Evidence of symptom specificity for depression in multiple sclerosis: A two sample Mendelian randomization study

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Depression is a common and varied condition in multiple sclerosis (MS).
• MS may influence the risk of certain affective symptoms, or conversely, some symptoms might increase MS risk.

Purpose of the Study:

• To investigate the causal relationship between distinct depressive symptoms and MS.
• To determine the directionality of causality using two-sample Mendelian randomization (MR).

Main Methods:

• Utilized genome-wide association study data for MS (n=115,776) and depressive symptoms (n=117,713).
• Assessed nine depressive symptoms: anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems, and suicidality.
• Employed two-sample MR with inverse-variance models and sensitivity analyses, adjusting for body mass index in multivariable-MR.

Main Results:

• Found genetic liability to MS associated with anhedonia, concentration difficulty, and psychomotor changes.
• Sensitivity analyses confirmed these associations.
• No evidence of a causal relationship was found for any depressive symptom influencing MS risk.

Conclusions:

• Genetic susceptibility to MS is specifically associated with anhedonia, concentration difficulties, and psychomotor changes.
• These findings suggest a distinct depressive symptom phenotype in individuals with MS.