Identifying and from a Sea of Mimics

Michael Sean Stanley, MD Assistant Professor OHSU Department of Identifying Schizophrenia and Bipolar Disorder from a Sea of Mimics

No Disclosures. • Objectives: – Understand the clinical presentation and approach to treatment of Schizophrenia and Bipolar Disorder Psychotic disorders are: Disorders are: • primarily problems of • Primarily problems of sensory processing prolonged extreme and association, not emotional tone (mood). emotion • Exhibit excessive high or • Exhibit profound low mood/motivation disconnection from from normal state sensory reality

Schizophrenia • a neurodevelopmental • associated with functional impairments Schizophrenia • no single unifying cause • emerges when environmental accelerants act upon genetic predisposition • May be at the more severely impairing end of a spectrum of disorders.

+ - C

Positive Symptoms Negative Symptoms Cognitive Symptoms

New abnormal sx Loss of normal fxn Accompany and likely - - Affective flattening precede +/- sx (auditory most - - Attentional problems commonly) - - Slower processing - - - Difficulty with - Significant planning/prob disorganization of solving /behavior - problems

May come and go A stable loss, do not Prodromal sx? fluctuate significantly once lost. May decrease to some May be responsive to Minimally responsive to degree with tx of pos sx, meds antipsychotic meds if at but rarely completely. all.

For 6 mo or longer; Not due to medical or substance use cause. Positive Symptoms Most commonly during teens-20s Neuro-Cognitive Inappropriate Network Imbalance Pruning or Synaptic • Lack of coordination Changes: of neural tasks • Decr • Lack of inhibition of • Prefrontal neural tasks • Parahippoca Inappropriate – mpal hallucinations/delusions • Temporal • thalamic • Decr dendritic spines

Inflammatory Events Damage Events

Genetics: • Pathways implicated by (a selection) • Highly heritable – 30% of offspring • Synaptic function (DRD2, GlutR, voltage- • Many genes with small effect size dependent calcium channels) • Some genetic overlap with other psych dx: • Synaptic plasticity BPAD, MDD, Spectrum DO • Cytoskeletal development • Genes point to multiple mechanisms • Immune response/modulation Schizophrenia

Onset • One peak in men: generally to early 20s • Two peaks in women: similar as above + over 40s Prevalence • Lifetime likelihood of 0.7% • 80-90% unemployed • Life-expectancy 10-20 years reduced • Most likely due to cardiovascular and other problems • High prev of • High prev of dietary indiscretions • Low medical care use • Cardiometabolic effects of treatments Schizophrenia Illness Template Schizophrenia Template Present? DSM5 Stereotypic Positive Sx (Hallucinations, Delusions, Disorg) Stereotypic Negative Sx (Affective Flattening, Alogia, , Asociality) Functional Impairment Duration > 6 mo Absence of Medical/Substance Cause Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) Family History of psychotic disorder – cognitive, negative sx Course – subacute onset, fluc +, stable - Typical Treatment Response? Schizophrenia Template Case • 19 yo male • CC: Presents for auditory hallucinations of his high school physics professor arguing with his parents about implanting novel “microcircuits” in his body. Feels this might be true, and has shaved parts of his body to the “microcircuits” • HPI (from collateral): sx began about 1 year ago, have fluctuated, and have been associated w/ performance decline at community college, last quarter his teachers expressed concern and he was on monitoring plan by student health center. Per family, throughout high school, patient displayed some of supernatural causes, but they had not caused functional problems. Gradually late in high school he became increasingly reclusive, stopped being interested in things that previously interested him, these sx have continued. • Family Hx: Paternal uncle with schizophrenia • Exam: Medical exam benign, has never used other than . • Mental Status Exam: + AH and delusions, , appeared to attend to internal stimuli, flat , paucity of spontaneous thought. • Course: saw psychiatrist who Rx’d 2mg qhs, which significantly decreased AH. Stopped medication after 6 mo, when noticed , and AH restarted. Schizophrenia Illness Template Schizophrenia Template Present? DSM5 Stereotypic Positive Sx (Hallucinations, Delusions, Disorg) Yes Stereotypic Negative Sx (Affective Flattening, Alogia, Apathy, Asociality) Yes Functional Impairment Yes Duration > 6 mo Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) Yes Family History of psychotic disorder Yes Prodrome – cognitive, negative sx Yes Course – subacute onset, fluc +, stable - Yes Typical Treatment Response? Yes of Schizophrenia

