Neuropsychological impairment in major depression: its nature, origin and clinical significance.

Neuropsychological impairment is well established as a feature of major depressive disorder (MDD) but studies have shown a variable pattern of impairment. This paper seeks first to clarify this by examining methodological and clinical factors that give rise to variability in study findings. Second, it examines theories of the origin of these neuropsychological abnormalities. Third, it reviews evidence regarding the clinical significance of different patterns of deficit. A selective review was undertaken of the literature with a particular emphasis on methodological factors, the influence of clinical subtypes and prevalent theories of neuropsychological abnormality. Methodological issues and the heterogeneity of MDD account for considerable variability in results. Specific investigation of the subtypes of psychotic MDD, melancholic MDD and bipolar depression reduces this heterogeneity and results are more consistent in the elderly. Hypothalamic-pituitary-adrenal axis dysfunction is associated with neuropsychological dysfunction in MDD although evidence of direct causation is not definitive at present. Impairment of executive and psychomotor function is a consistent finding, particularly in the elderly, and may reflect frontostriatal-limbic dysfunction. There is growing evidence that this may have clinical significance. It is suggested that future research take very careful account of the exact phenotype of MDD. Classification based on neuropsychological profile may, in fact, be useful. Further research should examine further the clinical importance of patterns of neuropsychological impairment.