Method: Fifty unmedicated patients in a major depressive episode (21 with no his- tory of suicide attempts and 14 and 15 pa- tients with previous attempts of low ...
Article
Neuropsychological Dysfunction in Depressed Suicide Attempters John G. Keilp, Ph.D. Harold A. Sackeim, Ph.D. Beth S. Brodsky, Ph.D. Maria A. Oquendo, M.D. Kevin M. Malone, M.D. J. John Mann, M.D.
Objective: Neuropsychological deficits in the context of psychiatric disease may be associated with suicide risk. In this study, neuropsychological performance was compared among depressed patients with at least one prior suicide attempt of high lethality, depressed patients with low-lethality prior attempts, depressed patients with no prior suicide attempts, and nonpatients. Method: Fifty unmedicated patients in a major depressive episode (21 with no history of suicide attempts and 14 and 15 patients with previous attempts of low and high lethality, respectively) and 22 nonpatients were assessed. Groups were comparable in age, education, occupational level, and estimated premorbid intelligence. The neuropsychological battery produced scores within five composite domains: general intellectual functioning (current), motor functioning, attention, memory, and executive functioning. Results: Patients whose prior suicide attempts were of high lethality performed significantly worse than all groups on tests of executive functioning and were the only
group to perform significantly worse than nonpatients on tests of general intellectual functioning, attention, and memory. A discriminant function analysis revealed two prominent dimensions in the data: one that discriminated high-lethality suicide attempters from all other groups (primarily associated with performance on tests of executive functioning) and another that discriminated all depressed patient groups from nonpatients (associated with performance on measures of attention and memory). For the patients with high-lethality prior suicide attempts, deficits did not appear to reflect diffuse brain damage from past attempts, since the results of tests commonly affected by diffuse injury were not selectively impaired. Conclusions: Neuropsychological deficits in depressed patients with high-lethality prior suicide attempts suggest impairment of executive functioning beyond that typically found in major depression. This more extensive neuropsychological impairment in the context of depression may be a risk factor for severe suicide attempts. (Am J Psychiatry 2001; 158:735–741)
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ystematic knowledge regarding the “state of mind” of those who attempt suicide remains elusive. Ratings of thoughts and attitudes around the time of a suicidal act have some power to predict future suicidal behavior (1–3), but little is known about the most basic aspects of cognitive processing in suicidal individuals, even though impaired cognitive functioning is common in psychiatric disorders for which suicide risk is elevated (4, 5). Suicide attempters have been characterized as “cognitively rigid” on the basis of self-ratings and performance on mental flexibility tasks (6–13). From case studies (14), Rourke et al. (15) suggested that a specific nonverbal learning disability may predispose individuals to suicidal behavior. Bartfai et al. (16), using standard neuropsychological measures, found poorer performance on measures of fluency (verbal as well as nonverbal) and reasoning in a small sample of recent suicide attempters compared to chronic pain patients and nonpatients. Ellis et al. (17), on the other hand, found no neuropsychological differences Am J Psychiatry 158:5, May 2001
between diagnostically heterogenous groups of suicidal and nonsuicidal patients. In this study, neuropsychological performance was assessed in a group of well-characterized, unmedicated subjects who met DSM-III-R criteria for a major depressive episode with or without a history of suicidal behavior. Past attempters were divided into two groups on the basis of the severity of their attempts. Prior research has suggested that those making more severe attempts are a distinct subgroup (18–20) who are demographically and biologically more similar to suicide completers (21–24). The depressed patient groups were also compared to a nonpatient group. On the basis of prior studies of neuropsychological functioning in patients with depression (25–27), all depressed subjects were expected to perform poorly, relative to nonpatients, on measures of general intellectual functioning (because of deficits on performance IQ-type tasks), motor functioning, attention, and memory. On the basis of these studies and on potential links between suicidal behavior
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and prefrontal cortical dysfunction (28, 29), past suicide attempters were expected to perform relatively more poorly on executive functioning measures.
tests were administered in one to three sessions over the course of 1–2 days. All neuropsychological testing was conducted blind to clinical ratings and suicide history.
