Background-Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies.

ObjectiveTo determine whether exposures to infectious illness during childhood involving the CNS or elsewhere is associated with adult schizophrenia or other psychoses.MethodSystematic review and meta-analysis of published literature identified by electronic and manual search meeting three inclusion criteria: population-base, objective assessment of childhood infection at the individual level, standard definition of adult psychotic outcomes. We calculated risk ratio for all CNS infection, and separately for viral and bacterial infection in relation to non-affective psychosis and schizophrenia, which was combined in meta-analysis.ResultsSeven studies were included. Meta-analysis involving 2424 cases and over 1.2 million controls showed CNS viral infection was associated with nearly two-fold increased risk of adult non-affective psychosis (risk ratio 1.70; 95% CI 1.13–2.55; p = 0.01). There was no significant heterogeneity between studies (p = 0.26; I2 = 20%). Separate meta-analysis involving 1035 cases and over 1.2 million controls suggested all childhood CNS infections, particularly viral infections, may be associated with nearly two-fold risk of adult schizophrenia. However, there was evidence of some heterogeneity between these studies (p = 0.07; I2 = 70%). CNS bacterial infections were not associated with risk of psychosis. Data on childhood infections with no obvious involvement of the CNS is insufficient.ConclusionsThese findings indicate childhood CNS viral infections increase the risk of adult psychotic illness. Possible mechanisms may include both direct effects of pathogens, and the effects of inflammatory response on the developing brain.

Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine.