotine action on, 956f ropinirole, 718 opiate action in, 979f rosiglitazone, for Alzheimer’s disease, 936 and psychiatric disorders, 943 rough endoplasmic reticulum, 8f,10f,11f sedative-hypnotics and benzodiazepines localization of, 9f actions, 987f peptide synthesis in, 11, 12 sexual desire and, 996f RSK (ribosomal S6 kinase), 66f,76 stimulants action on, 982f rush, from opiates, 977 varenicline actions on, 962f reward conditioning, 959 S-adenosyl-methionine (SAMs), 630 RGH188, 380f in combos for bipolar disorder, 714 testing for cocaine abuse treatment, 986 trimonoamine modulation of, 632f RGS4 (regulator of G-protein signaling), 317 S enantiomer genes for, 318f for citalopram, 538 ribosomes, 10f in escitalopram, 539 protein synthesis in, 11 at serotonin transporter, 540f riluzole, 686 sad temperament, 460f and glutamate reduction, 708f sadness, depressed patient neuronal response, icon, 686f 508f mechanism of action sagittal plane, for brain visualization, 200f on GABA, glutamate, sigma, and SALAs (selective amyloid lowering agents), 939 dopamine, 676t salience of stimulus, 868 VSSCs, synaptic vesicles, and carbonic SAMs. See S-adenosyl-methionine (SAMs) anhydrase, 675t sarcosine, 442 possible actions in bipolar disorder, 698f saredutant, 665 putative clinical actions, 673t SARIs. See serotonin antagonist/reuptake sites of action, on glutamate release, 685f inhibitors (SARIs) RIMA (reversible inhibitor of MAO-A), 587, sarizotan (EMD128130), 380f 590f SB277011A, testing for cocaine abuse rimonabant, 449, 973, 990 treatment, 986 for alcohol dependency, 977 Scale for Assessment of Negative Symptoms, for marijuana dependency, 987 253t risk gene, with no symptoms, 187f “scared to death”, 731 risk taking, orbital frontal cortex and, 502f scary faces, schizophrenic patient response to, risperidone, 412, 429, 559f 323f actions as mood stabilizer, 693f SCH1390499, 939

1104 Index

SCH1396674, 939 positive symptom pharmacy, 425, 426f Schedule for the Deﬁcit Syndrome, 253t positive symptoms, 250, 251t schizoaffective disorder, 461, 462f link to mesolimbic/nucleus accumbens symptoms shared with schizophrenia, 258, area, 262 259f shared with other disorders, 259f schizophrenia presymptomatic and prodromal treatment, 5HT2A receptors activation in prefrontal 438, 439f cortex, 360 progressive nature of, 298 acquired vs. inherited, 302 rapid clinical assessment, 255t atypical antipsychotics to improve symptoms, risperidone effectiveness for, 413 355 stages, 301f best long-term outcomes, 400f substance abuse incidence in, 276 bifeprunox for treating, 424 subtle molecular abnormalities and, brain restructuring and, 44 192f cognitive symptoms, 259, 259t susceptibility genes for, 309t combination chemotherapies for, 450 symptoms, 248, 257f diagnosis, value of deconstructing, 264 overlap, 258f excessive excitatory neurotransmission and, shared with other illnesses, 258–264 43 treatment, vs. disease treatment, 425 excitotoxicity and, 48f, 302, 303f ziprasidone for, 416 fetal brain insult and, 303 schizophrenic patients free radical scavengers, 442f life expectancy of, 250 genetic basis, 304 siblings of, 320 glutametergic treatments for, 442f n-back test in, 322f ideal treatment of, 358 smoking and drug abuse by, 336, 449 integrated dopamine hypothesis, 279, 281f suicide in, 250 integrated theory Schwann cells, cytokines from, 787 and dopamine partial agonists, 378f SCN (suprachiasmatic nucleus), and hit-and-run actions, 373f melatonin-sensitive neurons in, 820 and serotonin-dopamine antagonists, scolopamine, and memory disturbance, 367f 918 mesocortical dopamine hypothesis of SDA. See serotonin-dopamine antagonists negative, cognitive, and affective (SDA) symptoms of, 277f second messenger G protein-linked receptors, as more than psychosis, 249–253 110t negative symptoms, 251, 251t secretory granule, 8f causes, 260f localization of, 9f observation to identify, 252, 254f secretory proteins, 11f,12 primary and secondary, 253t fast transport of, 14, 16f in prodomal phase, 252, 256f secretory vesicles, fast transport of, 14, 15f questioning to identify, 254f sedation, 818 reasons to measure, 253t antipsychotic agents and, 396–400 scales for assessing, 253t avoiding, 399, 401f shared with other disorders, 258 as goal, 398 neurodegenerative hypothesis, 298, 300f histamine 1 receptors and, 830 neurodevelopmental hypothesis, 308f long-term avoidance, 399f neuroimaging circuits in, 319 NET inhibition and, 558 neuron wiring and, 33f quetiapine and, 415 neutral stimuli and, 324f receptors mediating, 397f NMDA receptor hypofunction hypothesis of, as short-term therapeutic tool, 398f 288, 290f vs. somnolence, 400f patient responsiveness to antipsychotic as valproic acid side effect, 677 treatment, 300 zotepine and, 418 positive and negative symptoms, 250f sedation pharmacy, 430, 432f

