Metabolic Syndrome In Schizophrenia Patients Research Articles

Pharmacogenetic Factors of Clozapine-Induced Metabolic Syndrome

(1) Introduction: Despite modern therapies, approximately 20-30% of patients with schizophrenia remain resistant to psychopharmacotherapy. Clozapine is the only antipsychotic with proven efficacy for treatment resistance in schizophrenia (TRS). The most common adverse drug reaction (ADR) during clozapine administration are metabolic disturbances, particularly metabolic syndrome (MS). Because MS leads to a twofold increase in mortality from cardiovascular disease and a 1.5-fold increase in mortality from all causes, and clozapine is often the only treatment option for TRS, it is critical to monitor and management metabolic abnormalities. The high interindividual differences in the development of clozapine-induced MS suggest that genetic factors may play an important role. (2) Purpose: The aim of this study was to identify relevant single nucleotide polymorphisms (SNPs) of candidate genes for clozapine-induced MS, because based on these data, a genetic risk panel can be constructed to assess the likelihood of developing clozapine-induced MS in patients with schizophrenia. (3) Materials and Methods: We searched for full-text publications in PubMed, Web of Science, Springer, Google Scholar, and electronic libraries in English and Russian, available from inception to 30 October 2023. Keywords were the following: metabolic disturbances, clozapine, metabolic syndrome, schizophrenia, genes, adverse drug reactions, antipsychotics, pharmacogenetics, genetic biomarker, single nucleotide variant, polymorphism, association, variation, and metabolic syndrome genes. (4) Results: we included 6 naturalistic cross-sectional open-label trials, included patients with schizophrenia, schizoaffective, schizophreniform disorder or psychotic disorder, who were treated with first and second generations antipsychotics, among which there was also clozapine and 1 meta-analysis which reviewed association between HTR2C gene polymorphisms and anti-psychotic-induced MS in schizophrenia patients. According to the results of our scoping review the carriage of SNPs in the studied candidate genes associated with clozapine-induced MS are the following: 1) CYP1A2 gene: genotype AA of rs762551 (NG_008431.2:g.32035C>A); 2) CYP2C19 gene: CYP2C19*2 polymorphism; 3) HTR2C gene: genotype CC of rs518147 (NM_000868.2:c.-697G>C), minor allele C of rs1414334 (NG_012082.3:g.324497C>G), genotype CC of rs518147 (NM_000868.2:c.-697G>C), genotype GG of rs12836771 (NG_012082.3:g.71829A>G); 4) LEP gene: genotypes AG and GG of rs7799039 (NG_044977.1:g.475G>A); 5) LEPR gene: genotypes AG and GG of rs1137101 (NG_015831.2:g.177266A>G). (4) Conclusions: Uncovering the genetic biomarkers of clozapine-induced MS may provide a key to developing a strategy for the personalized prevention and treatment of this ADRs of clozapine in patients with schizophrenia spectrum disorders in real clinical practice.

Comparative predictive efficacy of atherogenic indices on metabolic syndrome in patients with schizophrenia

BackgroundSchizophrenia patients endure high risks of metabolic syndrome and related cardiovascular mortality. Evidence on comparing detective power among atherogenic indices of the metabolic syndrome in schizophrenia patients with antipsychotics treatment is still lacking. MethodWe recruited 128 schizophrenia patients and collected blood samples to determine plasma levels of fasting glucose, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol. Five components of metabolic syndrome were assessed. Atherogenic indices, such as atherogenic index of plasma (AIP), atherogenic coefficient (AC), Castelli's risk index-I (CRI-I) and Castelli's risk index-II (CRI-II), were calculated. The area under the receiver operating characteristics curve (AUC) and regression analysis were adopted to compare the detective power of each atherogenic index for metabolic syndrome. The optimal cutoff points using maximization of Youden's index and the positive likelihood ratios were calculated. Results51 (39.8 %) had metabolic syndrome. AIP (0.2 ± 0.2 vs. 0.6 ± 0.2), AC (2.5 ± 0.9 vs. 3.4 ± 0.9), CRI-I (3.5 ± 0.9 vs. 4.4 ± 0.9,) and CRI-II (2.1 ± 0.7 vs. 2.6 ± 0.7) were higher in the group with metabolic syndrome (all p < 0.001). AIP had the highest AUC (0.845, 95 % CI: 0.770, 0.920). The optimal cut-off point of AIP to predict metabolic syndrome was 0.4 with the corresponding sensitivity 83.7 %, specificity 80.3 %, and positive likelihood ratio 4.2. Regression analysis revealed that only AIP significantly correlated with the metabolic syndrome (p < 0.001). ConclusionAmong atherogenic indices, only AIP has superior discrimination for detecting metabolic syndrome in schizophrenia with antipsychotics treatment.

