Predictors of cognitive impairment in treatment-resistant depression

Cognitive impairment is a well-recognized symptom of major depressive disorder; however, contributing factors are not fully characterized. The present study examined the neurocognitive profiles and predictors of cognitive impairment in patients with treatment-resistant depression (TRD).

Moderate to severely depressed TRD patients were compared to matched healthy volunteers (HV) in verbal learning and recall and executive functions. Based on cognitive scores, cluster analysis was performed to identify subsets within the TRD sample. Predictors of cognitive impairment were also investigated.

TRD patients showed worse performance in tests assessing verbal memory, executive attentional shifting, and inhibitory control. The cluster analysis revealed two groups: a cognitively impaired (CI) group that showed a generalized deficit across cognitive domains, and a relatively cognitively intact group that performed better than CI in all domains except attentional shifting. A logistic binomial regression of the two groups revealed three significant contributing risk factors for CI: 1) older age, 2) lower premorbid IQ, and 3) benzodiazepine use. Cognitive impairment and benzodiazepine use were associated with worse functioning.

Significant cognitive impairment is present in TRD and is associated with worse functioning. Age, lower premorbid IQ, and benzodiazepine use increased the likelihood of generalized cognitive impairment in TRD patients. The detrimental effect of benzodiazepine on cognitive impairment is independent of anxiety symptoms. Further research is needed to characterize the timeline of cognitive impairment in depression.