O10.7. SIMILARLY ALTERED PROTEIN MARKERS IN DRUG-NAïVE FIRST-EPISODE PATIENTS WITH SCHIZOPHRENIA OR MAJOR DEPRESSIVE DISORDER. A META-ANALYSIS

BACKGROUND: Traditionally, schizophrenia and major depressive disorder (MDD) are seen as separate disorders based on their distinct clinical presentation. In clinical practice however, overlapping symptoms are noticeable such as psychotic symptoms, apathy and cognitive decline. Schizophrenia and MDD are both associated with increased risks of immune disorders and metabolic syndrome. However, it is unclear whether dysfunctions in growth factors, the immune and metabolic system underlie the psychopathology of both schizophrenia and MDD without the influence of chronic illness and treatment. In this meta-analysis we aimed to answer the following question: which peripheral growth, immune and glucose metabolism proteins are similarly altered in drug-naïve first-episode patients with either schizophrenia or MDD compared with healthy controls? METHODS: We conducted a meta-analysis of studies providing serum or plasma measurements (in mean and standard deviation) of peripheral protein markers regarding growth, immune and glucose metabolism proteins in drug-naïve first-episode patients with schizophrenia or MDD and healthy controls. We used a random-effects meta-analysis for which mean differences were quantified with Hedges’ g (g). RESULTS: A total of 65 case-control studies were retrieved comprising of 3156 drug-naïve and first-episode schizophrenia patients and 3687 controls, and a total of 29 studies were retrieved comprising of 1077 drug-naïve and first-episode MDD patients and 1405 controls. In schizophrenia patients brain-derived neurotrophic factor (BDNF) (g = -0.80, 95% CI -1.00 to -0.61; P < 0.01) and nerve growth factor (NGF) (g = -3.28, 95% CI -6.35 to -0.21; P = 0.04) were significantly decreased, and interleukin 6 (IL-6) (g = 1.03, 95% CI 0.61 to 1.46; P < 0.01), interleukin 8 (IL-8) (g = 0.65, 95% CI 0.11 to 1.18; P = 0.02), tumor necrosis factor alpha (TNFα) (g = 0.51, 95% CI 0.19 to 0.83; P < 0.01), fasting glucose concentration (g = 0.26, 95% CI 0.08 to 0.44; P < 0.01) and fasting insulin concentration (g = 0.40, 95% CI 0.13 to 0.68; P < 0.01) were all significantly elevated compared with controls. In MDD patients C-reactive protein (CRP) (g = 0.45, 95% CI 0.18 to 0.71; P < 0.01), interleukin 1 beta (IL-1β) (g = 1.52, 95% CI 0.38 to 2.66; P < 0.01), interleukin 2 (IL-2) (g = 4.41, 95% CI 0.13 to 8.69; P = 0.04), IL-6 (g = 0.62, 95% CI 0.17 to 1.06; P < 0.01) and TNFα (g = 1.21, 95% CI 0.57 to 1.85; P < 0.01) were all significantly elevated compared with controls. IL-8 was significantly decreased in MDD patients compared with controls (g = -0.84, 95% CI -1.48 to -0.20; P < 0.01). CRP, IFNγ, IL-1β, IL-2, IL-4, interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were not significantly altered in schizophrenia patients compared with controls. However, for IL-4 we observed a trend of increased levels in schizophrenia. BDNF, NGF, IFNγ, IL-10, fasting insulin concentration and MCP-1 were not significantly altered in MDD patients compared with controls. However, a similar trend of increased levels of CRP was seen for schizophrenia when compared to MDD, and decreased levels of BDNF and NGF and elevated levels of fasting glucose concentration were seen for MDD when compared to schizophrenia. DISCUSSION: This meta-analysis suggests that dysfunctions in growth, immune and glucose metabolism markers are already present in patients with schizophrenia and MDD from disease onset without the influence of psychotropic treatment. Strikingly, of the 14 proteins identified in this meta-analysis, 10 (71%) are changed in the same direction (trends included) or unchanged in both schizophrenia and MDD. Our findings indicate shared preventive strategies and on-time treatment for immune and metabolic dysfunctions prevalent in these disorders.