Newswise — Philadelphia, June 27, 2023Major depressive disorder (MDD) not only affects over 8% of Americans, making it one of the most common mental illnesses, but it also exhibits significant variability from person to person. Recent advancements in research have started shedding light on the neurophysiology that underlies different subtypes of depression, offering the potential for improved treatment development. However, there is still much to uncover. In a groundbreaking study published in Biological Psychiatry by Elsevier, researchers have identified multiple subtypes of MDD using brain imaging techniques.

Dr. John Krystal, the Editor of Biological Psychiatry, expressed his thoughts on the study, stating, "It has long been recognized that disorders such as major depressive disorder exhibit considerable heterogeneity. This study, conducted on a large sample of individuals with depression, provides valuable insights that can guide further investigations into subtyping depression based on functional magnetic resonance imaging (fMRI) tests. These tests measure the extent of coordination among different brain regions, commonly known as 'functional connectivity'."

The study encompassed a vast cohort of more than 1,000 individuals diagnosed with major depressive disorder (MDD) and an additional 1,000 healthy controls (HC), spanning various clinical sites. The researchers employed resting-state functional magnetic resonance imaging (fMRI) to collect data. To assess individual variances, similar to how growth charts are used by pediatricians, they utilized a normative model that drew upon data from a large reference population. By examining the functional connectivity among different brain regions, the researchers were able to map unique functional deviations in MDD patients when compared to the normative predictions, encompassing the entire lifespan.

Dr. Mingrui Xia, the senior author from Beijing Normal University, explained, "By adopting this approach, we successfully identified two distinct and consistent neurophysiological subtypes characterized by specific deviation patterns, depressive symptom scores, and their predictive response to treatment over time."

One subgroup of patients displayed prominent positive deviations, indicating increased connectivity, in regions such as the default mode network, limbic system, and subcortical areas. Conversely, they exhibited negative deviations in sensorimotor and attention-related areas. The second subgroup of patients demonstrated a milder yet contrasting pattern of deviations, emphasizing the neurophysiological heterogeneity present in depression. The researchers suggest that these altered activity patterns may be linked to the tendency of individuals with MDD to ruminate.

This research is particularly noteworthy as it advances the field toward identifying biomarkers that can serve as biological indicators for depression. Currently, the diagnosis, treatment, and prognosis of depression rely heavily on patient-reported clinical symptoms. The discovery of biomarkers holds the potential to enhance all these aspects of MDD management.

Dr. Xia further elaborated, stating, "These findings provide valuable insights into the complex neurobiological mechanisms underlying the clinical diversity observed in individuals with depression, from a connectomics perspective. The implications of this study are vast, as it paves the way for the development of imaging-based biomarkers. These biomarkers could guide future diagnostic and treatment strategies tailored to the specific neurophysiological subtypes of each patient."

Dr. Xia highlighted the significance of embracing the concept of neurophysiological subtypes, stating that it has the potential to revolutionize the field of mental health. By utilizing an individual's unique connectome characteristics, clinicians can personalize treatments, leading to advancements in precision medicine. This approach opens up new possibilities for improving therapeutic interventions for depression.

Journal Link: Biological Psychiatry