scholarly journals Probiotic supplements reduce antipsychotic-induced metabolic disturbances in drug-naïve first-episode schizophrenia

2021 ◽  
Author(s):  
Dongyu Kang ◽  
Fengyu Zhang ◽  
Ye Yang ◽  
Chenchen Liu ◽  
Jingmei Xiao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Metabolic Disturbance ◽  
First Episode ◽  
Controlled Clinical Trial ◽  
Fasting Insulin ◽  
Metabolic Disturbances ◽  
Drug Naïve ◽  
Level Of Significance ◽  
First Episode Schizophrenia

ABSTRACTProbiotic supplements have demonstrated efficacy in improving metabolic abnormalities and may prevent antipsychotic-induced metabolic disturbance and weight gain. A few studies in rodents have found that antipsychotic-induced metabolic dysfunctions are associated with the altered composition of gut microbiota. Here, we conducted a randomized-controlled clinical trial to determine the effectiveness and safety of probiotic supplements on antipsychotic-induced metabolic disturbance and weight gain. Patients with drug-naïve first-episode schizophrenia were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy and scheduled to evaluate with follow-ups for clinical and metabolic profiles. After a treatment of 12 weeks with addition of probiotics, the increase of mean fasting insulin was significantly lower than olanzapine monotherapy. Insulin resistance increased considerably in the olanzapine plus probiotics, but also significantly lower than olanzapine monotherapy. We noted a difference in the increase in body mass index and body weight between treatments at a nominal level of significance, but it became non-significant after adjusting for appetite increase. Probiotics concurrently used with olanzapine is effective and safe in attenuating antipsychotic-induced elevation of fasting insulin and insulin resistance, but not the weight gain in drug-naïve first-episode schizophrenia. Further study is warranted to assess the longer-term maintenance of efficacy and safety.

scholarly journals Metabolic disturbance in first-episode schizophrenia

2004 ◽  
Vol 184 (S47) ◽  
pp. s76-s79 ◽  
Author(s):  
Jogin H. Thakore
Keyword(s):  
Visceral Obesity ◽  
Stress Axis ◽  
First Episode ◽  
Metabolic Disturbances ◽  
Drug Naïve ◽  
First Episode Schizophrenia ◽  
Medication Status ◽  
Pituitary Adrenal Axis ◽  
Inherent Part

BackgroundSchizophrenia shortens life, e.g. through suicide and obesity-related diseases such as type 2 diabetes mellitus. It is assumed that medications play a major role, but most of the evidence for this comes from studies poorly controlled for variables such as lifestyle and medication status.AimsTo determine whether schizophrenia is associated (independently of medication) with the development of certain metabolic disturbances and whether these might be explained by stress axis dysfunction.MethodLiterature review.ResultsMost studies did not control for confounding factors such as previous usage of medication, lifestyle, age and ethnicity. A few conducted in drug-naive patients with first-episode schizophrenia appear to indicate that these patients have higher than expected rates of visceral obesity and impaired fasting glucose concentrations, which may be related to a subtle disturbance of the hypothalamic–pituitary–adrenal axis.ConclusionsSchizophrenia is independently associated with physical illnesses that have a metabolic signature. Therefore, patients need to have a thorough physical assessment at diagnosis and at regular intervals thereafter. Metabolic disturbances have been found in drug-naïve patients with first-episode illness and may be an inherent part of the illness.

scholarly journals Assessment of Insulin Resistance Among Drug-Naive Patients With First-Episode Schizophrenia in the Context of Hormonal Stress Axis Activation

2017 ◽  
Vol 74 (9) ◽  
pp. 968 ◽  
Author(s):  
Johann Steiner ◽  
Maximus Berger ◽  
Paul C. Guest ◽  
Henrik Dobrowolny ◽  
Sabine Westphal ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stress Axis ◽  
First Episode ◽  
Drug Naïve ◽  
First Episode Schizophrenia

Peripheric Metabolic Abnormalities in Schizophrenia Patients

2017 ◽  
Vol 41 (S1) ◽  
pp. s802-s802
Author(s):  
M. Amorim ◽  
A. Moreira ◽  
A. Marques ◽  
T. Summavielle
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Fasting Blood Glucose ◽  
Disease Onset ◽  
First Episode ◽  
Metabolic Abnormalities ◽  
Metabolic Disturbances ◽  
Antipsychotic Therapy ◽  
Glucose Levels ◽  
Drug Naïve

IntroductionSchizophrenia (SCZ) is frequently associated with metabolic symptoms including dyslipidaemia, hyperinsulinemia, type 2 diabetes and obesity. In fact, SCZ patients have been reported to present higher prevalence of these conditions than general population, commonly associated to second generation antipsychotic therapy. Recent studies, however, have demonstrated that peripheral metabolic disturbances can appear at disease onset or drug-naïve patients.Objectives/aimsTo assess metabolic disturbances in first episode and/or drug-naïve SCZ patients.MethodsWe conducted a literature review through Pubmed search for MeSH: schizophrenia, metabolism, glucose, insulin. Controlled studies on first episode and/or drug-naïve SCZ patients were included.ResultsSeveral studies showed no change in SCZ patients’ fasting blood glucose, while others found increased glucose levels and impaired glucose tolerance in SCZ patients compared to healthy controls in several recent studies. Hyperinsulinemia and insulin resistance have also been identified in antipsychotic-naïve SCZ patients and it has been suggested that early onset patients are more likely to present insulin resistance. In addition, there's evidence of increased circulating levels of chromogranin A, pancreatic polypeptide, prolactin, cortisol, progesterone, thus emphasising that multiple components of the hypothalamic-pituitary-adrenal-gonadal axis may be affected in SCZ. These elevations were associated to normal glycaemia suggesting there may be insulin intolerance during early stages of SCZ, requiring an increased secretion from pancreatic Bcells to maintain normal glucose levels.ConclusionsRecent studies of first onset and/or drug-free schizophrenia patients have shown impaired fasting glucose tolerance, hyperinsulinemia and insulin intolerance, suggesting that metabolic abnormalities may play a role in SCZ onset and pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Unveiling the Metabolic Profile of First-Episode Drug-Naïve Schizophrenia Patients: Baseline Characteristics of a Longitudinal Study Among Han Chinese

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Zhang ◽  
Hui He ◽  
Xia Bai ◽  
Liping Jiang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Medical Conditions ◽  
Metabolic Disturbances ◽  
Cognitive Assessments ◽  
Laboratory Assessment ◽  
History Of ◽  
Drug Naïve ◽  
First Episode Schizophrenia

Objective: Metabolic and other medical conditions are frequently comorbid with schizophrenia. As they might be the side-effects of antipsychotic treatment, studying first-episode drug-naïve schizophrenia (FDSZ) provides a unique opportunity to investigate a direct pathogenic link between metabolic changes and schizophrenia. Here, we presented the methods and baseline unique metabolic profile of FDSZ patients without medical comorbidities unveiling subthreshold indices of metabolic disturbances.Method: Drug-naïve individuals diagnosed with schizophrenia but without any previous medical conditions were invited to participate in the study. Participants were submitted to structured psychiatric and cognitive assessments, laboratory and neuroimaging tests. Subjects will be followed after antipsychotic treatment at 6, 24 and 48 weeks.Results: During an 8-month-period, out of 103 patients presenting with first episode psychosis, 67 subjects (43.3% men, 56.7% women) were enrolled in the study. They had a mean ± SD age of 32.1 ± 8.7 years, with a mean BMI of 21.1 kg/m2 and 11.3 ± 3.6 years of schooling. Less than 1/3 reported a family history of mental illness. Upon laboratory assessment, 10.4%, 7.5%, and 11.9% of patients were identified with hyperhomocysteinemia, hypertriglyceridemia and hyperprolactinemia, respectively, with percentages of women relatively higher than men except for hypertriglyceridemia.Conclusions: First episode schizophrenia patients, especially women, present subclinical metabolic abnormalities, independent of antipsychotic treatment.

scholarly journals Insulin-signaling abnormalities in drug-naïve first-episode schizophrenia: Transduction protein analyses in extracellular vesicles of putative neuronal origin

2019 ◽  
Vol 62 ◽  
pp. 124-129 ◽  
Author(s):  
Dimitrios Kapogiannis ◽  
Henrik Dobrowolny ◽  
Joyce Tran ◽  
Maja Mustapic ◽  
Thomas Frodl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Extracellular Vesicles ◽  
Insulin Signaling ◽  
Total Protein ◽  
Small Sample ◽  
First Episode ◽  
Model Assessment ◽  
Drug Naïve ◽  
Threonine Kinases ◽  
First Episode Schizophrenia

Abstract Background: Metabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of peripheral insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of neuronal insulin signaling in DNFES. Methods: To gain insight into neuronal insulin-signaling in vivo, we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting. Results: Upstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3β, mTOR, p70S6K) revealed lower phosphorylated/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3β (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends. Conclusion: These findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores.

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and antipsychotic-induced metabolic disturbances in first-episode schizophrenia patients

2016 ◽  
Vol 33 (S1) ◽  
pp. S104-S104 ◽  
Author(s):  
B. Misiak ◽  
Ł. Łaczmański ◽  
K. Słoka ◽  
E. Szmida ◽  
R. Ślęzak ◽  
...  
Keyword(s):  
Weight Gain ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Serum Levels ◽  
Mthfr Gene ◽  
First Episode ◽  
Metabolic Disturbances ◽  
Competing Interest ◽  
First Episode Schizophrenia ◽  
677T Allele

IntroductionThere is a scarcity of prospective studies addressing the influence of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on antipsychotic-induced metabolic changes in first-episode schizophrenia (FES) patients.ObjectivesWe aimed at investigating metabolic side effects of second-generation antipsychotics (SGAs) with respect to the MTHFR gene polymorphisms in FES patients.MethodsPolymorphisms in the MTHFR gene (C677T and A1298C) were investigated with respect to changes in body mass index (BMI) and waist circumference (WC) together with serum levels of glucose, lipids, homocysteine, vitamin B12 and folate after 12 weeks of treatment with SGAs in 135 FES patients.ResultsThe 677TT genotype was associated with significantly higher BMI, WC and serum levels of triglycerides, as well as significantly lower folate levels at baseline. Additionally, the 677T allele was associated with significantly lower folate levels at baseline. The 677CC homozygotes had significantly higher increase in BMI and serum levels of triglycerides. The 677TT genotype predicted significantly higher increase in homocysteine levels and significantly higher decrease in folate levels. These associations were also significant in the allelic analysis. Only the patients with the 677T allele had significantly lower folate levels and significantly higher homocysteine levels at the follow-up. The 677T allele was also related to significantly lower increase in WC. The 1298CC homozygotes had significantly higher weight gain in the course of treatment with SGAs.ConclusionsThe MTHFR gene polymorphisms might predict antipsychotic-induced weight gain in FES patients. In addition, the MTHFR C677T polymorphism might be also predictive with respect to other metabolic adversities of SGAs.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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