Structural abnormalities associated with aging, such as white matter lesions and subcortical volumetric changes, may explain some of the cognitive disturbances reported in elderly depressed patients (Alexopoulus et al 1997
; Krishnan et al 1993
). Moreover, altered glucocorticoid activity (i.e., hypercortisolemia), a correlate of more severe depression, has also been associated with atrophy and neurotoxicity in human and animal models of stress and aging (Lupien et al 1998
; McIntosh et al 1998
) and with cognitive disturbances primarily involving memory (Bemelmans et al 1996
; Silberman et al 1983
Although the precise mechanism is not clear, neuropsychological findings to date argue for a possible cumulative pathologic effect of recurrent episodes of depression or protracted duration of illness on frontostriatal and mesio-temporal brain regions in relation to depression. Animal models, for example, suggest repeated exposure to stress-induced secretion of corticosteroids may alter functioning of specific neural circuits, particularly those involving the hippocampus (McIntosh et al 1998
). As well, hippocampal volume loss among depressed patients has been associated with the extent of past history of depression, plausibly mediated by glucocorticoid-induced neurotoxicity (Bremner et al 2000
; Sheline et al 1999
). Together, these studies suggest a possible mechanism for why more profound disturbances of cognitive function have been observed in elderly rather than younger adult depressed patients.
Remarkably few investigations of cognitive functioning have focused on younger depressed adult patients, and those that have been completed have reported inconsistent and contradictory findings. For instance, Austin et al (1992
, in comparisons of endogenous and nonendogenous midlife medicated inpatients, found nonendogenous patients to be largely intact in most areas of functioning except memory (i.e., verbal learning and recall). This is similar to our recent findings (Sweeney et al 2000
) in which nonbipolar depressed inpatients demonstrated deficits only on tests of episodic memory. In contrast, a recent study of young medicated inpatients (Fossati et al 1999
) found no evidence of memory impairment but reported disturbances in several areas of executive functioning in relation to concept formation, cognitive flexibility, and response initiation. Similarly, Purcell et al (1997)
reported only mild disturbances of executive functioning on a small number of attentional set shifting tasks and found no evidence of memory impairment. Discrepant outcomes across these few existing studies of younger depressed patients likely reflect the complex effects of psychotropic medications, small sample sizes, and the small number of tests often utilized to evaluate cognitive status.
Clarifying the extent of cognitive deficits in younger adults with depression is critical to the development of models of pathophysiology of the disorder. Specifically, it is important to determine whether cognitive deficits are the result of progressive effects over the course of illness and whether these deficits are present in younger as well as elderly adults. Determining the neuropsychological status of ambulatory depressed younger adults also may have important implications for clinical management. Such cognitive deficits could have a significant impact on social and occupational role functioning and may affect suitability of specific psychotherapeutic strategies and subsequent illness course (e.g., Thase et al 1996
The aim of our study was to comprehensively assess a large cohort of unmedicated outpatients with major depression in the age range of young adulthood to midlife. We utilized both a battery of standardized neuropsychological tests of attention, memory, abstract problem solving, and motor skills and a computerized battery of cognitive tests, the Cambridge Neuropsychological Test Automated Battery (CANTAB; Fray et al 1996
), to further target cognitive functions subserved primarily by the frontal and temporal lobes.