Index 1105

sedative-hypnotics l-serine, glycine synthesis from, 285 actions on reward circuits, 987f serotonergic agents, therapeutic effects, 745f binding site of, 988f serotonergic hypnotics, 845 dependency/addiction, 986 serotonergic neurons, descending, and pain, segmental central sensitization syndromes, 795, 793f 799f serotonin 1A combo, for depression, 652f seizures serotonin 2A combo, 652f clozapine or zotepine and increased risk, 404, serotonin-2C antagonist, histamine-1 with, and 410 appetite stimulation, 387f excess neurotransmission and, 47f serotonin (5HT), 220, 318f excessive excitatory neurotransmission and, 1A agonists or antagonists, 447 43 5HT1A agonist, mirtazapine action, 561 reduction with Levetiracetam, 102 5HT1A partial agonist, and anxiety, 746f zotepine and, 418 5HT1A receptors selective amyloid lowering agents (SALAs), 939 effect on gluatmate release, 361f selective attention, 211 SARIs action at, 570f circuits, 866f 5HT1D antagonist action by ziprasidone, selective norepinephrine reuptake inhibitors 418 (NRIs). See norepinephrine selective 5HT2A antagonist binding to 5HT2A reuptake inhibitors (NRIs) receptor, and dopamine release, 358 selegiline, 576, 579t 5HT2A antagonists for Alzheimer’s disease, 936 and D2 antagonists, 365 for Parkinson’s disease, 582 hyperprolactinemia reduction, 362 transdermal delivery system for, 587, 588, and inhibitory action of serotonin 1A on 591f glutamate release, 571 MAO inhibitors, 591 reduction of positive symptoms, 362f for treating nicotine dependence, 967 5HT2A receptors self-conﬁdence, loss blockade at, 574f bupropion for, 556 effect on gluatmate release, 361f as SSRI side effect, 530 and gene expression from 5HT1A self-esteem, 506 receptors, 573f self-mutilation, 425 hallucinogen stimulation, 991 semaphorins, 31 NE and DA disinhibition at HT1A sensitization receptors, 571–574 in central nervous system, 795, 797f and positive symptoms improvment, 359, to stress, 749–755 362 child abuse, 751 regulation of NE and DA release, 484f in normal circuits, 225, 225f SARIs action at, 569, 569f preemptive treatments, 226 5HT2A-selective antagonists/inverse presymptomatic and prodromal treatment, agonists, 446 227f 5HT2C antagonist, mirtazapine action, progression to psychiatric symptoms, 226, 563 226f 5HT2C receptors, 659 sensory/discriminatory pathway, 784 agonists or antagonists, 447 SEP 227, 229, 556f ﬂuoxetine blockade of, 534f Sequenced Treatment Alternatives to Relieve functions, 349f Depression (STAR-D) trial, 516 NE and DA disinhibition at HT1A Serentil (mesoridazine), 331t receptors, 571–574 serial learning, impaired, in schizophrenia, 257 olanzapine and, 411 d-serine, 441, 443f regulation of dopamine in nucleus production, 283, 284f accumbens, 486f serine hydroxyl methyl transferace (SHMT), regulation of NE and DA release, 485f 627f serotonin action, 532 d-serine racemase, 285 and weight gain, 383

1106 Index

5HT3 antagonists, 563 serotonin antagonist/reuptake inhibitors 5HT3 receptors (SARIs), 565, 567f pentameric structure, 126 actions at serotonin synapses, 567f stimulation of, 531 mechanism of action 5HT6 antagonists, physiological role, 447 5HT2A antagonism and inhibitory action 5HT7 antagonists, 447 at 5HT1A, 577f 5HT21 receptors, agonism of, 381f baseline postsynaptic actions, 568f and alpha 2 antagonists, 560f disinhibition of norepinephrine and antagonists synergy with SERT inhibition, dopamine, 578f 568–574 gene expression, 573f antidepressants’ enhancement of, 98 glutamate release inhibition, 576f antidepressants impact on synaptic action, glutamate release stimulation, 575f 520 serotonin excitatory at 5HT2A receptors, antipsychotic agents and, 691, 692f 569f and anxiety regulation in amygdala, 241 serotonin inhibitory at 5HT1A receptors, and arousal spectrum, 817, 817f 570f depression from deficiency, 520f synergy between 5HT1A and 5HT2A, disinhibition, 562f 571f dorsolateral prefontal cortex regulation by, serotonin deficiency syndrome, 530 265f serotonin-dopamine antagonists (SDA), 342, and fear processing by amygdala, 234 343f genes, expression stimulation through for aggression management, 427f 5HT1A receptors, 572f for cognitive function improvement, 428f genetics, and life stressors, 747f in development, 368f glutamate release stimulation, 575f for first-line treatment of schizophrenia increasing release after alpha 2 antagonist, positive symptoms, 425 559 integrated theory of schizophrenia and, 367f information processing in amygdala and, 744 and mesocortical dopamine pathway, 359f interaction with dopamine, in nigrostriatal for negative symptoms in schizophrenia, 428f dopamine pathway, 353f new options, 446 mirtazapine actions at synapses, 564f switching to DPA, 436f and mood disorders, 474 serotonin neuron, somatodendritic area of, 526, norepinephrine regulation of, 480, 480f 527f as accelerator, 482f serotonin neurotransmitter, 128t bidirectional control, 483f as psychotropic drug indirect target, 116 as brake, 481f as psychotropic drug target, 114 novel targets, 659 serotonin norepinephrine disinhibitors production, 344f (SNDIs), 558 projections, 205, 206f serotonin-norepinephrine-dopamine-reuptake prolactin stimulation of, 363f inhibitors (SNDRIs), 661 as psychotropic drug target, 128 serotonin norepinephrine reuptake inhibitors psychotropic drugs and, 53 (SNRIs), 99t, 541, 793f regulation of dopamine release, 354f actions, 543f regulation of NE and DA release, 477 bicifidine, 552, 552f release for chronic pain, 774 within CSTC loop, 211 for dementia, 935 norepinephrine regulation of, 476 for depressed women with fluctuating reuptake, 98f estrogen, 623f synthesis and termination of action, 343 desvenlafaxine, 549 termination of action, 345f icon, 549f tricyclic antidepressant to block reuptake duloxetine (Cymbalta, Xeristar), 550 pump, 598 icon, 550f serotonin agonists, and 5HT2A antagonists, for fibromyalgia, 808 378 for generalized anxiety disorder, 765

