Nuray Çakici1, Arjen L Sutterland2, Brenda W J H Penninx3, Virgil A Dalm4, Lieuwe de Haan2, Nico J M van Beveren5. 1. Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Parnassia Academy, Parnassia Psychiatric Institute, The Hague, the Netherlands. Electronic address: cakici.n@gmail.com. 2. Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 3. Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands. 4. Department of Internal Medicine, Division of Clinical Immunology and Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands. 5. Parnassia Academy, Parnassia Psychiatric Institute, The Hague, the Netherlands; Department of Psychiatry, Department of Neuroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Abstract
IMPORTANCE: Schizophrenia 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. OBJECTIVE: To 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 SELECTION: Case-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 SYNTHESIS: Two independent authors extracted data for a random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Peripheral growth, immune or glucose metabolism compounds in schizophrenia or MDD compared with controls. Standardized mean differences were quantified with Hedges' g (g). RESULTS: 74 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 RELEVANCE: Both 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.
IMPORTANCE: Schizophrenia 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. OBJECTIVE: To 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 SELECTION: Case-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 SYNTHESIS: Two independent authors extracted data for a random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Peripheral growth, immune or glucose metabolism compounds in schizophrenia or MDD compared with controls. Standardized mean differences were quantified with Hedges' g (g). RESULTS: 74 studies were retrieved comprising 3453 drug-naïve first-episode schizophreniapatients and 4152 controls, and 29 studies were retrieved comprising 1095 drug-naïve first-episode MDDpatients 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 RELEVANCE: Both 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.
Authors: Malcolm P Forbes; Adrienne O'Neil; Melissa Lane; Bruno Agustini; Nick Myles; Michael Berk Journal: Drugs Aging Date: 2021-04-29 Impact factor: 3.923
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