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Objective: Basal levels of glucocorticoids, such as cortisol, are generally unaltered in bipolar disorder. However, neuroendocrine tests of glucocorticoid receptor (GR) function such as the dexamethasone suppression test (DST) are frequently abnormal. Neuropsychological impairment is well documented in healthy volunteers after administration of glucocorticoids and in patients with bipolar affective disorder. This suggests a potential link between neuropsychological and hypothalamic-pituitary-adrenal axis function. We examined the hypothesis that neuropsychological impairment in bipolar disorder is associated with abnormal GR function., Methods: Seventeen euthymic bipolar patients and 16 controls completed tests of verbal declarative and working memory (WM) tests and the DST. The correlation between neuroendocrine and neuropsychological function was examined., Results: Bipolar patients made significantly more errors of omission and commission on the WM paradigm and demonstrated impaired verbal recognition memory. Patients' post-dexamethasone cortisol correlated with WM commission errors (r(s) = 0.64, p = 0.0006). No such relationship was evident in controls., Conclusion: Deficits in declarative memory and WM are evident in patients with bipolar disorder. The deficit in retrieval accuracy from WM appears to be correlated with abnormal GR function.

Objectives: Converging evidence suggests that patients with remitted bipolar disorder (BD) have a persistent cognitive deficit in the executive control of working memory (WM). However, the component operations that contribute to this deficit remain unclear. The aim of the present study was to further profile the nature and specificity of WM impairment in euthymic BD. Methods: Fifty DSM-IV-confirmed patients with euthymic BD and demographically matched controls completed a modified version of the Self-Ordered Pointing Task (SOPT) and the Cambridge Neuropsychological Test Automated Battery Pattern Recognition Test along with traditional executive and WM tasks [Stroop, initial letter Verbal Fluency (FAS), Trail-Making, Digits Forwards and Backwards]. Prospective clinical ratings over one month prior to testing confirmed that patients were euthymic at test. Absence of basal hypercortisolaemia was confirmed by serial saliva sampling. Results: Error analysis revealed that whilst patients made more errors on the SOPT overall, they were no more likely to perseverate than controls. Patients’ erroneous responses did not proliferate across trials, suggesting that proactive interference did not contribute to their poor performance, but serial position effects were evident where patients’ errors clustered towards the end of a trial. No differences were found on the recognition memory test, in WM capacity, or on two of the three traditional executive procedures (FAS and Trail-Making). However, patients’ Digits Backwards was impaired. Conclusions: These data suggest that patients with BD have a deficit in their ability to monitor the contents of WM. This deficit is not an epiphenomenon of mood, but may be due to enduring brain dysfunction, integral to bipolar illness. [ABSTRACT FROM AUTHOR]

Ferrier IN, Chowdhury R, Thompson JM, Watson S, Young AH. Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report. Bipolar Disord 2004: 6: 319–322. © Blackwell Munksgaard, 2004 Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [ Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first-degree relatives of patients with BD. A cross-sectional design was employed to compare the performance of 17 unaffected first-degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests. Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non-working memory aspects of executive performance. The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD. [ABSTRACT FROM AUTHOR]