We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (−2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (−15.58 ± 1.58 versus −12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

Background. Oxidative stress in schizophrenia may be caused partially by the treatment of patients with antipsychotics. The aim of the study was to establish the effects of polyphenol compounds derived from berries of Aronia melanocarpa (Aronox) on the plasma lipid peroxidation induced by ziprasidone in vitro. Methods. Lipid peroxidation was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml) alone and with Aronox (5 ug/ml; 50 ug/ml). Results. We observed a statistically significant increase of TBARS level after incubation of plasma with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml) (after 24 h incubation: P = 7.0 × 10−4, P = 1.6 × 10−3, and P = 2.7 × 10−3, resp.) and Aronox lipid peroxidation caused by ziprasidone was significantly reduced. After 24-hour incubation of plasma with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml) in the presence of 50 ug/ml Aronox, the level of TBARS was significantly decreased: P = 6.5 × 10−8, P = 7.0 × 10−6, and P = 3.0 × 10−5, respectively. Conclusion. Aronox causes a distinct reduction of lipid peroxidation induced by ziprasidone.

Although nonadherence to antipsychotic medication poses a threat to outcome of medical treatment, the processes preceding the intake behavior have not been investigated sufficiently. This study tests a process model of medication adherence derived from the Health Belief Model which is based on cost-benefit considerations. The model includes an extensive set of potential predictors for medication attitudes and uses these attitudes as a predictor for medication adherence. We conducted an online study of 84 participants with a self-reported psychotic disorder and performed a path analysis. More insight into the need for treatment, a higher attribution of the symptoms to a mental disorder, experience of less negative side effects, presence of biological causal beliefs, and less endorsement of psychological causal beliefs were significant predictors of more positive attitudes towards medication. The results largely supported the postulated process model. Mental health professionals should consider attitudes towards medication and the identified predictors when they address adherence problems with the patient in a shared and informed decision process.

Background. Numerous studies have been conducted with a view to developing strategies for improvement of medical compliance in patients with schizophrenia. All of the studies conducted so far have had an individual approach to compliance based on the assumption that noncompliance is determined individually due to inappropriate behavior in the patient. We conducted a pragmatic controlled trial with a system-oriented approach, to provide a new perspective on compliance and test the efficacy of a multifactorial intervention at the system level in a routine clinical setting, an approach that has not previously been used for the improvement of compliance. Methods. 30 patients were allocated to the system-oriented therapy and 40 patients were allocated to the reference intervention, which consisted of individually based compliance therapy. The follow-up period was six months. Primary endpoint was improvement in compliance, measured by improvement in a compliance scale specifically developed for the project. Results. When accounting for missing values with a multiple imputation approach, we found a tendency toward a difference in both the compliance scale and PANSS favoring the system-oriented therapy, although it did not reach statistical significance. A significant difference in incidence of adverse events and time to first readmission was found. Attrition rates were significantly higher in the reference group and nonsignificant among individuals with lower compliance, which may have diluted effect estimates. This was reflected by significant differences found in an analysis based on a last observation carried forward approach. Conclusion. This study suggests that compliance problems are better solved by a multifactorial intervention at the system level than at the individual level.

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients drawn from a larger study received quetiapine treatment for twelve weeks. Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched healthy controls and to levels following treatment. Linear regression analyses were performed to determine the relationship of BDNF and VEGF levels with outcome measures at baseline and week 12. Results. The mean serum BDNF level was significantly higher at week 12 compared to baseline and correlated with reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology scores. Changes in serum VEGF levels also correlated significantly with a reduction in BPRS scores, a significant improvement in PANNS positive symptoms scores, and displayed a positive relationship with changes in BDNF levels. Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for gauging improvement of psychotic symptoms. This suggests a novel neurotrophic-based mechanism of the drug effects of quetiapine on psychosis. This is the first report of VEGF perturbation in psychosis.

Altered facial expressions of emotions are characteristic impairments in schizophrenia. Ratings of affect have traditionally been limited to clinical rating scales and facial muscle movement analysis, which require extensive training and have limitations based on methodology and ecological validity. To improve reliable assessment of dynamic facial expression changes, we have developed automated measurements of facial emotion expressions based on information-theoretic measures of expressivity of ambiguity and distinctiveness of facial expressions. These measures were examined in matched groups of persons with schizophrenia (n = 28) and healthy controls (n = 26) who underwent video acquisition to assess expressivity of basic emotions (happiness, sadness, anger, fear, and disgust) in evoked conditions. Persons with schizophrenia scored higher on ambiguity, the measure of conditional entropy within the expression of a single emotion, and they scored lower on distinctiveness, the measure of mutual information across expressions of different emotions. The automated measures compared favorably with observer-based ratings. This method can be applied for delineating dynamic emotional expressivity in healthy and clinical populations.