Other Psychiatric Disorders • Schizophrenia spectrum • Bipolar Disorder, Manic with Psychotic features • with Psychotic features •

Non-Psychiatric Disorders • Medication-Induced Psychosis • Substance-Induced Psychosis • • Cerebrovascular Disorders • Neoplasm • with Lewy bodies • • Autoimmune: Anti-NMDA receptor encephalitis Schizophrenia Spectrum

Del only 2+ sx 1 mo 6 mo

Normal

Cognitive or perceptual distortions Delusions only, or behavioral function not eccentricities that grossly affect social impaired Schiz + connections, but not prominent gross biological affective sx function Psychotic symptoms, such as auditory hallucinations and paranoid thinking, occur in attenuated forms in 5–8% of the healthy population • a disorder of emotional tone Bipolar Disorder – Elevated = hypo/ – Low = major depressive episodes • associated with functional impairments at peaks • emerges when environmental accelerants act upon genetic predisposition Bipolar Disorder !!MANIC EPISODE!!

majordepressiveepisode Epidemiology of Bipolar Disorders: Bipolar Disorder • Lifetime prevalence of Bipolar Disorders is 1-3% worldwide • Female:Male = 1:1 • Mean onset of Bipolar I DO is 18yo • About 1/3 of patients with a parent with Bipolar Disorder will go on to have Bipolar Disorder • Depressive Episodes are actually more common in Bipolar Disorder than are Manic/Hypomanic Episodes • 10-15% of patients with Bipolar Disorder die by , which is estimated at 12-15x greater rate than in the general population Elation, irritable mood, MDD with excess energy, subsyndromal talkativeness, racing mania, cylothymia, Mood lability, thoughts, decreased or psychosis subsyndromal need for or mania symptoms

Genetic Risk Gestational or Birth Head Injury Life Stressors Substance Early Life Stress Use Prodrome Comparison

Bipolar Prodrome Schizophrenia Prodrome

• Strange/Unusual Ideas • Frequent Mood Swings • • Physical Agitation • Suspiciousness • Concentration/ Probs • Hallucinatory Experiences • Difficulty • Anhedonia Thinking/Communicating Clearly • Decreased Functioning • Obsessions Compulsions • • Depressed Mood • Tiredness Lack of Energy • Thinking About Suicide Bipolar DO Illness Template

Bipolar Disorder Template Present? DSM5 Manic Episode (Mood&Energy +3/7sx) x 1 week or hospitalition Major Depressive Episode (not needed if manic) Functional Impairment Absence of Medical/Substance Cause Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s Family History of Bipolar Disorder Prodrome – isolated manic sx Course – episodic, relapsing/remitting Typical Treatment Response? Absence of other atypical features Bipolar DO Template Case • 20 yo male • CC: Elevated mood, Increased energy, beliefs of God-given mission to spread “heal broken street children” through “parkour science”. Accompanied by agitation, decreased need for sleep, disorganized behaviors, rapid . • HPI: sx started ~10 days ago, after returned from study abroad in Europe, increased gradually over 2-3 days. • Collateral noted the following: • Cousin with on • Successfully recently completed 6 mo study abroad program in global finance in Switzerland. • Has a girlfriend and 2 friends who accompanied him to ED, and who are very worried about him, as this is very different behavior for him, as he has not been spiritual. • Girlfriend noted that he had had sporadic periods of decreased need for sleep in past, but never like this. • Med hx/Psych hx: no med probs, no psych dx, has never used drugs other than remote brief trial in high school • Exam: agitation, talking mildly rapidly, focuses on spiritual mission, requires interruption, denies AH/VH, denies SI/HI. • Course: Risperidone 2mg qhs, responded well, tapered off 12 mo later, did not have recurrence of delusions immediately, although 2 years later had beginning of similar sx. Bipolar DO Illness Template

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) Yes x 1 week or hospitalition Major Depressive Episode (not needed if manic) N/A Functional Impairment Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s Yes Family History of Bipolar Disorder Yes Prodrome – isolated manic sx Yes Course – episodic, relapsing/remitting Yes Typical Treatment Response? Yes Absence of other atypical features Yes Differential Diagnosis of Bipolar DO

Other Psychiatric Disorders Bipolar Disorder • Schizophrenia & spectrum • Major Depressive Disorder • Premenstrual Dysphoric Disorder • Borderline • Attention-deficit Hyperactivity Disorder

Non-Psychiatric Disorders • Medication-Induced Mania – Corticosteroids, Isoniazid, Levodopa • Substance-Induced Mania – , , Cannabis • • //Neoplasm • • Encephalitis Identifying whether a primary psychiatric or secondary disorder: • there are no pathognomonic signs to differentiate primary from secondary disorders.

• Early differentiation is observational, based on • The known epidemiology and course of primary disorders • The known presentations of primary disorders: • History • physical exam • mental status exam • Any confounding features

• Follow-up over long-term watching for symptoms or signs that increase or decrease probability of primary psychiatric diagnosis Cases Case: “I’ve killed them all”

• 80 yo female • CC: New onset fixed false beliefs in the last few days that she has caused the death of multiple friends, and the only way to atone is to starve herself. No hallucinations. Affect flattened. • HPI: Adult daughter noted that her sx started 3 weeks ago, slowly becoming more encompassing; that she had stopped going to church, was isolating more over last month, staying in bedroom sleeping a lot, eating little. • Past Med/Psych hx: mild vascular dz, a few episodes of major depression, but never tolerated long- term. Rare glass of red wine, no other substances. • Fam Hx: depression, no psychosis. • Exam: psychomotor slowing, slowed responses, seems distracted, flattened or sad affect, repeatedly comes back to thought that she must have caused deaths of friends. • Course: Receives visits from members of church who have missed her leadership of their benevolent services committee. Referred to Electroconvulsive therapy (ECT) under daughter as POA, improves within a few weeks. Case: “I’ve killed them all”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx Yes Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) No Family History of psychotic disorder No Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? ? Absence of other atypical features No Diagnosis: Major Depression with Psychosis Case: “they’re telling me to kill myself”

• 16 yo female • CC: New onset auditory hallucinations telling her to end her life, tactile hallucinations of worms under her skin. • HPI: Started 1 week ago per friend, one day she was good the next hallucinating. Per community health case worker who brought her to the ED, pt was recently homeless, has hx of DV trauma and parents with significant substance use disorders. Case worker had never seen her like this. • Med/Psych Hx: no known medical conditions, hx of substance use, but no prior psychosis known. • Exam: somewhat cooperative with exam, scratching at skin, asked if ED staff could see the worms, disorganized speech at times, agitation, teary at times. • Labs: UDS +, no other abnormalities. • Course: Started on 50mg BID and 100mg QHS, kept in ED obs, calms over 24 hours to cooperative with nursing staff, very congenial and thankful upon discharge. Sees outpatient psychiatrist who quickly tapers her quetiapine, offers hydroxyzine and PRN as she enters treatment program. Case: “they’re telling me to kill myself”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx No Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause No Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) Yes Family History of psychotic disorder No Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? No Absence of other atypical features? No

Diagnosis: Psychosis due to Use Case “I’m so tired of this!”

