TY - JOUR
T1 - Behavioral response inhibition in psychotic disorders
T2 - Diagnostic specificity, familiality and relation to generalized cognitive deficit
AU - Ethridge, Lauren E.
AU - Soilleux, Melanie
AU - Nakonezny, Paul A.
AU - Reilly, James L.
AU - Kristian Hill, S.
AU - Keefe, Richard S E
AU - Gershon, Elliot S.
AU - Pearlson, Godfrey D.
AU - Tamminga, Carol A.
AU - Keshavan, Matcheri S.
AU - Sweeney, John A.
N1 - Funding Information:
This research was funded in part by NIMH grants MH078113 , MH077945 , MH077852 , MH077851 , MH077862 , MH072767 , and MH083888 . The NIMH had no further role in development of the paradigm or interpretation of experimental findings.
Funding Information:
Author RSEK currently or in the past has received investigator-initiated research funding support from the Allon, AstraZeneca, Department of Veteran's Affair, Feinstein Institute for Medical Research, GlaxoSmithKline, National Institute of Mental Health, Novartis, Psychogenics, Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. He currently or in the past has received honoraria, served as a consultant, or advisory board member for Abbott, Abbvie, Akebia, Amgen, Astellas, Asubio, BiolineRx, Biomarin, Boehringer-Ingelheim, BrainCells, Bristol-Myers Squibb, CHDI, Eli Lilly, EnVivo, Helicon, Lundbeck, Memory Pharmaceuticals, Merck, Mitsubishi, NeuroSearch, Novartis, Orion, Otsuka, Pfizer, Roche, Shire, Solvay, Sunovion, Takeda, Targacept, and Wyeth. RSEK also receives royalties from the BACS testing battery and the MATRICS Battery (BACS Symbol Coding). He is also a shareholder in NeuroCog Trials, Inc. Author GDP- consulted for Bristol-Myers Squibb. Author CAT discloses the following financial interests and associations: Intracellular Therapies (ITI, Inc.) — Advisory Board, drug development; PureTech Ventures — Ad Hoc Consultant; Eli Lilly Pharmaceuticles — Ad Hoc Consultant; Sunovion — Ad Hoc Consultant; Astellas — Ad Hoc Consultant; Merck — Ad Hoc Consultant; International Congress on Schizophrenia Research — Organizer; Unpaid volunteer; NAMI — Council Member; Unpaid Volunteer; American Psychiatric Association — Deputy Editor; and Finnegan Henderson Farabow Garrett & Dunner, LLP — Expert Witness. Author MSK has received a grant from Sunovion Pharmaceuticals Inc. Author JAS has served as a consultant for Takeda, Inc., Eli Lilly Pharmaceuticals, BMS, and Roche and has received grant funding from Janssen, Inc. The remaining authors (LEE, MS, PAN, JLR, SKH, ESG) report no competing interests.
Funding Information:
This research was funded in part by NIMH grants MH078113 , MH077945 , MH077852 , MH077851 , MH077862 , MH072767 , and MH083888 . We thank Dr. Gunvant Thaker for his input and collaboration on this project.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n = 523), their available first-degree biological relatives (n = 656), and healthy participants (n = 223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors.
AB - Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n = 523), their available first-degree biological relatives (n = 656), and healthy participants (n = 223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors.
KW - Family study
KW - Psychotic bipolar disorder
KW - Response inhibition
KW - Schizophrenia
KW - Stop signal
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U2 - 10.1016/j.schres.2014.08.025
DO - 10.1016/j.schres.2014.08.025
M3 - Article
C2 - 25261042
AN - SCOPUS:84922429113
VL - 159
SP - 491
EP - 498
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
IS - 2-3
ER -