Existing treatments for schizophrenia can improve positive symptoms, but it is unclear if they have any impact on negative symptoms. This meta-analysis was conducted to assess the efficacy of available treatments for negative symptoms in schizophrenia. All randomized-controlled trials of interventions for negative symptoms in schizophrenia until December 2013 were retrieved; 168 unique and independent placebo-controlled trials were used. Negative symptom scores at baseline and follow-up, duration of illness, doses of medication, type of interventions, and sample demographics were extracted. Heterogeneity was addressed with the I² and Q statistic. Standardized mean difference in values of the Negative Symptom Rating Scale used in each study was calculated as the main outcome measure. 6503 patients in the treatment arm and 5815 patients in the placebo arm were included. No evidence of publication biases found. Most treatments reduced negative symptoms at follow-up relative to placebo: second-generation antipsychotics: −0.579 (−0.755 to −0.404); antidepressants: −0.349 (−0.551 to −0.146); combinations of pharmacological agents: −0.518 (−0.757 to −0.279); glutamatergic medications: −0.289 (−0.478 to −0.1); psychological interventions: −0.396 (−0.563 to −0.229). No significant effect was found for first-generation antipsychotics: −0.531 (−1.104 to 0.041) and brain stimulation: −0.228 (−0.775 to 0.319). Effects of most treatments were not clinically meaningful as measured on Clinical Global Impression Severity Scale. Although some statistically significant effects on negative symptoms were evident, none reached the threshold for clinically significant improvement.

Background: The nosology of the psychosis high-risk state is controversial. Traditionally conceived as an ‘at risk’ state for the development of psychotic disorders, it is also conceptualised as a clinical syndrome associated with functional impairment.Aims: To investigate meta-analytically the functional status of patients at high clinical risk for psychosis and its association with longitudinal outcomes.Method: Three meta-analyses compared level of functioning (n = 3012) and quality of life (QoL) (n = 945) between a high-risk group, a healthy control group and group with psychosis, and baseline functioning in people in the high-risk group who did or did not have a transition to psychosis at follow-up (n = 654).Results: People at high risk had a large impairment in functioning (P<0.001) and worse QoL (P = 0.001) than the healthy control group, but only small to moderately better functioning (P = 0.012) and similar QoL (P = 0.958) compared with the psychosis group. Among the high-risk group, those who did not develop psychosis reported better functioning (P = 0.001) than those who did.Conclusions: Our results indicate that the high-risk state is characterised by consistent and large impairments of functioning and reduction in QoL similar to those in other coded psychiatric disorders.

Patients at ultra-high risk for psychosis (UHR) are a highly heterogeneous group in terms of clinical and functional outcomes. Several non-psychotic mental disorders co-occur together with the UHR state. Little is known about the impact of non-psychotic comorbid mental disorders on clinical and functional outcomes of UHR patients. The sample included 154 UHR help-seeking patients (identified with the CAARMS, comprehensive assessment of the at-risk mental state), evaluated at baseline on the Ham-D, Ham-A (Hamilton depression/anxiety rating scale), and PANSS (positive and negative syndrome scale). 74 patients completed the 6-year follow-up assessment (mean=6.19, SD=1.87). Comorbid disorders at follow-up were assessed with the SCID I and II. Global functioning was rated on the global assessment of functioning (GAF) scale. In the present sample, 6-year risk of psychosis transition was 28.4%. Among non-transitioned UHR patients, 28.3% reported attenuated psychotic symptoms (APS) and 45.3% remained functionally impaired at follow-up (GAF<60). 56.8% patients were affected by at least one comorbid disorder at follow-up. Among UHR patients who presented with some comorbid disorder at baseline, 61.5% had persistent or recurrent course. Incident comorbid disorders emerged in 45.4% of baseline UHR patients. The persistence or recurrence of non-psychotic comorbid mental disorders was associated with poorer global functional outcomes at follow-up. A substantial proportion of the initial sample was not available for follow-up interviews and some groups in the analyses had small sample size. Predictors of longitudinal outcomes were not explored. Among UHR patients, persistence or recurrence of non-psychotic comorbid mental disorders, mostly affective disorders, is associated with 6-year poor functional outcomes.

A large array of studies have investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. We searched Web of KnowledgeSM and Scopus® for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized.