No abstract

Major depression is a mood disorder that is often accompanied by the impairment of cognitive functions. Although suggestive, the large range of existing neuropsychological, neuropsychiatric, and, lately, neuroimaging investigations have not yet given a consistent picture of the psychological and biological disturbances involved in this psychiatric disorder. The present study of the cognitive functions in depression was part of an extensive investigation, including neuropsychological testing, psychiatric examination, and neuroimaging. A representative sample of 40 severely depressed hospitalized patients and a group of 49 closely matched control subjects were tested with an extensive neuropsychological test battery. Results, corrected for various confounding factors, confirmed the current notion that depressed patients suffer from wide-spread cognitive impairments. The group analysis did not allow any hypothesis on a possible pattern to the dysfunctions, but heterogeneity in the test performances calls for further analysis of the data in patient subgroups in relation to neuroimaging results.

The profile of the four WHOQOL-BREF domains is a more adequate expression of quality of life than the total score of all 26 items. Although none of the subscales are statistically sufficient measures of their domains, the profile scores seem to be adequate approximations to the optimal score.

Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stablize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a ␥-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 ± 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients ( 2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.

Our findings support the notion that depressed patients have disturbances in the loops connecting the frontal lobes, limbic system, basal ganglia, and cerebellum.