Statistical Analyses
Method Subjects The study group consisted of 50 patients who met DSM-III-R criteria for a current major depressive episode (either part of a major depressive disorder [N=38] or the depressed phase of a bipolar disorder [N=12]) and 22 nonpatients. All patients had a Hamilton Depression Rating Scale (24-item) score ≥16. All nonpatients were free of any current or past axis I or axis II disorder. All subjects were free of neurological disease as determined by clinical history and examination. A detailed history of past suicidal behavior was obtained for all subjects by using a standard, structured interview (30). All past suicide attempts were rated for severity based on Beck’s medical damage scale (31), which quantifies the degree of physical injury resulting from an attempt. Scores range from 0 (no physical damage) to 8 (death). Low-lethality attempts were defined as attempts rated between 0 and 4, and high-lethality attempts were those with ratings of 5–7 (involving, at minimum, coma and intensive care). This definition of high lethality is more stringent than in prior research (30, 31) but divided the sample into two equivalent-sized groups around the median score.
Clinical and Neuropsychological Assessment Diagnoses were determined in patients by using the Structured Clinical Interview for DSM-III-R (SCID) (for axis I and axis II) and were ruled out in nonpatients by using the nonpatient version of the SCID (32). Other clinical ratings and methods to ascertain reliability have been described previously (5). The neuropsychological battery included tests that assessed five general domains: general intellectual functioning, motor functioning, attention, memory, and executive functioning. General intellectual functioning was measured with the Mini-Mental State (33) and an abbreviated version (i.e., minus the Comprehension and Object Assembly subtests) of the Wechsler Adult Intelligence Scale, Revised (WAIS-R) (34). Motor functioning was assessed with the Finger Tapping Test (35) and a computerized choice reaction time task (36). Attention was assessed with the computerized Continuous Performance Test, Identical Pairs version (37), a computerized, single-item Stroop task (38, 39), and the Attention/Concentration subtest of the Wechsler Memory Scale, Revised (WMS-R) (40). Memory was measured by performance on the WMS-R Verbal and Visual Memory subtests (40), the Buschke Selective Reminding Test (41), and the Rey-Osterrieth Complex Figure (42). Last, executive functioning was assessed with the FAS tests of letter fluency and animal category fluency (42, 43), the Trail Making Test (35), Wisconsin Card Sorting Test (44), and a computerized A not B reaction time task (45) that measures logical reasoning and working memory.
Procedures Patient subjects were recruited by referral from local clinicians. Nonpatients were recruited by advertisement. After providing informed consent, patient subjects underwent a medication washout, generally as inpatients. Suicide risk was a determinant of the need for hospitalization, so past attempters were more likely to be studied as inpatients. Subjects had been free of psychotropic medication for at least 2 weeks before testing. This drug-free period was extended to 4 weeks for those receiving oral neuroleptics and 5 weeks for those receiving fluoxetine. Clinical ratings were conducted at the end of the washout just before neuropsychological testing. Neuropsychological
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Groups were first compared on demographic and clinical variables by using analyses of variance (ANOVAs), chi-square analyses, and t tests. The analyses of neuropsychological test data were carried out in a hierarchical fashion. First, all test scores were converted to z scores normatively corrected according to external normative values (culled from test manuals [34, 40, 44], a compendium of normative tables [42], or performance standards from an external normative study group [N=60, age range=20–75]). Domain scores were then computed by averaging the z scores of the primary measure for each test within each domain (global intellectual functioning: full-scale IQ and Mini-Mental State total score; motor functioning: finger tapping [averaged across hands] and choice reaction time; attention: performance on the WMS-R Attention/Concentration subtest, Continuous Performance Test, and Stroop interference task; memory: scores on the WMS-R Verbal and Visual Memory subtests, Buschke Selective Reminding Test total recall, and Rey-Osterrieth Complex Figure recall; executive functioning: average of letter and category fluency totals, Wisconsin Card Sorting Test categories, time score on part B of the Trail Making Test, and A not B reaction time). Domain scores were entered into a multivariate analysis of variance (MANOVA) comparing four groups. Given a significant main effect of group in the omnibus MANOVA, the groups were compared with univariate ANOVAs and post hoc comparisons (Tukey B procedure). Domain score analyses were followed by univariate analyses of individual test scores (including measures from each test that were not included in domain computations). To characterize the underlying dimensions that accounted for group differences, scores with significant ANOVAs (one from each task) were submitted to a descriptive discriminant function analysis (46). This analysis was used to derive a structure matrix that grouped individual tests by their correlations with the empirically derived discriminant functions. The hierarchical nature of the data analysis provided some protection for multiple comparisons, since univariate analyses were used to characterize multivariate effects or composite score differences. Significance level was set at p
