Neuropsychological performance in patients with depression is associated with clinical, etiological and genetic risk factors.

The present study explores neuropsychological functioning in patients with depression with reference to key clinical, etiological and genetic features. In comparison to healthy volunteers, patients with severe depression demonstrated poorer performance on all neuropsychological tests except for WAIS-R Vocabulary and a 64-item computerized version of the Wisconsin Card Sorting Test. On average, patients exhibited significant impairments (greater than -2 standard deviation units) on tests of simple reaction time, Part B of the Trail Making Test and Raven's Colored Progressive Matrices. When performance decrements were analyzed with reference to key clinical features, patients with melancholia performed more poorly on WAIS-R Vocabulary, semantic fluency and choice reaction time than those with nonmelancholic depression. After controlling for age, those patients with late-onset depression (i.e., age of onset > or =50 years) exhibited poorer performance on a computerized version of the Tower of London test in comparison to those with an early onset. While there was no relationship between neuropsychological test scores and summed vascular risk factors or apolipoprotein E genotypes, presence of the methylenetetrahydrofolate reductase gene mutation was associated with slowed reaction time. The differential relationships between clinical, etiological and genetic risks and neuropsychological performance supports the presence of unique pathophysiological mechanisms in distinct subgroups of patients. These findings underscore the need to consider subtypes when investigating neuropsychological deficits in patients with depression.