Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)

Objective Treatment resistance complicates the management of schizophrenia. Research and clinical translation is limited by inconsistent definitions. To address this we evaluated current approaches and then developed consensus criteria and guidelines. Method A systematic review of randomized antipsychotic clinical trials in treatment resistant schizophrenia was performed. Definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed by a working group of researchers and clinicians through i) a multi-phase, mixed methods approach; ii) identifying key criteria via an online survey; and iii) meetings to achieve consensus. Results 42 studies met inclusion criteria. Of these, 21 (50%) studies did not provide operationalized criteria, whilst in others, criteria varied considerably, particularly regarding symptom severity, prior treatment duration and antipsychotic dose thresholds. Important for the inability to compare results, only two (5%) studies utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) ≥moderate functional impairment; 3) prior treatment consisting of ≥2 different antipsychotic trials, each for a minimum duration and dose; 4) adherence systematically assessed and meeting minimum criteria; 5) ideally at least one prospective treatment trial; 6) criteria that clearly separated responsive from treatment resistant patients. Conclusions There is considerable variation in current approaches to defining treatment resistance in schizophrenia. We present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment and treatment response in schizophrenia, providing a benchmark for research and clinical translation.

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy‐genetic liability measures suggest gene‐environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS‐SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene‐environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS‐SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early‐life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS‐SCZ at 75% with alternative cut‐points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

People with schizophrenia are amongst the most stigmatized of those with mental illnesses. The purpose of this study was to examine whether an antistigma program which consists of education, contact, and viewing a film that depicts an individual with schizophrenia, can change attitudes towards people with schizophrenia. The antistigma program was carried out with first-year medical students ( n = 25). Students' attitudes towards people with schizophrenia were assessed before and after the program. In parallel, a control group of first-year medical students were questioned ( n = 35). Assessment was repeated after 1 month. Favorable attitudinal changes were observed in terms of 'belief about the etiology of schizophrenia', 'social distance to people with schizophrenia', and 'care and management of people with schizophrenia'. In contrast, no significant change was observed in the control group. Attitude changes tended to decrease at the 1-month follow up. These results suggest that attitudes towards schizophrenia could be changed favorably with this program. To sustain changed attitudes towards people with schizophrenia, antistigma programs should be offered on a regular basis.

Patients with schizophrenia suffer from increased rates of multiple medical problems, due to their lifestyle (high smoking prevalence, high-fat diet), inherent neglect of personal care, and barriers to treatment of physical illness (1). A further important contributor to adverse health outcomes is the side effect profile of antipsychotic medications. Since the introduction of the second generation or atypical antipsychotics (AAP), these agents have been widely prescribed for the management of patients with schizophrenia, bipolar disorders, other psychotic disorders or conditions with severe behavioral disturbance. The increasing use of AAP is in part due to their lower propensity to induce extrapyramidal symptoms and tardive dyskinesia compared to typical antipsychotics. Now, more than 15 years after the first atypical antipsychotic entered the market, psychiatrists have gradually come to realize that while extrapyramidal symptoms and tardive dyskinesia occur less frequently with atypical agents, these medications may present a different set of adverse effects. The quality of available evidence for the association of specific antipsychotics with particular side effects varies considerably. In this article, we review the recent findings concerning weight gain, diabetes mellitus (DM), hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract in patients receiving AAP. WEIGHT GAINForty to sixty-two percent of people with schizophrenia are overweight or obese. Obesity increases these patients' risk for cardiovascular morbidity and mortality. In addition, excessive weight and obesity can have important effects on an individual's adjustment in the community, adherence to prescribed medication, ability to participate in rehabilitation efforts, and self-image (2).Treatment with first-and second-generation antipsychotics can contribute to weight gain (3-5). A meta-analysis by Allison and Casey (4) provided an estimate of the mean weight gain in patients receiving standard doses of antipsychotics over a 10-week period: the mean increases were 4.45 kg with clozapine, 4.15 kg with olanzapine, 2.92 kg with sertindole, 2.10 kg with risperidone, and 0.04 kg with ziprasidone. Data on quetiapine have been variable, but it seems that the weight gain liability on this drug may be similar to that of risperidone (6). Weight gain with olanzapine at the commonly used dose of 15mg/day may exceed 10 kg during the first year of treatment (7). On the other hand, weight gain seems to be dose-dependent: Rondanelli et al (8) reported no change in weight in elderly patients who received 1.4 mg/day risperidone or 4.4 mg/day olanzapine or 75 mg/day quetiapine over a 12-month period.Marder et al (9) recommended that the patient's body mass index (BMI) should be recorded before medication initiation or change and at every visit for the first 6 months. The patient should be weighed (and the BMI recorded) at least quarterly when he stabilizes, and more often if he is overweight. BMI monito...

Our findings suggest that childhood trauma may alter the presentation of schizophrenia in first admission.

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

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