DOCSLIB.ORG

Prepulse Inhibition in Patients with Bipolar Disorder

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Prepulse Inhibition in Patients with Bipolar Disorder Mao et al. BMC Psychiatry (2019) 19:282 https://doi.org/10.1186/s12888-019-2271-8 RESEARCH ARTICLE Open Access Prepulse inhibition in patients with bipolar disorder: a systematic review and meta-analysis Zhen Mao1,2, Qijing Bo1,2* , Weidi Li1,2, Zhimin Wang1,2, Xin Ma1,2 and Chuanyue Wang1,2 Abstract Background: Prepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients with bipolar disorder (BD). This study investigated PPI deficits in BD and pooled the effect size of PPI in patients with BD. Methods: We conducted a literature search on PPI in patients with BD from inception to July 27, 2019 in PubMed, Embase, Cochrane Library databases, and Chinese databases. No age, sex, and language restriction were set. The calculation formula was PPI = 100 - [100*((prepulse - pulse amplitude) / pulse amplitude)]. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies. Results: Ten eligible papers were identified, of which five studies including a total of 141 euthymic patients and 132 healthy controls (HC) were included in the meta-analysis. Compared with HC, euthymic patients with BD had significantly lower PPI at the 60 ms interstimulus interval (ISI) between pulse and prepulse (P = 0.476, I2 = 0.0%, SMD = − 0.32, 95% CI = − 0.54 - -0.10). Sensitivity analysis shows no significant change in the combined effect value after removing any single study. There was no publication bias using the Egger’s test at 60 ms (P = 0.606). The meta-analysis of PPI at the 60 ms ISI could have significant clinical heterogeneity in mood episode state, as well as lack of data on BD I or II subtypes. Conclusions: Euthymic patients with BD show PPI deficits at the 60 ms, suggesting a deficit in the early sensory gate underlying PPI. The PPI inhibition rate at a 60 ms interval is a stable index. More research is needed in the future to confirm this outcome, and to delve deeper into the mechanisms behind deficits. Keywords: Bipolar disorder, Healthy controls, Prepulse inhibition, Systematic review, Meta-analysis Background ms before a strong stimulus. This interferes with and re- In mammals, the startle reflex is caused by a sudden and duces the effects of the strong stimulus on the startle re- intense sensory stimulation. It is an evolved defensive re- flex [5]. PPI has good plasticity and has been widely flex activity that can interrupt and interfere with on- used in various human and animal studies [6–10]. going cognitive and behavioral activities [1–4]. A gating Previous studies have shown that PPI is regulated by the mechanism can effectively inhibit the startle reflex, to limbic-cortical-striatal-pallidal-thalamic (CSPT) neural ensure normal brain function. The prepulse inhibition circuit and the dopaminergic system [11, 12]. Further, it is (PPI) is the application of a weak prepulse stimulus that found that injecting glutamatergic N-methyl-d-aspartate does not trigger a startle reflex during the first 30–500 (NMDA) into the hippocampus can disrupt PPI by affect- ing the expression of Gamma-Aminobutyric Acid (GABA) * Correspondence: [email protected] neurotransmitters and the neural circuit [11, 13]. Braff et 1The National Clinical Research Center for Mental Disorders & Beijing Key al. (1978) first found that patients diagnosed with schizo- Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center phrenia had lower PPI than normal controls [14], and sub- of Schizophrenia, Beijing Anding Hospital, Capital Medical University, No.5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing 100088, China sequent PPI research has focused on the schizophrenia 2Advanced Innovation Center for Human Brain Protection, Capital Medical spectrum population [15]. Moreover, PPI research with University, Beijing 100069, China © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Mao et al. BMC Psychiatry (2019) 19:282 Page 2 of 10 other mental disorders, including bipolar disorder (BD), sensorimotor gating; and sensory gating. We also searched obsessive-compulsive disorder, and autism spectrum dis- for relevant references in known quantitative papers, in- orders, has also been conducted [16–18], indicating that cluding non-English papers. The search strategy has been PPI abnormalities may be related to common psycho- provided as supplementary material (Additional file 1). pathological mechanisms of various disorders. PPI deficits This review performed according to the Preferred Report- have also been reported in first-degree relatives of patients ing Items for Systematic reviews and Meta-Analyses with schizophrenia and BD, indicating that PPI may be a (PRISMA) guidelines, which provides an evidence-based heritable phenotype [19, 20]. minimum set of items for reporting in systematic reviews Although the neuromodulatory circuits of PPI are and meta-analyses. PRISMA Checklist has been included mainly at the brainstem level, many studies have con- as supporting information “PRISMA checklist.doc” firmed that PPI is regulated by higher cognitive processes (Additional file 2). such as attention and emotion. Selective attention to pre- pulse stimulation can specifically enhance PPI in healthy Study selection criteria subjects, while the enhancement effect in schizophrenia Two authors independently screened the literature by patients disappears due to attention deficit [21, 22]. Cur- reading the titles, abstracts, and the full text. The criteria rently, some studies have shown that perceived spatial for inclusion in the meta-analysis were: (1) Presence of a separation-induced PPI paradigm based on the priority ef- HC group. When participants included people with fect can improve the individual recognition of prepulse schizophrenia, BD, and first-degree relatives, information sound and thus increase PPI [6]. Emotions play an import- on patients with BD was extracted. (2) The paper con- ant role in the selective attention and cognitive processes tained PPI data or histograms and corresponding general of people facing complex situations. For example, there demographic information with a PPI formula of PPI = 100 can be higher PPI in response to pleasant or fearful pic- - [100*((prepulse - pulse amplitude) /pulse amplitude)]. tures than to neutral pictures [23, 24]. Moreover, the (3) Presence of PPI data at 60 ms interstimulus interval CSPT circuit in BD patients may be impaired [25]. Deficits (ISI). If the article contains both 60 ms and 120 ms PPI, in this gating circuit could have adverse effects on cogni- 60 ms PPI data was extracted. (4) The quality of the re- tive information filtering, perhaps contributing to depres- search was evaluated by Newcastle-Ottawa Scale (NOS) sive thinking, manic thinking, and delusions. [31]. This consists of nine items divided into three do- Because of the complexity of BD, previous studies have mains: selection of research subjects (four items); inter- drawn inconsistent conclusions. Some studies have found group comparability (two items); and measurement of ex- that, compared with healthy controls (HC), euthymic, or posure factors (three items). The star system is used for acute manic patients with BD, and first-degree relatives semi-quantitative evaluation of research quality. The range had significantly lower PPI levels [16, 20, 26, 27]. How- of NOS is from zero to nine stars. Only papers with more ever, other studies found that patients with BD in the than 4 stars were included in this study. Review papers, euthymic period and pediatric BD did not show PPI defi- abstracts from conference proceedings and case reports cits [28–30]. There has been no systematic review or were excluded. If the data were incomplete, the author meta-analysis of PPI in patients with BD to assess the was contacted by email to ask for information. If the au- overall magnitude of these effects. The present study com- thor did not give a reply, we used the GetData software to prehensively retrieved the literature on PPI in patients extract the data in the paper. The two authors independ- with BD, then systematically reviewed the available data ently intercepted data to minimize errors in this study. Fi- and conducted meta-analysis, comparing BD with HC. nally, we converted all standard error (SE) data into standard deviation (SD) form according to the formula Methods pffiffiffiffi (SD = SE× N). Due to incomplete data, studies that can- Search strategy not be converted are included in the qualitative descrip- Two authors independently searched relevant articles tion. When the two authors reached different conclusions from the start of the database to July 27, 2019 in PubMed, about eligibility, the third author was consulted. Embase, the Cochrane Library databases, and the Chinese databases (VIPS, CNKI, and Wan Fang). Searches used medical subject headings (MESH), text words, and Bool- Data analyses ean calculations. Main search terms included: bipolar dis- Statistical analysis was performed using the software order; bipolar affective disorder; mania; manic-depressive; STATA 11.0 (Stata Corporation, USA). The heterogen- manic episode; hypomania; hypomanic episode; bipolar eity test was evaluated using the I2 value. When I2 ≤ depression; bipolar I disorder; bipolar II disorder; bipolar 50.0% and P ≥ 0.10, it indicated that the included studies type I; bipolar type II; psychosis; psychoses; psychotic; pre- are homogeneous, and the model of fix effect was pulse inhibition; PPI; startle reflex; startle reaction; adopted. If I2 is greater than 50.0% and P value is less Mao et al.