• 24 yo female • CC: Mood lability, irritability. Wants referral for Bipolar DO. • HPI: mood sx + easily tearing, attention/memory problems, lethargy, low motivation, quick temper flares, seem to come and go from one week to next. Most recently over last 7 days, but has happened previously many times. She is a junior manager at a local IT firm, and has had to take days off recently because of her symptoms, and worries that because of some irritable outbursts she may be on the verge of being fired. No history of mania or prolonged periods of depression lasting 2 weeks. • Medical hx: No medical problems, uses intermittently in evening only • Exam: physical exam nl, labs nl; mental status exam: patient tearing often, complains that she wishes she could communicate what is happening better, and does lose train of thought a couple times, is mildly irritable, but displays no agitation, rapid speech, or psychotic sx. She reports her sleep is good. • Course: PCP refers to psychiatrist, but patient calls 2 days later to state she feels so much better and just started menstruation. PCP has patient track mood symptoms over 2 menstrual cycles. Case “I’m so tired of this!”

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) No x 1 week or hospitalition Major Depressive Episode (not needed if manic) No Functional Impairment Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s Yes Family History of Bipolar Disorder No Prodrome – isolated manic sx No Course – episodic, relapsing/remitting Yes Typical Treatment Response? - Free of confounding features No – rapid remittance,

Diagnosis: Premenstrual Dysphoric Disorder Case: “we’re surrounded” • 48 yo male • CC: new onset auditory hallucinations of people outside , paranoid – checking locks, agitation, • HPI: Started rapidly 3 days ago; brought to ED by brother, wife and teenage daughter who note he has never had sx like this; was recently working as middle school science teacher for last 22 years, assistant coaches school basketball team; recently treated for severe asthma for first time with high-dose • Medical hx: severe asthma from childhood, moderate alcohol use, but no hx of use disorder or withdrawal. No prior psychiatric hx. • Family Hx: cousin with schizophrenia • Exam: Well-groomed male with mild agitation, restlessness, tremor, exhibiting paranoid thoughts, appears distracted at time, but accepts reassurance from brother, no SI/HI, accepting of help. • Course: Started on 2.5mg for duration of prednisone treatment, then decreased slowly 1 week after prednisone treatment completed, psychotic sx do not recur. Case: “we’re surrounded”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx No Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause No Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) No Family History of psychotic disorder Yes Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? No Absence of other atypical features No

Diagnosis: Psychosis due to Steroid Treatment Case “people piss me off”

• 30 yo male • CC: Irritability, rapid anger, impulsive behaviors • HPI: Was recently seen in ED for multiple cuts to wrists which required minor bandaging, cuts occurred in context of his girlfriend breaking up with him. Was not hospitalized for SI, was told to get referral to psychiatry from PCP. Works as truck driver to avoid people. Similar symptoms, including quick anger, chronic feelings of emptiness, , impulsive -harm, spending, substance use - have been around since teens. Was diagnosed in teens with “Bipolar Disorder” and started on multiple medications while at a home for teen boys. Denied hx of mania or prolonged depressions with severe veg sx. • Med/Psych hx: HTN, chronic pain, hx of opioid pain medication overuse. • Family Hx: depression and various substance use disorders, including heroin. No Bipolar or Psychotic Disorders. • Exam: No agitation, no psychotic sx, no pressured speech, no flight of ideas, normal, but irritability, chronic SI • Course: With psychiatrist, discusses of abandonment, cutting to “feel something” and to get girlfriend back. Feels good when “on the same page” as others, black/white thinking. Psychiatrist refers patient to Dialectical Behavioral Therapy. Over time works to reduce medications when patient expresses openness to it. Case “people piss me off”

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) No x 1 week or hospitalition Major Depressive Episode (not needed if manic) Yes Functional Impairment Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s Yes Family History of Bipolar Disorder No Prodrome – isolated manic sx No Course – episodic, relapsing/remitting Yes Typical Treatment Response? Yes/No Free of confounding features No: of abandonment, sx peak in interpersonal situations, cutting Diagnosis: Borderline Personality Disorder Case: “they’re putting it in my food.”

• 75 yo female • CC: New onset visual hallucinations, tactile hallucinations, that staff are poisoning her; • HPI: Brought to ED by assisted living care staff, for rapid onset over last 1 week of hallucinations/paranoid delusions; found searching halls for lost dog which she doesn’t have, then locking herself in her room. Is former executive assistant, of 3, grandmo of 6, was cooperative 1 week prior • Med/Psych Hx: osteoporosis, osteoarthritis on low-dose for chronic pain, , mild neurocognitive disorder. No prior Psych hx. • Family Psych Hx: none • Exam: fluctuating sensorium and disorientation - she thought date was 1985 and that the ED physician was her son. At times she would lose track of the conversation or become upset and hit out at staff. Bladder distention, . • Labs: • Course: Was given 0.25mg haldol, and she calmed and cleared for 6 h, but then disorientation, VH came back. Case: “they’re putting it in my food.”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx No Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause No Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) No Family History of psychotic disorder No Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? Yes Absence of other atypical features No – fluctuating consciousness, VH, disorientation Diagnosis: Delirium from multiple potential causes Case: “can you see them?”

• 79 yo male • CC: New onset visual hallucinations of children outside room at assisted living facility where lives with wife • HPI: last 3 weeks has had VH, are distracting, but don’t strike fear, and have led him to wander outside to look for the children. Also has had severe sleep probs, mild cognitive problems. Worked in healthcare for 40 years, with ~20 years as hospital administrator for single local children’s hospital. Was seen in ED 1 weeks ago where UA showed equivocal UTI, and superimposed delirium was considered, was given haldol once – had severe medication-induced parkinsonism, and flattening. • Medical hx: Hx hip replacement, no prior psych hx, no alcohol or substance use. • Fam hx: grandson with Autism, father had Parkinsons, no other disorders. • Exam: fluctuating vitals, parkinsonism (now off haldol), mild cognitive impairments, fleeting VH. Case: “can you see them?”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes/No Stereotypic Negative Sx No Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause ?? Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) No Family History of psychotic disorder No Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? No Absence of other atypical features No - VH only, fluct vitals, sleep probs, Parkinsonism Diagnosis: Lewy-Body Dementia Case “I get bored” • 15 yo male • CC: Anger, Agitation, Poor Sleep, Impulsive behaviors. Brought to PCP by parents for worry about risky behaviors. • HPI: Recently got caught for stealing a neighbors car and going for a joyride with a friend in the middle of the night on a weeknight. Has court date coming up. Father notes he is “up at all hours”, “can’t finish anything at school or home” and “won’t listen to anything we say”. With father in room, sulks with arms folded, doesn’t speak. With father gone talks about hating school, not knowing if its worth continuing to go, he doesn’t feel good about himself there, just wishing he could leave home or die, but doesn’t have active SI. He says he gets to sleep at 1-2am most nights because it is hard to shut his body down, barely wakes in time for school at 7am feeling exhausted, and on weekends sleeps until noon. Chronically impulsive, attention problems, no , likes to sleep, no psychosis. • Med/Psych Hx: ADHD since age 8, multiple broken ; Has tried many substances, but nothing repeatedly. • Social hx: High school sophomore in IEP for ADHD, performing poorly, and missing classes. Enjoys skateboarding and rock climbing. Has girlfriend and multiple friends. • Family Hx: ADHD • Exam: phys exam normal, mental status exam: exhibits mild hyperactivity, overtalks at times, but shows no severe agitation, no flight of ideas or loose associations, no psychosis sx. UDS neg. Case “I get bored”

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) No x 1 week or hospitalition Major Depressive Episode (not needed if manic) No Functional Impairment Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s No - before Family History of Bipolar Disorder No Prodrome – isolated manic sx No Course – episodic, relapsing/remitting No Typical Treatment Response? - Free of confounding features No: chronic hyperactivity, , not decreased need for sleep Diagnosis: ADHD +/- Oppositional Defiant/conduct DO and Case: “tell them to stop shouting at me”

