Cross-sectional association between metabolic parameters and psychotic-like experiences in a population-based sample of middle-aged and elderly individuals.

BACKGROUND: Metabolic alterations are often found in patients with clinical psychosis early in the course of the disorder. Psychotic-like experiences are observed in the general population, but it is unclear whether these are associated with markers of metabolism. METHODS: A population-based cohort of 1890 individuals (mean age 58.0 years; 56.3% women) was included. Metabolic parameters were measured by body-mass index (BMI), concentrations of low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol, triglycerides, and fasting glucose and insulin in blood. Frequency and distress ratings of psychotic-like experiences from the positive symptom dimension of the Community Assessment of Psychic Experience questionnaire were assessed. Cross-sectional associations were analysed using linear regression analyses. RESULTS: Higher BMI was associated with higher frequency of psychotic-like experiences (adjusted mean difference: 0.04, 95% CI 0.02-0.06) and more distress (adjusted mean difference: 0.02, 95% CI 0.01-0.03). Lower LDL-C was associated with more psychotic-like experiences (adjusted mean difference: -0.23, 95% CI -0.40 to -0.06). When restricting the sample to those not using lipid-lowering medication, the results of BMI and LDL-C remained and an association between lower HDL-C and higher frequency of psychotic-like experiences was found (adjusted mean difference: -0.37, 95% CI -0.69 to -0.05). We observed no significant associations between cholesterol, triglycerides, glucose, insulin or homeostatic model assessment and psychotic-like experiences. CONCLUSIONS: In a population-based sample of middle-aged and elderly individuals, higher BMI and lower LDL-C were associated with psychotic-like experiences. This suggests that metabolic markers are associated with psychotic-like experiences across the vulnerability spectrum.

Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis.

BACKGROUND: This meta-analysis on peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder (MDD) examined which compounds change following psychopharmacological treatment. METHODS: The Embase, PubMed and PsycINFO databases were systematically searched for longitudinal studies reporting measurements of blood compounds in drug-naïve first-episode schizophrenia or MDD. RESULTS: For this random-effects meta-analysis, we retrieved a total of 31 studies comprising 1818 schizophrenia patients, and 14 studies comprising 469 MDD patients. Brain-derived neurotrophic factor (BDNF) increased following treatment in schizophrenia (Hedges' g (g): 0.55; 95% confidence interval (CI) 0.39-0.70; p < 0.001) and MDD (g: 0.51; CI 0.06-0.96; p = 0.027). Interleukin (IL)-6 levels decreased in schizophrenia (g: -0.48; CI -0.85 to -0.11; p = 0.011), and for MDD a trend of decreased IL-6 levels was observed (g: -0.39; CI -0.87 to 0.09; p = 0.115). Tumor necrosis factor alpha (TNFα) also decreased in schizophrenia (g: -0.34; CI -0.68 to -0.01; p = 0.047) and in MDD (g: -1.02; CI -1.79 to -0.25; p = 0.009). Fasting glucose levels increased only in schizophrenia (g: 0.26; CI 0.07-0.44; p = 0.007), but not in MDD. No changes were found for C-reactive protein, IL-1ß, IL-2 and IL-4. CONCLUSIONS: Psychopharmacological treatment has modulating effects on BDNF and TNFα in drug-naïve first-episode patients with either schizophrenia or MDD. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune dysfunctions.

Altered peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis.

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-1ß (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.

Increased serum levels of leptin and insulin in both schizophrenia and major depressive disorder: A cross-disorder proteomics analysis.

We investigated whether there are similar serum alterations in schizophrenia and major depressive disorder (MDD). We investigated serum analytes in two epidemiological studies on schizophrenia (N = 121) and MDD (N = 1172) versus controls. Serum analytes (N = 109) were measured with a multi-analyte profiling platform and analysed using linear regression models, adjusted for site, age, gender, ethnicity, anti-inflammatory agents, smoking, cardiovascular disease and diabetes, and adjusted for multiple comparisons. An increase in leptin and insulin levels was observed for both schizophrenia patients (Cohen's d (d): 0.26 and 0.65, respectively) and MDD patients (d: 0.29 and 0.12, respectively) compared to their respective controls. Lower angiopoietin-2 levels were seen in both schizophrenia (d: -0.22) and MDD (d: -0.13). Four analytes differed in only schizophrenia patients (increased levels of C-peptide and prolactin, and decreased levels of CD5 antigen-like and sex hormone binding globulin) and one analyte differed in only MDD patients (increased angiotensinogen levels) compared to their respective controls. Restricting analyses to patients with a current episode of disease showed even more marked elevations of insulin and leptin. Our results suggest the presence of insulin and leptin resistance as cross-disorder mechanisms that could contribute to the higher somatic comorbidity and decreased life-span seen in both disorders.