Unraveling Depression Heterogeneity Across the Lifespan: Gene-Environment Interactions, Social Determinants, and Treatment Outcomes

Depression is a heterogeneous psychiatric disorder characterized by substantial variation in symptom presentation, illness trajectories, treatment response, and recovery across the lifespan. This heterogeneity is increasingly understood as the product of dynamic interactions among genetic vulnerability, environmental exposures, social determinants, lifestyle factors, and treatment-related processes. Understanding how these layers interact, from molecular vulnerability to social context to clinical intervention, is essential for explaining why individuals with similar risk profiles follow markedly different depressive trajectories.This Research Topic brings together three complementary perspectives on depression heterogeneity. First, we welcome studies examining gene-environment interactions and biological pathways, including genetic, epigenetic, and other genome-wide or multi-omic approaches, as well as meta-analyses that clarify how genetic susceptibility interacts with life stress, trauma, and other environmental exposures to shape depression risk and clinical heterogeneity. Second, we welcome longitudinal and population-based studies examining social determinants of depressive symptoms across the lifespan, including social activity and isolation, dietary and lifestyle factors, socioeconomic conditions, and multimorbidity, with particular interest in aging populations and large cohort studies. Studies examining how social and environmental factors influence symptom dimensions, illness trajectories, persistence, remission, or functional outcomes are particularly encouraged. Third, we welcome clinical trials, treatment response studies, and digital or remote assessment approaches that contribute to understanding variability in depressive symptom trajectories, treatment response, remission, or recovery. These may include pharmacological and adjunctive treatment trials, multi-site international collaborations, and mobile or remote monitoring of depressive symptoms and treatment-related changes. Studies addressing symptom architecture, dimensional psychopathology, and longitudinal patterns of depressive symptoms are also encouraged, particularly when these approaches help explain differences in risk, course, or treatment response.Contributions that integrate two or more of these perspectives, for example studies examining how gene-environment interactions moderate treatment response, or how social determinants identified in longitudinal cohorts inform intervention design, are particularly encouraged. Studies focused on isolated pharmacokinetic or pharmacogenomic mechanisms without connection to depression heterogeneity, or purely descriptive prevalence surveys without analytic modeling of contributing factors, fall outside the primary scope of this Research Topic.Welcomed themes include, but are not limited to:Gene-environment interactions and biological determinants of depression heterogeneity; Genetic, epigenetic, and multi-omic approaches to depression risk, psychopathology, and treatment response; Social determinants of depressive symptoms and longitudinal trajectories, including social isolation, socioeconomic conditions, lifestyle, and environmental exposures; Depression across the lifespan, including developmental differences, aging, multimorbidity, and changing symptom trajectories; Symptom architecture, dimensional psychopathology, and clinically meaningful heterogeneity in depressive symptoms; Longitudinal patterns of depression, including persistence, remission, recurrence, and functional outcomes; Predictors and moderators of treatment response, remission, recovery, and relapse, including pharmacological and adjunctive interventions; Integrative approaches linking biological, environmental, social, psychopathological, and clinical factors to explain and address depression heterogeneity.Article types: Original Research, Systematic Reviews, Meta-Analyses, Brief Research Reports, Clinical Trials, Study Protocols, Reviews, Mini Reviews, Perspectives, Hypothesis and Theory articles. Topic editors: Mingzhe Zhao, Preethi Veerappa Reddy, Lei Shi, Bowen Xue Source: https://www.frontiersin.org/research-topics/86245/unraveling-depression-heterogeneity-across-the-lifespan-gene-environment-interactions-social-determinants-and-treatment-outcomes