| 1 | Conf Proc IEEE Eng Med Biol Soc 2005 -1 5: 4638-41 |
|---|---|
| PMID | 17281274 |
| Title | Use of ANN and Complexity Measures in Cognitive EEG Discrimination. |
| Abstract | The purpose of this paper is to apply BP ANN to the discrimination of three kinds of subjects (clinical diagnosed 62 schizophrenic patients, 48 depressive patients and 26 normal controls) respectively in resting state with eyes closed and three cognitive tasks, with EEG complexity measures used as feature vectors. EEG activity is recorded from 16 scalp electrodes and recordings are digitized for off-line processing. Features vectors based on LEP-Ziv complexity and classification with ANN are implemented in Matlab6.5. The comparison between the results of classifying in four states is illustrated and discussed. The classification accuracies achieved are 60% and over. The results show that ANN is an effective approach for discrimination of these three kinds of objects both in baseline and some cognitive states. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Pharmacogenomics 2010 Jun 11: 773-80 |
| PMID | 20504252 |
| Title | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. |
| Abstract | Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and LEPtin (LEP). We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Schizophr. Res. 2010 Aug 121: 213-7 |
| PMID | 20591628 |
| Title | Polymorphisms of the LEP- and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin. |
| Abstract | The role of LEPtin in atypical antipsychotic-induced metabolic dysfunction was explored by assessing the anthropometric and metabolic profile and the response to metformin (MET) of clozapine- (CLZ) treated schizophrenia patients according to their single nucleotide polymorphisms (SNPs) in the LEPtin promoter (LEP2548/GA) and LEPtin receptor (LEPR Q223R) genes. Phase 1. Body mass index (BMI), waist circumference, serum glucose, HbA1C, lipids, LEPtin, cortisol, insulin resistance index (HOMA-IR), metabolic syndrome and the frequencies of SNPs were assessed in 56 CLZ-treated patients (78.6% males). Phase 2. Fifty two phase 1 subjects were randomly assigned to MET XR (n=23) (1000 mg/day) or placebo (n=29) for 14 weeks. Changes in anthropometric and biochemical variables were compared between the SNPs. Phase 1. The QQ group displayed the lowest triglyceride levels (p<0.05). No other significant difference was observed. Phase 2. Change in anthropometric variables did not differ between the genotypes in any treatment group. After MET, glucose levels significantly increased in the GG group (p<0.05), whereas the HOMA-IR and the low density cholesterol significantly decreased in the QQ- but not in the (QR+RR) group (p<0.05). No differences were observed after placebo. BW response to CLZ was not related to LEP- and LEPR-SNPs. The GG and (QR+RR) genotypes showed an unexpectedly opposite and blunted response to MET administration respectively. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | J Clin Psychopharmacol 2011 Dec 31: 705-11 |
| PMID | 22020349 |
| Title | Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. |
| Abstract | schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity- and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and LEPtin and LEPtin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan. Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment - Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients. Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | J Clin Psychopharmacol 2011 Dec 31: 705-11 |
| PMID | 22020349 |
| Title | Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. |
| Abstract | schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity- and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and LEPtin and LEPtin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan. Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment - Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients. Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Sleep 2012 Mar 35: 315-23 |
| PMID | 22379237 |
| Title | Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse prefrontal cortex. |
| Abstract | The atypical antipsychotic olanzapine is used effectively for treating symptoms of schizophrenia and bipolar disorder. Unwanted effects of olanzapine include slowing of the electroencephalogram (EEG) during wakefulness and increased circulating levels of LEPtin. The mechanisms underlying the desired and undesired effects of olanzapine are poorly understood. Sleep and wakefulness are modulated by acetylcholine (ACh) in the prefrontal cortex, and LEPtin alters cholinergic transmission. This study tested the hypothesis that olanzapine interacts with LEPtin to regulate ACh release in the prefrontal cortex. Within/between subjects. University of Michigan. Adult male C57BL/6J (B6) mice (n = 33) and B6.V-LEP(ob) (LEPtin-deficient) mice (n = 31). Olanzapine was delivered to the prefrontal cortex by microdialysis. LEPtin-replacement in LEPtin-deficient mice was achieved using subcutaneous micro-osmotic pumps. Olanzapine caused a concentration-dependent increase in ACh release in B6 and LEPtin-deficient mice. Olanzapine was 230-fold more potent in LEPtin-deficient than in B6 mice for increasing ACh release, yet olanzapine caused a 51% greater ACh increase in B6 than in LEPtin-deficient mice. Olanzapine had no effect on recovery time from general anesthesia. Olanzapine increased EEG power in the delta (0.5-4 Hz) range. Thus, olanzapine dissociated the normal coupling between increased cortical ACh release, increased behavioral arousal, and EEG activation. LEPtin replacement significantly enhanced (75%) the olanzapine-induced increase in ACh release. Replacing LEPtin by systemic administration restored the olanzapine-induced enhancement of ACh release in the prefrontal cortex of LEPtin-deficient mouse. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2012 Aug 38: 134-41 |
| PMID | 22426215 |
| Title | Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. |
| Abstract | Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding LEPtin, LEP, and LEPtin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG. A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, LEPtin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate. ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain. Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the LEPtin-melanocortin pathway. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Psychiatr. Genet. 2014 Dec 24: 249-56 |
| PMID | 25304226 |
| Title | Polymorphisms of the leptin and HTR2C genes and clozapine-induced weight change and baseline BMI in patients with chronic schizophrenia. |
| Abstract | We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia. A total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records. Clozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, ?=-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.4±3.1?kg/m), followed by those with the AG (-0.2±3.3?kg/m) and GG (-1.6±3.4?kg/m) genotypes. We also found a significant association between the LEPtin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4±4.3?kg/m), followed by those with the AG (24.1±4.4?kg/m) and GG (28.8±7.3?kg/m) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051]. This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Eur. Psychiatry 2015 Feb 30: 296-302 |
| PMID | 25284335 |
| Title | Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia. |
| Abstract | Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of LEPtin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum LEPtin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of LEPtin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of LEPtin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women LEPtin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men LEPtin vs. weight gain, P=0.026, LEPtin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of LEPtin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Psychiatry Res 2015 Jul 228: 177-8 |
| PMID | 25841316 |
| Title | Effects of LEP, LEPR, ADIPOQ, MC4R and FTO polymorphisms on dyslipidemia in Korean patients with schizophrenia who are taking clozapine. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Schizophr. Res. 2016 Jan 170: 1-17 |
| PMID | 26621002 |
| Title | A systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia. |
| Abstract | Metabolic 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 Keywords | schizophrenia, schizophrenic |