Index 1107

serotonin norepinephrine reuptake inhibitors escitalopram, 99t, 539 (SNRIs) (Contd.) icon, 541f icon, 541f and estrogen impact, 624 interference with slow-wave sleep, 848 fluoxetine (Prozac), 532–536. See also listing, 541t fluoxetine (Prozac) LuAA34893, 552, 552f fluvoxamine, 99t, 405, 446, 537 milnacipran (Ixel, Toledomin), 551 icon, 538f icon, 551f for generalized anxiety disorder, 765 for neuropathic pain, 792 interference with slow-wave sleep, 848 for panic disorder, 742, 768 listing, 523t potential side effects of NET inhibition, 546 mechanism of action, 525f remission rates compared with SSRIs, 543 and pain treatment, 789 serotonergic, noradrenergic and for panic disorder, 742, 768 dopaminergic pathways and, 544–547 paroxetine, 99t, 536 sibutramine, 552, 552f icon, 537f for social anxiety disorder, 769 patient response to different, 532 for vasomotor symptom treatment, 626f pharmacological and molecular mechanism of venlafaxine XR (Effexor XR; Efexor XR), action, 524–528 547–549 plus NDRI, conversion to desvenlafaxine, 548, 548f remission rates compared with SNRIs, 543 icon, 548f secondary pharmacological properties, 531f serotonin partial agonists (SPAs), 342, 382f serotonin pathways and receptors that atypical antipsychotic agents and, 377 hypothetically mediate actions, 529–531 serotonin receptors, 343, 346f sertraline, 535 5HT1A and 5HT2A, 345 icon, 536f 5HT1A autoreceptors, 348f side effects of, 530 5HT1A receptors, 351f for social anxiety disorder, 769 5HT1B/D autoreceptors, 347f tolerance to side effects, 527 5HT2A antagonist reduction of EPS, for vasomotor symptom treatment, 625f 351–353 serotonin, stress and anxiety disorders, 741–749 5HT2A receptors, 351, 351f serotonin syndrome, 595 antagonist reduction of negative serotonin transporter (SERT), 93, 94, 95f, 221f symptoms, 354–358 and amygdala overreaction to fearful faces, 5HT3 receptors, 349f 745 5HT6 receptors, 349f cocaine ability to inhibit, 983 5HT7 receptors, 349f gene for, 319f postsynaptic, 343–351 inhibition of, 524 excessive stimulation of, 597 MDMA as inhibitor, 991 impact of, 344 R vs. S enantiomer at, 540f possible functions, 349f SSRI block of, 529f presynaptic, 343–351 subtle molecular abnormalities and, 237f serotonin reuptake inhibitor (SRI), 543f transport of “ecstacy”, 95 interaction with MAOIs, 595, 596f SERT. See serotonin transporter (SERT) serotonin reuptake pump. See serotonin sertindole, 404, 419 transporter (SERT) 5HT6-antagonist properties of, 447 serotonin selective reuptake inhibitors (SSRIs), dosage with carbamazepine, 407f 99t, 244f pharmacological icon, 420f action potential, 524f and QTc prolongation, 417 citalopram, 538 sertraline, 99t, 535 icon, 538f and CYP 450 3A4, 608 common features, 524 icon, 536f for dementia, 935 potency for CYP450 2D6 inhibition, 605 for depressed women with fluctuating setiptilene, 565 estrogen, 622f sexual desire, and reward circuits, 996f

