Depression accounts for executive function deficits in obsessive-compulsive disorder.

OBJECTIVE: To examine the relative impact of depression on executive function deficits in obsessive-compulsive disorder (OCD). BACKGROUND: Existing data suggest that OCD is associated with basal ganglia and orbital frontal dysfunction, and neurobehavioral abnormalities that are putatively associated with these regions have been demonstrated in OCD. Nonetheless, few studies have accounted for the effects of depression, which is a common concurrent symptom among those with OCD. METHOD: A broad battery of neuropsychological tests, including measures of executive function and sensory-motor function, was administered to 20 adults with OCD and 31 control subjects. To assess depressive severity, participants were administered the depression scale from the Minnesota Multiphasic Personality Inventory. RESULTS: Data were analyzed using a regression model in two steps. In step one, patient group was entered, and patients with OCD demonstrated a pattern of executive function and sensory-motor deficits, similar to those shown in previous research. In step two, self-reported depressive symptom severity was entered as a predictor. As a consequence, depression accounted for some executive function deficits, whereas presence of OCD only predicted performance on measures of sensory-motor function. CONCLUSIONS: These data suggest that abnormalities involving executive function in OCD are related to co-morbid depressive severity. However, sensory-motor deficits seem to be more consistent with basal ganglia/orbital frontal dysfunction in OCD.

Practice effects on the Wisconsin Card Sorting Test-64 Card version across 12 months.

The Wisconsin Card Sorting Test (WCST: Heaton, Chelune, Talley, Kay, & Curtiss, 1993) is among the most commonly administered measures of executive function. Recently, a short form of the test was developed (WCST-64: Kongs, Thompson, Iverson, & Heaton, 2000), and it affords psychometric properties commensurate with the full version of the test. Yet, similar to other measures of executive function, relatively little is known concerning the effects of repeated administration on the WCST-64. Towards this end, 53 men (age M = 32.38) were administered the WCST-64 twice over 12 months, and scores on several indices improved significantly during this interval. Suggestions concerning the use of these measures in longitudinal research designs and clinical follow-up examinations are offered, and reliable change indices concerning these measures are included.

Neurobehavioural consequences of substance abuse and HIV infection.

Although our understanding of how human immunodeficiency virus (HIV)-related neurobehavioural deficits develop is nascent and preliminary, some clues have emerged which may clarify lingering uncertainties. In particular, HIV seems to yield brain dysfunction by mediating pathological changes upon neuronal function. HIV also compromises immunological integrity, thereby resulting in secondary infections that may further increase brain dysfunction. Notably, many individuals with HIV tend to be current or past abusers of drugs, and, in some cases, their drug use may have actually presented a pathway for initial HIV infection. Similar to HIV, many drugs tend to yield pathological changes upon neuronal function. Further paralleling HIV, some drugs seem to compromise immune function, which in turn may yield secondary detrimental effects upon the brain. Yet, despite the relatively high comorbidity rates of HIV infection and substance abuse, few investigations have addressed the potential interaction between these two factors upon neurobehavioural status. Towards this end, the present paper reviews the existing literature concerning neuropsychological effects of HIV and substance use, and suggests potential mechanisms whereby substance use may potentiate and exacerbate the onset and severity of neurobehavioural abnormalities in HIV infection.

Estimated premorbid intelligence mediates neurobehavioral change in individuals infected with HIV across 12 months.

This study tested whether estimated premorbid intelligence moderates worsening neurobehavioral dysfunction in HIV infection. 155 homosexual men (54 controls, 49 HIV+ asymptomatic, 24 HIV+ symptomatic, 28 AIDS) with stable disease status were tested on measures of executive function at baseline and 12-month follow-up. Premorbid intelligence was estimated on the basis of a demographically-based regression equation (Hamsher, 1984), and participants were classified as average or above-average intelligence. Regardless of disease status, participants with above-average IQ showed no declines on measures of executive function across time. In contrast, among those with average IQ, symptomatic groups showed declines, whereas the asymptomatic group did not. The findings support the hypothesis that estimated premorbid intelligence mediates declines in neuropsychological function in patients with stable HIV status. These findings are consistent with theoretical models of cognitive reserve capacity.

Effects of immunosuppression and disease severity upon neuropsychological function in HIV infection.

