Background: Cortisol and inflammatory markers have been increasingly reported as abnormal at psychosis onset. The main aim of our study was to investigate the ability of these biomarkers to predict treatment response at 12 weeks follow-up in first episode psychosis. Methods: In a longitudinal study, we collected saliva and blood samples in 68 first episode psychosis patients (and 57 controls) at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. Moreover, we repeated biological measurements in 39 patients at the same time we assessed the response. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ (IFN-γ) levels were analyzed from serum samples. Patients were divided into Non-Responders (n = 38) and Responders (n = 30) according to the Remission symptom criteria of the Schizophrenia Working Group Consensus. Results: At first onset, Non-Responders had markedly lower CAR (d = 0.6, P = .03) and higher IL-6 and IFN-γ levels (respectively, d = 1.0, P = .003 and d = 0.9, P = .02) when compared with Responders. After 12 weeks, Non-Responders show persistent lower CAR (P = .01), and higher IL-6 (P = .04) and IFN-γ (P = .05) when compared with Responders. Comparison with controls show that these abnormalities are present in both patients groups, but are more evident in Non-Responders. Conclusions: Cortisol and inflammatory biomarkers at the onset of psychosis should be considered as possible predictors of treatment response, as well as potential targets for the development of novel therapeutic agents.

Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF.

Background Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported. Objectives The aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs. Data Sources Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations. Study Eligibility Criteria Eligibility criteria included (a) primary studies reporting data on NMS, with at least 50 % of the sample receiving SGAs; or (b) case reports and case reviews reporting on NMS induced by SGA monotherapy, excluding those due to antipsychotic withdrawal. Study Appraisal and Synthesis Methods A standardized method for data extraction and coding was developed for the analysis of eligible case reports. Results Six primary studies and 186 individual cases of NMS induced by SGAs were included. Primary studies suggest that SGA-NMS is characterized by lower incidence, lower clinical severity, and less frequent lethal outcome than NMS induced by first-generation antipsychotics. Systematic analysis of case reports suggests that even the most recently marketed antipsychotics are not free from the risk of inducing NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can present with atypical features more frequently than other SGA-NMS, i.e. displaying less intense extrapyramidal symptoms or high fever. Limitations Case reports report non-systematic data, therefore analyses may be subject to bias. Conclusions and Implications of Key Findings Clinicians should be aware that NMS is virtually associated with all antipsychotics, including those most recently marketed. Although apparently less severe than NMS induced by older antipsychotics, SGA-NMS still represent a relevant clinical issue.