1108 Index

sexual dysfunction, 537, 651, 993–1007 second messenger formation, 65–71 compulsive sexual behavior, 1007 slow onset, 62f,63f erectile dysfunction, 999, 1003f time course of, 64f,65f age and, 1000f types, 65, 66f prevalence of, 1000f ultimate target, 71 psychopharmacology, 1002 valproate and, 674, 679f treatment, 1003f signals, neuron reception of, 6 hypoactive sexual desire disorder (HSDD), sildenafil (Viagra), 1002 1004, 1005f “silent” agonists, 111f dopamine and, 1007f vs. inverse agonist, 121 matching to circuits, 1006f simvastatin treatment, 1008f and CYP 450 3A4, 608 mirtazapine to avoid, 562 risk of muscle damage, 609 pharmacology and, 1009t Sinequan. See doxepin (Sinequan, Adapin) from SSRIs, 531 skeletal muscle, insulin resistance in, 387, sexual response phases, 993–1007 390f arousal, 995 SLC 1 gene family, 100 neurotransmitters and, 997f as psychotropic drug target, 99 nitric oxide (NO) and, 998f SLC 6 gene family, 94–99, 100 libido, 993 as psychotropic drug target, 99 orgasm, 999 SLC 18 gene family, 93 psychopharmacology of, 995f vesicular monoamine transporters (VMATs) shift-work sleep disorder, 856 in, 102 symptoms shared with other disorders, 869t sleep SHMT (serine hydroxyl methyl transferase), 5HT2A receptors and, 349f 627f benzodiasepine-sensitive GABA-A receptors shopping, compulsive, 1011 for regulating, 738 siblings of schizophrenic patients, 320 circuits, 494f n-back test in, 322f histamine 1 receptors and, 830 sibutramine, 552, 552f histamine and, 209f interaction with MAOIs, 595t neurobiology of, 816–831 with MAOIs, and hypertension, 593t processes regulating, 823f sigma-1 agonists/antagonists, 446 quetiapine for improving, 414f sigma-1 receptor binding serotonin projections regulation of, 205, of fluvoxamine, 537 206f of sertaline, 535 serotonin receptors and, 345 sigma 1 site, 718 slow-wave, 848 “sigma enigma”, 446, 537 trazodone to improve, 566 signal cascade molecules, 36 as vital sign, 816 for posthemisynapse, 43f sleep aids, for fibromyalgia, 811 signal propagation, from presynaptic to sleep disturbances, 506, 804 postsynaptic, 166f brain areas impacting, 491 signal-to-noise ratio, 220f gabapentin for, 688 enhancing, 220 pregabalin for, 688 in prefrontal cortex, 873, 875f sleep hygiene, 850t signal transduction cascades, 61–88 sleep promoter, 819, 822f biological responses to long term effects of sleep/wake disorders, arousal networks and, late gene products, 78 873 first messengers, 67 sleep/wake switch, 207, 819, 822f gene expression, 73–88 delayed turn on, 826f gene products targeted by, 77 in elderly, 824, 827f later messengers, 71–73 insomnia and, 825f as psychotropic drug target, 65 neurotransmitters regulating, 821 second messenger, 67 and sleepiness, 824f

Index 1109

sleepiness/hypersomnia in daytime, 650 sodium-dependent cotransporters, monamine vs. alcohol consumption, 851t transporters as, 95 causes, 850t sodium ions, 124f in depression, 649 sodium oxybate, 859. See also gamma evaluating, 852t hydroxybutyrate (GHB) explained, 850 sodium potassium ATPase (adenosine impact of, 851t triphosphatase), 95, 96f initial assessment, 852t “sodium pump”, 95, 96f problems from, 854 solute carrier SLC6 gene family, 93 quantifying severity, 851, 853f soma, 1, 2f sleepiness circuits, 821f in basket neurons, 4f treatment cell nucleus in, 8 agents for, 857 and dendrites, 6 decision process, 854 in double bouquet cells, 4f slow transport motor, 13f genome in, 7 for microtubules and neurofilaments, 14f in pyramidal cell, 3f slow-wave sleep, 848 synapse formation on, 36 SLV313, 375, 380f somatic syndromes, functional, 777t SLV314, 375, 380f somatic zone, 7f SM13493/lurasidone, 368f somatization disorder, 771 “smoked over”, 962 somatodendritic alpha 2 receptors, 475, 479f smoking. See also nicotine somatodendritic autoreceptor, 344, 348f by ADHD patients, 880 somatodendritic dopamine D2 receptors, 271f CYP450 1A2 and, 404, 404f somatodendritic receptors, 60 as CYP450 inducer, 609 somatodendritic zone, 6, 7f power of addiction, somatosensory association cortex, 196f by schizophrenic patients, 336, 449 somatosensory cortex, 775 vs. transdermal nicotine administration, 966f somnolence, vs. sedation, 400f smoking cessation, treatment, 128 SPAs. See serotonin partial agonists (SPAs) smooth muscle “special K”, 993 L channel and, 155 spinal cord, 203f relaxation, and erection, 1004 facilitation pathways, 789 SNAP 25, 157f neurotransmitters modulating pain snare proteins, 155, 157f processing in, 783f for prehemisynapse, 43f nociceptive pathways to, 778 SNDRIs (serotonin-norepinephrine-dopamine- nociceptive pathways to brain from, 782 reuptake inhibitors), spinal norepinephrine pathway, descending, 661 789 SNRIs. See serotonin norepinephrine reuptake spinal serotenergic pathway, descending, 789 inhibitors (SNRIs) spines, in double bouquet cells, 4f social anxiety disorder, 724f spinobulbar tracts, 775 fluvoxamine for, 538 spinophylin, genes for, 319f pharmacy, 769f spinothalamic tract, 775 treatment, 769 spiny dendrites, 5f social phobia, MAO inhibitors for, 575 spiny neurons, 5f social stigma, of electroconvulsive therapy, sprouting, 797f 634 SR 147778, 449 sodium SR 241586, 450 and monoamine transporter affinity for SR141716 A, 449 substrates, 95 SR31742A, 446 in presynaptic nerve, 61 SSR 146977, 450 sodium channels, 145 SSR-591813 (dianicline), 960 voltage-sensitive (VSSCs), 60, 148, 149f SSR125047, 446 sodium/chloride-coupled transporters, 93 SSR180711, 449

