Discussion
cognitive impairment, cognitive impairments, insomnia, depressed, depression
Overall, 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). 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. The extent of cognitive control impairment also mediated the extent of (or lack of) symptom and psychosocial improvement posttreatment.The identification of a distinctive cognitive biotype identified by a machine learning clustering algorithm highlights the value of disentangling the heterogeneity of depression to understand the source of mean cognitive impairments within the diagnosis of depression as a broad category. This biotype might be a major contributor to prior mean observations of impaired executive function and response inhibition within the depression diagnosis compared with healthy peers.Adding further to the value of disentangling heterogeneity in depression, the cognitive biotype identified in this study was distinguished more by a specific profile of individual symptoms than by overall depression severity. This biotype was characterized by slowed thinking (which could be anticipated given the cognitive focus of this biotype) as well as sleep problems, and aligns with prior observed associations between depression, executive function, and sleep.Our observation that the cognitive subtype was characterized by reduced activation of the dLPFC and dACC within the cognitive control circuit suggests a distinct neural mechanistic process underlying this biotype. Reduced activation in these prefrontal regions aligns with the prior proposed cognitive control biotype based on a synthesis of neuroimaging findingsOur findings add to the growing evidence that treatments specifically targeting cognitive impairment and its mechanisms in depression are urgently needed.