Marianne Gorlyn

Questionable Dementia: Clinical Course and Predictors of Outcome

OBJECTIVE: To evaluate the clinical course and predictors of outcome in outpatients with cognitive impairment who do not meet criteria for dementia at initial evaluation.

Attention Deficit in Depressed Suicide Attempters

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 scores 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 attentional control may play a role in risk for suicidal behavior, and may contribute to a variety of cognitive deficits in suicidal patients. Brain regions subserving attentional 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.

Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters with major depression

BACKGROUND Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals. METHOD Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status. RESULTS As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness. CONCLUSIONS Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk.

Suicidal ideation and the subjective aspects of depression.

BACKGROUND Suicidal ideation is common in depression, but only moderately related to depression severity - in part because certain clusters of symptoms, such as those related to core mood disturbance, have a differential relationship to suicidal thinking. METHODS 400 medication free participants with current major depression were assessed with either or both the Hamilton Depression Rating Scale (HDRS, n=396) and Beck Depression Inventory (BDI, n=366), and the Scale for Suicide Ideation (SSI). Depression rating scales were decomposed into symptoms clusters previously reported (Grunebaum et al., 2005), in order to evaluate their association to suicidal thinking. RESULTS Correlations between overall depression severity ratings and the measure of suicidal ideation were modest, and reduced when specific items assessing suicidal thinking on these depression scales were removed. Symptom clusters assessing Psychic Depression (HDRS), Subjective Depression (BDI), and Self-Blame (BDI) were the strongest correlates of suicidal ideation; other somatic and vegetative symptoms had little or no association to suicidal ideation. Severity of these symptom clusters effectively discriminated those with (SSI>0) and without (SSI=0) ideation; severity of these symptom clusters was less strongly associated with the severity of ideation once ideation was present. LIMITATIONS This is a cross-sectional study, and the dynamic relationship between changes in the severity of various depressive symptoms and change in suicidal thinking remains to be explored. CONCLUSIONS Depression severity is moderately associated with suicidal ideation, and accounted for primarily by core mood disturbance symptoms and self-punitive thinking. These associations may explain why suicide risk might remain high during treatment even though somatic and vegetative symptoms improve.

The WAIS-III and Major Depression: Absence of VIQ/PIQ Differences

Poor Performance IQ (PIQ) relative to Verbal IQ (VIQ) is a standard finding in depressed patients administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R). This study examined performance of depressed subjects on the instruments latest revision, the WAIS-III, which provides a more detailed subdomain profile of intellectual functioning. WAIS-III IQ, index and subscale scores were compared between 121 unmedicated subjects in major depressive episode and 41 healthy volunteers, using demographically adjusted T-score conversions. Depressed subjects had significantly lower PIQ scores, but neither the absolute VIQ/PIQ difference nor prevalence of VIQ/PIQ discrepancies >1 SD differed between groups. Index score differences were exclusively in Processing Speed, and subtest differences only on timed tasks. WAIS-III scores did not differ between subjects with major depressive and bipolar disorders, nor between subjects with and without melancholia or history of suicidal behavior. Results suggest general intellectual performance in depression is best characterized by deficits in processing speed, rather than global nonverbal abilities, and that this deficit is consistent across depression subtypes.

Iowa gambling task performance in currently depressed suicide attempters.

Deficits in decision-making using the Iowa Gambling Task (IGT) have been found in past suicide attempters, but primarily euthymic and/or medicated patients. This study compared IGT performance among medication-free, currently depressed patients (unipolar and bipolar) with (n=26) and without (n=46) a past history of suicide attempt, and healthy volunteers (n=42). Attempter status, in a sample whose attempts were predominantly non-violent, was not associated with impaired IGT performance even when accounting for sex, mood disorder type, and comorbid Borderline Personality Disorder. A non-significant trend towards poorer performance was found in a small subgroup of past attempters who had used a violent method, consistent with prior studies. Suicide intent and ideation were unrelated to IGT scores. There were no consistent associations between IGT performance and ratings of impulsiveness (Barratt Impulsiveness Scale (BIS)), hostility (Buss-Durkee Hostility Inventory (BDHI)) or aggression (Brown-Goodwin Aggression Inventory (BGAI)). Results suggest that decision-making impairment is related to specific subtypes of suicidal behavior, but may not be universally sensitive to suicide risk in all types of attempters, especially those using non-violent means. Psychometric and conceptual issues surrounding the IGT also appear to affect its utility as a general marker of suicidal behavior risk.

Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease.

Verbal fluency tasks are used to assess language functioning in Alzheimers disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of fluency tasks was associated with different patterns of cerebral blood flow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood flow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the difference between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal flow, a focal AD-related deficit. Additional variance in Category fluency, however, was predicted by global mean flow, while additional variance in Letter Fluency was predicted by frontal flow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean flow; the primary predictor of Letter Fluency was left-sided frontal flow. Analysis of the fluency difference score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related deficits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related deficits were accompanied by marked deficits in frontal perfusion. These findings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluencys stronger association to the most typical CBF deficits of AD account for its greater sensitivity to this disease. Letter Fluency deficits, on the other hand, carry significant information about the degree to which perfusion deficits have spread to frontal cortex.

Family-based association study of 5-HT(2A) receptor T102C polymorphism and suicidal behavior in Ashkenazi inpatient adolescents.

UNLABELLED Suicidal behavior runs in families and is partially genetically determined. Since greater serotonin 5-HT(2A) receptor binding has been reported in postmortem brain and platelets of suicide victims, the 5-HT(2A) receptor gene polymorphism T102C became one of the candidate sites in the study of suicide and impulsive-aggressive traits. However, studies that examined the association of this polymorphism with suicidality have contradictory results. This study used a family-based method and one homogenous ethnic group to overcome ethnic stratification in order to test this association. METHODS Thirty families of inpatient adolescents from Jewish Ashkenazi origin, with a recent suicide attempt, were genotyped. All subjects were interviewed for clinical diagnosis, depressive and impulsive-aggressive traits and demographic data. Allele frequencies were assessed using the Haplotype Relative Risk method for trios. RESULTS No difference was found in allelic distribution between transmitted and non-transmitted alleles. There was no significant association of genotype with any of the clinical traits CONCLUSIONS These preliminary results suggest that the 5-HT(2A) T102C polymorphism is unlikely to be associated with suicidal behavior and related traits in adolescent suicide attempters.

Impulsivity in the prediction of suicidal behavior in adolescent populations.

Impulsivity has been identified as a key factor in risk of suicidal behavior in adolescent and adult patients. However, a lack of consensus about the definition of impulsivity has led to difficulty in its measurement. Impulsivity self-report scales exhibit low intercorrelations, are subject to response bias, and incorporate multiple subfactors. Performance tests may be less sensitive to response biases, as well as be more precise measures of dimensions of impulsivity, but each test alone does not provide a comprehensive measure of the trait. Assessing impulsivity in child and adolescent groups presents additional methodological problems, such as an overlap between limited impulse control due to developmental factors and psychopathology. A multiple measures approach to assessing impulsivity is suggested.

Treatment-related improvement in neuropsychological functioning in suicidal depressed patients: Paroxetine vs. bupropion

Neuropsychological dysfunction is associated with risk for suicidal behavior, but it is unknown if antidepressant medication treatment is effective in reducing this dysfunction, or if specific medications might be more beneficial. A comprehensive neuropsychological battery was administered at baseline and after 8 weeks of treatment within a randomized, double-blind clinical trial comparing paroxetine and bupropion in patients with DSM-IV Major Depressive Disorder and either past suicide attempt or current suicidal thoughts. Change in neurocognitive performance was compared between assessments and between medication groups. Treatment effects on the Hamilton Depression Rating Scale and Scale for Suicide Ideation were compared with neurocognitive improvement. Neurocognitive functioning improved after treatment in all patients, without clear advantage for either medication. Improvement in memory performance was associated with a reduction in suicidal ideation independent of the improvement of depression severity. Overall, antidepressant medication improved neurocognitive performance in patients with major depression and suicide risk. Reduced suicidal ideation was best predicted by a combination of the independent improvements in both depression symptomatology and verbal memory. Targeted treatment of neurocognitive dysfunction in these patients may augment standard medication treatment for reducing suicidal behavior risk.