# Social inhibition in depressed patients is associated with an altered activation profile of the interleukin-6-inducible transcription factor STAT3

## TL;DR

Depressed patients with social inhibition show altered STAT3 activation, suggesting a link between immune signaling and social withdrawal symptoms.

## Contribution

This study identifies a novel association between STAT3 signaling and social inhibition in depression.

## Key findings

- SI-positive patients had higher baseline STAT3 activation and reduced sensitivity to IL-6 stimulation.
- Lower IL-6-induced pSTAT3 levels correlated with higher SI scores in depressed patients.
- Altered STAT3 sensitivity remained significant after adjusting for clinical confounders.

## Abstract

Numerous studies have described the role of STAT3 (signal transducer and activator of transcription 3) in infections, but little is known on whether this transcription factor is linked to negative affectivity (NA) and social inhibition (SI), leading to social withdrawal as a typical symptom of various infections.

In this study, we isolated peripheral blood mononuclear cells (PBMCs) from 63 consecutive depressed patients (mean age 41.4 ± 16.1 years; 40 females) before and after psychotherapeutic intervention and measured STAT3 tyrosine phosphorylation (pSTAT3) with and without in vitro interleukin-6 (IL-6) stimulation of these cells using flow cytometry. In addition, all study participants were assessed for NA and SI using the German version of the Type D Scale-14 (DS-14) questionnaire with a cut-off level of ≥10 for each subscale.

While NA was unrelated to STAT3 activity, PBMCs from SI-positive patients had an increased baseline STAT3 activation level, which made the cells less sensitive to in vitro IL-6 stimulation (11.5% vs. 9.1%, p = 0.036). The stimulatory capacity, defined as the difference in pSTAT3 levels from IL-6-stimulated to unstimulated cells during hospitalization, was significantly lower in PBMCs from SI-positive than from SI-negative patients (−1.7% vs. 6.6%, p = 0.007). The sensitivity of PBMCs to IL-6 stimulation was negatively correlated with the SI score (r = −0.295, p = 0.019). Of note, the altered sensitivity to STAT3 phosphorylation remained stable, when adjusted for clinically relevant confounders in multivariate analysis (Exp(β) = 0.891, 95%-confidence interval = 0.804–0.988, p = 0.029).

These findings point towards a possible relationship between STAT3 signaling and social inhibition in depressed patients.