The Effects of Hopelessness and Some Variables on Metabolic Syndrome in Schizophrenia Patients.

This is a descriptive study conducted to determine the prevalence of Metabolic Syndrome (MetS) in Schizophrenia patients and identify the effects of hopelessness and some variables on MetS. The study was conducted at the Psychiatry Clinic of a university hospital in Turkey between May and August 2020 with 105 schizophrenia patients receiving treatment as inpatients. The data of the study were collected by a Personal Information Form, a Physiological Measurements Form and (BHS). The data were analyzed by using SPSS 25. The mean age of the patients was 35.31 ± 9.07, their mean duration of disease was 11.35 ± 9.07 years, and 60.0% of the patients were using atypical antipsychotics as their latest drug treatment. 42.9% of the patients had MetS, while the mean hopelessness level of those with MetS was 10.84 ± 3.81. It was determined that hopelessness levels and some sociodemographic (age) and clinical variables significantly predicted the MetS status in the schizophrenia patients.

Search for Possible Associations of FTO Gene Polymorphic Variants with Metabolic Syndrome, Obesity and Body Mass Index in Schizophrenia Patients.

PurposeMetabolic syndrome (MetS) is characterized by abdominal obesity, hyperglycaemia, dyslipidaemia and hypertension. FTO gene has been implicated in the pathogenesis of obesity, but the available scientific data concerning their relationship to antipsychotic drug-induced obesity and metabolic syndrome is still incomplete and inconsistent, which indicates that continuing the investigation of this gene’s role is necessary.Patients and MethodsIn the present study, 517 patients with schizophrenia underwent antipsychotic drug treatment, and two groups were identified: patients with MetS and without MetS. Genotyping of 6 SNPs in the FTO gene was performed, and the results analyzed using R-programme.ResultsWe performed a statistical analysis to identify possible associations of the frequencies of genotypes and alleles of the studied polymorphisms with the presence of metabolic syndrome in schizophrenia patients, with the presence of abdominal obesity, and with an increased body mass index. The rs7185735 polymorphism did not meet the Hardy-Weinberg criterion and was excluded. After correcting for differences in age, gender and duration of illnesses, none of the variants was shown to be related to metabolic syndrome or abdominal obesity, but rs9939609, rs1421085, rs3751812 and rs8050136 were associated with body mass index.ConclusionThe present study provides additional support for these SNP’s roles as a pharmacogenetic biomarker that may become useful in the framework of the personalized medicine approach.

Investigation of the role of polymorphic variants FTO gene in schizophrenia patients with metabolic syndrome

IntroductionMedication is primary tactics in schizophrenia treatment. First and second generation antipsychotics (FGA and SGA respectively) affect on core symptoms. Unfortunately, it causes side effects. Metabolic syndrome one of them and includes large number of affections like body mass index changes, lipidemias, hypertension and others.ObjectivesTo study the role of polymorphic variants FTO gene in metabolic syndrome in schizophrenia patients.MethodsWe were investigated 480 patients. Main criteria for inclusion in study was using antipsychotics, verified diagnosis of schizophrenia and metabolic syndrome. Mean age was 42,1±1,4 years. The metabolic syndrome was assessment based on clinical data. Standard phenol-chloroform protocol for DNA isolation was used. Genotyping was carried out on six SNP’s of FTO gene with real-time PCR. Statistical analysis was carried out with R 3.6.2 with basic functions and SNPassoc package.ResultsThe distribution of genotypes for variants rs7185735 and rs9939609 was not in according to Hardy-Weinberg equilibrium (a p-value less than 0.05) and excluded from further analysis. Patients with schizophrenia were divided into two groups: patients with metabolic syndrome and patients without it. We did not identify any statistically significant associations between genotypes and alleles of FTO gene and metabolic syndrome.ConclusionsWe did not find any associations of alleles and genotypes of FTO gene with metabolic syndrome in schizophrenia patients from Siberia region. Metabolic syndrome needs more further studies with larger number of samples and different populations. Conflict of interest. The authors declare no conflict of interests. Supported by Grant of RSF 19-75-10012.

