Research Suggests Existence of Cognitive Biotype of Depression


A new cognitive biotype for depression may impact symptoms and treatment outcomes.



According to recent research, there may be a cognitive biotype for depression that impacts symptoms and treatment outcomes.

Using a machine learning method of cluster analysis, Hack et al sought to identify a cognitive biotype within the broader major depressive disorder (MDD) diagnosis by determining if this profile is characterized by baseline symptom and function profiles, by baseline neural dysfunctions in the cognitive control circuit, and by poorer response to standard antidepressants. Participants were assessed on several domains: cognitive testing, symptoms, functional capacity, and functional neuroimaging at baseline. Additionally, they were randomized to receive 1 of 3 antidepressants: escitalopram (336 patients), sertraline (336 patients), or venlafaxine-XR14 (336 patients). After 8 weeks of treatment, participants were reassessed on the same measures.

Out of 1008 participants with MDD, 27% showed cognitive impairment prior to treatment, significantly decreased brain response to a cognitive task, and worse outcomes (lower rates of response and remission) with standard pharmacotherapy with a particularly poor response to sertraline. This suggests the existence of a cognitive biotype and the need for treatments that target cognitive dysfunction to improve overall depression symptoms.

“Our multimodal findings suggest the presence of a cognitive biotype of depression that represents about a quarter of all depressed patients and is characterized by prominent impairments in 2 domains of cognitive control (executive function and response inhibition),” said the study authors. “This cognitive biotype has greater severity in baseline symptoms of slowed information processing and insomnia, poor psychosocial function, reduced neural function of the brain’s cognitive control circuit, and poorer outcomes following first-line antidepressant treatment.”

Hack et al also indicated that if their cognitive deficit prevalence was applied to the general population, approximately 5.7 million individuals with depression have cognitive impairments, suggesting a pressing need for more research.

Vortioxetine is the only antidepressant currently approved by the US Food and Drug Administration that shows promise in improving cognition, but its underlying mechanisms for cognitive enhancement are unknown. Hack et al suggest further research should incorporate the biomarker designs into evaluation of biotype outcomes when patients are matched to a treatment with mechanisms targeting cognitive control.


1. Hack LM, Tozzi L, Zenteno S, et al. A cognitive biotype of depression linking symptoms, behavior measures, neural circuits, and differential treatment outcomes: a prespecified secondary analysis of a randomized clinical trial. JAMA Netw Open. 2023;6(6):e2318411.

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