The impact of familial risk for schizophrenia or bipolar disorder on cognitive control during episodic memory retrieval.

Episodic memory impairment is a robust correlate of familial risk for schizophrenia (SZ) and bipolar disorder (BD); still much is unknown about the processes that underlie this deficit and how they may be implicated in BD and SZ. We examined the possibility that (a) episodic memory impairment may arise from abnormalities in the cognitive control of interference between task-relevant and task-irrelevant memories during retrieval; inability to suppress task-irrelevant representations could give rise to intrusions of inappropriate memories and increased rate of forgetting, (b) cognitive control deficits during retrieval may be differentially affected by familial predisposition to SZ or BD. We examined episodic memory in relatives of patients with SZ (SZ-R) (n=15) or BD (BD-R) (n=17) compared to healthy controls (n=23) using the California Verbal Learning Test (CVLT) and the Doors and People Test (DPT). All relatives were free of any psychiatric morbidity and were matched to controls on age, sex, educational achievement and general intellectual ability. During the CVLT, both relatives' groups made significantly more perseverative recall errors than controls. However, intrusion errors were significantly increased in SZ-R only. SZ-R also showed increased rate of forgetting in the DPT while BD-R were comparable to controls. Familial predisposition to SZ, compared to that of BD, was associated with significantly greater impairment in cognitive control processes during episodic memory retrieval with some evidence of specificity for SZ in connection with mechanisms relating to increased forgetting.

Dissociable and common deficits in inhibitory control in schizophrenia and bipolar disorder.

Current research focuses on delineating the neurobiological boundaries between familial risk for schizophrenia (SZ) and bipolar disorder (BD). Available evidence suggests that inhibitory control may be affected in both disorders. Inhibitory control relies on the dual processes of contextual information maintenance and response inhibition. This study investigated the effect of familial risk of SZ or BD on these two aspects of inhibitory control. Seventeen healthy first-degree relatives of patients with BD (BD-R), 15 healthy relatives of patients with SZ (SZ-R) and 23 demographically matched controls were compared in terms of their performance during Controlled Oral Word Association (COWA), which measures contextually driven response selection, and during the Hayling Sentence Completion Test (HSCT), which assesses contextual response selection and inhibition. Compared to controls and BD-R, SZ-R showed deficits in contextual information processing that resulted in spontaneous errors in the COWA as well as deficits in response inhibition during the HSCT that resulted in higher error rates. BD-R also showed deficits in response inhibition during the HSCT relative to controls, which were, however, less pronounced than for SZ-R. Both relatives groups had longer response times. Our results suggest that failure in contextual maintenance is primarily associated with familial risk for SZ, while response inhibition may be a shared marker of familial risk for both disorders.

Color Trails Test: normative data and criterion validity for the greek adult population.

The Color Trails Test (CTT) was developed as a culturally fair analog of the Trail Making Test. In the present study, normative data for the CTT were developed for the Greek adult population and further the criterion validity of the CTT was examined in two clinical groups (29 Parkinson's disease [PD] and 25 acute stroke patients). The instrument was applied to 163 healthy participants, aged 19-75. Stepwise linear regression analyses revealed a significant influence of age and education level on completion time in both parts of the CTT (increased age and decreased educational level contributed to slower completion times for both parts), whereas gender did not influence time to completion of part B. Further, the CTT appears to discriminate adequately between the performance of PD and acute stroke patients and matched healthy controls.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with Bipolar Disorder and their relatives.

BACKGROUND: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. METHODS: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. LIMITATIONS: Cross-sectional design. RESULTS: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. CONCLUSIONS: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions.

No gender differences in brain activation during the N-back task: an fMRI study in healthy individuals.

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.

No differential effect of age on brain matter volume and cognition in bipolar patients and healthy individuals.

BACKGROUND: Bipolar disorder (BD) is associated with brain structural and cognitive abnormalities. There is a paucity of evidence regarding the evolution of these deficits over time. This study examined the relationship between age and brain morphology and cognition in patients with BD type I. METHODS: Brain structural magnetic resonance imaging data were acquired using a 1.5T scanner from 71 BD patients and 82 age- and gender-matched controls and analysed using Statistical Parametric Mapping. In addition, participants were evaluated using the Wechsler Adult Intelligence Scale, Revised; the Wechsler Memory Scale, third edition; the Hayling Sentence Completion Task, a measure of response inhibition; and the Wisconsin Card Sorting Test, which reflects rule discovery and perseveration. RESULTS: We found a significant effect of age but not of diagnosis and no age-by-diagnosis interaction in global gray and white matter and cerebrospinal fluid volumes. There was no differential effect of age on the two diagnostic groups with respect to cognitive task performance. CONCLUSIONS: Our findings do not support differential age-related changes in brain structure and cognition in patients with bipolar disorder compared to healthy individuals. Cross-sectional studies are, however, limited and longitudinal data will be required to further explore this issue.

The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.