Effects of immunosuppression and illness severity upon neuropsychological function were assessed in a group of homosexual men with AIDS across 6 months. Participants included 62 who were seronegative (HIV-), 74 asymptomatic seropositives (HIV+A), 31 symptomatic seropositives (HIV+S), 23 with AIDS defining illnesses (AIDS-DI), and 10 who were diagnosed with AIDS solely on the basis of CD4+ levels falling below 200 /mm3 (AIDS-CD4). Groups were equivalent in age, education, and IQ. None were drug users, and none experienced a change in disease status across the 6-month inter-test interval. There was little evidence of cognitive decline across time. Nonetheless, after collapsing across time intervals, the AIDS-DI group had worse new-learning than all other groups. Additionally, the AIDS-DI demonstrated a greater number of impaired performances than the other participant groups. The data suggest that cognitive impairment in AIDS is unlikely due to independent contributions of immunosuppression and illness. Rather neurobehavioral deficits are more likely attributable to a combination of the two.

Limited accuracy of premorbid intelligence estimators: a demonstration of regression to the mean.

Regression-based premorbid intelligence estimators have been devised by Barona, Reynolds, and Chastain (1984), Barona and Chastain (1986), Hamsher (1984), Krull, Scott, and Sherer (1995; the Oklahoma Premorbid Intelligence Estimate: OPIE), and Vanderploeg, Schinka, and Axelrod (1996; BEST-3 approach), but little is known of their relative accuracy, particularly in outer ranges of intellectual ability (e.g., below-average, superior, etc.). Towards this end, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was administered to 150 neurologically normal adults, and estimated VIQ, PIQ, and FSIQ scores were computed according to each regression method. Results showed that methods based solely on demographic factors were most susceptible to meanward regression, rendering them poor estimators of IQ scores in outer ranges. Although the OPIE and BEST-3 performed somewhat better, their accuracy remained relatively weak. The findings suggest that regression-based estimates of premorbid IQ are very susceptible to error, particularly in outer ranges of intellectual function.

Relative memory deficits in recurrent versus first-episode major depression on a word-list learning task.

Although memory deficits are associated with major depressive disorder, few studies have identified which patient characteristics predict impairment. Because recurrent depression appears related to more severe cerebral dysfunction, the present study tested whether recurrent depressed individuals have worse memory function than first-episode depressed individuals. Two groups of young-adult, nonpsychotic, depressed inpatients (20 single episode [SE] and 46 recurrent episode [RE]) were administered the California Verbal Learning Test within a broader battery of neuropsychological tests. The groups were equivalent in age, education, estimated IQ, severity of depression, and demographic composition. The RE group demonstrated memory deficits relative to both the SE group and published norms, but no other significant difference was found across the battery. Data indicate that abnormal memory performance is associated with recurrent depression, whereas memory deficits are not prominent in first-episode depressed individuals.

Neuropsychological deficits in psychotic versus nonpsychotic unipolar depression.

A broad range of neuropsychological function was compared in samples of young adult unipolar depressed inpatients with and without psychotic features. Consistent with expectations, the psychotic depressive group demonstrated a broad range of deficit and had more impaired performances than the nonpsychotic group. Relevance of these data for hypotheses concerning psychotic depression as a unique diagnostic entity is discussed. In the context of previous research, the current findings suggest that accounting for individual differences in depression may clarify discrepancies between earlier studies of neuropsychological function in depression, and our understanding of the mechanisms by which depression influences cognition may be refined.

Practice effects on commonly used measures of executive function across twelve months.

Fifty men (age M = 32.50; education M = 14.98 years) were administered the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (FFT), Verbal Concept Attainment Test (VCAT) Trail Making Test, Parts A and B (TMT), and F-A-S Verbal Fluency at baseline and 12 months later. WCST, FFT, and VCAT scores improved significantly over a 12-month interval. In contrast, TMT and F-A-S scores did not change. Level of intellectual ability failed to moderate the effect of previous testing upon performance. Suggestions concerning the use of these measures in longitudinal research designs and clinical follow-up examinations are offered, and reliable change indices concerning these measures are included.

Neuropsychological correlates of negative, disorganized and psychotic symptoms in schizophrenia.