Load more

Recommended publications
  • Alterations in Behavioral Responses to a Cholinergic Agonist In
    Neuropsychopharmacology (2005) 30, 1076–1087 & 2005 Nature Publishing Group All rights reserved 0893-133X/05 $30.00 www.neuropsychopharmacology.org Alterations in Behavioral Responses to a Cholinergic Agonist in Post-Pubertal Rats with Neonatal Ventral Hippocampal Lesions: Relationship to Changes in Muscarinic Receptor Levels 1,2 1 1 ,1,2 Franc¸ois Laplante , Osamu Nakagawasai , Lalit K Srivastava and Re´mi Quirion* 1 2 Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Que´bec, Canada; Department of Pharmacology/ Therapeutics, McGill University, Montre´al, Que´bec, Canada Excitotoxic neonatal ventral hippocampal (NVH) lesion in rats is considered as a putative animal model of schizophrenia as lesioned animals show characteristic post-pubertal emergence of neurochemical and behavioral abnormalities analogous to some of those seen in this disease. Converging evidence points to the involvement of central cholinergic system in this neuropsychiatric disorder, and our previous studies have suggested that cholinergic neurotransmission may be altered in post-pubertal NVH lesioned rats. We investigated here muscarinic receptor reactivity in NVH lesioned animals by measuring the effects of the muscarinic receptor agonist oxotremorine on physiological responses known to be modulated by these receptors such as body temperature, salivation, tremor, pain, and prepulse inhibition of the acoustic startle (PPI). Quantitative receptor autoradiography revealed that post-pubertal NVH lesioned animals display increased levels of [3H]pirenzepine/M -like and [3H]AFDX-384/M -like receptor binding sites in the striatum, nucleus accumbens, and in 1 2 subareas of the dorsal hippocampus. Moreover, in response to the systemic administration of oxotremorine (0.25 mg/kg), post-pubertal NVH lesioned rats exhibited increases in salivation and tremor, and a greater reduction in body temperature compared to sham control animals.
    [Show full text]
  • Lamotrigine Effects Sensorimotor Gating in WAG/Rij Rats
    Published online: 2019-11-13 Original Article Lamotrigine effects sensorimotor gating in WAG/Rij rats Ipek Komsuoglu Celikyurt, Guner Ulak, Oguz Mutlu, Furuzan Yildiz Akar, Faruk Erden, Sezer Sener Komsuoglu1 Department of Pharmacology, Faculty of Medicine, Psychopharmacology Laboratory, Kocaeli University, 1Department of Neurology, Faculty of Medicine, Kocaeli University, Kocaeli,Turkey ABSTRACT Introduction: Prepulse inhibition (PPI) is a measurable form of sensorimotor gating. Disruption of PPI reflects the impairment in the neural filtering process of mental functions that are related to the transformation of an external stimuli to a response. Impairment of PPI is reported in neuropsychiatric illnesses such as schizophrenia, Huntington’s disease, Parkinson’s diseases, Tourette syndrome, obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is an antiepileptic drug that is preferred in absence epilepsy and acts by stabilizing the voltage-gated sodium channels. Aim: In this study, we have compared WAG-Rij rats (genetically absence epileptic rats) with Wistar rats, in order to clarify if there is a deficient sensorimotor gating in absence epilepsy, and have examined the effects of lamotrigine (15, 30 mg/kg, i.p.) on this phenomenon. Materials and Methods: Depletion in PPI percent value is accepted as a disruption in sensory-motor filtration function. The difference between the Wistar and WAG/Rij rats has been evaluated with the student t test and the effects of lamotrigine on the PPI percent have been evaluated by the analysis of variance (ANOVA) post-hoc Dunnett’s test. Results: The PPI percent was low in the WAG/Rij rats compared to the controls (P<0.0001, t:9,612).
