Biomedical subjects

John G Keilp

Publications and source records attributed to John G Keilp.

11 recordsLinked to original sources

PubMed2006

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.

Adolescent↗

PubMed2006

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.

Adult↗

PubMed2006

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.

Adult↗

PubMed2006

Are BPI and BPII suicide attempters distinct neuropsychologically?

UNLABELLED: It is not clear if bipolar disorder I (BPI) and bipolar disorder II (BPII) represent the same disorder on a continuum of severity or two distinct syndromes. Neuropsychological functioning is a means of understanding similarities and differences between diagnostic groups. OBJECTIVE: To compare the neuropsychological functioning of depressed suicide attempters with BPI or BPII and healthy controls. METHODS: Fifty-one individuals with bipolar disorder (BPI n=32, BPII n=19) and a history of suicide attempt were compared with 58 healthy controls with respect to neuropsychological functioning in the following domains: motor functioning, psychomotor performance, attention, memory, working memory, impulsiveness and language fluency. RESULTS: Participants with BPI and BPII performed significantly more poorly than healthy controls on tests of Digit Symbol Test of psychomotor functioning, the N Back Test of working memory and the Go-No-Go Test of impulsiveness. Participants with BPI were significantly worse than controls but not those with BPII on the Test of Verbal Fluency. Participants with BPII performed significantly worse than either controls or those with BPI on the Simple Reaction Time Motor Test and the Stroop Test of attention. CONCLUSION: While participants with both BPI and BPII performed more poorly than healthy controls, individuals with BPII also performed more poorly than those with BPI on some tests suggesting that they may have a unique syndrome. The findings have implications for assessment and treatment in bipolar disorder.

Adolescent↗

PubMed2006

WAIS-III and WMS-III performance in chronic Lyme disease.

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects.

Adult↗

PubMed2006

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.

Adult↗

PubMed2006

The impact of borderline personality disorder and anxiety on neuropsychological performance in major depression.

Previous studies of neuropsychological performance in borderline personality disorder (BPD) have exhibited mixed results. The high rate of co-occurring major depressive disorder (MDD) in BPD makes it difficult to specify whether neuropsychological deficits in BPD predominantly reflect co-occurring MDD or unique aspects of their psychopathology. To address this issue, 22 participants with borderline personality disorder and concurrent major depressive disorder (BPD-MDD) and 33 participants with MDD and no concurrent personality disorder were compared on a neuropsychological battery that assessed seven domains of performance: general intellectual functioning, motor skill, psychomotor speed, attention, memory, working memory, and executive function. Neuropsychological performance did not differ between BPD-MDD and MDD. However, BPD-MDD participants reported higher levels of anger, anxiety, and of overall emotional distress compared to MDD. When levels of anxiety were controlled, BPD-MDD participants exhibited superior general intellectual performance, psychomotor speed, and attention. Deficits found in previous BPD samples may reflect their susceptibility to co-occurring MDD. The impact of anxiety on neuropsychological performance in BPD, though, indicates a need for future experimental studies of the effects of mood on cognitive function to determine whether mood dysregulation, rather than core depressive symptoms, underlie cognition impairments in BPD.

Adult↗

PubMed2005

Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. METHODS: A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter-Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. RESULTS: Letter-Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. CONCLUSIONS: COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter-Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.

Adolescent↗

PubMed2005

Correlates of trait impulsiveness in performance measures and neuropsychological tests.

Performance measures of impulsiveness offer great promise for assessing this trait in clinical and experimental studies. However, little is known about their relative superiority or inferiority to standard cognitive performance measures as correlates of this trait. In this study, 58 healthy volunteers completed a self-rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of neuropsychological tests. The test battery included measures of reaction time, attention, memory, fluency, and executive function, as well as two performance measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings correlated moderately with a number of these test scores, but many correlations became non-significant after adjustment for age and education. Correlations with the Go-No Go task, verbal fluency, executive function measures (Trails B), and tasks requiring decision-making against time (Choice Reaction Time, Reaction Time to Paired Words and Paired Faces Memory Tasks, and response bias on the Continuous Performance Test) remained significant. Performance on the Go-No Go task was the strongest correlate of self-rated impulsiveness. The findings suggest that once general demographic or ability factors are accounted for, specialized performance tasks requiring decision-making and response organization under time pressure provide the most effective means of assessing this behavioral trait.

Adult↗

PubMed2005

Altered subicular MAP2 immunoreactivity in schizophrenia.

We wished to test independently a previously reported loss of subicular microtubule-associated protein 2 (MAP2) in the brains of deceased individuals who had suffered from schizophrenia, and to determine whether there were any clinical characteristics attached to such a loss. Immunohistochemistry for MAP2 was examined in the hippocampal region from 94 psychiatric patients: 64 with a primary diagnosis of schizophrenia or schizoaffective disorder, 12 with a primary diagnosis of major depressive or bipolar disorders, and 18 with a primary diagnosis of dementia; and from 17 individuals without psychiatric disease. Lifelong symptomatology was evaluated with the modified Diagnostic Evaluation After Death. Subicular MAP2 immunoreactivity was prominently depressed in 20% of schizophrenia cases, 8% of mood disorder cases, 22% of dementia cases, and in no nonpsychiatric cases. Among dementia cases, those with loss of subicular MAP2 immunoreactivity displayed more subicular gliosis, while among the schizophrenia cases, there was no such association. Among schizophrenia subjects, loss of subicular MAP2 immunoreactivity was associated with fewer positive and negative symptoms over the course of the illness. Subicular MAP2 immunoreactivity is markedly diminished in a significant proportion of individuals chronically institutionalized for schizophrenia, and this does not represent a generalized destruction of subicular neurons. In contrast, among individuals institutionalized for dementia, loss of subicular MAP2 immunoreactivity is accompanied by gliosis. The loss of MAP2 immunoreactivity is associated with fewer clinical symptoms, suggesting that it may represent an adaptive response to schizophrenia. The chemical or structural abnormalities underlying decreased MAP2 immunoreactivity in schizophrenia remain to be determined.

Aged↗

PubMed2003

Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders.

OBJECTIVE: In subjects with mood disorders, positron emission tomography (PET) with [(18)F]fluorodeoxyglucose has shown prefrontal cortical metabolism deficits, including in a subgenual region in subjects with familial illness. The authors applied a dl-fenfluramine challenge method to study metabolic response in this region to serotonergic challenge in familial major depression. METHOD: The study group consisted of 19 depressed subjects with major depressive disorder or bipolar disorder, all of whom had at least one first-degree relative with history of major depression, and 10 healthy volunteers with similar age and gender distributions. PET images were acquired under placebo and challenge conditions, and volumetric MRI scans were also obtained. Group comparisons of metabolic and volumetric data were performed. Ratings of acute mood change during serotonergic challenge were compared with the imaging data. RESULTS: Within Brodmann's area 32, a glucose metabolism deficit in the depressed subjects on placebo day was observed by voxel-level analysis, but no volumetric deficit was found in the subgenual regions examined. Under challenge, both groups suppressed metabolism similarly. Within the patient group, the correlation between acute mood improvement during challenge and greater metabolic suppression approached significance. CONCLUSIONS: In familial mood disorders, a ventromedial prefrontal cortical deficit in baseline metabolism is not due to altered structural volume, and the response to serotonergic challenge appears predictive of acute mood response. The potential to predict treatment response can be tested by a combined challenge and treatment study.

Adult↗