1110 Index

SSR181507, 380f and mental illness, 185 SSR591813, 449 and normal circuits, 224, 224f SSRIs. See serotonin selective reuptake and personality, 190–191, 191f inhibitors (SSRIs) progression to anxiety disorders, treatment, ST198, testing for cocaine abuse treatment, 986 754 stabilizers, 111f sensitization, 749–755 partial agonists as, 134, 135 child abuse, 751 Stablon (tianeptine, Coaxil), 597t in normal circuits, 225, 225f Stahl, S.M., Essential Psychopharmacology: The preemptive treatments, 226 Prescriber’s Guide, 408, 409 presymptomatic and prodromal treatment, STAR-D (Sequenced Treatment Alternatives to 227f Relieve Depression) trial, 516 progression to psychiatric symptoms, 226, statins, for Alzheimer’s disease, 936 226f Stelazine (trifluoperazine), 331t and synapse loss, 25f stem cells stress diathesis hypothesis, 185, 186f embryonic, differentiation, 24 breaking point, 190 precursor multiple risk genes with breakdown, 189f potential for transplant, 27 multiple risk genes with no breakdown, transplantation of, 189f steroids, 66f no risk gene and normal function, 188f Stevens-Johnson syndrome, 683, 687 one risk gene and normal function, 189f stimulants with psychiatric symptoms, 188f abuse, 981 stress-induced affective disorders, novel by ADHD patients, 870 treatments, 754f long-term effects, 984 stress-related brain atrophy, reversing, 891 progression, 985f striatal complex actions, on reward circuits, 982f and CSTC loop, 211f for ADHD, 884 and executive function, 212f with atypical antipsychotics, 879 striatum, 3, 203f mechanism of action, 887f cell bodies for acetylcholine in, 206 pulsatile vs. slow/sustained, 890f dopamine reuptake pumps in, 59 and blood pressure, 593 interaction with cortex, 210 interference with slow-wave sleep, 848 NDRI actions in, 555f mechanism of action, 103 SPA action in, 377 monoamine transporters as targets, 99t spiny neurons in, 5f paranoid psychosis from, 985 stroke, 426 probability of dependence, 968t from cortisol in fear response, 730 and reward, 982 excitotoxicity and, 48f, 302, 303f SNRI plus, 656f Stroop test, 235, 238f for wakefulness, 858 and dorsal anterior cingulate cortex, 238f stimulus, salience of, 868 subcellular organelles,b 6–10 stress localization of, 9f and ADHD and comorbidity, 893f subgenual area, 200, 212 benefits of mild, in childhood, 750 substance abuse, 704f. See also specific substance brain atrophy from, 748 types comorbidities, and arousal levels in ADHD, with ADHD, 880 877 as treatment priority, 880, 881f development of psychiatric symptoms, 186f bipolar disorder associated with, 463 early exposure to, 752f diabolical learning and, 948, 951, 953, 959 genetics and response to, 747f incidence in schizophrenia, 276 hippocampal volume reduction with, 748f orbital frontal cortex and, 870 hippocampus sensitivity to, 24, 24f overvalued reward in addiction, 951 and hypothalamic-pituitary-adrenal axis, 752, probability after use, 968t 753f questions for treating, 944t

Index 1111

substance abuse (Contd.) deconstructing syndromes into, 240f topiramate and, 687 localization in brain, 241 treatment, 959 matching to circuits, 242f will power vs. temptation, 952, 954f overlapping among many syndromes, 869t “substance-induced mood disorder”, 463 treatment based on, 244f substance P antagonists, 449, 665 synapses, 1 substantia nigra, 277 communication between neurons at, 54 spiny neuron input from, 3 competitive elimination, 41–49 transplantation of fetal cells, enlarged, 38f substrates, 167 formation by age, 49f subsyndromal states, 227 formation failure, 34 suicidal ideation, 493 formation process, 36, 39f,45f in young adults, from antidepressants, 520 decorating, 43f suicidality intraneuronal scaffolding, 42f circuits, 498f ordering supplies, 40f in female adolescents, from antidepressants, scaffolding, 41f 617 loss of, 24, 25f,35 in schizophrenic patients, 250 sustained symptoms and, 230 attempts, 425 many vs. few connections, 35f clozapine to reduce, 410, 429, 430f maximum in brain, at age 6, 41 unrecognized bipolar disorder and, 468 normal connection, 25f “suicide inhibitor”, 168, 168f removal of connections during adolescence, suicide, risk in depressed mothers, 618 42 sulpiride (Dolmatil), 331t strength of, and survival or elimination, 313 clinical actions of, 371 strengthening, 44f pharmacological icon, 423f synaptic cleft, 38f sundowning, 942 synaptic ﬂexibility, 44f superiority, attitude of, 249 synaptic plasticity, 35–41, 144 supplemental motor area, 197 synaptic vesicles, 8f suprachiasmatic nucleus (SCN), fast transport of, 14, 15f melatonin-sensitive neurons in, 820 levetiracetam mechanism of action at SV2A “suprasegmental” central sensitization sites, 690f syndromes, 798, 801f localization of, 9f Surmontil (trimipramine), 597t for prehemisynapse, 43f susceptibility genes, 304 synaptobrevin, 157f for schizophrenia, 309t synaptogenesis, 22, 31–35, 167 sustained attention circuit, 867f abnormal, 307 SV2A transporter, 102, 156, 157f genes causing, 311f switching antipsychotic agents, 431, 433f from gene expression, 78, 304 process to avoid, 433f messenger triggering of, 64 sympathetic nervous system synaptotagmin, 157f and neuropathic pain, 786 syndromes, 178 noradrenergic receptor simulation in, 547 deconstructing into symptoms, 240f sympathomimetic amines, decongestant syntaxin, 157f interaction with drugs boosting, 591 synthetic enzymes, 36 symptom-based selection of antidepressants, for prehemisynapse, 43f 643, 644f algorithm for, 645f T channels, 155, 155t symptom domains, localization of, 261, 262f T3, in combos for bipolar disorder, 714 symptom endophenotypes, 180f tachykinins, 52t, 664, 664t vs. biological endophenotype, 229 tacrine, 923 in path between gene and mental illness, 185 tadalaﬁl (Cialis), 1002 symptoms talnetant, 450 clinical strategy to reduce, 239 tandospirone, 447