STUDY OF METABOLIC SYNDROME IN SCHIZOPHRENIC PATIENTS TREATED WITH ANTIPSYCHOTICS

Background: There are limited data on the prevalence of metabolic side effects with the anti­psychotic drugs in Nepal. The objective was to study the prevalence of metabolic syndrome in schizophrenia patients treated with antipsychotics drugs. The second objective was to test the relationship of metabolic syndrome with different socio-demographic and clinical variables Methods: This was hospital based cross sectional study conducted in the outpatient’s unit of De­partment of Psychiatry, Manipal Teaching Hospital, Pokhara. Ethical approval was taken from the Institutional Review Committee of Manipal College of Medical Sciences, Pokhara. A total of 60 patients (age between 16 and 65 years) who had fulfilled the diagnostic criteria of schizophrenia according to International Classification of Disease – 10 guidelines and who had taken a single antipsychotic drug for at least 6 months were enrolled after taking informed written consent. Data were collected from April 2020 to July 2020.Patients were diagnosed to have metabolic syndrome according to adapted National Cholesterol Education Program Adult Treatment Panel III criteria by the American Heart Association (NCEP ATP III-A). Data entry and analysis was done using SPSS ver­sion 16.0. The statistical method used were percentage and chi-square test. Results: The prevalence of metabolic syndrome was 30%. There was association of metabolic syn­drome with socioeconomic status. There was no statistical association of metabolic syndrome with gender, residence, type and duration of antipsychotics use. Conclusions: The prevalence of metabolic syndrome was high. Therefore, proper monitoring of metabolic syndrome and adequate treatment of cardio-metabolic risk factors are required for op­timum long-term management.

Prevalence of metabolic syndrome in schizophrenia patients treated with antipsychotic medications.

Background:This study was conducted to determine the prevalence of metabolic syndrome (Mets) in schizophrenic patients in a 6-month period of treatment with antipsychotic medications.Methods:In this study, 60 volunteer schizophrenic patients were included. At the onset and 6 months after treatment with antipsychotic medications, fasting blood sugar (FBS), serum triglyceride (TG), high density lipoprotein (HDL), weight, waist circumference (WC), and blood pressure were determined. We defined Mets according to ATPIII criteria.Results:After a 6-month treatment with antipsychotic drugs, the mean WC, serum TG, HDL, systolic and diastolic blood pressure increased but the changes of WC and HDL were statistically significant (p<0.05). We found that the percentage of patients with high WC, low HDL levels, and Mets increased after treatment which was statistically significant (p<0.05).Conclusion:It is recommended that nutritional and lifestyle changes intervention should be implanted for schizophrenic patients undergoing treatment.

Dietary Behaviors and Metabolic Syndrome in Schizophrenia Patients.

The metabolic syndrome (MS) is highly prevalent in schizophrenia patients, resulting from both pharmacotherapy and their lifestyle. To avoid its development, the analysis of patients’ eating behaviors followed by the necessary nutritional changes should become a routine element of treatment. The aim of this study is to investigate the effect of dietary habits on the course of schizophrenia and MS, cognitive performance, symptom severity, and subjective assessment of eating behaviors in schizophrenia patients. Total of 87 participants (63.2% women) aged 19 to 67 years (M = 41.67; SD = 12.87), of whom 60 met the IDF criteria for MS, completed the PANSS, the verbal fluency test, the Stroop Color-Word Test, and the digit span task, followed by a thorough nutritional interview. There were no significant differences in the dietary behaviors between investigated schizophrenia patients with and without comorbid MS. Interestingly, their eating habits compared quite favorably to those described in the literature. No associations were found between positive eating habits and other tested variables in patients with MS. They were, however, linked to lower PANSS scores in the entire sample. In addition, positive eating habits correlated with better cognitive performance and a more adequate subjective assessment of dietary habits. It would be amiss to assume that schizophrenia patients lack the ability to control their eating behaviors. Nutrition education may foster desirable dietary changes and improve the sense of agency, thus helping to reduce symptom severity and enhancing cognitive performance in this patient population.

Common Side Effects and Metabolic Syndrome due to Clozapine: Relationship with the Clinical Variables and Disability.

Common side effects of clozapine may affect the treatment process negatively. In this study, we aimed to assess the common side effects and the prevalence of metabolic syndrome in schizophrenia patients treated with clozapine, and to study their relationship with clinical variables and disability. One hundred and twenty two patients who met DSM-IV criteria for schizophrenia, and were on clozapine treatment were included in the study. Clinical status was evaluated through a clinical interview and review of the medical records, and physical measures and laboratory tests were recorded. Patients were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders, UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale, World Health Organization (WHO)-Disability Assessment Schedule II, Positive and Negative Syndrome Scale, Global Assessment Scale, Clinical Global Impression Scale. Common side effects of clozapine were hypersalivation, fatigue, sedation and constipation. The relationship between constipation and clozapine dose, and dizziness and norclozapine plasma levels were significant. The prevalence of metabolic syndrome was 50%, and patients with metabolic syndrome had higher means of age and lifetime cigarette consumption. Disability was positively correlated with the severity of psychopathology and the number of side effects, and negatively correlated with the age at onset of illness. Severity of the psychopathology and the number of side effects predicted the severity of the disability. Clozapine was associated with various side effects and half of the patients had metabolic syndrome. Assessment of common side effects due to clozapine is important for reducing disability.

Association between IL-6 and metabolic syndrome in schizophrenia patients treated with second-generation antipsychotics.

ObjectiveSecond-generation antipsychotics (SGAs) have a high risk of causing metabolic syndrome (MetS). There is accumulating evidence supporting the fact that the activation of inflammatory pathway contributes to the development of MetS and further aggravates cognitive impairment. This study aimed to investigate the relationship between interleukin-6 (IL-6), cognitive function, and MetS in schizophrenia patients treated with SGAs.MethodsOne hundred and seventy-four patients with schizophrenia using SGAs were divided into MetS and non-MetS group, based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 138 patients and 29 healthy controls were examined in the plasma IL-6 levels.ResultsThe prevalence of MetS in schizophrenia patients treated with SGAs was 33% in this study. There were no significant differences in cognitive functions (both RBANS total score and subscale score) between MetS and non-Mets patients (P>0.05). Patients with MetS had higher plasma levels of IL-6 compared to non-MetS patients (P=0.019). However, such difference was only found in male patients (male: P=0.012; female: P=0.513). The partial correlational analysis further showed that IL-6 levels were notably negative related to the HDL levels in male schizophrenia patients after age, years of education, body mass index (BMI), age of onset, total disease course, and equal dose of olanzapine were controlled (male: P=0.009; female: P=0.450). In addition, the multiple regression analysis (stepwise model) performed in the male patient subgroup showed that IL-6 (beta =−0.283, t=−2.492, P=0.015) was an independent contributor to the HDL levels. However, the IL-6 was not an independent contributor to the HDL levels in female patients.ConclusionOur findings provide evidence suggesting that the immune-inflammatory effect of IL-6 on SGAs-induced MetS may be in a gender manner.

Insulin Resistance in Schizophrenia.

Schizophrenia and diabetes have been known to be linked disorders for decades. One reason is due to the fact that a major side effect of antipsychotic medication treatment is metabolic syndrome, which increases the risk of the patients developing type 2 diabetes and cardiovascular disorders. However, signs of metabolic syndrome in schizophrenia patients were identified more than 100years ago, even before the development of antipsychotic drugs. This suggests that schizophrenia itself predisposes towards diabetes and, in turn, insulin resistance may be a risk factor for the development of schizophrenia. This review summarizes the findings surrounding this issue and places them into context with regards to increasing our understanding of the aetiology of schizophrenia and in support of biomarker and drug discovery efforts.

Peripheral kynurenine-3-monooxygenase deficiency as a potential risk factor for metabolic syndrome in schizophrenia patients.

