Toby Pillinger

Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis.

Importance Schizophrenia is associated with an increased risk of type 2 diabetes. However, it is not clear whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term treatment. Objective To conduct a meta-analysis examining whether individuals with first-episode schizophrenia already exhibit alterations in glucose homeostasis compared with controls. Data Sources The EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining measures of glucose homeostasis in antipsychotic-naive individuals with first-episode schizophrenia compared with individuals serving as controls. Study Selection Case-control studies reporting on fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in first-episode antipsychotic-naive individuals with first-episode schizophrenia compared with healthy individuals serving as controls. Two independent investigators selected the studies. Data Extraction Two independent investigators extracted study-level data for a random-effects meta-analysis. Standardized mean differences in fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and HbA1c levels were calculated. Sensitivity analyses examining the effect of body mass index, diet and exercise, race/ethnicity, and minimal (⩽2 weeks) antipsychotic exposure were performed. Data Synthesis Of 3660 citations retrieved, 16 case-control studies comprising 15 samples met inclusion criteria. The overall sample included 731 patients and 614 controls. Fasting plasma glucose levels (Hedges g = 0.20; 95% CI, 0.02 to 0.38; P = .03), plasma glucose levels after an oral glucose tolerance test (Hedges g = 0.61; 95% CI, 0.16 to 1.05; P = .007), fasting plasma insulin levels (Hedges g = 0.41; 95% CI, 0.09 to 0.72; P = .01), and insulin resistance (homeostatic model assessment of insulin resistance) (Hedges g = 0.35; 95% CI, 0.14 to 0.55; P = .001) were all significantly elevated in patients compared with controls. However, HbA1c levels (Hedges g = −0.08; CI, −0.34 to 0.18; P = .55) were not altered in patients compared with controls. Conclusions and Relevance These findings show that glucose homeostasis is altered from illness onset in schizophrenia, indicating that patients are at increased risk of diabetes as a result. This finding has implications for the monitoring and treatment choice for patients with schizophrenia.

Cholesterol and triglyceride levels in first-episode psychosis: systematic review and meta-analysis

Background The extent of metabolic and lipid changes in first-episode psychosis (FEP) is unclear. Aims To investigate whether individuals with FEP and no or minimal antipsychotic exposure show lipid and adipocytokine abnormalities compared with healthy controls. Method We conducted a meta-analysis of studies examining lipid and adipocytokine parameters in individuals with FEP and no or minimal antipsychotic exposure v. a healthy control group. Studies reported fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and leptin levels. Results Of 2070 citations retrieved, 20 case-control studies met inclusion criteria including 1167 patients and 1184 controls. Total cholesterol and LDL cholesterol levels were significantly decreased in patients v. controls, corresponding to an absolute reduction of 0.26 mmol/L and 0.15 mmol/L respectively. Triglyceride levels were significantly increased in the patient group, corresponding to an absolute increase of 0.08 mmol/L. However, HDL cholesterol and leptin levels were not altered in patients v. controls. Conclusions Total and LDL cholesterol levels are reduced in FEP, indicating that hypercholesterolaemia in patients with chronic disorder is secondary and potentially modifiable. In contrast, triglycerides are elevated in FEP. Hypertriglyceridaemia is a feature of type 2 diabetes mellitus, therefore this finding adds to the evidence for glucose dysregulation in this cohort. These findings support early intervention targeting nutrition, physical activity and appropriate antipsychotic prescription.

Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia

Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non‐adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment‐resistant by their treating clinician.

