Background Executive dysfunction, distinct from other cognitive deficits in depression, has been associated with suicidal behavior. However, this dysfunction is not found consistently across samples. Method Medication-free subjects with DSM-IV major depressive episode (major depressive disorder and bipolar type I disorder) and a past history of suicidal behavior (n=72) were compared to medication-free depressed subjects with no history of suicidal behavior (n=80) and healthy volunteers (n=56) on a battery of tests assessing neuropsychological functions typically affected by depression (motor and psychomotor speed, attention, memory) and executive functions reportedly impaired in suicide attempters (abstract/contingent learning, working memory, language fluency, impulse control). Results All of the depressed subjects performed worse than healthy volunteers on motor, psychomotor and language fluency tasks. Past suicide attempters, in turn, performed worse than depressed non-attempters on attention and memory/working memory tasks [a computerized Stroop task, the Buschke Selective Reminding Task (SRT), the Benton Visual Retention Test (VRT) and an N-back task] but not on other executive function measures, including a task associated with ventral prefrontal function (Object Alternation). Deficits were not accounted for by current suicidal ideation or the lethality of past attempts. A small subsample of those using a violent method in their most lethal attempt showed a pattern of poor executive performance. Conclusions Deficits in specific components of attention control, memory and working memory were associated with suicidal behavior in a sample where non-violent attempt predominated. Broader executive dysfunction in depression may be associated with specific forms of suicidal behavior, rather than suicidal behavior per se.

Attention is typically impaired in depression and may play a role in risk for suicidal behavior. In this study, 66 non-patients, 83 depressed subjects with no past history of suicide attempt, 53 depressed subjects with one or more low lethality suicide attempts, and 42 depressed subjects with at least one high lethality attempt were compared on two computerized measures of attention, a Continuous Performance Test (CPT) and a Stroop task. All subjects were medication free at the time of assessment. Attention was impaired in all depressed subjects but worse in those with a past history of suicidal behavior. CPT performance did not differ among the groups, but Stroop interference was significantly poorer in all depressed subjects relative to non-patients, and poorer still in high lethality suicide attempters relative to all other groups. Interference score correlated modestly with subjective depression, functional level, suicide ideation, number of past suicide attempts, and lethality of past attempts. Depression-related impairments of attention, especially susceptibility to interference, are accentuated in those with a past history of suicidal behavior. Fundamental deficits in attention control may play a role in risk for suicidal behavior, and may contribute to a variety of cognitive deficits in suicidal patients. Brain mechanisms subserving attention control, which overlap considerably with regions implicated in affective disorders, may be a useful target for studies seeking to characterize neuropsychological factors associated with suicidal behavior.

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Studies suggest that neuropsychological measures may provide prognostic information regarding SSRI treatment response, yet it is unclear which specific cognitive domains are the most effectual predictors. The aim of this study was to characterize the cognitive profile associated with SSRI nonresponse using a comprehensive set of neuropsychological tests. Participants (N = 32) met criteria for current major depressive episode. Assessment followed pre-treatment medication washout. Clinical response was measured after 3-month open-label SSRI treatment. Groups did not differ by demographic characteristics, intelligence or depression severity. Responders outperformed nonresponders across all cognitive domains, with the largest differences observed in executive, language and working memory functions. Results indicate poorer global cognitive functioning is predictive of treatment nonresponse. Deficits were most pronounced in tests demanding greater mental search and manipulation rather than speeded motor output. Cognitive slowing may mediate the working memory and executive function deficits found in nonresponders. These findings can inform exploration for pharmacogenetic endophenotypes.