Infectious biomarkers in patients with primary mental disorders: a comprehensive systematic review and meta-analysis

Understanding the risk of infections and the role they play in the etiology of mental disorders can offer ways to optimize the care for patients suffering from mental illnesses. However, a comprehensive systematic review and meta-analysis on the prevalence of infectious biomarkers reaching positive thresholds and their corresponding titer-levels in patients with severe mental illness compared to controls has been lacking.

PubMed, Cochrane Library, Clinical Trials, PsychINFO and Embase were searched for eligible studies up until December 2023. All studies measuring the prevalence or the levels of infectious biomarkers in blood (n = 191), cerebrospinal fluid (CSF, n = 8) or brain samples (n = 13) in patients with primary mental disorders (ICD-10: F20-F98) compared to a control group were included. Bias assessment was performed using the Newcastle-Ottawa scale.

208 studies were included in the meta-analysis. Overall, an infection screening reaching threshold for a positive test was more common among individuals with mental disorders compared to healthy controls (OR = 1.97; 95% CI: 1.67-2.32, 98 studies), and specifically for neurotropic infections (OR = 1.84; 95% CI: 1.55-2.17, 75 studies). The increased occurrence of infections was observed specifically for schizophrenia (OR = 2.14; 95% CI: 1.71-2.70, 63 studies) and mood disorders (OR = 1.82; 95% CI: 1.45-2.30, 42 studies). Levels of infection biomarkers of immunoglobulins or infection-specific antibodies were higher in individuals with mental disorders compared to healthy controls (standard mean difference = 0.43; 95% CI: 0.25-0.60, 27 studies). Looking only at brain samples compared to controls, results were non-significant (OR = 1.31; 95% CI: 0.64-2.68, I2 = 60.8%, 7 studies) CONCLUSION: These results show increased odds and higher infection load in patients with mental disorders and cement this association across several disorders and microbiological agents. However, the included studies were cross-sectional only, and thus causality cannot be inferred. Moreover, all outcomes had substantial heterogeneity and wide prediction intervals. Future studies should focus on examining infectious biomarkers in CSF in patients with new-onset mental disorders and include data on symptom severity while routinely examining biomarkers in blood and exploring newer advanced methods of infection detection.