Deficits in response inhibition are a prominent feature of Bipolar Disorder, type I (BDI). The purpose of this study was to examine the relationship between inhibitory control and cerebral structure as it may inform our understanding of the pathophysiology of BDI. Inhibitory control was measured in remitted patients with BDI (n = 44) and healthy controls (n = 44), using the interference score from the Stroop Colour Word Task and the scaled total error score from the Hayling Sentence Completion Test. Structural magnetic resonance imaging brain scans were also obtained for all participants. For both measures, better performance in controls correlated positively with gray matter volume in the dorsal and ventral prefrontal cortical (PFC) regions with parietal involvement additionally seen for the interference score. In contrast, better inhibitory control in BDI patients correlated positively with gray matter volume in the right parietal cortical regions, namely the cuneus for the scaled total error score and the inferior parietal lobule for the interference score. The observed lack of correlation between PFC grey matter and measures of inhibitory control in BDI patients is suggestive of PFC dysfunction; the correlation between response inhibition and parietal grey matter volume may be indicative of a compensatory involvement of the parietal cortices in BDI.

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Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states.

Gender differences have been well established in verbal and spatial abilities but few studies have examined if these differences also extend into the domain of working memory in terms of behavioural differences and brain activation. The conclusions that can be drawn from these studies are not clear cut but suggest that even though gender differences might not be apparent from behavioural measures, the underlying neural substrate associated with working memory might be different in men and women. Previous research suggests activation in a network of frontal and parietal regions during working memory tasks. This study aimed to investigate gender differences in patterns of brain activation during a verbal version of the N-back working memory task, which incorporates the effects of increased demands on working memory. A total of 50 healthy subjects, aged 18 to 58 years, that were equally split by gender were recruited matched for age, levels of education and ethnicity. All subjects underwent functional magnetic resonance imaging. We found that men and women performed equally well in terms of accuracy and response times, while using similar brain regions to the same degree. Our observations indicate that verbal working memory is not affected by gender at the behavioural or neural level, and support the findings of a recent meta-analysis by Hyde ([ 2005]: Sex Roles 53:717-725) that gender differences are generally smaller than intra-gender differences in many cognitive domains.