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This study suggests that cognitive vulnerability in patients with bipolar disorder is similar to that described in unipolar disorders. It is not clear whether this dysfunction is a cause or an effect of repeated episodes of bipolar disorder. However, the findings may have implications for clinical treatment as well as suggesting a number of important new avenues of research into psychological models of affective disorder.

These data confirm previous suggestions of elevated IL-1beta levels in major depression and postviral depression. IL-1beta is known to induce depressive symptoms as well as sickness behaviour and may contribute to the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

Several recent autopsy studies suggest that senile dementia of Lewy body type (SDLT) may be the second most common neuropathologic cause of dementia in the elderly, accounting for 7 to 30% of all cases. Operational criteria for the antemortem clinical diagnosis of SDLT have already been proposed by our group. The performance of these is now examined by randomizing the case notes from a new series of SDLT, Alzheimer, and multi-infarct dementia patients for psychiatric assessment by four raters of varying clinical experience and blind to pathologic diagnosis. Using the SDLT criteria, the two most experienced raters agreed in 94% of cases (kappa = 0.87), with the least experienced rater agreeing in 78% (kappa = 0.50). Diagnostic specificity for SDLT was uniformly high (90.0 to 97.0%), with a mean sensitivity of detection of 74%, and was greater by the experienced (90.0%) than the least experienced (55%) clinician. The antemortem identification of SDLT patients can therefore be achieved with a high degree of diagnostic specificity using such operationalized criteria, although there remains a minority of patients who present with either "typical" Alzheimer-type symptoms or with paranoid or delusional symptoms in the absence of substantial cognitive impairment. Sensitivity to neuroleptics may be a useful diagnostic pointer in these patients.

Medications did not have any significant influence on neurocognitive performance, suggesting that neurocognitive deficits are an integral part of bipolar disorder.

The effects of the neuroleptic flupenthixol on the expression of the genes coding for the mitochondrial ubiquinone and cytochrome b 5 reductases have been studied because of the importance of these enzymes in energy metabolism, oxidative stress and also because similar but oppositely directed changes have been previously observed in the cerebral cortex from schizophrenics. The neuroleptic flupenthixol reduces the expression in rats of the gene coding for NADH-cytochrome b 5 reductase as measured by in situ hybridisation and its enzymic manifestation. Flupenthixol also reduces the enzymic activity of the mitochondrial NADHubiquinone reductase, and it has been previously shown that mRNA from the mitochondrially coded parts of the enzyme are reduced by the drug. Both the cis-and therapeutically less active trans-flupenthixol were found to produce these changes in rats. Post-mortem brain tissue from schizophrenics who have received neuroleptic medication have reduced levels of both reductases as measured enzymically, Lymphocyte samples from schizophrenics also have reduced levels of both reductases compared with normals. The superoxide anion O − 2 is the principle agent of oxidative stress and both the cytochrome b 5 and the ubiquinone reductase enzymes were semi-purified from sheep liver and shown to produce appreciable amounts of superoxide. Superoxide production is reduced in brain homogenates from rats treated with flupenthixol. Its production is also reduced in brain tissue and lymphocytes from schizophrenics receiving neuroleptic medication. We conclude that neuroleptic medication reduces the expression of both the ubiquinone and cytochrome b 5 reductase and among the effects of this reduction is a decrease in the production of neurotoxic superoxide.

Eight normal volunteers had IV infusions of 200 micrograms clonidine (a centrally-acting adrenergic agonist which reduces noradrenaline release), and saline in a "double-blind" cross-over design. Clonidine reduced subjective estimates of arousal but did not affect performance on the Digit Symbol Substitution Test. Clonidine impaired paired-associate learning, but it did not affect performance on a number of measures of short and long term memory. The findings suggest either 1) that there is a specific (adrenergic) mechanism involved in the acquisition of novel associations, but not in other types of learning, or 2) that paired associate learning is more vulnerable than other learning tasks to disruption of adrenergic transmission.

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