Predictors of neurocognitive impairment at 2 years after a first-episode major depressive disorder

Abstract

Background

Neurocognitive impairment is a contributor to major depressive disorder (MDD). However, MDD patients show great variability in the level and course of deficits. The present longitudinal study was to identify predictors of neurocognitive impairment in first-episode MDD patients.

Methods

Neurocognitive performance was analyzed in a cohort of 100 patients at 2 years after a first-episode MDD. Subgroups, deficit type vs. non-deficit type, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. The analysis was performed using the multivariate logistic regression to obtain a model for neurocognitive impairment determination. The predicted probabilities of multivariate logistic regression were analyzed using receiver operating characteristic (ROC) curve.

Results

Fifty-two percent of MDD participants presented general neurocognitive impairment. The regression analyses demonstrated that clinical and sociodemographic characteristics were not predictive variables. A model composed of processing speed, executive function, and attention, dexterity correctly classified 85.8% of the MDD patients with deficit type. ROC curve indicated that the changes of these three cognitions could identify MDD with deficit type from MDD with non-deficit type. In addition, ROC curve also indicated that processing speed and executive function could identify MDD from CN subjects. Finally, processing speed performance was negatively correlated with Hamilton Depression Scale scores in both MDD with deficit and non-deficit type.

Conclusion

The present study provides novel insights on frequency and neurocognitive profile of subtypes of patients showing impairment. Our results suggest that processing speed impairment is a trait dimension of the disorder related to specific cognitive dysfunctions and the severity of depression.

Introduction

Major depressive disorder (MDD) is a severe and common psychiatric disorder affecting millions of people worldwide [1], [2], [3], [4]. Although this psychiatric disorder primarily involves mood disturbances, neurocognitive impairment is now a well-established feature of MDD [5], [6], [7], [8], [9], [10], with more than two-thirds of depressed patients showing deficits in one or more domains of cognitive function [11], [12], [13]. Impaired ability to think, concentrate or make decisions is a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) [4] diagnostic criterion for the episode of MDD. However, there are noticeable differences among patients with a subgroup showing severe and debilitating cognitive dysfunctions [14], [15], [16], and other subgroup considered to be “neuropsychologically normal” [9], [10], [16]. Therefore, the existence of such a subgroup could have important implications for efforts to understand that not only the neuropathology of MDD but also the etiological heterogeneity of MDD and possibly has important implications for treatment of MDD.

These studies, which selected first episode MDD as subjects, avoid the influence of secondary effects of chronic use of medication and hospitalization on cognition. Previous studies confirm that cognitive deficits may be present before MDD [17], and remain relatively stable over the course of illness [18], [19]. These cognitive deficits appear to be separable from symptomatology and medication effects [9], and to some extent of premorbid and sociodemographic characteristics [10]. Given the strong evidence for variability in neuropsychological deficits in MDD [9], [10], [19], to identify neuropsychological markers to predict long-term evolution toward neurocognitive impairment is particularly relevant. However, little is known about the exact nature of the interdependent relationship between neurocognition and other factors, as well as the relative contribution of these factors to adequate neurocognitive functioning. Thus, we attempted to elucidate which among several cognitive domains and other previously related factors, most effectively discriminate long-term neurocognitive impaired MDD patients from unimpaired MDD patients.

The goal of the present study was thus to identify predictive variables for long-term neurocognitive functioning among clinical, neuropsychological, premorbid and sociodemographic variables. We hypothesize that a considerable rate of MDD patients followed for 2 years represents a subgroup of general neurocognitive impairment, being deficits likely explained by specific cognitive dysfunction rather than by other aspects of the illness. Furthermore, we further hypothesize that the specific cognitive dysfunction may be associated with the severity of depression. Identifying more homogeneous neurocognitive functioning subgroups early in the illness would help on clinical decisions and stimulate the development of more suitable treatments.