5-HTTLPR and MTHFR 677C>T polymorphisms and response to yoga-based lifestyle intervention in major depressive disorder: A randomized active-controlled trial

Abstract

Background:

There is growing evidence suggesting that both genetic and environmental factors modulate treatment outcome in, a highly heterogeneous, major depressive disorder (MDD). 5-HTTLPR variant of the serotonin transporter gene (SLC6A4) and MTHFR 677C>T polymorphisms have been linked to the pathogenesis of MDD, and antidepressant treatment response. The evidence is lacking on the clinical utility of yoga in patients with MDD who have 5-HTTLPR and MTHFR 677C>T polymorphisms and less likely to respond to medications (SSRIs).

Aims:

We aimed to examine the impact of YBLI in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are less likely to drug therapy with SSRIs.

Settings and Design:

In a 12 week randomized active-controlled trial, MDD patients ( n = 178) were randomized to receive YBLI or drug therapy.

Methods:

Genotyping was conducted using PCR-based methods. The clinical remission was defined as BDI-II score ≤ 9.

Statistical Analysis Used:

An intent-to-treat analysis was performed, and the association of genotype with treatment remission consisted of the logistic regression model. A P value of <0.05 was considered statistically significant.

Results:

Multivariate logistic regression models for remission including either 5-HTTLPR or MTHFR 677C>T genotypes showed statistically significant odds of remission in YOGA arm vs. DRUG arm. Neither 5-HTTLPR nor MTHFR 677C>T genotype showed any influence on remission to YBLI ( P = 0.73 and P = 0.64, respectively). Further analysis showed childhood adversity interact with 5-HTTLPR and MTHFR 677C>T polymorphisms to decrease treatment response in DRUG treatment arm, but not in YOGA arm.

Conclusions:

YBLI provides MDD remission in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are resistant to SSRIs treatment. YBLI may be therapeutic for MDD independent of heterogeneity in its etiopathogenesis.