title: Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia.
abstract: OBJECTIVE
  Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia.
  
  
  METHODS
  35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity.
  
  
  RESULTS
  Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n=18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex.
  
  
  CONCLUSIONS
  This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Further work should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk.
authors: Department of Psychiatry, University of California, San Francisco School of Medicine, San Francisco, CA, United States; Veterans Affairs Medical Center, San Francisco, CA, United States. Electronic address: Michael.minzenberg@ucsf.edu.
authors: Michael J
authors: MJ
authors: Minzenberg
authors: Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, United States.
authors: Tyler A
authors: TA
authors: Lesh
authors: Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, United States.
authors: Tara A
authors: TA
authors: Niendam
authors: Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Palo Alto, CA, United States; VA Palo Alto Health Care System, Palo Alto, CA, United States.
authors: Jong H
authors: JH
authors: Yoon
authors: Department of Psychiatry, University of California, San Francisco School of Medicine, San Francisco, CA, United States; Veterans Affairs Medical Center, San Francisco, CA, United States.
authors: Remy N
authors: RN
authors: Rhoades
authors: Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, United States; Center for Neuroscience, University of California, Davis, CA, United States.
authors: Cameron S
authors: CS
authors: Carter
mesh_terms: D001931:Brain Mapping; D039721:Diagnostic and Statistical Manual of Mental Disorders; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006040:Goals; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012044:Regression Analysis; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D059020:Suicidal Ideation; D013405:Suicide; D055815:Young Adult
keywords: Cognitive control; Frontal cortex; Schizophrenia; Suicide; fMRI