Cognitive dysfunction in unipolar depression: Implications for treatment

Abstract

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.

Introduction

Cognitive symptoms are common among patients with major depressive disorder (MDD) (Fava et al., 2006, Lee et al., 2012, Wagner et al., 2012a, Murrough et al., 2011, Millan et al., 2012), although the true prevalence is not known. We do know cognitive difficulties associated with depression, such as memory impairment, difficulty making decisions, and loss of cognitive flexibility are associated with considerable disability and limited functional recovery (Jaeger et al., 2006, McCall and Dunn, 2003, Naismith et al., 2007). This is particularly troubling because these symptoms frequently persist after remission of a depressive episode (Hasselbalch et al., 2011, Herrera-Guzman et al., 2010, Weiland-Fiedler et al., 2004, Neu et al., 2005, Paelecke-Habermann et al., 2005, Clark et al., 2005, Marcos et al., 1994, Hammar et al., 2010, Airaksinen et al., 2006, Ardal and Hammar, 2011). Nonetheless, there is evidence that cognitive symptoms improve with antidepressant therapy (Wagner et al., 2012a, Herrera-Guzman et al., 2009), and preliminary results show that some classes of antidepressants may be more effective in improving specific cognitive symptoms than others (Herrera-Guzman et al., 2009). These findings suggest that functional outcomes should be monitored during treatment and raise the possibility that interventions which improve cognition may speed functional recovery in patients with MDD (Greer et al., 2010).

Many questions remain regarding the differential expression of cognitive impairment in patients with MDD, such as the timing and duration of their presence, the implications of their presence for long-term outcomes, and the role of treatment to mitigate these symptoms (Wagner et al., 2012a, Millan et al., 2012). This review will focus on: (1) cognitive deficits associated with depression, with an emphasis on those found early in the course of the disease, (2) the neural circuitry associated with cognition and its disruption in depression, (3) the impact of early cognitive dysfunction on recovery, and (4) the impact of antidepressant treatment on cognition. Additionally, the challenges in studying neurocognitive symptoms in patients with MDD will be discussed.