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Psychiatry AdvisorCognitive Biotype, New Depression Subtype, Resistant to Common Antidepressants

A study published in the JAMA Network Open introduces a new subtype of major depressive disorder (MDD) termed “cognitive biotype.” This subtype is characterized by significant cognitive impairments and shows a lower response rate to commonly prescribed antidepressants. The findings could have far-reaching implications for the diagnosis and treatment of depression.

HCN Medical Memo
For physicians treating patients with MDD, the identification of a new “cognitive biotype” subtype could be a game-changer. This group not only experiences significant cognitive impairments but also responds poorly to standard antidepressant treatments. As such, more targeted and possibly novel treatment strategies may be required for effective management. Biomarker trials targeting this specific subtype are urgently needed to develop more effective treatment options.

Key Points:
  • Researchers conducted a secondary analysis on 1,008 patients from the International Study to Predict Optimized Treatment in Depression (iSPOT-D).
  • The study included medication-free outpatients diagnosed with nonpsychotic MDD.
  • A total of 27% of the participants were identified as having the “cognitive positive biotype,” characterized by marked impairment in all cognitive measures and reduced activity in specific frontal brain regions.
  • This group showed lower rates of response and remission to antidepressants like escitalopram, sertraline, and venlafaxine compared to the “cognitive biotype negative” group.
  • Physicians’ Perspective: The identification of this new subtype could necessitate more targeted treatment strategies, including potential biomarker trials.
Additional Points:
  • Cognitive testing involved the computerized test IntegNeuro, which assessed nine cognitive domains including sustained attention, cognitive flexibility, and working memory.
  • A subsample of 96 individuals underwent MRI scans, revealing reduced activation in the dorsolateral prefrontal and dorsal anterior cingulate regions in the cognitive positive biotype group.
  • Study limitations include the possibility of unidentified behavioral or neurobiologic factors contributing to the cognitive biotype.
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“If the prevalence of cognitive deficits in our sample is generalized to the US population, then approximately 5.7 million individuals with depression have cognitive impairments.”
– Researchers, “A Cognitive Biotype of Depression Linking Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes”

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