Abstract
ImportanceSchizophrenia and major depressive disorder (MDD) are associated with increased risks of immunologic disease and metabolic syndrome. It is unclear to what extent growth, immune or glucose dysregulations are similarly present in these disorders without the influence of treatment or chronicity. ObjectiveTo conduct a meta-analysis investigating whether there are altered peripheral growth, immune or glucose metabolism compounds in drug-naïve first-episode patients with schizophrenia or MDD compared with controls. Data sources and study selectionCase-control studies reporting compound measures in drug-naïve first-episode patients with schizophrenia or MDD compared with controls in the Embase, PubMed and PsycINFO databases. Data extraction and synthesisTwo independent authors extracted data for a random-effects meta-analysis. Main outcomes and measuresPeripheral growth, immune or glucose metabolism compounds in schizophrenia or MDD compared with controls. Standardized mean differences were quantified with Hedges’ g (g). Results74 studies were retrieved comprising 3453 drug-naïve first-episode schizophrenia patients and 4152 controls, and 29 studies were retrieved comprising 1095 drug-naïve first-episode MDD patients and 1399 controls. Growth factors: brain-derived neurotrophic factor (BDNF) (g = -0.77, P < .001) and nerve growth factor (NGF) (g = -2.51, P = .03) were decreased in schizophrenia. For MDD, we observed a trend toward decreased BDNF (g = −0.47, P = .19) and NGF (g = −0.33, P = .08) levels, and elevated vascular endothelial growth factor levels (g = 0.40, P = .03). Immune factors: interleukin (IL)-6 (g = 0.95, P < .001), IL-8 (g = 0.59, P = .001) and tumor necrosis factor alpha (TNFα) (g = 0.48, P = .002) were elevated in schizophrenia. For C-reactive protein (CRP) (g = 0.57, P = .09), IL-4 (g = 0.44, P = .10) and interferon gamma (g = 0.33, P = .11) we observed a trend toward elevated levels in schizophrenia. In MDD, IL-6 (g = 0.62, P = .007), TNFα (g = 1.21, P < .001), CRP (g = 0.53, P < .001), IL-1β (g = 1.52, P = .009) and IL-2 (g = 4.41, P = .04) were elevated, whereas IL-8 (g = −0.84, P = .01) was decreased. The fasting glucose metabolism factors glucose (g = 0.24, P = .003) and insulin (g = 0.38, P = .003) were elevated in schizophrenia. Conclusions and relevanceBoth schizophrenia and MDD show alterations in growth and immune factors from disease onset. An altered glucose metabolism seems to be present from onset in schizophrenia. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune or metabolic dysfunctions.
Highlights
Schizophrenia and major depressive disorder (MDD)are seen as separate disorders based on their distinct clinical presentation
A better understanding of the underlying pathophysiology of both psychiatric disorders is mandatory in order to plan for shared preventive strategies and treatment regarding immune and metabolic dysfunctions prevalent in these disorders. In this meta-analysis we aimed to answer the following question: which peripheral growth, immune or glucose metabolism compounds are altered in drug-naïve first-episode patients with either schizophrenia or MDD compared with healthy controls? we aimed to answer the question whether altered compounds in schizophrenia or MDD are changed in a similar or dissimilar direction and magnitude
Of the following 17 compounds at least two studies were available for meta-analysis for both disorders: growth factors brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF); immune factors C-reactive protein (CRP), interferon gamma (IFNγ), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, monocyte Chemoattractant Protein-1 (MCP-1), and transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNFα); glucose factors fasting glucose and insulin concentration
Summary
Are seen as separate disorders based on their distinct clinical presentation. In clinical practice overlapping symptoms are noticeable such as psychotic symptoms, apathy and cognitive. ⁎ Corresponding author at: Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Behavior, and Immunity xxx (xxxx) xxx–xxx dysfunction (Hill et al, 2009). Genetic and environmental risk factors point towards shared vulnerability between both disorders. A large genome-wide study showed that single-nucleotide polymorphisms are shared between major psychiatric disorders including schizophrenia and MDD (Lee et al, 2013). Environmental risk factors for development of psychopathology such as the experience of stress, urbanicity or low socioeconomic status increase risk for all psychiatric diagnoses (Buckholtz and Meyer-Lindenberg, 2012)
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