Recent studies suggest that three dimensions (negative, disorganized and psychotic) categorize schizophrenic symptoms. A developing literature indicates distinct cerebral correlates of each symptom cluster, but few investigations have determined their neuropsychological correlates. In the present study, the Schedules of Negative and Positive Symptoms measured symptom severity in 62 schizophrenics, and a subsequent principal components analysis revealed three symptom dimensions. Factor scores, age and parental socio-economic status were simultaneously entered into regression equations to explain variance across a broad neuropsychological test battery. Negative symptoms were associated with deficits involving intelligence, executive function, memory, sustained-attention and sensory-motor function, whereas disorganized symptoms correlated with decreased intelligence, attention-span and sensory-motor function. Psychotic symptoms were unrelated to deficits. These data are consistent with hypotheses that these three symptom dimensions have distinct neurobehavioral correlates.

Impaired neuropsychological functioning in Tourette's syndrome subjects with co-occurring obsessive-compulsive and attention deficit symptoms.

This study examined neuropsychological performance by 92 children with Tourette's syndrome (TS) grouped by the presence or absence of obsessive-compulsive and/or attention deficit symptoms. The identified groups did not differ with respect to age, education, age at onset of TS symptoms, or medication use. After statistical control for complex motor symptoms, impaired performance on measures of achievement and executive functioning was correlated with obsessive and obsessive/attention symptoms, but not with attention symptoms alone. The presence of both obsessive and attention symptoms identified children with impairment across several tasks. Clinical and functional implications are discussed.

Cognitive deficits distinguish patients with adolescent- and adult-onset schizophrenia.

Recent studies have shown that patients with schizophrenia who have an adolescent-symptom onset (before age 21) have a worse clinical course and greater frequency of cerebral abnormalities than those with an adult-onset (after age 25). However, little is known about the neuropsychological functioning of these groups. A comprehensive neuropsychological examination was administered to groups of patients with schizophrenia with either an adolescent- or adult symptom-onset and a healthy control group. The adolescent-onset group performed worse than the adult-onset and control groups, particularly on measures of memory and executive function. The adult-onset group also performed worse than the controls, but to a lesser extent than did the adolescent-onset group. Results are discussed with reference to hypotheses that adolescent-onset schizophrenia represents a distinct neurodevelopmental disease entity.

Screening for cognitive dysfunction in multiple sclerosis.

BACKGROUND: With the use of comprehensive neuro-psychological assessments, a substantial proportion of patients with multiple sclerosis have been found to have substantial cognitive impairment. Although data generated from comprehensive examinations are useful in making recommendations for treatment interventions and compensatory strategies, the cost of such assessments prohibits their use with all patients. OBJECTIVE: To develop a screening battery to detect cognitive impairment in patients with multiple sclerosis that is sensitive, specific, brief, and cost-effective, and could identify patients who might benefit from a more comprehensive neuropsychological examination. DESIGN: On the basis of a comprehensive neuropsychological assessment battery, the presence of significant cognitive impairment was determined in patients with multiple sclerosis. The screening battery consisted of a subset of tests from the comprehensive battery. Performance on the screening battery was then used to predict presence of cognitive impairment on the comprehensive battery in validation and cross-validation samples. Severity of impairment on the screening battery was also regressed on ratings of functional impairment derived from the Expanded Disability Status Scale. RESULTS: In the validation sample, the screening battery had 100% sensitivity, 80% specificity, and 88.1% overall diagnostic accuracy. In the cross-validation sample, the screening battery had 100% sensitivity, 81.8% specificity, and an overall diagnostic accuracy rate of 90.7%. chi 2 tests showed that the accuracy of the screening battery was significantly better than chance in both samples. Performance on the screening battery also predicted the level of disability ratings on the Expanded Disability Status Scale and functional systems scales. CONCLUSIONS: The screening battery had a high degree of sensitivity, specificity, and diagnostic accuracy, while maintaining a brief administration time and high cost-effectiveness. The screening battery also predicted higher levels of disability and functional impairment as assessed by the Expanded Disability Status Scale, thereby enhancing its clinical utility. Despite its advantages, the findings do not suggest that the screening battery may be an effective substitute for a more detailed examination.

Neuropsychological correlates of learning disability subtypes in children with Tourette's syndrome.

