Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia

Michael Mizenberg, Tyler A. Lesh, Tara A. Niendam, Jong Yoon, Remy N. Rhoades, Cameron S. Carter

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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. Method: 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.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalSchizophrenia Research
Issue number1-3
StatePublished - 2014


  • Cognitive control
  • FMRI
  • Frontal cortex
  • Schizophrenia
  • Suicide

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Medicine(all)


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