Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms

J Frailty Aging. 2016;5(1):6-14. doi: 10.14283/jfa.2016.76.


Background: Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others.

Objectives: 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression.

Design: Randomized controlled trial.

Setting: Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University).

Participants: 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).

Intervention: 12-month PA intervention compared to an education control.

Measurements: Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales.

Results: Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms.

Conclusions: Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

Trial registration: NCT00116194.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Depression* / diagnosis
  • Depression* / genetics
  • Depression* / physiopathology
  • Depression* / therapy
  • Exercise Therapy / methods*
  • Female
  • Humans
  • Independent Living / psychology
  • Life Style*
  • Male
  • Motor Activity* / genetics
  • Motor Activity* / physiology
  • Polymorphism, Genetic
  • Psychiatric Status Rating Scales
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sex Factors
  • Treatment Outcome


  • Apolipoproteins E
  • Brain-Derived Neurotrophic Factor
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • BDNF protein, human

Associated data