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1.
Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review.
Levinta, A, Mukovozov, I, Tsoutsoulas, C
Advances in nutrition (Bethesda, Md.). 2018;(6):824-832
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Abstract
We performed a systematic review of the literature to determine whether adherence to a gluten-free diet (GFD) leads to improved outcomes for patients with schizophrenia. We searched the AMED (Allied and Complementary Medicine; 1985-June 2016), MEDLINE (1946-June 2016), and Embase (1980-2016 week 24) databases using the terms "wheat" or "glutenin" or "gliadin" or "gluten" AND "schizophrenia." A total of 9 studies met the inclusion criteria for this review: 1 randomized controlled trial, 7 crossover studies, and 1 open-label pilot study. Six of the included studies demonstrated beneficial effects including improved functioning and decreased symptom severity after the course of a GFD, whereas 3 studies found no benefits. All of the included studies found that a GFD is well tolerated and can be adhered to by patients with schizophrenia. The findings of this systematic review should be interpreted with caution due to limitations inherent to nonrandomized trials, as well as the heterogeneity in the study design and the length of the GFD applied in each study. Publication bias is another potential limitation. Further research is required to examine the biomarkers of gluten sensitivity and inflammation to effectively target those patients with schizophrenia who will benefit most from this dietary intervention.
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Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial.
Wang, X, Zhao, J, Hu, Y, Jiao, Z, Lu, Y, Ding, M, Kou, Y, Li, B, Meng, F, Zhao, H, et al
Psychiatry research. 2018;:271-277
Abstract
Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18-45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 μg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile.
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Convergence of placenta biology and genetic risk for schizophrenia.
Ursini, G, Punzi, G, Chen, Q, Marenco, S, Robinson, JF, Porcelli, A, Hamilton, EG, Mitjans, M, Maddalena, G, Begemann, M, et al
Nature medicine. 2018;(6):792-801
Abstract
Defining the environmental context in which genes enhance disease susceptibility can provide insight into the pathogenesis of complex disorders. We report that the intra-uterine environment modulates the association of schizophrenia with genomic risk (in this study, genome-wide association study-derived polygenic risk scores (PRSs)). In independent samples from the United States, Italy, and Germany, the liability of schizophrenia explained by PRS is more than five times greater in the presence of early-life complications (ELCs) compared with their absence. Patients with ELC histories have significantly higher PRS than patients without ELC histories, which is confirmed in additional samples from Germany and Japan. The gene set composed of schizophrenia loci that interact with ELCs is highly expressed in placenta, is differentially expressed in placentae from complicated in comparison with normal pregnancies, and is differentially upregulated in placentae from male compared with female offspring. Pathway analyses reveal that genes driving the PRS-ELC interaction are involved in cellular stress response; genes that do not drive such interaction implicate orthogonal biological processes (for example, synaptic function). We conclude that a subset of the most significant genetic variants associated with schizophrenia converge on a developmental trajectory sensitive to events that affect the placental response to stress, which may offer insights into sex biases and primary prevention.
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Use of a Mental Health Center Collaborative Care Team to Improve Diabetes Care and Outcomes for Patients With Psychosis.
Chwastiak, LA, Luongo, M, Russo, J, Johnson, L, Lowe, JM, Hoffman, G, McDonell, MG, Wisse, B
Psychiatric services (Washington, D.C.). 2018;(3):349-352
Abstract
OBJECTIVE This study aimed to evaluate the feasibility, acceptability, and preliminary effectiveness (compared with usual care) of a collaborative care model to treat community mental health center (CMHC) patients with psychosis and poorly controlled diabetes. METHODS Stakeholder input was used to adapt a primary care-based collaborative care intervention for CMHC settings. Thirty-five adult CMHC clients with type II diabetes and hemoglobin A1c (HbA1c) >8% or blood pressure >140/90 were randomized to receive either collaborative care or usual care. Change in HbA1c was evaluated between baseline and three months. Paired t tests were used for within-group comparisons. RESULTS After three months, intervention participants had a statistically significant mean decrease in HbA1c of 1.1% (p=.049). There was no significant change in HbA1c in the usual-care group. CONCLUSIONS This pilot demonstrates the feasibility and acceptability of implementing collaborative care in CMHC settings and its preliminary effectiveness in improving glycemic control in a high-risk population.
