Understanding treatment-resistant depression: The complicated relationships among neurocognition, symptoms, and functioning

Abstract

Background: Treatment-resistant depression (TRD) encompasses a segment of individuals with major depressive disorder who are severely ill in terms of chronicity, comorbidity, and prognosis. Although functional impairment is a prominent and costly feature of treatment-resistance, very little is known about the factors that contribute to and maintain functional impairment in TRD. Purpose: This study examined the relationships among neurocognition, symptoms, and functional impairment in TRD. Specifically, I examined the neurocognitive impairments that relate to different symptom domains and to level of symptom severity, as well as the predictors of functional outcomes and real-world behaviour in TRD. Method: Patients (N = 29) with a diagnosis of major depressive disorder were recruited from the Mood Disorders Treatment and Research Service at Providence Care Mental Health Services in Kingston, Ontario. Data were collected during a baseline assessment for a neurocognitive enhancement therapy program. Results: Individuals with TRD show mild to moderate impairments across all neurocognitive domains, with a superimposed severe impairment in verbal working memory. Verbal working memory significantly correlated with depressive symptoms and anxiety, such that increased verbal working memory capacity was related to more severe clinical symptoms. Greater response inhibition significantly correlated with less anxiety. Interpersonal competence was predicted by sustained attention and severity of depressive symptoms. Adaptive competence was significantly predicted by age at baseline and set shifting. Real-world work behaviour, interpersonal relations, and general satisfaction were predicted by the severity of depressive symptoms, whereas observed mood and anxiety predicted real-world recreational activity. Conclusions: The current study pioneered some of the first data regarding the relationships among neurocognition, symptoms, and functional outcomes in treatment-resistant depression. Verbal working memory appears to play an important role in the symptomatology of TRD. Neurocognitive variables and depressive symptoms are important in predicting functional competence (what one can do) but only depressive symptoms predict functional performance (what one actually does in the real world). There may be additional intrinsic or extrinsic factors that mediate the relationships among neurocognition, symptoms, and functioning in TRD.