1112 Index

tangles. See neurofibrillary tangles THC (delta-9-tetrahydrocannabinol), 986 tardive dyskinesia, 88, 332, 333f actions on reward circuits, 989f clozapine and, 409 theophyllin, interactions with fluvoxamine, 604 neuroleptic-induced, 277 theophylline, 606f reversal, 333 therapeutic nihilism, 976 SDAs and, thermoregulation, disruption in, 597 from unwanted D2 receptor blockade, 382 THF-R (methylene tetrahydrofolate reductase), tau proteins, hyper-phosphoylation, 906 627f taurine, 976 THF (tetrahydrofolate), 627f TC1734 (ispronicline), 941 thioridazine (Mellaril), 331t TC1827, 449 and CYP450 2D6 inhibitors, 608 TCAs. See tricyclic antidepressants (TCAs) thiothixene (Navane), 331t temazepam Thorazine (chlorpromazine), 328, 331t half-life of, 835f thyroid for insomnia, 837f dysfunction, men vs. women, 711 temperament, 190, 456 impact on cytoplasmic receptors, 75 depressive, 460f thyroid hormones, 631 hyperthymic, 460f as augmenting agent, 634f with depressive episode, 466f for bipolar disorder, 699 temporal lobe, 196f in combination treatments for depression, temptation, vs. will power, 952, 954f 652f Tennessee mood shine, 715, 716f and depressed mood, 633f tension, 260 tiagabine, 100 Tercian (cyamemazine), 331t for fibromyalgia, 810 pharmacological icon, 421f tianeptine (Coaxil, Stablon), 597t terminal autoreceptor, 344 tics testosterone, 1006 in children, 877 and sexual motivation, 994 dopamine hyperactivity in nigrostriatal tetrahydrobiopterin (BH4), 625 pathway and, 277, 278f cofactor for trimonoamine neurotransmitter tingling, from paroxetine withdrawal, 537 synthesis, 629f tissue damage, 779f MTHF regulation of, 628f tissue growth factors, in brain, 174 delta-9-tetrahydrocannabinol (THC), 986 TMMs (trimonoaminergic modulators), actions on reward circuits, 989f 609–639 tetrahydrofolate (THF), 627f estrogen as, 610 thalamic dopamine pathway, 204, 279 L-5-methyltetrahydrofolate (MTHF) as, thalamocortical glutamate pathways, 289f 625 thalamus, 202f TMS (transcranial magnetic stimulation), 637, and CSTC loop, 211f 637f filters and sleep/wake disorders, 818 tobacco. See nicotine dopamine pathway to, 272f Tofranil. See imipramine (Tofranil) dopamine projections to, 204f TOH (tyrosine hydroxylase), 266, 266f GABA in, and insomnia, 820f Toledomin (milnacipran, Ixel), 99t, 541t glutamatergic excitatory projections from, tolerance, 945 219f tonic inhibition, 737 inefficient information processing, and sleep topiramate, 686, 709 disturbances, 503f in combos for bipolar disorder, 715 interaction with cortex, 210 for fibromyalgia, 811 mesolimbic dopamine hyperactivity and, 296f icon, 687 sensory filter from GABA neurons, 292, 293f mechanism of action dopamine and, 294f on GABA, glutamate, sigma, and sensory input inhibition from, 295f dopamine, 676t and sleep disturbances, 491, 494f VSSCs, synaptic vesicles, and carbonic spiny neuron input from, 3 anhydrase, 675t