Schizophrenia is a subtle disorder of brain development and plasticity; it affects the most basic human processes of perception, emotion, and judgment. In Bangladesh the traditional medical practitioners of rural and remote areas characterized the schizophrenia as an insanity or a mental problem due to possession by ghosts or evil spirits and they have used various plant species' to treat such symptoms. The aim of the present study was to conduct an ethnomedicinal plant survey and documentation of the formulations of different plant parts used by the traditional medical practitioners of Rangamati district of Bangladesh for the treatment of schizophrenia like psychosis. It was observed that the traditional medical practitioners used a total of 15 plant species to make 14 formulations. The plants were divided into 13 families, used for treatment of schizophrenia and accompanying symptoms like hallucination, depression, oversleeping or insomnia, deterioration of personal hygiene, forgetfulness, and fear due to evil spirits like genies or ghost. A search of the relevant scientific literatures showed that a number of plants used by the medicinal practitioners have been scientifically validated in their uses and traditional medicinal knowledge has been a means towards the discovery of many modern medicines. Moreover, the antipsychotic drug reserpine, isolated from the dried root of Rauvolfia serpentina species, revolutionized the treatment of schizophrenia. So it is very much possible that formulations of the practitioner, when examined scientifically in their entireties, can form discovery of lead compounds which can be used as safe and effective antipsychotic drug to treat schizophrenia.

Patients with schizophrenia often present sleep complaints, but its relationship with general satisfaction with life (SWL) and burden for caregivers has been understudied. We aimed to assess the differences in SWL between patients with and without self-reported sleep disturbances and that of their caregivers. In a noninterventional study, 811 schizophrenia adult outpatients were screened for their subjective perception of having (or not) sleep disturbances and evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Pittsburgh Sleep Quality Index (PSQI). Patients self-reporting sleep disturbances were significantly more symptomatic (P < 0.001), presented significantly worse family support (P = 0.0236), and self-reported worse SWL in all domains. Caregivers of patients with schizophrenia self-reporting sleep disturbances also reported worse SWL in all domains, as compared to caregivers of patients without subjective sleep disturbances. Patient and caregivers' SWL was significantly correlated to patients' quality of sleep (P < 0.0001 for all domains). Patient' and caregivers' SWL was negatively affected by patients' poor quality of sleep. We found that patients self-reporting sleep disturbances showed greater symptom severity, worse quality of sleep, worse SWL, and less caregiver support. SWL was also worse for caregivers of patients with schizophrenia reporting sleep disturbances.

Social cognitive impairments are core features of schizophrenia and are closely associated with poor functional outcome. This study sought to identify specific aspects of social cognition and their relationships to measures of social function, quality of life, and neurocognition. Principal component analysis was performed using social cognitive measures in patients with schizophrenia and healthy matched controls and revealed three factors: Interpersonal Discomfort, Basic Social Cognition, and Empathy. Patients had higher scores on Interpersonal Discomfort and lower scores on Basic Social Cognition than controls, but the two groups were the same on Empathy. Lower social performance was significantly correlated with poor Basic Social Cognition in patients and with high Interpersonal Discomfort in controls. While neurocognition was significantly associated with Basic Social Cognition in both groups, it was not associated with Empathy. Social cognitive interventions should emphasize improving basic social cognitive processing deficits, managing Interpersonal Discomfort, and utilizing preserved capacity for empathy as a potential strength in social interactions.

Psychotic disorders carry social and economic costs for sufferers and society. Recent evidence highlights the risk posed by urban upbringing and social deprivation in the genesis of paranoia and psychosis. Evidence based psychological interventions are often not offered because of a lack of therapists. Virtual reality (VR) environments have been used to treat mental health problems. VR may be a way of understanding the aetiological processes in psychosis and increasing psychotherapeutic resources for its treatment. We developed a high-fidelity virtual reality scenario of an urban street scene to test the hypothesis that virtual urban exposure is able to generate paranoia to a comparable or greater extent than scenarios using indoor scenes. Participants (n = 32) entered the VR scenario for four minutes, after which time their degree of paranoid ideation was assessed. We demonstrated that the virtual reality scenario was able to elicit paranoia in a nonclinical, healthy group and that an urban scene was more likely to lead to higher levels of paranoia than a virtual indoor environment. We suggest that this study offers evidence to support the role of exposure to factors in the urban environment in the genesis and maintenance of psychotic experiences and symptoms. The realistic high-fidelity street scene scenario may offer a useful tool for therapists.