Increased predisposition of schizophrenia patients (SP) to development of obesity and insulin resistance suggested common signaling pathway between metabolic syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase (KMO), enzyme catalyzing formation of 3-hydroxykynurenine (3-HK) from kynurenine (Kyn), a tryptophan (Trp) metabolite, might contribute to development of MetS as suggested by non-expression of KMO genes in human fat tissue and elevated serum concentrations of Kyn and its metabolites, kynurenic (KYNA) and anthranilic (ANA) acids, in diabetic patients and Zucker fatty rats (ZFR). Markers of KMO deficiency: decreased 3-HK and elevated Kyn, KYNA and ANA, were observed in brains and spinal fluids of SP, and in brains and serum of experimental animals with genetically- or pharmacologically-induced KMO deficiency. However, elevated concentrations of ANA and decreased 3-HK were reported in serum of SP without concurrent increase of Kyn and KYNA. Present study aimed to re-assess serum Kyn metabolites (HPLC-MS) in a sub-group of SP with elevated KYNA. We found increased Kyn concentrations (by 30%) and Kyn:Trp ratio (by 20%) in serum of SP with elevated KYNA concentrations (by 40%). Obtained results and our previous data suggest that peripheral KMO deficiency might be manifested by, at least, two different patterns: elevated ANA with decreased 3-HK; and elevated KYNA and KYN. The latter pattern was previously described in type 2 diabetes patients and might underline increased predisposition of SP to development of MetS. Assessment of peripheral KMO deficiency might identify SP predisposed to MetS. Attenuation of the consequences of peripheral KMO deficiency might be a new target for prevention/treatment of obesity and diabetes in SP.

Prevalence and predictors of metabolic syndrome in schizophrenia patients from Assam.

Background:Metabolic abnormalities contribute enormously to morbidity and mortality in schizophrenia.Objectives:Our objectives were to determine the (i) prevalence of metabolic syndrome (MS); and (ii) predictors for MS in schizophrenia patients from Assam.Materials and Methods:Seventy-five schizophrenia patients were evaluated for MS. Risk factors were assessed by odds ratios (ORs) with 95% confidence intervals (CIs).Results:Fifty-nine patients (78.7%) had a metabolic abnormality. Twenty-two patients (29.3%, 95% CI: 19.9%–40.8%) fulfilled the criteria for MS. Female gender (adjusted OR = 7.8, 95% CI: 1.7–36.4), smoking (adjusted OR = 7.9, 95% CI: 1.7–35.8), family history of chronic lifestyle disease (adjusted OR = 4.4, 95% CI: 1.3–15.2), and atypical antipsychotic use (adjusted OR = 4.3, 95% CI: 1.1–16.9) significantly predicted MS.Conclusion:Metabolic abnormalities exist widely in schizophrenics from Assam. Females, smokers, and those with family history of chronic diseases and using atypical antipsychotics are at greater risk.

Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics

Objectives: The use of atypical antipsychotics (AAPs) in the treatment of schizophrenia has been relevant because of the high prevalence of metabolic syndrome (MetS). The sterol-regulatory element-binding protein (SREBP) pathway may contribute to the underlying pathophysiology of AAP-induced metabolic adverse effects. We explored the association between the variants of the sterol-regulatory element-binding transcription factor-1 (SREBF1) gene and the SREBP cleavage-activation protein (SCAP) gene with AAP-induced MetS in a genetic case–control study. Methods: Eleven single nucleotide polymorphisms (SNPs) of SREBF1 and five of SCAP were genotyped in a Han Chinese population in Beijing, China: a sample of 722 schizophrenia patients on monotherapy with AAPs (clozapine, olanzapine or risperidone). Metabolic parameters were collected and evaluated for MetS criteria. Results: The rs11654081 T-allele of the SREBF1 gene was significantly associated with an increased risk for MetS after correction (P = 0.019, odds ratio, OR =2.56, 95% confidence interval, CI: 1.4 4–4.54). The rs11654081-TT genotype appeared more frequently in MetS than in non-MetS after correction (P = 0.026, OR =2.37, 95% CI: 1.3 6–4.12). SCAP polymorphisms with drug-induced MetS were negative in this study. Conclusions: The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS.

Metabolic syndrome in schizophrenia patients associated with poor premorbid school performance in early adolescence

More than 40% of patients with schizophrenia have an additional diagnosis of the metabolic syndrome (MS), possibly related to poor cognition. This study investigated premorbid and current cognitive functioning in schizophrenia and co-occurrence of MS. A total of 104 participants with schizophrenia with MS and 142 without MS were included. Neuropsychological assessment was carried out using the Wechsler Adult Intelligence Scale-III, Word Learning Task, and Continuous Performance Test-HQ. Premorbid functioning was assessed retrospectively with the Premorbid Adjustment Scale. anovas were used to examine differences between participants with and without MS. Subjects with and without MS did not differ concerning current, lifetime and amount substance use, duration/severity of illness, parental socioeconomic status (SES), and type/amount of antipsychotic medication. We found that poor school performance between the ages 12 and 16 is associated with MS in schizophrenia. Educational level and current cognitive functioning in participants with MS deviate as compared to those without MS. Subjects with MS had impaired premorbid cognition in adolescence and lower educational achievement, irrespective of parental SES. This suggests poor premorbid cognitive functioning is a risk factor for metabolic complications later in life. Future studies are needed to examine whether cognitive interventions have beneficial effects on general health in schizophrenia.

HTR2C polymorphisms, olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: A meta-analysis

Objective. To conduct meta-analyses of all published association studies on the HTR2C -759C/T (rs3813829) polymorphism and olanzapine-induced weight gain in schizophrenia patients and on the HTR2C -759C/T, -697G/C (rs518147) and rs1414334:C> G polymorphisms and olanzapine/clozapine/risperidone-induced metabolic syndrome in schizophrenia patients. Methods. Eligible studies were identified by searching PubMed and Web of Science databases. Meta-analyses were performed using Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). Results. Our meta-analyses revealed both a significant positive association between the rs1414334 C allele and olanzapine/clozapine/risperidone-induced metabolic syndrome and a marginally significant positive association between the -697C allele and the induced metabolic syndrome in schizophrenia patients, but no significant association between the -759C/T polymorphism and the induced metabolic syndrome in schizophrenia patients. Our analysis further revealed a pronounced trend toward a significant negative association between the -759T allele and high olanzapine-induced weight gain and a trend toward a significant positive association between the -759C allele and high olanzapine-induced weight gain in Caucasian schizophrenia patients. Conclusions. Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.

Association of FTO , LEPR and MTHFR Gene Polymorphisms with Metabolic Syndrome in Schizophrenia Patients Receiving Antipsychotics

The occurrence of metabolic syndrome (MS) in schizophrenia patients receiving long-term antipsychotics (APs) contributes to their high mortality rate. We aimed to determine whether genetic polymorphisms of identified candidate genes are associated with MS in our study population. We recruited 206 schizophrenia patients receiving AP treatment for at least a year. Cross-sectional measurements of weight, height, blood pressure, waist and hip circumference, and other lipid profiles were recorded. Patient DNA was genotyped for 16 candidate gene polymorphisms. Of these patients, 59.7% were found to have MS while 40.3% did not. All metabolic parameters were significantly different between the two groups. Only three of the 16 polymorphisms studied showed significant association with MS; rs9939609 of the FTO gene confers risk for MS (odds ratio [OR]: 1.73, 95% CI: 1.07-2.78, p = 0.026), while rs1137101 of the LEPR gene (OR: 0.47, 95% CI: 0.28-0.80, p = 0.005) and rs1801133 of the MTHFR gene (OR: 0.59, 95% CI: 0.35-0.99, p = 0.049) are protective against MS. Polymorphisms of the FTO, LEPR and MTHFR genes may play a role in MS in Malaysian schizophrenia patients receiving long-term treatment with APs.

Detection of Metabolic Syndrome in Schizophrenia and Implications for Antipsychotic Therapy

In general, the presence of metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the USA. Patients with schizophrenia have a three times greater risk of death than the general population, with cardiovascular disease being the most common cause of this mortality. Use of atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular risk. While several different clinical guidelines currently exist to monitor the metabolic consequences of AAP use, implementation is lacking. Because of under-monitoring of side effects and the lack of alternative treatment choices in schizophrenia, research has focused on identification of various biomarkers and pharmacogenomic targets to focus on the patients at greatest risk of metabolic syndrome, thus aiming to increase the efficacy and minimize the side effects of AAPs. This has led to several different lines of research. This review focuses on summarizing the differing metabolic syndrome criteria, monitoring guidelines for use of AAPs, and the role of folic acid as it relates to metabolic syndrome within the schizophrenia population. It concentrates not only on the pharmacogenomics of folic acid metabolism but also on its epigenetic interaction with the environment. From this work, genetic variation within both the methylenetetrahydrofolate reductase (MTHFR) gene and the catechol-O-methyltransferase (COMT) gene has been associated with an increased risk of metabolic syndrome in schizophrenia patients treated with AAPs. Furthermore, work on the combination of folate pharmacogenetics and epigenetics has uncovered relationships between methylation, schizophrenia disease, treatment type, and metabolic syndrome. Despite several areas of biomarker research into schizophrenia-related metabolic syndrome, translation into the clinical setting is still lacking, and further studies are needed to bridge this gap. In the future, folate supplementation may prove to be an easy and effective clinical tool for prevention and/or treatment of metabolic syndrome associated with AAP treatment, but clearly more research needs to be done in this area.