Index 1113

topiramate (Contd.) major limitation, 598 putative clinical actions, 673t for panic disorder, 768 and VSSCs, 707f side effects and weight loss, 1011 coma, seizures, arrhythmia, death, 604f topographical representation of function, 211 constipation, blurred vision, dry mouth, Tourette’s syndrome, 771 and drowsiness, 602f toxic epidermal necrolysis, 683, 687 dizziness, drowsiness, decreased blood toxins, neuron or DNA damage from, 28 pressure, 603f tramadol, interaction with MAOIs, 595, 595t weight gain and drowsiness, 602f transcranial magnetic stimulation (TMS), 637, therapeutic actions of 637f 5HT2A receptor block, 601f transcription factor, 87 5HT2C receptor block, 601f and gene activation, 79f norepinephrine reuptake inhibition (NRI), transdermal nicotine administration, vs. 600f smoking, 966f serotonin reuptake inhibitor (SRI), 600f transmembrane region receptors, 109f trifluoperazine (Stelazine), 331t top view, 110f triglycerides, elevated, atypical antipsychotic transmembrane segments, of alpha agents and, 390f pore-forming protein, 147 trimers, glutamate transporters as, 101 transport function. See also fast transport trimipramine (Surmontil), 597t axons and dendrites for, 10 trimonoamine neurotransmitter synthesis, tranylcypromine (Parnate), 575, 576, 579t tetrahydrobiopterin (BH4) cofactor for, trazodone, 565, 839, 846f 629f 5HT2A inhibition by, 569 trimonoaminergic modulators (TMMs), for anxiety disorders, 767 609–639 for fibromyalgia, 811 estrogen as, 610 half-life of, 836f L-5-methyltetrahydrofolate (MTHF) as, as hypnotic, 845 625 icon, 567f trimonoaminergic neurotransmitter system, for insomnia, 566 453, 474 for panic disorder, 768 antipsychotic agents and, 691 for social anxiety disorder, 769 dysregulation of, 620 treatment-resistant mood disorders, 473 trip, 990 treatment, symptoms and circuits for approach triple monoamine modulators (TMMs). See to selecting, 239t trimonoaminergic modulators (TMMs) tremor triple reuptake inhibitors (TRIs), 658, 661 as antipsychotic side effect, 341 icon, 661f nigrostrial pathway dopamine deficiencies TrkA (antiaptotic receptors), 29t and, 277 trophic actions, and estrogen, on dendritic spine triazolam formation, 612 and CYP 450 3A4, 608 trophic factors, 28 half-life of, 836f Tryptizol (amitriptyline, Elavil, Endep, for insomnia, 837f Loroxyl), 53, 572, 597t and sedation, 609 tryptophan, 343, 344f trichotillomania, 771 tryptophan hydroxylase (TRY-OH), 343, 344f tricyclic antidepressants (TCAs), 99t, 542, tuberoinfundibular dopamine pathway, 272f 597–603 and D2 antagonists, 334f for anxiety disorders, 767 dopamine output and, 366f archaic terminology, 602 hypoactivity of, 281f chemical structure, 598f tuberomammillary nucleus (TMN), 207 development, 597 of hypothalamus, 819, 822f for fibromyalgia, 810 and insomnia, 825f icons, 599f tumor growth factor beta, 174 listing of those still in use, 597t tumor necrosis factor, 174

1114 Index

tyramine valproic acid, 157t and blood pressure, 589 icon, 676t cheese content, 587f side effects, 677 dangerous levels with irreversible MAO-A vanillinoid 1 receptor (VR1) ion channel, 779, inhibitors, 592f 779f MAO-A inhibition and, 586f vardenafil (Levitra), 1002 MAO-A inhibitor and, 590f varenicline, 449 and norepinephrine release, 585f actions on reward circuits, 962f pizza chain content of, 588f in combos for bipolar disorder, 715 reactions and dietary restrictions, 582, for nicotine addiction, 960, 964 584t vasomotor symptoms, 620 wine content, 589f from estrogen interaction with monoamines, tyrosine, 266, 266f 524f norepinephrine synthesis from, 474, 475f link to depression, 650 tyrosine hydroxylase (TOH), 266, 266f in perimenopause, 619 genes for, 319f treatment, 621 with desvenlafaxine, 550 ultradian sleep cycle, 820, 823f with SNRIs, 626f undeveloped neuron, 34f with SSRIs, 625f unipolar depression, 454 vasopressin 1B antagonists, 663 distinguishing from bipolar depression, 468, vasopressin, blocking receptors for, 754 469t venlafaxine XR (Effexor XR; Efexor XR), 99t, impact of chronic and widespread 541t undertreatment, 473 conversion to desvenlafaxine, 548, 548f misdiagnosis, 468 CYP450 2D6 impact on plasma levels, 607 unstable form of, 461 for fibrofog, 810 upregulation, 87f,88 for fibromyalgia, 808 urinary hesitancy, from milnacipran, 552 icon, 548f urinary retention, from NET inhibition, 547 for neuropathic pain, 792 ventral mesencephalon, 204 vabicaserin, 447 dopamine pathway from, 272f vaccines, for Alzheimer’s disease, 937 ventral tegmental area (VTA), 202f VAChT (vesicular acetylcholine transporter), alcohol actions in, 972f 94 naltrexone actions in, 974f vagus nerve stimulation (VNS), 634, 636f opiate action in, 978f val carriers, 233 ventrolateral preoptic (VLPO) nucleus, of valine, 233 hypothalamus, 819, 822f Valium (diazepam), 53 ventromedial nucleus, and sexual drive, 994 valproate ventromedial prefrontal cortex (VMPFC), 199f actions as mood stabilizer, 680f amygdala activation by, 760 for bipolar disorder, 701 blockade of beta receptors in, 763f vs. carbamazepine, 679 dopamine deficit in mesocortical projections in combos for bipolar disorder, 713 to, 274 GABA and, 674 emotional symptom regulation by, 508f for manic phase of bipolar disorder, 672 fear extinction and, 760 mechanism of action and input to lateral amygdala, 760 on GABA, glutamate, sigma, and manic episode symptoms linked to, 506 dopamine, 676t mesocortical dopamine pathway to, 276f VSSCs, synaptic vesicles, and carbonic and schizophrenia symptoms, 261, 262f anhydrase, 675t and stress, 759f possible sites of action on GABA, 678f verbal abuse, 425 possible sites of action on VSSCs, 677f verbal fluency, impaired, in schizophrenia, 257 putative clinical actions, 673t vesicles, 12, 474 and VSSCs, 707f vesicular acetylcholine transporter (VAChT), 94

