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-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

Accumulation rate of advanced glycation end products in recent onset psychosis: A longitudinal study

Schizophrenia is associated with excessive oxidative stress. Production of advanced glycation end products (AGEs) in the skin is strongly associated with oxidative stress. Increased skin AGE-levels have been demonstrated at cross-sectional level in recent onset psychosis and chronic schizophrenia, indicating increased cardiovascular risk. We aimed to investigate factors underlying AGE-accumulation and accumulation rate of AGEs in recent onset psychosis. From December 2016 through May 2017, 66 patients and 160 (highly educated) healthy controls from a previous case-control study of AGE-levels were assessed for a follow-up measurement 12–24 months after baseline. Possible determinants of AGE-accumulation were analyzed. AGE-accumulation rates in patients and controls were compared adjusted for relevant confounders. In healthy controls, a significant association of AGE-accumulation with ethnicity and tobacco exposure was found. An indication of a markedly higher AGE-accumulation rate was found in patients suffering from recent onset psychosis compared to healthy controls, independent of ethnicity and tobacco smoking, but not independent of cannabis use (more prevalent in patients than controls), although results were not significant

Association of Toxoplasma gondii Seropositivity with Cognitive Function in Healthy People: A Systematic Review and Meta-analysis

Importance: The parasite Toxoplasma gondii has been associated with behavioral alterations and psychiatric disorders. Studies investigating neurocognition in people with T gondii infection have reported varying results. To systematically analyze these findings, a meta-analysis evaluating cognitive function in healthy people with and without T gondii seropositivity is needed. Objective: To assess whether and to what extent T gondii seropositivity is associated with cognitive function in otherwise healthy people. Data Sources: A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A systematic search of PubMed, MEDLINE, Web of Science, PsycInfo, and Embase was performed to identify studies from database inception to June 7, 2019, that analyzed cognitive function among healthy participants with available data on T gondii seropositivity. Search terms included toxoplasmosis, neurotoxoplasmosis, Toxoplasma gondii, cognition disorder, neuropsychological, and psychomotor performance. Study Selection: Studies that performed cognitive assessment and analyzed T gondii seroprevalence among otherwise healthy participants were included. Data Extraction and Synthesis: Two researchers independently extracted data from published articles; if needed, authors were contacted to provide additional data. Quantitative syntheses were performed in predefined cognitive domains when 4 independent data sets per domain were available. Study quality, heterogeneity, and publication bias were assessed. Main Outcomes and Measures: Performance on neuropsychological tests measuring cognitive function. Results: The systematic search yielded 1954 records. After removal of 533 duplicates, an additional 1363 records were excluded based on a review of titles and abstracts. A total of 58 full-text articles were assessed for eligibility (including reference list screening); 45 articles were excluded because they lacked important data or did not meet study inclusion or reference list criteria. The remaining 13 studies comprising 13 289 healthy participants (mean [SD] age, 46.7 [16.0] years; 6586 men [49.6%]) with and without T gondii seropositivity were included in the meta-analysis. Participants without T gondii seropositivity had favorable functioning in 4 cognitive domains: processing speed (standardized mean difference [SMD], 0.12; 95% CI, 0.05-0.19; P =.001), working memory (SMD, 0.16; 95% CI, 0.06-0.26; P =.002), short-term verbal memory (SMD, 0.18; 95% CI, 0.09-0.27; P <.001), and executive functioning (SMD, 0.15; 95% CI, 0.01-0.28; P =.03). A meta-regression analysis found a significant association between older age and executive functioning (Q = 6.17; P =.01). Little suggestion of publication bias was detected. Conclusions and Relevance: The study's findings suggested that T gondii seropositivity was associated with mild cognitive impairment in several cognitive domains. Although effect sizes were small, given the ubiquitous prevalence of this infection globally, the association with cognitive impairment could imply a considerable adverse effect at the population level. Further research is warranted to investigate the underlying mechanisms of this association.

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-1β, 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

Advanced Glycation End Products in Recent-Onset Psychosis Indicate Early Onset of Cardiovascular Risk

Profoundly increased mortality rates in schizophrenia, largely caused by a higher risk and earlier onset of cardiovascular disease, remain a major challenge. During the human lifespan, advanced glycation end products (AGEs) accumulate, and their concentration is strongly linked to cardiovascular mortality. AGE accumulation can be accelerated by several pathways, including oxidative stress. From March 2015 through January 2016, a case-control study including 111 patients with a recent-onset psychosis, 135 controls from a validation cohort, and 286 healthy controls was performed. Patients fulfilled the DSM-IV criteria for schizophrenia spectrum disorders with an illness duration shorter than 5 years. Main outcome parameters were skin autofluorescence levels of AGEs, controlled for age, gender, and smoking. Correlations of AGEs with cardiovascular risk factors and clinical variables were analyzed by hierarchical linear regression analyses. An AGE measurement was possible in 77.4% of cases. AGEs were elevated by 15.1% in recent-onset psychosis compared to healthy controls (P <.001), corresponding to an increased accumulation of AGEs normally occurring in approximately 10 years. AGEs were not related to traditional risk factors. However, duration of illness (P = .008), duration of antipsychotic treatment (P = .009), and cumulative exposure to antipsychotics (P = .023) correlated with AGEs. Patients with a recent onset of psychosis have increased AGE levels compared to healthy controls. These findings argue for an earlier implementation of treatment strategies aimed at preventing cardiovascular disease. Also, low-dose strategies of antipsychotics in schizophrenia could beneficially influence AGE level

Driving us mad: the association of Toxoplasma gondii with suicide attempts and traffic accidents - a systematic review and meta-analysis

Unnatural causes of death due to traffic accidents (TA) and suicide attempts (SA) constitute a major burden on global health, which remained stable in the last decade despite widespread efforts of prevention. Recently, latent infection with Toxoplasma gondii (T. gondii) has been suggested to be a biological risk factor for both TA and SA. Therefore, a systematic search concerning the relationship of T. gondii infection with TA and/or SA according to PRISMA guidelines in Medline, Pubmed and PsychInfo was conducted collecting papers up to 11 February 2019 (PROSPERO #CRD42018090206). The random-effect model was applied and sensitivity analyses were subsequently performed. Lastly, the population attributable fraction (PAF) was calculated. We found a significant association for antibodies against T. gondii with TA [odds ratio (OR) = 1.69; 95% confidence interval (CI) 1.20-2.38, p = 0.003] and SA (OR = 1.39; 95% CI 1.10-1.76, p = 0006). Indication of publication bias was found for TA, but statistical adjustment for this bias did not change the OR. Heterogeneity between studies on SA was partly explained by type of control population used (OR healthy controls = 1.9, p < 0.001 v. OR psychiatric controls = 1.06, p = 0.87) and whether subjects with schizophrenia only were analysed (OR schizophrenia = 0.87, p = 0.62 v. OR various = 1.8, p < 0.001). The association was significantly stronger with higher antibody titres in TA and in studies that did not focus on schizophrenia subjects concerning SA. PAF of a T. gondii infection was 17% for TA and 10% for SA. This indicates that preventing T. gondii infection may play a role in the prevention of TA or SA, although uncertainty remains whether infection and outcome are truly causally related

Skin autofluorescence of advanced glycation end products and course of affective disorders in the lifelines cohort study, a prospective investigation

Background: Skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, is cross-sectionally associated with affective disorders. Prospective studies of oxidative stress markers will help to clarify the pathophysiological role of oxidative stress. Methods: Data of a population-based cohort study were used. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed at baseline and at 5-year follow-up with the Mini-International Neuropsychiatric Interview. Associations between SAF at baseline and incidence and persistence/recurrence of affective disorders were assessed with logistic regression. Results: Of 43,267 participants with no disorder at baseline, 2885 (6.7%) developed an incident disorder during follow-up. In 1360 of 3648 participants (37.3%) with an affective disorder at baseline, a persisting/recurrent disorder was present at follow-up. A modest association existed between SAF and incident affective disorders (OR=1.07 [95%CI 1.03–1.12], P<.001), specifically major depressive disorder (OR=1.11 [95%CI 1.04–1.19], P=.003); this association lost statistical significance after adjustment for sociodemographic factors. Associations between SAF and persistence/recurrence were not significant. Limitations: Many confounders might also act as intermediate: extensive adjustment for confounders caused overfitting and possibly masked effects of SAF on course of affective disorders. Relatively small sample sizes for analyses of SAF and persistence/recurrence of affective disorders resulted in a low power. Conclusions: Increased SAF modestly raises the odds of incident affective disorders, particularly major depressive disorder, providing evidence that oxidative stress plays a role in subsequent occurrence of affective disorders. However, significance of effects faded after adjustment for socioeconomic status

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-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