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Psychopharmacological Treatment in the RAISE-ETP Study: Outcomes of a Manual and Computer Decision Support System Based Intervention.
Robinson, DG, Schooler, NR, Correll, CU, John, M, Kurian, BT, Marcy, P, Miller, AL, Pipes, R, Trivedi, MH, Kane, JM
The American journal of psychiatry. 2018;(2):169-179
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Abstract
OBJECTIVE The Recovery After an Initial Schizophrenia Episode-Early Treatment Program compared NAVIGATE, a comprehensive program for first-episode psychosis, to clinician-choice community care over 2 years. Quality of life and psychotic and depressive symptom outcomes were found to be better with NAVIGATE. Compared with previous comprehensive first-episode psychosis interventions, NAVIGATE medication treatment included unique elements of detailed first-episode-specific psychotropic medication guidelines and a computerized decision support system to facilitate shared decision making regarding prescriptions. In the present study, the authors compared NAVIGATE and community care on the psychotropic medications prescribed, side effects experienced, metabolic outcomes, and scores on the Adherence Estimator scale, which assesses beliefs related to nonadherence. METHOD Prescription data were obtained monthly. At baseline and at 3, 6, 12, 18, and 24 months, participants reported whether they were experiencing any of 21 common antipsychotic side effects, vital signs were obtained, fasting blood samples were collected, and the Adherence Estimator scale was completed. RESULTS Over the 2-year study period, compared with the 181 community care participants, the 223 NAVIGATE participants had more medication visits, were more likely to receive a prescription for an antipsychotic and more likely to receive one conforming to NAVIGATE prescribing principles, and were less likely to receive a prescription for an antidepressant. NAVIGATE participants experienced fewer side effects and gained less weight; other vital signs and cardiometabolic laboratory findings did not differ between groups. Adherence Estimator scores improved in the NAVIGATE group but not in the community care group. CONCLUSIONS As part of comprehensive care services, medication prescription can be optimized for first-episode psychosis, contributing to better outcomes with a lower side effect burden than standard care.
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Pharmacotherapy for schizophrenia in postmenopausal women.
González-Rodríguez, A, Seeman, MV
Expert opinion on pharmacotherapy. 2018;(8):809-821
Abstract
INTRODUCTION Reduced estrogen levels at menopause mean a loss of the neuroprotection that is conferred, from puberty until menopause, on women with schizophrenia. The postmenopausal stage of schizophrenia requires therapeutic attention because women with this diagnosis almost invariably experience increased symptoms and increased side effects at this time. So far, few targeted therapies have been successfully developed. AREAS COVERED This non-systematic, narrative review is based on the relevant published literature indexed in PubMed. A digital search was combined with a manual check of references from studies in the field of gender differences, menopause and schizophrenia. Aside from the inclusion of a few early classic papers, the review focuses on 21st century basic, psychopharmacologic, and clinical literature on the treatment of women with schizophrenia after menopause. EXPERT OPINION Beyond a relatively low dose threshold, all antipsychotic medications have adverse effects, which become more prominent for women at the time of menopause. Estrogen modulators may not help all symptoms of schizophrenia but are, nevertheless, relatively safe and, when used as adjuncts, help to keep antipsychotic doses low, thus reducing the side effect burden. The field is currently moving towards precision medicine and individual genetic profiles will help to determine the efficacy of available treatments in the future.
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Effects of intranasal oxytocin on satiety signaling in people with schizophrenia.
Warren, KR, Wehring, HJ, Liu, F, McMahon, RP, Chen, S, Chester, C, Kelly, DL
Physiology & behavior. 2018;:86-91
Abstract
Overweight and obesity in schizophrenia are prevalent, affecting half to three-quarters of people with schizophrenia. Hyperphagia and increased meal size have also been implicated as significant contributors to the weight gain problem. Oxytocin has shown to play a role in appetite control in humans and is considered an anorexigenic peptide. This two-day, within-subjects, challenge study involved the examination of satiety after administration of 24 IU oxytocin (intranasal) vs. placebo in participants with a DSM-IV diagnosis of schizophrenia (N = 16). Self reported satiety along with a preload-test meal paradigm were utilized as well as related laboratory measures (insulin, glucose, and leptin), and measures of taste and smell. There were no statistically significant differences between the groups on self-reported satiety or test meal consumption, insulin or glucose levels, or sensory measures. A significant treatment difference was found (F = 5.22, df = 1,97.6, p = 0.025), with a decrease in leptin in the oxytocin group post-administration, but no time effect (F = 1.67, df = 6,95.1, p = 0.180) or treatment by time interaction (F = 1.36. df = 3,4.16, p = 0.261). Despite the small sample and mostly negative findings, we encourage more work to use higher and repeated doses of oxytocin, and to further examine the effect of oxytocin on leptin in schizophrenia as this may be important for understanding both weight control and psychopathology.