• 17 yo female • CC: Auditory hallucinations, paranoia, possible , mutism • HPI: last 2 weeks experienced fairly fast onset of above sx. Brought to parents who are very concerned because this was a very sudden change for her, and she has never had such symptoms prior, has had to stay home from school. She is an A student and vice president of her class at high school, who recently helped lead organization of the high school dance. • Past Medical Hx: No medical problems, had tried cannabis once in last month • Family Hx: and Borderline Personality Disorder • Exam: patient had some to of thinking, some attention-problems, headache, autonomic instability, odd posturing, periods of mutism, fluctuating paranoia and hallucinations. Mother sat with her to calm her. • Course: Low dose olanzapine given, but did not help much. Head MRI showed mesiotemporal , EEG showed generalized slowing, LP showed oligoclonal bands, and ovarian teratoma discovered. Removal of ovarian teratoma and immunosuppression led to symptom remission. Case: “tell them to stop shouting at me”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx No Functional Impairment Yes Duration > 6 mo No Absence of Medical/Substance Cause No Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) Yes Family History of psychotic disorder Yes Prodrome – cognitive, negative sx No Course – subacute onset, fluc +, stable - No Typical Treatment Response? No Absence of other atypical features No – some insight, headache, autonomic instability, MRI findings Diagnosis: Anti-NMDA receptor encephalitis Case “I don’t know what’s happening to me” • 37 yo female • CC: Rapid onset over a week of agitation, mood irritability and lability, increased energy, decreased ability to sleep, “because I can’t stop my brain”, rapid speech, agitation. • HPI: Had some recent viral infection, was just getting over it, when she began to feel less herself, have harder time sleeping, more moody, difficulty controlling thoughts and attention, lost track of what she was doing several times during the day. • Med/Psych Hx: Depression stable on for many years. No other problems. Not pregnant. • Social hx: Works in mayor’s office on regional planning team. • Family Hx: Depression • Physical exam: double vision, mild ataxia • Mental Status Exam: well-groomed female appearing stated age, mild agitation, but not requiring redirection, no tremor, speech mildly pressured, some challenges with attention, seems to lose track of course of conversation, memory poor for short term, but can remember things from a few weeks ago, problem finding words at times, mood/affect labile and irritable, insight fair to “something being wrong”, judgment fair. • Course: Received Olanzapine 2.5mg which helped her sleep and improved mood. Referred for urgent MRI brain, which showed a few scattered T2 hyperintensities. Referred to neurology. Case “I don’t know what’s happening to me”

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) Yes x 1 week or hospitalition Major Depressive Episode (not needed if manic) Yes Functional Impairment Yes Absence of Medical/Substance Cause ?? Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s No Family History of Bipolar Disorder No Prodrome – isolated manic sx No Course – episodic, relapsing/remitting No Typical Treatment Response? Yes Free of confounding features? No: Sudden onset outside typical years, with MRI hyperintensities

Diagnosis: Bipolar Disorder due to Multiple Sclerosis Case “We’re connected” • 17 yo female • CC: Referred to Psychiatry for bizarre thoughts • HPI: Over course of last year has begun to voice that she feels she is directing the actions of a K-pop band from afar, and they communicate to each other through a special “radio-force- channel” that others do not experience. • Collateral: parents note she has become more isolative, spends much of her time drawing pictures of K-pop stars and collating memorabilia, and school engagement and performance has declined over last year, does not complete much school work. Denies significant mood sx or clear hallucinations. Reported does not go away, but intensity fluctuates. • Past Med Hx/Psych Hx: no medical conditions, has been diagnosed with cognitive processing disorder, on IEP in school for last 3 years. • Family Hx: unknown, patient adopted at age 12 months • Exam/Labs: normal • Mental Status Exam: Speech normal, thought content +delusions, thought process mildly slowed, cognition mild attention probs, orientation good, memory fair, affect is flat, insight poor to delusional process, judgment fair to care. • Course: Referred to Early Assessment and Support Alliance, started in activities, and started on 5mg twice daily, responds well. Case “We’re connected”