Metabolic syndrome and antipsychotic monotherapy treatment among schizophrenia patients in Malaysia

ObjectiveThe objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia. MethodA cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference. ResultsIn the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA. ConclusionThe prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems.

Comparing Tolerability of Olanzapine in Schizophrenia and Affective Disorders

Background: Olanzapine is prescribed for a number of psychiatric disorders, including schizophrenia, bipolar mania, and unipolar and bipolar depression. Olanzapine treatment is associated with tolerability issues such as metabolic adverse effects (e.g. weight gain, increase in blood glucose, triglycerides and total cholesterol levels), extrapyramidal symptoms [EPS] (e.g. parkinsonism, akathisia, tardive dyskinesia) and sedative adverse effects. Metabolic issues lead to some long-term consequences, which include cardiovascular diseases (CVD) and type 2 diabetes mellitus, and these complications cause high rates of mortality and morbidity among patients with severe mental illnesses. The expanded indications of olanzapine in psychiatry suggest a need to investigate whether there is a difference in the incidence and severity of adverse effects related to category diagnosis. Are the adverse effects expressed differently according to phenotype? Unfortunately, there are no reported studies that investigated these differences in adverse effects associated with olanzapine treatment in psychiatric patients with different phenotypes. Objective: The aim of the present meta-analysis is to separately examine olanzapine-induced cardiometabolic adverse effects and EPS in patients with schizophrenia and affective disorders. Data Sources: A search of computerized literature databases PsycINFO (1967–2010), PubMed (MEDLINE), EMBASE (1980–2010) and the clinicaltrials.gov website for randomized clinical trials was conducted. A manual search of reference lists of published review articles was carried out to gather further data. Study Selection: Randomized controlled trials were included in our study if (i) they assessed olanzapine adverse effects (metabolic or extrapyramidal) in adult patients with schizophrenia or affective disorders; and (ii) they administered oral olanzapine as monotherapy during study. Data Extraction: Two reviewers independently screened abstracts for choosing articles and one reviewer extracted relevant data on the basis of predetermined exclusion and inclusion criteria. It should be mentioned that for the affective disorders group we could only find articles related to bipolar disorder. Data Synthesis: Thirty-three studies (4831 patients) that address olanzapine monotherapy treatment of adults with schizophrenia or bipolar disorder were included in the analysis. The primary outcomes were metabolic adverse effects (changes in weight, blood glucose, low-density lipoprotein, total cholesterol and triglyceride levels). The secondary outcomes of our study were assessing the incidence of some EPS (parkinsonism, akathisia and use of antiparkinson medication). The tolerability outcomes were calculated separately for the schizophrenia and bipolar disorder groups and were combined in a meta-analysis. Tolerability outcomes show that olanzapine contributes to weight gain and elevates blood triglycerides, glucose and total cholesterol levels in both schizophrenia and bipolar disorder patients. However, olanzapine treatment produced significantly more weight gain in schizophrenia patients than in bipolar disorder patients. In addition, increases in blood glucose, total cholesterol and triglyceride levels were higher in the schizophrenia group compared with the bipolar disorder group, even though these differences were not statistically significant. Based on our results, the incidence of parkinsonism was significantly higher in the schizophrenia group than in the bipolar disorder group. Subgroup analysis and logistic regression were used to assess the influence of treatment duration, dose, industry sponsorship, age and sex ratio on tolerability outcome. Conclusions: Our results suggest that schizophrenia patients may be more vulnerable to olanzapine-induced weight gain. The findings may be explained by considering the fact that in addition to genetic disposition for metabolic syndrome in schizophrenia patients, they have an especially high incidence of lifestyle risk factors for CVD, such as poor diet, lack of exercise, stress and smoking. It might be that an antipsychotic induces severity of adverse effect according to the phenotype.