Altered function of peripheral organ systems in first-episode drug naive mental illnesses: A systematic review and meta-analysis

Background Although mental illness is primarily regarded as a disorder of the brain, body system dysfunction is increasingly recognized as a salient biomarker in psychiatry, often emerging before the onset of overt symptoms. Here, we systematically review studies on peripheral organ systems (cardiovascular, metabolic, immune, liver, kidneys, lungs and muskeloskeletal) in schizophrenia, major depressive disorder (MDD), bipolar disorder (BD) and generalized anxiety disorder (GAD), aiming to synthesize findings on the function of multiple body systems in the early stages of mental illness. Methods EMBASE, MEDLINE and PsycINFO were searched from inception until 19 November 2024, identifying case-control studies comparing physiological markers of peripheral organ systems (i.e., cardiovascular, metabolic, immune, liver, kidney, lung and muskeloskeletal) in adults with one of the four mental illnesses at first-episode and drug naive, with healthy controls. We followed the PRISMA 2020 guidelines (PROSPERO: CRD42023408594). Results Of 2,637 citations retrieved, 138 studies met inclusion criteria for review with 52 markers of immune (n=32), metabolic (n=11), cardiovascular (n=6), liver (n=2) and musculoskeletal (n=1) function identified. 105 studies were eligible for meta-analysis, including 80, 26, 4 and 0 studies on schizophrenia, MDD, BD and GAD respectively. Meta-analysis revealed increased HDL-cholesterol, waist-hip-circumference ratio, triglycerides, insulin, insulin resistance, 2-hr glucose, neutrophil, monocyte, white blood cell, IL-4 and systolic blood pressure, and reduced albumin in schizophrenia; increased TNF- and IL-10 in MDD; and increased IL-6 and IFN-{gamma} in both schizophrenia and MDD. Other results were narratively discussed. Conclusions Alterations in peripheral organ function across multiple systems characterizes the onset of psychiatric disorders. However, research on peripheral organ function in psychiatry is limited and primarily focusses on the immune and metabolic systems.