To determine effects of physical activity on depressive symptoms (primary objective), symptoms of schizophrenia, anthropometric measures, aerobic capacity, and quality of life (secondary objectives) in people with mental illness and explore between-study heterogeneity. MEDLINE, Cochrane Controlled Trials Register, PsycINFO, CINAHL, Embase, and the Physiotherapy Evidence Database (PEDro) were searched from earliest record to 2013. Randomized controlled trials of adults with a DSM-IV-TR, ICD-10, or clinician-confirmed diagnosis of a mental illness other than dysthymia or eating disorders were selected. Interventions included exercise programs, exercise counseling, lifestyle interventions, tai chi, or physical yoga. Study methodological quality and intervention compliance with American College of Sports Medicine (ACSM) guidelines were also assessed. Two investigators extracted data. Data were pooled using random-effects meta-analysis. Meta-regression was used to examine sources of between-study heterogeneity. Thirty-nine eligible trials were identified. The primary meta-analysis found a large effect of physical activity on depressive symptoms (n = 20; standardized mean difference (SMD) = 0.80). The effect size in trial interventions that met ACSM guidelines for aerobic exercise did not differ significantly from those that did not meet these guidelines. The effect for trials with higher methodological quality was smaller than that observed for trials with lower methodological quality (SMD = 0.39 vs 1.35); however, the difference was not statistically significant. A large effect was found for schizophrenia symptoms (SMD = 1.0), a small effect was found for anthropometry (SMD = 0.24), and moderate effects were found for aerobic capacity (SMD = 0.63) and quality of life (SMD = 0.64). Physical activity reduced depressive symptoms in people with mental illness. Larger effects were seen in studies of poorer methodological quality. Physical activity reduced symptoms of schizophrenia and improved anthropometric measures, aerobic capacity, and quality of life among people with mental illness. PROSPERO registration #CRD42012002012.

Patients with first-episode psychosis have a high prevalence of tobacco use. We aimed to examine the prevalence and course of tobacco use during early psychosis using meta-analysis. Systematic search of MEDLINE (1948-2011), Embase (1947-2011), CINAHL (1984-2011), PsycINFO (1967-2011), and ISI Web of Science (1900-2011) using the search terms [psychosis OR schizophrenia] AND [tobacco OR smoking OR nicotine]. We located 10 studies reporting the age at initiation of daily tobacco use and the age at onset of psychosis, 31 studies reporting prevalence of tobacco use in patients with first-episode psychosis, 10 studies comparing smoking to age-/gender-matched controls, and 7 studies reporting prevalence of tobacco use at intervals after treatment. The following data were extracted: age at initiation of daily tobacco use and at onset of psychosis, the proportion of patients with first-episode psychosis who used tobacco, the proportion of the general population who used tobacco, and the proportion of patients with psychosis who used tobacco at various intervals after initiation of antipsychotic treatment. The pooled estimate for the interval between initiation of tobacco use and the onset of psychosis was 5.3 years (standardized mean difference = 0.85). The estimated prevalence of tobacco users in first episode of psychosis is 58.9% (95% CI, 54.3%-63.4%). There is a strong association between first-episode psychosis and tobacco use (OR = 6.04; 95% CI, 3.03-12.02) compared with healthy controls. The prevalence of tobacco use at intervals between 6 and 120 months after treatment remained unchanged (OR = 0.996; 95% CI, 0.907-1.094). Patients with first-episode psychosis tend to have smoked for some years prior to the onset of psychosis, have high prevalence of tobacco use at the time of presenting for treatment, and are much more likely to smoke than aged-matched controls. Their apparent difficulty in quitting has implications for tobacco cessation programs and efforts to reduce cardiovascular disease among people with mental illness.

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia.