1Pharmacopsychiatry 2011 Jan 44: 15-20
TitleAssociation study of energy homeostasis genes and antipsychotic-induced weight gain in patients with schizophrenia.
AbstractMarked inter-individual variation has been observed with respect to the risk of weight gain and related metabolic disturbances during antipsychotic treatment, which in part could be explained by heritability. Such adverse effects have been proposed to occur through drug-induced mechanisms involving both the central nervous system and different peripheral tissues.
We genotyped tagSNPs in several genes ( ADIPOQ, PRKAA1, PRKAA2, PRKAB1, PRKAG1, PRKAG2, PRKAG3, FTO and FABP3) that regulate lipid and energy homeostasis for their possible association to antipsychotic-induced weight gain.
In a sample of 160 patients of German origin with schizophrenia who had been monitored with respect to body weight, we found marked association between antipsychotic-related changes in BMI and 6 markers in the adiponectin gene ( ADIPOQ).
These findings support previous observations (in patients' serum) that adiponectin is involved in antipsychotic-mediated metabolic adverse effects.
SCZ Keywordsschizophrenia
2Front Genet 2011 -1 2: 56
TitleAssociation of Allelic Variation in Genes Mediating Aspects of Energy Homeostasis with Weight Gain during Administration of Antipsychotic Drugs (CATIE Study).
AbstractAntipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the clinical antipsychotic trials in intervention effectiveness study, we found that rs2237988 in Potassium Channel Inwardly Rectifying Subfamily J Member 11 (KCNJ11), rs13269119 in Solute carrier family 30 member 8 (SLC30A8), and rs9922047 in fat mass and obesity associated (FTO) were associated with percent weight gain. We also observed the significant interaction of rs11643744 by treatment effect on the weight gain.
SCZ Keywordsschizophrenia
3Clin Psychopharmacol Neurosci 2012 Aug 10: 71-7
TitlePharmacogenetic Aspects of Antipsychotic Drug-induced Weight Gain - A Critical Review.
AbstractTreatment with several antipsychotic drugs can result in weight gain, which may lead to further morbidity such as type 2 diabetes and cardiovascular disease via the development of metabolic syndrome. These important and problematic metabolic consequences of antipsychotic drug treatment probably reflect a pharmacological disruption of the mechanisms involved in control of food intake and body weight. The extent of weight gain following antipsychotic drug treatment shows substantial variability between individuals, due in part to genetic factors. Common functional polymorphisms in many candidate genes implicated in the control of body weight and various aspects of energy and lipid metabolism have been investigated for association with weight gain in subjects receiving antipsychotic drug treatment, and with metabolic pathology in chronic schizophrenia. Perhaps the strongest and most replicated findings are the associations with promoter polymorphisms in the 5-HT2C receptor and leptin genes, although many other possible genetic risk factors, including polymorphisms in the fat mass and obesity associated (FTO) gene and genes for the alpha2A adrenoceptor and melanocortin4 receptor, have been reported. Genome-wide association studies (GWAS) have also addressed antipsychotic-induced weight gain and other indicators of metabolic disturbances. However there is as yet little consistency between these studies or between GWAS and classical candidate gene approaches. Identifying common genetic factors associated with drug-induced weight gain and its metabolic consequences may provide opportunities for personalized medicine in the predictive assessment of metabolic risk as well as indicating underlying physiological mechanisms.
SCZ Keywordsschizophrenia
4Clin Psychopharmacol Neurosci 2012 Dec 10: 185-9
TitleAssociation Study of Fat-mass and Obesity-associated Gene and Body Mass Index in Japanese Patients with Schizophrenia and Healthy Subjects.
AbstractFat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects.
Three hundred fifty one patients with schizophrenia and 342 age- and sex-matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays.
There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects.
Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia.
SCZ Keywordsschizophrenia
5Int. J. Neuropsychopharmacol. 2013 Jul 16: 1421-5
TitleThe obesity risk gene FTO influences body mass in chronic schizophrenia but not initial antipsychotic drug-induced weight gain in first-episode patients.
AbstractGenetic factors contribute to the individual variability in weight gain caused by several antipsychotic drugs. The FTO gene is associated with obesity in the general population; we have investigated whether a common risk polymorphism (rs9939609) in this gene is associated with antipsychotic drug-induced weight gain and obesity. Two samples were studied: (1) 93 first-episode patients receiving antipsychotic drugs for the first time and having body weight monitored for up to 12 months; (2) 187 chronic patients with schizophrenia assessed for measures of obesity and metabolic dysfunction. No association of FTO genotype with weight gain was found in initially drug-naive patients. The chronically treated patients had a significant association of genotype with body mass index (BMI), reflected in associations with waist circumference, waist:hip ratio and the frequency of central obesity. These findings indicate that FTO genotype has a major effect on body weight determined by BMI in chronically treated patients with schizophrenia.
SCZ Keywordsschizophrenia
6J Clin Psychopharmacol 2014 Feb 34: 162-5
TitleThe genetic association of FTO variants with metabolic traits in patients with schizophrenia may be modified by antipsychotics.
SCZ Keywordsschizophrenia
7Pharmacogenomics 2014 Mar 15: 477-85
TitleAssociation of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics.
AbstractThe 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.
SCZ Keywordsschizophrenia
8Behav Brain Funct 2014 -1 10: 35
TitleFat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia.
AbstractObesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear.
Two hundred and fifty drug na´ve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment.
At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p's <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p's < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001).
The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.
SCZ Keywordsschizophrenia
9Neuropsychobiology 2014 -1 69: 59-63
TitleFat mass- and obesity-associated (FTO) gene and antipsychotic-induced weight gain: an association study.
AbstractGenetic variation in the fat mass- and obesity-associated gene (FTO) has been associated with obesity in the general population. In this study we have investigated these variants for association with antipsychotic-induced weight gain (AIWG).
A total of 218 patients with chronic schizophrenia or schizoaffective disorder treated mostly with clozapine or olanzapine for up to 14 weeks were included in the study. We analyzed 4 polymorphisms in intron 1 of the FTO gene (rs1421085, rs8050136, rs9939609, rs9930506) for association with AIWG using ANCOVA.
No statistically significant associations were observed between the single nucleotide polymorphisms and AIWG. However, patients homozygous for the A-allele of rs9939609 gained numerically higher weight than the other genotypic groups (AA: 5.26 ▒ 6.7%; TA: 4.66 ▒ 5.6%; TT: 4.21 ▒ 5.3%).
Our current observations suggest that the FTO gene variants investigated may not play a major role in AIWG.
SCZ Keywordsschizophrenia
10Psychiatry Res 2015 Jul 228: 177-8
TitleEffects of LEP, LEPR, ADIPOQ, MC4R and FTO polymorphisms on dyslipidemia in Korean patients with schizophrenia who are taking clozapine.
SCZ Keywordsschizophrenia
11Schizophr. Res. 2016 Jan 170: 1-17
TitleA systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia.
AbstractMetabolic syndrome (MetS) is a cluster of factors that increases the risk of cardiovascular disease (CVD), one of the leading causes of mortality in patients with schizophrenia. Incidence rates of MetS are significantly higher in patients with schizophrenia compared to the general population. Several factors contribute to this high comorbidity. This systematic review focuses on genetic factors and interrogates data from association studies of genes implicated in the development of MetS in patients with schizophrenia. We aimed to identify variants that potentially contribute to the high comorbidity between these disorders. PubMed, Web of Science and Scopus databases were accessed and a systematic review of published studies was conducted. Several genes showed strong evidence for an association with MetS in patients with schizophrenia, including the fat mass and obesity associated gene (FTO), leptin and leptin receptor genes (LEP, LEPR), methylenetetrahydrofolate reductase (MTHFR) gene and the serotonin receptor 2C gene (HTR2C). Genetic association studies in complex disorders are convoluted by the multifactorial nature of these disorders, further complicating investigations of comorbidity. Recommendations for future studies include assessment of larger samples, inclusion of healthy controls, longitudinal rather than cross-sectional study designs, detailed capturing of data on confounding variables for both disorders and verification of significant findings in other populations. In future, big genomic datasets may allow for the calculation of polygenic risk scores in risk prediction of MetS in patients with schizophrenia. This could ultimately facilitate early, precise, and patient-specific pharmacological and non-pharmacological interventions to minimise CVD associated morbidity and mortality.
SCZ Keywordsschizophrenia