A new Psych-STRATA-supported study explores inflammatory biomarkers and their potential role in treatment outcomes across schizophrenia, bipolar disorder and major depressive disorder.
Poor treatment outcomes worsen prognosis in schizophrenia, bipolar disorder (BD) and major depressive disorder (MDD). These outcomes likely involve shared mechanisms, including alterations in inflammatory protein markers. However, previous research had not examined the role of these markers in treatment outcomes across diagnoses. To address this gap, we performed a systematic review and meta-analysis.
We searched major scientific databases for studies providing quantitative data on the association between peripheral inflammatory protein markers and psychopharmacological treatment outcomes in schizophrenia, BD and MDD. We performed cross-diagnostic random-effects meta-analyses and evaluated heterogeneity, publication bias and study quality. In addition, we conducted sensitivity analyses and meta-regressions. The study protocol followed the PRISMA guideline and was preregistered.
A total of 105 studies entered the systematic review, while 42 entered the meta-analysis. Sixty-one samples (N = 5,787) considered MDD and 26 samples (N = 2,113) focused on schizophrenia. BD was the least represented diagnosis, with 12 samples (N = 342).
IL-6 was the most investigated biomarker, but the analysis found no evidence of an association with treatment outcomes. For TNF-α, responders demonstrated a greater decrease in concentration from baseline to endpoint (SMD = 0.75, 95% CI [0.14–1.35]; k = 7).
In addition, lower baseline CRP levels were associated with remission (OR = 1.84, 95% CI [1.33, 2.54]; k = 6), although cut-off definitions varied across studies. Most other markers showed no associations. However, IL-8 levels were higher at baseline in non-responders with mood disorders (SMD = −0.38; 95% CI [−0.73, −0.03]; k = 6).
Heterogeneity was high across most analyses. Moreover, sensitivity analyses and meta-regressions generally did not add meaningful findings.
Overall, inflammatory biomarkers still offer limited predictive value for treatment outcomes across psychiatric disorders. The available evidence also focuses substantially on MDD. Therefore, standardised methodological workflows and a shift from candidate proteins to hypothesis-free proteomics are key considerations for future research.
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