# Significant beneficial effects of 12-weeks add-on yoga therapy on antipsychotic-stabilized schizophrenia patients through epigenetic modulation: novel findings from a randomized controlled study

## TL;DR

A 12-week yoga therapy program improved immune function in schizophrenia patients, possibly through changes in gene activity and DNA methylation.

## Contribution

This is the first study to show yoga's epigenetic effects on immune pathways in schizophrenia.

## Key findings

- Yoga therapy significantly reduced plasma IL-1β and increased C2 levels in schizophrenia patients.
- Yoga therapy downregulated Il1b and Il6 gene expression while upregulating C4 gene expression.
- Yoga therapy altered DNA methylation patterns in genes related to inflammation and immunity.

## Abstract

Complementary and alternative therapy, especially yoga, is emerging as an important treatment modality for various complex disorders. Yoga therapy has reportedly been demonstrated to exhibit clinical benefits in schizophrenia. However, the modulatory effects of yoga therapy on the pathobiological pathways of schizophrenia are inadequately explored. Immune dysregulation is a widely recognized etiopathological construct of schizophrenia. It is not precisely known whether yoga therapy can modulate the expression of immune molecules by regulating gene expression and epigenetic processes in schizophrenia.

To understand the impact of 12-weeks add-on yoga therapy on the immune-inflammatory pathway in schizophrenia by examining plasma levels and gene expression levels of cytokines and complement proteins as well as by profiling promoter DNA methylation pattern of genes coding for cytokines and complement proteins.

Fifty-seven schizophrenia patients fulfilling DSM-V criteria were recruited into the study and randomized into Yoga therapy (n=28) and waitlist control (n=29) groups. Plasma levels of IL-1β, IL-6, IL-10, IL-17, C1q, C2, C3, C4, C5, C5a, Factor B and Factor H by Multiplex Suspension Assay, quantification of gene expression of Il1b, Il6, Il10, IL17, C3, C4 and C5 genes by quantitative PCR and promoter DNA methylation of Il1b, Il6, Il10, Il17, C3, C4 and C5 genes by pyrosequencing were carried out in all the study participants.

Plasma levels of IL-1β (Z score= 2.42, p=0.02) dropped significantly and C2 (Z score= 2.24, p=0.03) levels increased after 12-weeks of yoga therapy. The expression of Il1b (Z score=2.45, p=0.01) and Il6 (Z score=2.07, p=0.04) genes were significantly downregulated, while the levels of C4 (Z score=2.23, p=0.03) gene was upregulated in schizophrenia patients of yoga therapy group. Two CpG sites in the promoter region of Il1b (all p≤0.05) and Il6 (all p≤0.05) genes and three CpG sites in the promoter region of C4 (all p<0.05) gene were hypermethylated, while two CpG sites in the gene body of Il6 (all p≤0.05) gene and two CpG sites in the promoter region of Il10 (all p ≤0.05) gene were hypomethylated after 12-weeks of yoga therapy in schizophrenia patients.

Our findings provide important insights into the mode of action of yoga therapy in schizophrenia. This study for the first time reports the epigenetic effects of yoga therapy on immune-inflammatory pathway in schizophrenia.

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