In a recent publication in The American Journal of Psychiatry, researchers sought to examine the genetic characterization of MDD heterogeneity.

The authors wrote, “Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder’s symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive.”

The researchers employed the Swedish patient register data that included 1.5 million individuals and identified 46,255 people with MDD who were diagnosed by a specialist.

A total of 18 subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis.

To approximate the heritability of MDD subgroups and genetic correlations between subgroups, researchers employed a sibling-based design and classic quantitative genetic models.

The authors noted that their results were essentially consistent with previous work using genomic data. The findings revealed that hereditability ranged from 30.5% to 58.3% across the subgroups. Additionally, the disabled and early age–onset subgroups presented with meaningfully more significant heritability (55.1%–58.3%) than the overall MDD sample (45.3%; 95% CI, 43.0–47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity demonstrated considerably lesser estimates (30.5%–34.4%). The authors also noted that estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90.

The results also revealed, “Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data.”

Based on their findings, the authors concluded, “This study has produced important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.”

The authors also indicated that treating MDD warrants an individualized approach. Lastly, the authors wrote that further studies should be conducted to discover if there are exact genetic factors and biomarkers and to match subgroups to outcomes, thus fostering more research efforts on developing novel and optimized treatments tailored to patient needs.

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