Neuropsychological deficits in Tourette's syndrome (TS) may be associated with learning disabilities. We examined the neuropsychological performance of 70 children with TS between the ages 6 and 18 years who were classified into four groups based on their pattern of performance on the Wide Range Achievement Test-Revised. The groups included three learning disability subtypes and a nonlearning disabled comparison group. The groups differed significantly on several measures in a comprehensive neuropsychological test battery. The pattern of differences was not entirely consistent with previous research, however, suggesting that neuropsychological correlates of learning disabilities may be influenced by the specific pathophysiology associated with TS. Thus, previous research on the neuropsychology of learning disability subtypes might not be generalizable to children with discrete neuropsychiatric disorders such as TS.

Neuropsychological function in patients with end-stage heart failure before and after cardiac transplantation.

This study was performed to examine cognitive function in patients with end-stage heart failure, to identify possible cardiovascular factors associated with cognitive function, and to evaluate changes in cognitive function in a subgroup of patients who received heart transplantation. An extensive battery of neuropsychological tests were given to 62 patients with end-stage cardiac failure as part of their evaluation for cardiac transplantation. Most patients were consecutive referrals, not selected because of cognitive complaints. A small subgroup of transplanted (n = 7) and non-transplanted (n = 4) patients received a repeat neuropsychological examination. At initial examination, approximately 50% of the patients met criteria for impairment in reference to normal control values. Higher stroke volume index and cardiac index and lower right atrial pressure were correlated with better cognitive function. In the subgroup of patients re-examined, the transplanted patients demonstrated significantly improved cognitive function, whereas the non-transplanted subjects were unchanged. These data indicate that in patients with end-stage heart failure there is a high prevalence of impaired cognitive function which is related to measures of cardiovascular efficiency. Preliminary evidence suggests that these impairments may be partially ameliorated by cardiac transplantation.

Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome.

This study was conducted to identify clusters of obsessive-compulsive characteristics in Tourette syndrome subjects and to explore their neurochemical correlates. Patients completed a 40-item questionnaire assessing obsessive-compulsive symptoms. Each subject had a 24-hour urine specimen collected and analyzed for a variety of biogenic amines and their metabolites. Factor analysis identified eight symptom clusters, the majority of which appeared to reflect obsessive symptoms. Consistent relationships were observed between symptom clusters and levels of catecholamine and indolamine amines and metabolites. Overall, the primary metabolite of serotonin, 5-hydroxyindoleacetic acid, appeared to be the most highly correlated with the individual obsessive-compulsive symptoms.

Clinical predictors of psychopathology in children and adolescents with Tourette Syndrome.

Tourette Syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by vocal and motor tics and associated psychopathologies. The current study was undertaken to explore the associations between tic symptomatology, related clinical variables and behavioral dysfunction within a cohort of TS subjects. Ninety-two child and adolescent TS subjects were rated through self-measure, and by parents on measures of tic symptomatology, OC characteristics, and dysfunctional behaviors including learning difficulties and attention deficits. Statistical modeling revealed associations among tic clusters, clinical items and behavioral measures, which were unique for the child and adolescent subgroups.

Neurochemical and some related psychopharmacological aspects of Tourette's syndrome: an update.

Neurochemical investigations of Tourette's syndrome (TS) suggest that the symptoms of this disorder may be the result of an imbalance among several neurotransmitter and/or neuromodulator systems. Neurochemicals which have been studied included: catecholamines; acetylcholine; tryptophan and its metabolites; the amino acids γ-aminobutyric acid (GABA), glutamate, phenylalanine and p-tyrosine; trace amines; opioid peptides; cyclic AMP and androgenic hormones. A suitable animal model of TS would do much to advance our understanding of this disorder, and there are some interesting recent developments in this regard.

The course of tics in Tourette syndrome: a 5-year follow-up study.

The current study was undertaken to explore the course of tics in Gilles de la Tourette's syndrome (TS). As part of a prospective 5-year follow-up of non-clinically based TS subjects who had originally participated in a comprehensive research protocol, 23 subjects (ages 11 to 53 years) were reevaluated for tics and obsessive-compulsive (OC) characteristics. Three (13%) of the subjects had an improvement in total tic symptomatology, while 15 (65.2%) had no change and 5 (21.7%) worsened. Improvement or worsening was independent of baseline developmental age across child, adolescent, and adult subgroups. Complex motor tics at baseline predicted complex motor tics and simple phonic tics at follow-up. Baseline OC and complex motor tics independently predicted subsequent OC and complex motor symptoms. Data from the current study provide evidence of the stability of tic subtypes over time and developmental period.