    [Show full text]
  • Prepulse Inhibition of the Auditory Startle Reflex Assessment As A
    brain sciences Review Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms Ricardo Gómez-Nieto 1,2,3 , Sebastián Hormigo 1,4 and Dolores E. López 1,2,3,* 1 Institute of Neurosciences of Castilla y León, University of Salamanca, 37007 Salamanca, Spain; [email protected] (R.G.-N.); sebifi[email protected] (S.H.) 2 Institute Biomedical Research of Salamanca, University Hospital of Salamanca, 37007 Salamanca, Spain 3 Department of Cell Biology and Pathology, University of Salamanca, 37008 Salamanca, Spain 4 Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA * Correspondence: [email protected] Received: 11 August 2020; Accepted: 14 September 2020; Published: 16 September 2020 Abstract: When a low-salience stimulus of any type of sensory modality—auditory, visual, tactile—immediately precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and it provides a quantitative measure of central processing by filtering out irrelevant stimuli. As PPI implies plasticity of a reflex and is related to automatic or attentional processes, depending on the interstimulus intervals, this behavioral paradigm might be considered a potential marker of short- and long-term plasticity. Assessment of PPI is directly related to the examination of neural sensorimotor gating mechanisms, which are plastic-adaptive operations for preventing overstimulation and helping the brain to focus on a specific stimulus among other distracters. Despite their obvious importance in normal brain activity, little is known about the intimate physiology, circuitry, and neurochemistry of sensorimotor gating mechanisms.
    [Show full text]
  • Prepulse Inhibition of the Startle Response in Men with Schizophrenia Effects of Age of Onset of Illness, Symptoms, and Medication
    ORIGINAL ARTICLE Prepulse Inhibition of the Startle Response in Men With Schizophrenia Effects of Age of Onset of Illness, Symptoms, and Medication Veena Kumari, MA, PhD; William Soni, MB, BS, MSc; Vallakalil M. Mathew, MB, BS, MRCPsych; Tonmoy Sharma, MSc, MRCPsych Background: Prepulse inhibition of the startle reflex re- Methods: Thirty-eight male schizophrenic patients and sponse refers to the ability of a weak prestimulus to tran- 20 healthy male controls underwent testing for pre- siently inhibit the response to a closely following strong pulse inhibition of the acoustic startle response. sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be defi- Results: Earlier onset of illness was associated with re- cient in schizophrenia. Prepulse inhibition deficits in duced prepulse inhibition, while adult onset of illness was schizophrenia seem to be partially normalized by typi- not. No significant relationships occurred between cur- cal antipsychotics and more fully by some atypical anti- rent symptoms and prepulse inhibition. Patients given psychotics. Early onset of schizophrenia, particularly in typical, but not atypical, antipsychotics exhibited less men, has been associated with abnormal brain matura- prepulse inhibition compared with healthy controls. tion, profound neuropsychological deficits, and less re- sponsiveness to antipsychotic medication. We evalu- Conclusion: Early onset of illness is associated with pro- ated the effects of the age of onset of illness, current found deficits in prepulse inhibition of the startle re- positive and negative symptoms, and the type of medi- sponse in men with schizophrenia. cation (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia.