Index 1115

vesicular glutamate transporters (vGluT), 102, carbamazepine acton on, 678 282f mood stabilizers action on, 707f dysbindin regulation of, 317 and nontransmission, 159 vesicular inhibitory amino acid transporters oxcarbazepine and, 681 (VIAATs), 100f states, 152f vesicular monoamine transporters (VMATs), structure, 152f 93, 94, 95f, 157f subtypes, 150 and dopamine, 268f valproate and, 672 transport of amphetamine, 106f volume neurotransmission, 58, 58f vesicular neurotransmitter transporters, 94t dopamine and, 59f vesicular transporters, 103f monamine autoreceptors, 60f as psychotropic drug target, 102–105 vomiting subtypes and function, 102 from 5HT3 receptor stimulation, 531 VIAATs (vesicular inhibitory amino acid 5HT3 receptors and, 349f transporters), 100f bifeprunox and, 424 violence, 256 serotonin receptors and, 345 virtuous learning, VSF-173, for wakefulness, 857 viruses VSSCs. See voltage-sensitive sodium channels neuron or DNA damage from, 28 (VSSCs) transport to soma, 15, 17f visual association cortex, 196f waist circumference, monitoring, 392 visual illusions, from hallucinogens, 990 “wake promoter”, 819 vital sign, sleep as, 816 wake-up pharmacy, 861f Vitamin E wakefulness. See also daytime sleepiness; sleep for Alzheimer’s disease, 936 histamine and, 209f as free radical scavenger, 442f modaﬁnil for, 857 Vivactil (protriptyline), 597t “Walt Disney”, 717f inhibition of serotonin reuptake pump, 598 weight VMATs (vesicular monoamine transporters), baseline measurement, 395f 93, 157f changes in, 493 transport of amphetamine, 106f circuits, 498f VMPFC. See ventromedial prefrontal cortex weight gain (VMPFC) from 5HT2C antagonists and/or VNS (vagus nerve stimulation), 634, 636f mirtazapine, 563 voltage-sensitive calcium channels (VSCCs), antipsychotic agents and, 389f 60, 148, 151–158, 755 aripiprazole and, 422 amino acids’ regulation of, 153 atypical antipsychotic agents and, 383, 386t ionic ﬁlter of, 150f clozapine and, 410 multiple associated regulatory proteins, from histamine-1 receptor blockade, 341 155f low risk antipscychotic agents, 386t and nontransmission, 159 from mirtazapine, 564 proteins linking to, 157f monitoring, 396f subtypes, 153, 155t olanzapine and, 411 TCA blockade of, 599 quetiapine and, 415 voltage-sensitive ion channels, 92f, 124, as valproic acid side effect, 677 145–151, 158 ziprasidone and, 417 alpha pore, 148f zotepine and, 418 different states, 150 weight loss psychotropic drugs targeting, 157t topiramate and, 687, 1011 structure and function, 145 zonisamide and, 1011 voltage-sensitive sodium channels (VSSCs), 60, “Well-oft” (Wellbutrin with Zoloft), 536 148, 149f will power, vs. temptation, 952, 954f alpha pore, 151f “wind-up”, 795 anticonvulsant action at, 153f wine, tyramine content, 589f

1116 Index

withdrawal, 945 zipa-li, 717f opiates and, 979 zipa-li-do-la, 717f women ziprasidone, 382f bipolar disorder and, 710 with 5HT1D antagonist actions, 418 life cycle actions as mood stabilizer, 693f depression incidence across, 615f and cardiometabolic risk, 386t depression risk across, 615f in combos for bipolar disorder, 713, estrogen and/or antidepressant use across, 717f 617f dosage with carbamazepine, 407f estrogen regulation and major depression pharmacological actions, 693f over, 614 pharmacological icon, 416f reduction in sexual desire, 1004 and sedation, 430, 432f suicidality in adolescents, from and weight gain risk, 386t antidepressants, 617 zolpidem, 839, 839f thyroid dysfunction, 711 half-life of, 836f worry, 260, 726. See also anxiety zolpidem CR, 839, 839f diabolical learning hypothesis and, 230 half-life of, 836f linking symptoms to circuits, 764f zona incerta, 204 worry/obsessions circuit, 764f zonisamide, 157t worthlessness in combos for bipolar disorder, 715 circuits, 499f icon, 688f serotonin and, 493 mechanism of action on GABA, glutamate, sigma, and Xanax (alprazolam), 53 dopamine, 676t Xeristar. See duloxetine (Cymbalta, Xeristar) VSSCs, synaptic vesicles, and carbonic Xyrem, 859. See also gamma hydroxybutyrate anhydrase, 675t (GHB) putative clinical actions, 673t and VSSCs, 707f Y931, 368f and weight loss, 1011 YM992, 573 zopiclone, 842 yohimbine, 565 zotepine, 403, 403f 5HT6-antagonist properties of, 447 “Z” drugs, for insomnia, 838f binding properties, 418f zaleplon, 839f dosage with carbamazepine, 407f half-life of, 836f pharmacological icon, 418f zipa-do, 717f and QTc prolongation, 417 zipa-la, 717f zuclopenthixol (Clopixol), 331t

Index 1117