Schizophrenia Template Present in this case? DSM5 Stereotypic Positive Sx Yes Stereotypic Negative Sx Yes Functional Impairment Yes Duration > 6 mo Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Schiz Age of onset during teens-20s (or ~40s if F) Yes Family History of psychotic disorder unknown Prodrome – cognitive, negative sx Yes Course – subacute onset, fluc +, stable - Yes Typical Treatment Response? Yes Absence of other atypical features Yes

Diagnosis: Schizophrenia Case “Ommmmm”

• 23 yo female • CC: Brought to ED by police • HPI: Very little history, she is speaking rapidly, has difficulty sitting down at times, writes copious notes on every piece of paper she is given, disrobes and lays on the ground of her room repeating “Om” on repeat for over an hour, is irritable when others try to ask her to stop. While in ED, does not sleep. • Police match to missing persons report, calls point of contact, mother, who notes: • Patient went missing a week prior after displaying some bizarre behaviors at her academic lab job. • Police had contacted her lab PI who noted increasingly pressured speech, some bizarre associations and ideas about the research, and attending work disheveled, and a few times in the same clothes she wore the previous day. He said this was very uncharacteristic of her, and denied any known in-lab toxic exposures. • Exam: phys exam and labs are normal, UDS negative. • Family Hx: father has Bipolar Disorder w/ mult hospitalizations. • Course: She is admitted and started on olanzapine 20mg at bedtime, eventually started on lithium. Her mood normalizes over 10 days. Transfers to intensive outpatient program for 3 weeks. Back to work part time after 2 montha. Case “Ommmmm”

Bipolar Disorder Template Present in this case? DSM5 Manic Episode (Mood&Energy +3/7sx) Yes x 1 week or hospitalition Major Depressive Episode (not needed if N/A manic) Functional Impairment Yes Absence of Medical/Substance Cause Yes Research-based factors that increase probability of Bipolar DO Age of onset during teens-20s Yes Family History of Bipolar Disorder Yes Prodrome – isolated manic sx Unknown Course – episodic, relapsing/remitting Too early to tell Typical Treatment Response? Yes Free of confounding features? Yes

Diagnosis: Bipolar I Disorder, most recent episode manic Treatments – Schizophrenia Am Fam Physician. 2014;90(11):775-782 Antipsychotic • Most of effect comes from effect at Receptor 2 (D2) Medications – Some medications very potent – haldol – Some less potent – quetiapine – A few have very minimal effects at D2 –

• effective when the levels occupy approximately 70% of D2 receptors.

• Persons with schizophrenia vary in response to : – 10-30% of pts with schiz get no benefit – up to 30% may get partial benefit – 50%+ get strong positive response

• In patients with schizophrenia recommendation is to continue antipsychotic treatment life long. – 4-30% of patients with schizophrenia will have another during their lifetime – and no way to predict who will or won’t. – In studies of continuation, 64% of patients randomized to placebo had relapse within 1 year, 23% of patients randomized to continuation of antipsychotic had relapse with 1 year. Antipsychotic N Engl J Med. 2019;381:1753-61. Medications Antipsychotic Am Fam Physician. 2014;90(11):775-782 Medications Treatments – Bipolar Disorder Am Fam Physician. 2014;90(11):775-782 Medications to treat Bipolar Disorder Lancet 2016; 387: 1561–72 Extras

Medical Causes of psychosis Extras

Medical Causes of psychosis Extras

Medical Causes of mania N Engl J Med. 2019;381:1753-61. N Engl J Med. 2004; 351:476-486.

Am Fam Physician. 2014;90(11):775-782 Am Fam Physician. 2014;90(11):775-782

Lancet. 2016; 388: 86–97 Lancet 2016; 387: 1561–72 . 2010; 36 (1) pp 94-103

Bipolar Disorders. 2018; 20 (2):97-170.