    [Show full text]
  • A Study in D1 and D2 Receptor Knock-Out Mice
    The Journal of Neuroscience, November 1, 2002, 22(21):9604–9611 Differential Effects of Direct and Indirect Dopamine Agonists on Prepulse Inhibition: A Study in D1 and D2 Receptor Knock-Out Mice Rebecca J. Ralph-Williams,1 Virginia Lehmann-Masten,2 Veronica Otero-Corchon,3 Malcolm J. Low,3,4 and Mark A. Geyer2 1Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, 2Department of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, 3Vollum Institute and 4Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97201 Stimulation of the dopamine (DA) system disrupts prepulse indirect agonist in mice. As reported previously, amphetamine inhibition (PPI) of the acoustic startle response. On the basis of (10 mg/kg) failed to disrupt PPI in D2R knock-out mice, sup- rat studies, it appeared that DA D2 receptors (D2Rs) rather than porting a unique role of the D2R in the modulation of PPI. D1 receptors (D1Rs) regulate PPI, albeit possibly in synergism Dizocilpine (0.3 mg/kg) induced similar PPI deficits in D1R and with D1Rs. To characterize the DA receptor modulation of PPI in D2R mutant mice, confirming that the influences of the NMDA another species, we tested DA D1R and D2R mutant mice with receptor on PPI are independent of D1Rs and D2Rs in rodents. direct and indirect DA agonists and with the glutamate receptor Thus, both D1Rs and D2Rs modulate aspects of PPI in mice in antagonist, dizocilpine (MK-801). Neither the mixed D1/D2 ag- a manner that differs from dopaminergic modulation in rats.
    [Show full text]
  • Inhibition of Auditory Evoked Potentials and Prepulse Inhibition of Startle in DBA/2J and DBA/2Hsd Inbred Mouse Substrains
    Brain Research 992 (2003) 85–95 www.elsevier.com/locate/brainres Research report Inhibition of auditory evoked potentials and prepulse inhibition of startle in DBA/2J and DBA/2Hsd inbred mouse substrains Patrick M. Connollya,1, Christina R. Maxwella,1, Stephen J. Kanesb, Ted Abelc, Yuling Lianga, Jan Tokarczykb, Warren B. Bilkerd, Bruce I. Turetskyb, Raquel E. Gurb, Steven J. Siegela,b,* a Stanley Center for Experimental Therapeutics in Psychiatry, Division of Neuropsychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA b Division of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA c Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA d Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA Accepted 21 August 2003 Abstract Previous data have shown differences among inbred mouse strains in sensory gating of auditory evoked potentials, prepulse inhibition (PPI) of startle, and startle amplitude. These measures of sensory and sensorimotor gating have both been proposed as models for genetic determinants of sensory processing abnormalities in patients with schizophrenia and their first-degree relatives. Data from our laboratory suggest that auditory evoked potentials of DBA/2J mice differ from those previously described for DBA/2Hsd. Therefore, we compared evoked potentials and PPI in these two closely related substrains based on the hypothesis that any observed endophenotypic differences are more likely to distinguish relevant from incidental genetic heterogeneity than similar approaches using inbred strains that vary across the entire genome. We found that DBA/2Hsd substrain exhibited reduced inhibition of evoked potentials and reduced startle relative to the DBA/ 2J substrain without alterations in auditory sensitivity, amplitude of evoked potentials or PPI of startle.
    [Show full text]
  • The Effects of Memantine on Prepulse Inhibition
    Neuropsychopharmacology (2009) 34, 1854–1864 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org The Effects of Memantine on Prepulse Inhibition ,1 1 1 1 1 NR Swerdlow* , DP van Bergeijk , F Bergsma , E Weber and J Talledo 1Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA Reduced prepulse inhibition (PPI) of startle provides evidence of deficient sensorimotor gating in several disorders, including schizophrenia. The role of NMDA neurotransmission in the regulation of PPI is unclear, due to cross-species differences in the effects of NMDA antagonists on PPI. Recent reports suggest that drug effects on PPI differ in subgroups of normal humans that differ in the levels of baseline PPI or specific personality domains; here, we tested the effects of these variables on the sensitivity of PPI to the NMDA antagonist, memantine. PPI was measured in male Sprague–Dawley rats, after treatment with memantine (0, 10 or 20 mg/kg, s.c.). Baseline PPI was then measured in 37 healthy adult men. Next, subjects were tested twice, in a double-blind crossover design, comparing either (1) placebo vs 20 mg of the NMDA antagonist memantine (n ¼ 19) or (2) placebo vs 30 mg memantine (n ¼ 18). Tests included measures of acoustic startle amplitude, PPI, autonomic indices and subjective self-rating scales. Memantine had dose- and interval- dependent effects on PPI in rats. Compared with vehicle, 10 mg/kg increased short-interval (10–20 ms) PPI, and 20 mg/kg decreased long-interval (120 ms) PPI. In humans, memantine caused dose-dependent effects on psychological and somatic measures: 20 mg was associated with increased ratings of happiness, and 30 mg was associated with increased ratings of dizziness.
