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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.

Previous research has suggested that major depression and suicidal behavior may be associated with altered serotonin receptor function. In this study, platelet serotonin2 (5-HT2) receptor binding indices were measured in conjunction with serotonin-amplified platelet aggregation, a response mediated by the platelet 5-HT2 receptor complex, in depressed patients and normal controls. The magnitude of serotonin-amplified platelet aggregation was positively correlated with the number of platelet 5-HT2 receptor sites in both groups. Mean values for the receptor binding indices and the receptor-mediated response did not differ significantly between patients and controls, although patients exhibited a wider range of values for each parameter compared with controls. Exploratory analyses were undertaken to determine clinical variables that might contribute to the increased variance in depressed individuals. These analyses failed to reveal a statistically significant relationship between any of the platelet 5-HT2 receptor measures and the subtype or severity of depressive illness, or the presence of comorbid borderline personality disorder. Although the mean number of receptor sites did not differ between patients who had recently attempted suicide and those who had never attempted suicide, a strong positive correlation (p = 0.002) was found between receptor number and the degree of medical damage resulting from the suicidal act. Furthermore, the ratio of the serotonin-amplified platelet aggregation response to platelet 5-HT2 receptor number, an index of the mean responsivity of an individual receptor complex, was lower in suicide attempters versus nonattempters (p = 0.06) and normal controls (p = 0.01). Exploratory analyses also suggested that recent exposure to psychotropic medication may result in a significant increase in platelet 5-HT2 receptor number (p = 0.03). Thus, although the study did not show a consistent alteration in platelet 5-HT2 receptor indices in major depression, the data suggest that specific factors such as suicidality and drug exposure may explain some of the variance in depressed patients.

Psychopaths have been described as human predators who use charm, intimidation, and violence to control others and to satisfy their own needs. Underlying their propensity to violate social norms and expectations is a profound lack of empathy, guilt, or remorse, affective processes that have long resisted scientific investigation. Using brain imaging technology we found that psychopaths differed from nonpsychopaths in the pattern of relative cerebral blood flow during processing of emotional words. The results were consistent with the hypothesis that there are anomalies in the way psychopaths process semantic and affective information.

A number of studies of schizophrenia have demonstrated associations between cognitive impairment and both cerebral ventricle size and negative symptomatology. The nature of these associations, however, have been obscured by interstudy differences in the assessment of cognitive functioning and by the lack of function-related specificity in measures of structural brain abnormality. In this study, 28 SCID-diagnosed chronic schizophrenic inpatients were administered a brief comprehensive battery of neuropsychological tests, a computed tomography (CT) scan, and were rated for positive and negative symptomatology. Enlarged ventricle-to-brain ratio (VBR) of the anterior portion of the lateral ventricles, the frontal horns, was found to be related to deficits in general intellectual level, conceptual thinking, immediate verbal memory, and psychomotor speed. VBR of the more usually studied bodies of the lateral ventricles was associated only with deficits in verbal memory and motor speed. VBRs were unrelated to both positive and negative symptom measures in this sample. Results suggest that more widespread impairment of schizophrenics' cognitive functioning may be related to structural abnormality within the frontal lobes, complementing recent findings linking structural and metabolic abnormalities of this area of the brain to the disease itself.