Alterations in performance and discriminating power of the death/suicide implicit association test across the lifespan.

The Death/Suicide Implicit Association Test (d/s-IAT) has differentiated individuals with prior and prospective suicide attempts in previous studies, however, age effects on test results remains to be explored. A three-site study compared performance on the d/s-IAT among participants aged 16-80 years with depression and prior suicide attempt (n = 82), with depression and no attempts (n = 80), and healthy controls (n = 86). Outcome measures included the standard difference (D) score, median reaction times, and error rates. Higher D scores represent a stronger association between death/suicide and self, while lower scores represent a stronger association between life and self. The D scores differed significantly among groups overall. Participants with depression exhibited higher scores compared to healthy controls, but there was no difference between participants with and without prior suicide attempts(F[2,242]=8.76, p<.001). Response times for participants with prior attempts differed significantly from other groups, with no significant differences in error rates. The D score was significantly affected by age (ß =-0.007, t = 3.65, p<.001), with slowing of response times in older ages. Results suggest reaction time d/s-IAT D scores may not distinguish implicit thinking about suicide as response times slow with age, but slowed response times may be sensitive to suicide risk potentially indicating basic information processing deficits.

Language Fluency Deficits in Post-treatment Lyme Disease Syndrome.

OBJECTIVE: Recent neurocognitive studies of patients with post-treatment Lyme disease syndrome (PTLDS) find consistent deficits in memory and processing speed. Language fluency deficits are observed as well but may be secondary to poor memory and slowing rather than an independent deficit. METHOD: This study performed a secondary analysis of data presented previously, including individuals with PTLDS and comparison samples of healthy volunteers (HC) and patients with major depressive disorder (MDD), to determine if language fluency deficits could be accounted for by poor performance in these other neurocognitive domains. RESULTS: Basic verbal abilities, memory, and processing speed were all significantly associated with fluency performance. MDD patients' fluency deficits relative to HC were accounted for by these covariates. However, PTLDS patients' poorer fluency performance relative to both other groups was not. CONCLUSIONS: Language fluency appears to be an independent area of neurocognitive deficit within the constellation of PTLDS symptoms.

Neurocognition in Post-Treatment Lyme Disease and Major Depressive Disorder.

OBJECTIVE: Neurocognitive dysfunction in patients with residual or emergent symptoms after treatment for Lyme Disease is often attributed to comorbid depression. In this study, patients with Post-Treatment Lyme Disease Syndrome (PTLDS) were compared to patients with Major Depressive Disorder (MDD), as well as healthy comparison subjects (HC), on neurocognitive measures administered through the same laboratory, to determine if patterns of performance were similar. METHODS: Two analyses were conducted. First, performance on the Wechsler Adult Intelligence Scale (WAIS-III) and on subtests from the Wechsler Memory Scale (WMS-III) was compared among the groups. Second, comparable subgroups of PTLDS and MDD patients with at least one low WMS-III score were compared on an additional set of measures assessing motor function, psychomotor performance, attention, memory, working memory, and language fluency, to determine if the overall profile of performance was similar in the two subgroups. RESULTS: In the first analysis, PTLDS patients performed more poorly than both MDD and HC on tasks assessing verbal abilities, working memory, and paragraph learning. Processing speed in the two patient groups, however, was equally reduced. In the second analysis, MDD patients with low WMS-III exhibited concomitantly greater difficulties in psychomotor speed and attention, while low-WMS-III PTLDS patients exhibited greater difficulties in language fluency. CONCLUSIONS: MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD.

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.

The impact of cognitive reserve on neurocognitive performance in Major Depressive Disorder.

Cognitive reserve may mitigate the degree of cognitive deficit observed in Major Depressive Disorder (MDD), confounding attempts to fully characterize the nature of these deficits. In this study, cognitive reserve was examined as a potential moderator of neurocognitive deficits in MDD. Unmedicated, currently depressed patients with MDD (n = 269), and healthy volunteers (n = 143) were compared on measures assessing psychomotor speed, interference processing, verbal memory, visual memory, and executive functioning. Moderating effects of education level and estimated intelligence level were examined as interactions, along with age, in a regression model for each test. Differences between patients and non-patients were found with most measures, and sustained in regression models as main effects. However, the interaction of estimated intelligence and patient status was significant for processing speed, verbal memory, visual memory, and executive functioning, with patient/non-patient differences diminishing with higher estimated intelligence. Neither estimated intelligence nor education level impacted interference processing differences, which were reduced with increasing age. Better intellectual ability moderates the effect of MDD on neurocognitive test performance. This effect may confound attempts to characterize these deficits in higher functioning samples. More challenging tasks may be needed, given the potential predictive value of neurocognition for differential therapeutic and clinical outcomes.

The lack of meaningful association between depression severity measures and neurocognitive performance.

BACKGROUND: Neurocognitive deficits are common in depression, but most prior studies have not found strong associations between standard measures of symptom severity and the extent of these neurocognitive deficits. Diagnostic heterogeneity, or the lack of specific questions about neurocognition in these measures, may be undermining these associations. METHOD: Neuropsychological performance was assessed via 10 tasks in a sample of 262 unmedicated patients with Major Depressive Disorder (MDD) and compared to that in healthy volunteers (n = 140), then correlated with (1) standard measures of depression severity including the Hamilton Depression Rating Scale and Beck Depression Inventory, (2) previously established, factor-analytically derived symptom factors that characterize the heterogeneity of these scales, and (3) a separate measure of cognitive complaint (Cognitive Failures Questionnaire) that was included to address the absence of specific questions about cognition in standard rating scales. RESULTS: Neurocognitive performance in these unmedicated MDD patients was not significantly associated with either total scores on the depression severity measures, any of their derived symptom factors, or the degree of subjective cognitive complaint - which itself was most strongly associated with mood disturbance. LIMITATIONS: Depressed patients with the most prominent neurovegetative symptoms may be underrepresented in this sample. CONCLUSIONS: Neurocognitive deficits were only weakly associated with standard depression symptom ratings, and not captured by self-report ratings of cognitive complaint. Neurocognitive deficits appear to be a separate symptom dimension that cannot be inferred from overall depression severity and require their own assessment, given that they have prognostic value for functional outcomes, suicide risk, and differential therapeutics.

Suicidal ideation declines with improvement in the subjective symptoms of major depression.

BACKGROUND: Suicidal ideation appears to be more strongly associated with subjective rather than neurovegetative symptoms of depression. Effective treatment, then, should produce reductions in suicidal ideation to the degree that these subjective symptoms are alleviated relative to treatment effects on other symptoms. METHODS: In a randomized clinical trial comparing paroxetine and bupropion for treatment of depression in patients with either suicidal ideation or past attempt, depression severity and suicidal ideation were assessed weekly during the 8-week study. Depression rating scales - the 24-item Hamilton Depression Rating Scale [HDRS] and the Beck Depression Scale [BDI] - were decomposed into symptom clusters based on our published factor analyses, and their change over time compared to changes on the Beck Scale for Suicidal Ideation [SSI]. RESULTS: Improvement in factor scores associated with subjective symptoms of depression - HDRS Psychic Depression, BDI Subjective Depression, and BDI Self-Blame - were the best predictors of declining scores on the SSI regardless of type of drug treatment. BDI Subjective Depression was the best single predictor in the context of all other significant univariate predictors, accounting for 31.4% of the variance in the change in SSI. The three factors together accounted for 35.3%. LIMITATIONS: This is a secondary analysis of clinical trial data, with fixed treatments. CONCLUSIONS: Effective treatments to reduce suicidal ideation are associated with the reduction of the subjective symptoms of depression, which may not always decline in synchrony with improvement in neurovegetative symptoms. This asynchrony may result in a period of elevated risk after the initiation of therapy. Data indicate that subjective depression symptoms should be a primary target in the treatment of depressed suicidal patients.

Early visual information processing deficit in depression with and without Borderline Personality Disorder.

Backward masking is a measure of early visual information processing usually abnormal in psychotic disorders. Previous studies of subjects with Borderline Personality Disorder have been inconsistent regarding their impairment or lack of impairment on backward masking. We examined visual backward masking performance in samples of unmedicated depressed patients with (n=12) and without (n=16) Borderline Personality Disorder, and healthy volunteers (n=18). Accuracy was poorer in depressed BPD patients, relative to both non-BPD depressed and healthy comparison subjects. As in previous studies, no differences in accuracy were found between non-BPD depressed patients and healthy comparison subjects. Differences in BPD subjects' accuracy were most evident at the fastest ISI and were not attributable to intercurrent psychotic symptoms. Beyond these group differences, accuracy at faster ISI's correlated with self-ratings of impulsiveness in all patients, and may be a general correlate of this trait. Poor early information processing appears to be a feature of Borderline Personality Disorder, and may play a role in the impulsive behavior that is characteristic of the disorder.

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.

Supportive short-term family therapy by nursing staff in the inpatient unit: preventing dependence and rehospitalization in the acutely ill and suicidal adolescent.

Adolescents with acute mental illness or suicidal behavior are almost always hospitalized for safety and evaluation purposes. The tendency towards long-term or repeated hospitalizations has many adverse effects such as dependency on the mental health care system and increased chronicity of illness. The causes for these phenomena may be prevented in the early stages of hospitalization. We suggest a therapeutic model of supportive short-term family therapy. The family therapy component aims to enhance the quality of interaction and the level of support among family members. The therapy component dealing with the individual targets the patient's anxiety symptoms and coping strategies, and focuses on return to a healthy state. The child is encouraged to return home to a supportive family as soon as the treatment team feels this to be advisable. This paper discusses a case which highlights how a patient reacts in crisis, and ways in which a supportive environment can help bring about therapeutic success with reduced hospitalization.

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.

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.

Intact alternation performance in high lethality suicide attempters.

Suicide attempters often perform poorly on tasks linked to ventral prefrontal cortical (VPFC) function. Object Alternation (OA) - a VPFC probe - has not been used in these studies. In this study, currently depressed medication-free past suicide attempters whose most severe attempt was of high (n=31) vs. low (n=64) lethality, 114 medication-free depressed non-attempters, and 86 non-patients completed a computerized OA task. Participants also completed comparison tasks assessing the discriminant validity of OA (Wisconsin Card Sort), its concurrent validity relative to tasks associated with past attempt status (computerized Stroop task, Buschke Selective Reminding Test), and its construct validity as a VPFC measure (Go-No Go and Iowa Gambling Task). Against expectations, high lethality suicide attempters - the majority of whom used non-violent methods in their attempts with some planning - outperformed other depressed groups on OA, with no group differences observed on Wisconsin Card Sort. Despite intact performance on OA, past attempters exhibited deficits on the Stroop and Buschke. OA performance was associated with performance on Go-No Go and Iowa Gambling, confirming that OA measures a similar construct. VPFC dysfunction may not be a characteristic of all suicide attempters, especially those who make more carefully planned, non-violent - though potentially lethal - attempts.

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.

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.

Neuropsychological characteristics as predictors of SSRI treatment response in depressed subjects.

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.

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.

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 instrument's 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.