    [Show full text]
  • Reduced Prepulse Inhibition As a Biomarker of Schizophrenia
    fnbeh-10-00202 October 15, 2016 Time: 11:54 # 1 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by idUS. Depósito de Investigación Universidad de Sevilla ORIGINAL RESEARCH published: 18 October 2016 doi: 10.3389/fnbeh.2016.00202 Reduced Prepulse Inhibition as a Biomarker of Schizophrenia Auxiliadora Mena1, Juan C. Ruiz-Salas1, Andrea Puentes2, Inmaculada Dorado3, Miguel Ruiz-Veguilla3 and Luis G. De la Casa1* 1 Department of Experimental Psychology, University of Seville, Seville, Spain, 2 Neurosciences Institute, El Bosque University, Bogotá, Colombia, 3 Institute of Biomedicine, University Hospital Virgen del Rocío, Seville, Spain The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge.
    [Show full text]
  • Amphetamine Effects on Prepulse Inhibition Across-Species: Replication and Parametric Extension
    Neuropsychopharmacology (2003) 28, 640–650 & 2003 Nature Publishing Group All rights reserved 0893-133X/03 $25.00 www.neuropsychopharmacology.org Amphetamine Effects on Prepulse Inhibition Across-Species: Replication and Parametric Extension Neal R Swerdlow*,1, Nora Stephany1, Lindsay C Wasserman1, Jo Talledo1, Jody Shoemaker1 and Pamela P 1 Auerbach 1Department of Psychiatry, UCSD School of Medicine, La Jolla, CA, USA Despite the similarities of prepulse inhibition (PPI) of the startle reflex and its apparent neural regulation in rodents and humans, it has been difficult to demonstrate cross-species homology in the sensitivity of PPI to pharmacologic challenges. PPI is disrupted in rats by the indirect dopamine (DA) agonist amphetamine, and while studies in humans have suggested similar effects of amphetamine, these effects have been limited to populations characterized by smoking status and specific personality features. In the context of a study assessing the time course of several DA agonist effects on physiological variables, we failed to detect PPI-disruptive effects of amphetamine in a small group of normal males. The present study was designed to reexamine this issue, using a larger sample and a paradigm that should be more sensitive for detecting drug effects. PPI in rats was shown to be disrupted by the highest dose of amphetamine (3.0 mg/kg) at relatively longer prepulse intervals (430 ms). In humans, between-subject comparisons of placebo (n ¼ 15) vs 20 mg amphetamine (n ¼ 15) failed to detect significant PPI-disruptive effects of amphetamine, but significant PPI-disruptive effects at short (10–20 ms) prepulse intervals were detected using within-subject analyses of postdrug PPI levels relative to each subject’s baseline PPI.
