Cognitive dysfunction in unipolar depression: implications for treatment.

OBJECTIVE The primary objective of this review is to examine the literature assessing abnormalities in neural circuitry and cognition early in the course of major depressive disorder (MDD) and the impact of these features on treatment selection and long-term outcomes. DATA SOURCES English language and peer-reviewed publications were obtained by PubMed/Medline (www.pubmed.org) searches using combinations of major depressive disorder, major depression, or unipolar depression and "first episode", early, cognition, cognitive, executive function and memory. The terms bipolar and psychosis were excluded from the searches. These searches yielded 409 records. STUDY SELECTION A total of 12 studies, systematic reviews and meta-analyses were selected that evaluated learning, memory and executive function in individuals with major depressive disorder. Additional publications meeting these criteria were identified from the bibliographies of the 12 selected articles and from the "related citations" section of PubMed. RESULTS Difficulty in concentrating and indecisiveness are reported as among the most troubling symptoms by patients with MDD and may limit functional recovery. Cognitive deficits in memory and decision-making are present early in the course of MDD and may be accompanied by structural abnormalities in the hippocampus and prefrontal cortex involved in cognitive functions. Although resolution of cognitive symptoms of depression lags behind recovery from mood symptoms in many patients, preliminary evidence suggests they may improve with antidepressant therapy, but can also persist residually. CONCLUSIONS New strategies that target cognitive symptoms of depression in addition to mood symptoms are needed to improve long-term outcomes, particularly functional recovery.

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