In a study published in Biological Psychiatry, researchers employed brain imaging data from over 1,000 patients with MDD and healthy controls to detect distinct neurophysiological subtypes of depression.

The authors wrote, “Studies aimed at quantitatively uncovering the heterogeneity of individual functional connectome abnormalities in MDD and identifying reproducibly distinct neurophysiological MDD subtypes across the lifespan, which could provide promising insights for precise diagnosis and treatment prediction, are still lacking.”

The researchers used resting-state functional magnetic resonance imaging (fMRI) collected at multiple clinical sites from a large cohort of more than 1,000 MDD patients and over 1,000 healthy controls (HC). The study used the so-called normative model, which utilizes data from a large reference population to measure individual deviations comparable to the growth charts used by pediatricians. The researchers examined the functional connectivity among brain regions and mapped individual functional deviations in the MDD patients compared with this normative prediction across the lifespan.

The results revealed “great intersubject heterogeneity in the spatial distribution and severity of functional connectome deviations among patients with MDD, which inspired the identification of two reproducible neurophysiological subtypes. Subtype 1 showed severe deviations, with positive deviations in the default mode, limbic, and subcortical areas and negative deviations in the sensorimotor and attention areas. Subtype 2 showed a moderate but converse deviation pattern.”

The researchers also indicated that subtype differences were detected in depressive item scores and the predictive ability of baseline deviations for antidepressant treatment outcomes.

The authors concluded that their findings provide a greater understanding of different neurobiological mechanisms causing the clinical heterogeneity of MDD and are fundamental for developing personalized treatments for MDD.

In a statement, senior author Mingrui Xia, PhD, from Beijing Normal University, stated, “This approach led to the identification of two reproducible neurophysiological subtypes exhibiting distinct deviation patterns, depressive item scores, and longitudinal treatment predictability.”

Dr. Xia also stated, “These findings shed light on the diverse neurobiological mechanisms from a connectomics perspective underlying the complex clinical heterogeneity observed in individuals with depression. The implications of this research are far-reaching, providing valuable insights into the development of imaging-based candidate biomarkers. These biomarkers have the potential to guide future precise diagnostic and treatment strategies tailored to each patient’s specific neurophysiological subtype.”

Lastly, Dr. Xia added, “By embracing the concept of neurophysiological subtypes, we can potentially revolutionize the field of mental health by enabling clinicians to personalize treatments based on an individual’s unique connectome characteristics. This approach opens up new avenues for precision medicine and holds the promise of improving therapeutic interventions for depression.”

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