    [Show full text]
  • Deficient Prepulse Inhibition in Schizophrenia Detected by the Multi-Site COGS
    UC San Diego UC San Diego Previously Published Works Title Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS. Permalink https://escholarship.org/uc/item/3mg2c7tp Journal Schizophrenia research, 152(2-3) ISSN 0920-9964 Authors Swerdlow, Neal R Light, Gregory A Sprock, Joyce et al. Publication Date 2014-02-01 DOI 10.1016/j.schres.2013.12.004 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Schizophrenia Research 152 (2014) 503–512 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Review Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS Neal R. Swerdlow a,⁎, Gregory A. Light a,i,JoyceSprocka,i, Monica E. Calkins b, Michael F. Green e,f, Tiffany A. Greenwood a,RaquelE.Gurb, Ruben C. Gur b, Laura C. Lazzeroni g,h, Keith H. Nuechterlein e, Allen D. Radant c,d, Amrita Ray g,h, Larry J. Seidman j,k,LarryJ.Sieverl,m, Jeremy M. Silverman l,m, William S. Stone j,k, Catherine A. Sugar e,i,n, Debby W. Tsuang c,d,MingT.Tsuanga,o,p, Bruce I. Turetsky b, David L. Braff a,i a Department of Psychiatry, University of California San Diego, La Jolla, CA, United States b Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States c Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States d VA Puget Sound Health Care System, Seattle, WA, United States e Department of Psychiatry and Biobehavioral Sciences, Geffen School of
    [Show full text]
  • Sensorimotor Gating Deficits in Schizophrenia: Advancing Our Understanding of the Phenotype, Its Neural Circuitry and Genetic Substrates
    UC San Diego UC San Diego Previously Published Works Title Sensorimotor gating deficits in schizophrenia: Advancing our understanding of the phenotype, its neural circuitry and genetic substrates. Permalink https://escholarship.org/uc/item/82r82866 Authors Swerdlow, Neal R Light, Gregory A Publication Date 2018-08-01 DOI 10.1016/j.schres.2018.02.042 Peer reviewed eScholarship.org Powered by the California Digital Library University of California SCHRES-07735; No of Pages 5 Schizophrenia Research xxx (2018) xxx–xxx Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Guest editorial Sensorimotor gating deficits in schizophrenia: Advancing our understanding of the phenotype, its neural circuitry and genetic substrates ARTICLE INFO Article history: Received 21 February 2018 Accepted 23 February 2018 Available online xxxx Keywords: Antipsychotic Genetics Prepulse inhibition Schizophrenia Sensorimotor gating Startle reflex 1. Introduction In the 80 years since Peak's systematic studies of blink inhibition, and the 40 years since Braff's published observation of impaired In her 1936 report of paired-pulse blink inhibition in 13 Yale prepulse inhibition (PPI) in schizophrenia patients, PPI has been studied undergraduate men, Helen Peak described “quantitative variation in many thousands of patients, and PPI findings have been reported in in amount of inhibition of the second response incident to changes approximately 3000 Medline publications. While a relationship in intensity of the first
    [Show full text]
  • Nitric Oxide Synthase Inhibitors Attenuate Phencyclidine-Induced Disruption of Prepulse Inhibition Jenny L
    Nitric Oxide Synthase Inhibitors Attenuate Phencyclidine-Induced Disruption of Prepulse Inhibition Jenny L. Wiley, Ph.D. Glutamate stimulation of N-methyl-D-aspartate (NMDA) the NOS inhibitors, L-NOARG, 7-nitroindazole and receptors results in release of nitric oxide which may arcaine—but not the NR2B-selective polyamine site mediate the effects of NMDA receptor stimulation and/or NMDA antagonist, eliprodil—attenuated PCP-induced may result in feedback inhibition of the presynaptic neuron. disruption of prepulse inhibition of the acoustic startle Results of a previous study showed that nitric oxide response. These effects are similar to those produced by synthase (NOS) inhibitors blocked dizocilpine-induced many atypical antipsychotics and suggests that this class of behavior in mice. In the present study, NOS inhibitors were drugs should be investigated further for their potential tested in combination with phencyclidine (PCP), a drug utility as antipsychotics and as treatments for PCP abuse. which typically dose-dependently disrupts prepulse [Neuropsychopharmacology 19:86-94] © 1998 inhibition of the acoustic startle response in rats. Alone, American College of Neuropsychopharmacology. NOS inhibitors and promoters do not affect prepulse Published by Elsevier Science Inc. inhibition; however, when tested in combination with PCP, KEY WORDS: Antipsychotics; Nitric oxide synthase in the brain and is hypothesized to be involved in the inhibitors; NMDA antagonists; Phencyclidine; centrally mediated properties of nitric oxide (Lambert Schizophrenia et al. 1991). These central effects may include roles in Nitric oxide is a soluble gas that is synthesized from the memory formation (Chapman et al. 1992; Yamada et al. amino acid L-arginine by nitric oxide synthase (NOS).
    [Show full text]