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Mini-review: Update on the genetics of schizophrenia.
Coelewij, L, Curtis, D
Annals of human genetics. 2018;(5):239-243
Abstract
A number of important findings have recently emerged relevant to identifying genetic risk factors for schizophrenia. Findings using common variants point towards gene sets of interest and also demonstrate an overlap with other psychiatric and nonpsychiatric disorders. Imputation of variants of the gene for complement component 4 (C4) from GWAS data has shown that the predicted expression of the C4A product is associated with schizophrenia risk. Very rare variants disrupting SETD1A, RBM12 or NRXN1 have a large effect on risk. Other rare, damaging variants are enriched in genes that are loss of function intolerant and/or whose products localise to the synapse. These and particular copy number variants can result in increased risk of schizophrenia but also of other neurodevelopmental disorders. The findings for C4 and NRXN1 may be especially helpful for elucidating the biological mechanisms that can lead to disease.
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Association of Elements with Schizophrenia and Intervention of Selenium Supplements.
Li, Z, Liu, Y, Li, X, Ju, W, Wu, G, Yang, X, Fu, X, Gao, X
Biological trace element research. 2018;(1):16-21
Abstract
The purpose of this study is to explore more trace elements (zinc, potassium, copper, iron, boron, manganese, selenium, chromium and cadmium elements) in addition to calcium, magnesium, lead and arsenic in the sera of patients with schizophrenia and the general population in China and to determine the effect of selenium on schizophrenia patients. Participants were collected from the Pingyin County Mental Health Hospital and Pingyin County. A t test was used to analyse the differences between schizophrenia patients and healthy subjects, and element content differences in gender. Logistic multivariate regression analysis was applied to analyse the influence of elements to schizophrenia. Repeated measures analysis of variance was used to analyse differences in the elements after 1 and 3 months. Mn, Se, Cd, Pb, Ca, Cu and Fe were lower than those in the normal group, and B, Cr, As, K and Mg were higher than those in the control group. The odd ratios (ORs) of serum As and serum K were 2.624 and 1.035, respectively. The ORs of sera Cr, Mn, Se, Ca and Cu were all below one. After intervention of 'selenium weikang' about 1 and 3 months, the serum As was decreased and the serum selenium and copper were increased. Cr, Mn, Se, Ca and Cu might have beneficial, statistically significant effects on schizophrenia. Elements As and K might be harmful to schizophrenia with statistical significance. After selenium supplementation, the schizophrenia patients improved in some factors, like the appetite and memory, and the As element decreased.
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10.
Efficacy and metabolic effects of lurasidone versus brexpiprazole in schizophrenia: a network meta-analysis.
Ng-Mak, D, Tongbram, V, Ndirangu, K, Rajagopalan, K, Loebel, A
Journal of comparative effectiveness research. 2018;(8):737-748
Abstract
Aim: To assess the relative efficacy and metabolic effects of lurasidone and brexpiprazole in the acute treatment of schizophrenia. Methods: Five lurasidone and three brexpiprazole trials were identified. In the absence of head-to-head trials, a Bayesian network meta-analysis comparing lurasidone and brexpiprazole was performed. Results: Nonstatistically significant differences in efficacy measures were observed between lurasidone and brexpiprazole. Significant differences favoring lurasidone for weight change (-0.69 kg; 95% CrI: -1.22 to -0.15), total cholesterol (-7.60 mg/dl; 95% CrI: -13.94 to -1.22), and low-density lipoprotein (-6.58 mg/dl; 95% CrI: -12.11 to -1.04) were observed, with a trend indicating half the risk of experiencing ≥7% weight gain. Conclusion: This network meta-analysis suggested that lurasidone had similar efficacy and fewer metabolic effects than brexpiprazole in patients with acute schizophrenia.