In the prodromal phase of schizophrenia, severe alterations of the visual appearance of the environment have been found, accompanied by a state of intense anxiety. The present study considers the possibility that these alterations really exist in the appearance of objects, but that healthy people do not see them. The image of the world that we see is continuously deformed and fragmented by foreshortenings, partial overlapping, and so on and must be constantly reassembled and interpreted; otherwise, it could change so much that we would hardly recognize it. Since pleasure has been found to be involved in visual and cognitive information processing, the possibility is considered that anhedonia (the reduction of the ability to feel pleasure) might interfere with the correct reconstruction and interpretation of the image of the environment and alter its appearance. The possibility is also considered that these alterations might make the environment hostile, might at times evoke the sensation of being trapped by a predator, and might be the cause of the anxiety that accompanies them. According to some authors, they might also induce delusional ideas, in an attempt to restore meaning in a world that has become chaotic and frightening.

Background Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods Randomized controlled trials (RCTs) included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs). Results Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58]) in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration PROSPERO CRD42014009506.

Clozapine is the only antipsychotic with evidence for efficacy in treatment of resistant schizophrenia but it carries a high side effect burden. Patient information is provided but may be poorly retained. This study aims to examine the impact of pharmacist counselling upon patient knowledge of clozapine. Outpatients, aged 18 years and over, attending St. Patrick's University Hospital, Dublin, participated in this study between June and August 2015. The intervention consisted of pharmacist counselling on two occasions one month apart. Knowledge was assessed using a 28-point checklist devised from the currently available clozapine patient information sources, at baseline and after each counselling session. Ethics approval was obtained. Twenty-five participants (40% female; mean age 45.1 years, SD 9.82; 64% unemployed, 28% smokers) showed an improvement in knowledge scores of clozapine from baseline to postcounselling on each occasion with an overall improvement in knowledge score, from baseline to postcounselling at one month, of 39.43%; p < 0.001. This study adds to the evidence that interventions involving pharmacist counselling can improve patient knowledge, whilst the specific knowledge gained relating to recognition of side effects may help patients towards more empowerment regarding their treatment.

Objective Activation of semantic networks is indexed by the N400 effect. We used a twin study design to investigate whether N400 effect abnormalities reflect genetic/trait liability or are related to psychopathological processes in schizophrenia. Methods We employed robust linear regression to compare N400 and behavioral priming effects across 36 monozygotic twin pairs (6 pairs concordant for schizophrenia/schizoaffective disorder, 11 discordant pairs, and 19 healthy control pairs) performing a lexical decision task. Moreover, we examined the correlation between Brief Psychiatric Rating Scale (BPRS) score and the N400 effect and the influence of medication status on this effect. Results Regression yielded a significant main effect of group on the N400 effect only in the direct priming condition (p = 0.003). Indirect condition and behavioral priming effect showed no significant effect of group. Planned contrasts with the control group as a reference group revealed that affected concordant twins had significantly reduced N400 effect compared to controls, and discordant affected twins had a statistical trend for reduced N400 effect compared to controls. The unaffected twins did not differ significantly from the controls. There was a trend for correlation between reduced N400 effect and higher BPRS scores, and the N400 effect did not differ significantly between medicated and unmedicated patients. Conclusions Reduced N400 effect may reflect disease-specific processes in schizophrenia implicating frontotemporal brain network in schizophrenia pathology.

This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

Literature suggests that the effect of winter birth on vulnerability to schizophrenia might be mediated by increased expression of proinflammatory cytokines due to prenatal infection and its inadequate regulation by anti-inflammatory factors. As the response of the immune system depends on genotype, this study assessed the interaction effects of cytokine genes and season of birth (SOB) on schizotypy measured with the Schizotypal Personality Questionnaire (SPQ-74). We searched for associations of IL1B rs16944, IL4 rs2243250, and IL-1RN VNTR polymorphisms, SOB, and their interactions with the SPQ-74 total score in a sample of 278 healthy individuals. A significant effect of the IL4 X SOB interaction was found, p = 0.007 and η2 = 0.028. We confirmed this effect using an extended sample of 373 individuals. Homozygotes CC born in winter showed the highest SPQ total score and differed significantly from winter-born T allele carriers, p = 0.049. This difference was demonstrated for cognitive-perceptual and disorganized but not interpersonal dimensions. The findings are consistent with the hypothesis that the cytokine genes by SOB interaction can influence variability of schizotypal traits in the general population. The IL4 T allele appeared to have a protective effect against the development of positive and disorganized schizotypal traits in winter-born individuals.

Schizophrenia is associated with deficits in theory of mind (ToM) (i.e., the ability to infer the mental states of others) and cognition. Associations have often been reported between cognition and ToM, and ToM mediates the relationship between impaired cognition and impaired functioning in schizophrenia. Given that cognitive deficits could act as a limiting factor for ToM, this study investigated whether a cognitive remediation therapy (CRT) that targets nonsocial cognition and metacognition could improve ToM in schizophrenia. Four men with schizophrenia received CRT. Assessments of ToM, cognition, and metacognition were conducted at baseline and posttreatment as well as three months and 1 year later. Two patients reached a significant improvement in ToM immediately after treatment whereas at three months after treatment all four cases reached a significant improvement, which was maintained through 1 year after treatment for all three cases that remained in the study. Improvements in ToM were accompanied by significant improvements in the most severely impaired cognitive functions at baseline or by improvements in metacognition. This study establishes that a CRT program that does not explicitly target social abilities can improve ToM.

Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

Cognitive remediation therapy (CRT) has emerged as a viable treatment option for people diagnosed with schizophrenia presenting disabling cognitive deficits. However, it is important to determine which variables can influence response to CRT in order to provide cost-effective treatment. This study's aim was to explore cognitive insight as a potential predictor of cognitive improvement after CRT. Twenty patients with schizophrenia completed a 24-session CRT program involving 18 hours of computer exercises and 6 hours of group discussion to encourage generalization of cognitive training to everyday activities. Pre- and posttest assessments included the CogState Research Battery and the Beck Cognitive Insight Scale (BCIS). Lower self-certainty on the BCIS at baseline was associated with greater improvement in speed of processing (rs = −0.48; p < 0.05) and visual memory (rs = −0.46; p < 0.05). The results of this study point out potential associations between self-certainty and cognitive improvement after CRT, a variable that can easily be measured in clinical settings to help evaluate which patients may benefit most from the intervention. They also underline the need to keep investigating the predictors of good CRT outcomes, which can vary widely between patients.

This study examined factors associated with suicide attempts among those with schizophrenia (n = 101) versus those without (n = 21,643) in a representative sample of noninstitutionalized Canadians. The lifetime prevalence of suicide attempts among persons with schizophrenia was 39.2% versus 2.8% of nonafflicted individuals. After adjusting for sociodemographics, childhood adversities, substance abuse/dependence, depression/anxiety, and chronic pain, those with schizophrenia had 6 times the odds (OR = 6.47) of attempting suicide. Among persons with schizophrenia, suicide attempts were associated with female gender (OR = 4.59), substance abuse/dependence (OR = 6.31), depression (OR = 4.93), and childhood physical abuse (OR = 5.75). Community-dwelling persons with schizophrenia appear to be at high risk for suicide attempts.