Is psychosis a multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models

People with psychotic disorders show abnormalities in several organ systems in addition to the central nervous system (CNS); and this contributes to excess mortality. However, it is unclear how strong the evidence is for alterations in non-CNS systems at the onset of psychosis, how the alterations in non-CNS systems compare to those in the CNS, or how they relate to symptoms. Here, we consider these questions, and suggest potential models to account for findings. We conducted a systematic meta-review to summarize effect sizes for both CNS (focusing on brain structural, neurophysiological, and neurochemical parameters) and non-CNS dysfunction (focusing on immune, cardiometabolic, and hypothalamic–pituitary–adrenal (HPA) systems) in first-episode psychosis (FEP). Relevant meta-analyses were identified in a systematic search of Pubmed and the methodological quality of these was assessed using the AMSTAR checklist (A Measurement Tool to Assess Systematic Reviews). Case–control data were extracted from studies included in these meta-analyses. Random effects meta-analyses were re-run and effect size magnitudes for individual parameters were calculated, as were summary effect sizes for each CNS and non-CNS system. We also grouped studies to obtain overall effect sizes for non-CNS and CNS alterations. Robustness of data for non-CNS and CNS parameters was assessed using Rosenthal’s fail-safe N. We next statistically compared summary effect size for overall CNSand overall non-CNS alterations, as well as for each organ system separately. We also examined how non-CNS alterations correlate CNS alterations, and with psychopathological symptoms. Case-control data were extracted for 165 studies comprising a total sample size of 13,440. For people with first episode psychosis compared with healthy controls, we observed alterations in immune parameters (summary effect size: g = 1.19), cardiometabolic parameters (g = 0.23); HPA parameters (g = 0.68); brain structure (g = 0.40); neurophysiology (g = 0.80); and neurochemistry (g = 0.43). Grouping non-CNS organ systems together provided an effect size for overall non-CNS alterations in patients compared with controls (g = 0.58), which was not significantly different from the overall CNS alterations effect size (g = 0.50). However, the summary effect size for immune alterations was significantly greater than that for brain structural (P < 0.001) and neurochemical alterations (P < 0.001), while the summary effect size for cardiometabolic alterations was significantly lower than neurochemical (P = 0.04), neurophysiological (P < 0.001), and brain structural alterations (P = 0.001). The summary effect size for HPA alterations was not significantly different from brain structural (P = 0.14), neurophysiological (P = 0.54), or neurochemical alterations (P = 0.22). These outcomes remained similar in antipsychotic naive sensitivity analyses. We found some, but limited and inconsistent, evidence that non-CNS alterations were associated with CNS changes and symptoms in first episode psychosis. Our findings indicate that there are robust alterations in non-CNS systems in psychosis, and that these are broadly similar in magnitude to a range of CNS alterations. We consider models that could account for these findings and discuss implications for future research and treatment.

Lifetime self-reported arthritis is associated with elevated levels of mental health burden: A multi-national cross sectional study across 46 low- and middle-income countries

Population-based studies investigating the relationship of arthritis with mental health outcomes are lacking, particularly among low- and middle-income countries (LMICs). We investigated the relationship between arthritis and mental health (depression spectrum, psychosis spectrum, anxiety, sleep disturbances and stress) across community-dwelling adults aged ≥18 years across 46 countries from the World Health Survey. Symptoms of psychosis and depression were established using questions from the Mental Health Composite International Diagnostic Interview. Severity of anxiety, sleep problems, and stress sensitivity over the preceding 30 days were self-reported. Self-report lifetime history of arthritis was collected, including presence or absence of symptoms suggestive of arthritis: pain, stiffness or swelling of joints over the preceding 12-months. Multivariable logistic regression analyses were undertaken. Overall, 245,706 individuals were included. Having arthritis increased the odds of subclinical psychosis (OR = 1.85; 95%CI = 1.72–1.99) and psychosis (OR = 2.48; 95%CI = 2.05–3.01). People with arthritis were at increased odds of subsyndromal depression (OR = 1.92; 95%CI = 1.64–2.26), a brief depressive episode (OR = 2.14; 95%CI = 1.88–2.43) or depressive episode (OR = 2.43; 95%CI = 2.21–2.67). Arthritis was also associated with increased odds for anxiety (OR = 1.75; 95%CI = 1.63–1.88), sleep problems (OR = 2.23; 95%CI = 2.05–2.43) and perceived stress (OR = 1.43; 95%CI = 1.33–1.53). Results were similar for middle-income and low-income countries. Integrated interventions addressing arthritis and mental health comorbidities are warranted to tackle this considerable burden.

Community Treatment Orders—A pause for thought

Community Treatment Orders (CTO) have been available for several decades in some countries and are being progressively introduced worldwide, with significant uptake in Asian countries as they move more mental health care into the community. However the evidence for the effectiveness of CTOs is limited. The evidence from local audits and evaluations is conflicted with some studies showing clear benefit and others not. The same is the case for uncontrolled before and after studies. The higher levels of evidence such as randomised controlled trials, systematic reviews, and Cochrane reviews have consistently failed to demonstrate benefits from CTO use on key measures such as symptom levels, functioning, and healthcare use. Despite this they are increasingly available internationally and often greeted enthusiastically by clinicians and families who want to ensure care and follow up for the mentally ill. This article briefly discusses the evidence before describing potential alternatives to the use of compulsion that do have an evidence base, such as multidisciplinary community working, housing initiatives, and employment support.