Dissecting the causal association between social or physical inactivity and depression: a bidirectional two-sample...

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Research suggests a link between social/physical activity and Major Depressive Disorder (MDD) risk.
• The bidirectional relationship, particularly concerning inactivity and MDD, requires further clarification.

Purpose of the Study:

• To investigate the bidirectional causal relationships between various social and physical activities and MDD.
• To assess the mediating roles of obesity-related measures and brain imaging phenotypes in the inactivity-MDD link.

Main Methods:

• A two-sample Mendelian Randomization analysis was employed.
• Genetic variants associated with social/physical activities and MDD were utilized.
• Data from large cohorts (up to 500,199 individuals) for MDD, activities, BMI, body fat percentage, and brain imaging phenotypes were analyzed.

Main Results:

• Bidirectional causal links were found between specific activities (e.g., sports, exercise) and MDD.
• Leisure/social inactivity and physical inactivity significantly increased MDD risk (ORs 1.64-3.67).
• This increased risk was partially mediated by BMI/body fat percentage and masked by specific brain imaging indices (left acoustic radiation, right caudate volume).
• MDD also increased the risk of subsequent leisure/social and physical inactivity (ORs 1.03-1.01).

Conclusions:

• Social and physical activities appear to be protective against MDD.
• MDD can lead to reduced social and physical activity levels.
• Inactivity is a potential risk factor for MDD, with obesity and specific brain phenotypes playing mediating or masking roles.
• Findings offer insights into MDD manifestations and inform prevention/intervention strategies.