Summary: A new study adds to growing evidence that higher levels of physical activity can help reduce the risk of developing mental illness. Researchers found physical activity can reduce depression risks in those genetically vulnerable to depressive disorders.

Source: Mass General.

While many studies have found associations between greater levels of physical activity and lower rates of depression, a key question has remained – does physical activity actually reduce the risk of depression or does depression lead to reduced physical activity? Now a team led by Massachusetts General Hospital (MGH) investigators has used a novel research method to strongly support physical activity as a preventive measure for depression. Their report is being published online in JAMA Psychiatry.

“Using genetic data, we found evidence that higher levels of physical activity may causally reduce risk for depression,” says Karmel Choi, PhD, of the Psychiatric and Neurodevelopmental Genetics Unit in the MGH Center for Genomic Medicine, lead author of the report. “Knowing whether an associated factor actually causes an outcome is important, because we want to invest in preventive strategies that really work.”

The technique used in the study – Mendelian randomization – uses gene variants to study the effects of a non-genetic factor in a different approach from that of traditional research. The gene variants are studied as a type of natural experiment in which people show higher or lower average levels of a factor like physical activity that are related to gene variants they have inherited. Because genetic variants are inherited in a relatively random fashion, they can serve as less biased proxies to estimate the true relationship between physical activity and depression. This approach can also determine which of two traits is actually causative – if levels of trait A affects the levels of trait B but levels of trait B do not affect levels of trait A, that implies that trait A leads to trait B, but not vice versa.

For this study, the researchers identified gene variants from the results of large-scale genome-wide association studies (GWAS) that were conducted for physical activity in the U.K. Biobank and for depression by a global research consortium. GWAS results for physical activity were available for two different measures: one based on 377,000 participants’ self-reports of physical activity and the other based on readings of motion-detecting sensors called accelerometers, worn on the wrists of more than 91,000 participants. The GWAS for depression was based on data from more than 143,000 participants with and without this condition.

The results of the Mendelian randomization study indicated that accelerometer-based physical activity, but not self-reported activity, does appear to protect against the risk of depression. The differences between the two methods of measuring physical activity could result not only from inaccuracies in participants’ memories or desire to present themselves in a positive way but also from the fact that objective readings capture things other than planned exercise – walking to work, climbing the stairs, mowing the lawn – that participants may not recognize as physical activity. The analysis revealed no causal relationship in the other direction, between depression and physical activity.

“On average,” Choi says, “doing more physical activity appears to protect against developing depression. Any activity appears to be better than none; our rough calculations suggest that replacing sitting with 15 minutes of a heart-pumping activity like running, or with an hour of moderately vigorous activity, is enough to produce the average increase in accelerometer data that was linked to a lower depression risk.”

Senior author Jordan Smoller, MD, ScD, director of the Psychiatric and Neurodevelopmental Genetics Unit and a professor of Psychiatry at Harvard Medical School, says, “While gene variants like those used in this study do not determine a person’s behaviors or outcomes, their average associations with certain traits in these very large studies can help us look at a question such as whether physical activity – or the tendency to engage in more physical activity – has a likely causal effect on depression. And the answers to those questions could help researchers design large-scale clinical trials.”

Choi adds, “And of course it’s one thing to know that physical activity could be beneficial for preventing depression; it’s another to actually get people to be physically active. More work needs to be done to figure out how best to tailor recommendations to different kinds of people with different risk profiles. We currently are looking at whether and how much physical activity can benefit different at-risk groups, such as people who are genetically vulnerable to depression or those going through stressful situations and hope to develop a better understanding of physical activity to promote resilience to depression.”

About this neuroscience research article

Funding: Additional co-authors of the JAMA Psychiatry report are Chia-Yen Chen, PhD, Psychiatric and Neurodevelopmental Genetics Unit, MGH Center for Genomic Medicine; Murray Stein, MD, MPH, University of California, San Diego; Karestan Koenen, PhD, and Min-Jung Wang, MSc, Harvard T.H. Chan School of Public Health; and Yann Klimentidis, PhD, University of Arizona. Support for the study includes National Institute of Mental Health grants T32 MH017119 and K24 MH094614, the Demarest Lloyd Jr. Foundation and Tepper Family MGH Research Scholar funding.

Source: Noah Brown – Mass General

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Abstract for “Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults: A 2-Sample Mendelian Randomization Study” by Karmel W. Choi, PhD; Chia-Yen Chen, PhD; Murray B. Stein, MD, MPH; Yann C. Klimentidis, PhD; Min-Jung Wang, MSc; Karestan C. Koenen, PhD; Jordan W. Smoller, MD, ScD; for the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium in JAMA Psychiatrye. Published January 23 2019.

doi:10.1001/jamapsychiatry.2018.4175



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[cbtabs][cbtab title=”MLA”]Mass General”Physical Activity Can Prevent Against Depression.” NeuroscienceNews. NeuroscienceNews, 223 January 2019.

<https://neurosciencenews.com/exercise-depression-10619/>.[/cbtab][cbtab title=”APA”]Mass General(2019, January 223). Physical Activity Can Prevent Against Depression. NeuroscienceNews. Retrieved January 223, 2019 from https://neurosciencenews.com/exercise-depression-10619/[/cbtab][cbtab title=”Chicago”]Mass General”Physical Activity Can Prevent Against Depression.” https://neurosciencenews.com/exercise-depression-10619/ (accessed January 223, 2019).[/cbtab][/cbtabs]

Abstract

Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults: A 2-Sample Mendelian Randomization Study

Importance

Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.

Objective

To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.

Design, Setting, and Participants

This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes—self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)—and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR–Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.

Main Outcomes and Measures

MDD and physical activity.

Results

GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = −0.08 in mean acceleration per MDD vs control status; 95% CI, −0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, −0.008 to 0.05; P = .15).

Conclusions and Relevance

Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed—but not self-reported—physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.

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