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Hongrong Luo, Xun Hu,
Xiang Liu,
Xiaohong Ma,
Wanjun Guo,
Changjian Qiu,
Yingcheng Wang,
Qiang Wang,
Xiaowei Zhang,
Wei Zhang,
Gregory Hannum,
Kang Zhang,
Xiehe Liu,
Tao Li
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ABSTRACT: The present study evaluated the accumulated changes in hair cortisol levels of patients with posttraumatic stress disorder (PTSD) attributed to the 2008 Wenchuan earthquake in China.
Sixty-four female adolescents from two townships who experienced the earthquake were recruited 7 months after the disaster, including 32 subjects with PTSD (PTSD group) and 32 subjects without PTSD (non-PTSD group). Twenty matched adolescents were recruited from an area that was not affected significantly by the earthquake as the control group. Hair cortisol concentrations were measured by the electrochemiluminescence immunoassay in each 3-cm segment of hair sample from the scalp.
There was no significant difference at the baseline hair cortisol level in the three groups before the traumatic event (p > .6). Hair cortisol levels changed over time and differed among groups (p = .0042). The hair cortisol levels among the PTSD and non-PTSD subjects were elevated, suggesting increasing levels in response to stress. However, these two groups differed in their response. The non-PTSD subjects showed a significantly higher cortisol level than the PTSD group between month 2 and month 4 (p = .0137) and also between month 5 and month 7 (p = .0438) after the traumatic event.
This study revealed a blunted response curve to the disaster among PTSD subjects compared with subjects without PTSD. These findings suggest that hair cortisol level could be used to assess the integrated hypothalamic-pituitary-adrenal activity over a period of months after traumatic events and be used to serve as a biomarker in patients with PTSD.
Biological psychiatry 02/2012; 72(1):65-9. · 8.93 Impact Factor
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PLoS ONE 01/2012; 7(1). · 4.09 Impact Factor
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X Ma,
W Deng,
X Liu,
M Li,
Z Chen,
Z He,
Y Wang,
Q Wang, X Hu,
D A Collier,
T Li
[show abstract]
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ABSTRACT: Few genome-wide association studies (GWAS) of schizophrenia have included Chinese populations, and verification of positive genetic findings from other ethnic groups is rare in Chinese groups. We used fluid intelligence as the quantitative trait reflecting schizophrenia dysfunction in Chinese populations, and determined the impact of genetic variation on fluid intelligence phenotypic patterns to identify genetic influences in schizophrenia. The study sample comprised 98 patients with schizophrenia and 60 healthy controls. The general fluid intelligence of participants was assessed with Cattell's Culture-Free Intelligence Test (CCFIT). Subjects were genotyped using the Illumina HumanHap 660 beadchip. We identified the methionine sulfoxide reductase A (MSRA) gene on chromosome 8 as having an association with fluid intelligence. However, only CCFIT subtest 1 (series score) demonstrated a significant result for the interaction term using the criteria of the quantitative trait (QT) analysis of 10(-5) for at least three SNPs. There were 15 haplotype blocks of MSRA gene SNPs identified using Haploview 4.2 with solid spine D' > 0.80. The strongest QT interaction was noted in Block 3, with the most common haplotypes being AAACAGCAG and CGCAGAAGA. In conclusion, we report data from a GWAS with quantitative traits design from Chinese first-episode schizophrenia patients and matched controls. Although the gene identified requires confirmation in an independent sample, the MSRA gene located on chromosome 8 was found to be associated with the phenotype of schizophrenia.
Genes Brain and Behavior 06/2011; 10(7):734-9. · 3.48 Impact Factor
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Wan-Jun Guo,
Qiang Wang,
Gongga Lanzi,
Ouzhu Luobu,
Xiao-Hong Ma,
Ying-Cheng Wang,
Puo Zhen,
Geng Wei,
Wei Deng,
Basang Zhuoma,
Xiao-Ming Shi,
Xie-He Liu,
Yue-Jing Wu,
Yan Xu,
David A Collier,
David Ball, Xun Hu,
Tao Li
[show abstract]
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ABSTRACT: Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case-control study in a Tibetan population noted that the positive association between c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for 1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2 1/ 2, ADH1B1/2 and CYP2E1 c1/c2 and sex were analyzed in AUD cases and normal controls separately. The subjects with 2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2 1 and ADH1B 1 and with CYP2E1 c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.
Neuroscience Letters 03/2011; 495(1):22-5. · 2.11 Impact Factor
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ABSTRACT: In Chinese adolescents exposed to the Wenchuan earthquake, we used the Children's Revised Impact of Event Scale (CRIES) as the screening tool, and Post-traumatic Cognitions Inventory (PTCI) and the Social Support Rating Scale (SSRS) were used to assess the cognitive status and their social supports, to evaluate the prevalence and the predictors variables of post-traumatic stress disorder (PTSD) after the Wenchuan earthquake in China, which occurred on 12 May 2008. Subjects with a CRIES score greater than 30 were interviewed and assessed using the DSM-IV criteria for PTSD diagnosis by a trained psychiatrist with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Lifetime version (Kiddie-SADS-L). We found the overall prevalence of PTSD was 2.5% in 3208 adolescents from the surrounding areas of the epicentre 6months after the earthquake. Risk factors for post-traumatic stress symptoms are as follows: being female, being buried/injured during the earthquake, having parents who were severely injured, having classmate(s) who died, having a house destroyed, and witnessing someone buried/wounded/dying during the earthquake. Individuals with better social support had significantly lower scores on the CRIES. There were significant differences in cognitive style between individuals at low risk for PTSD (CRIES<30) and those at high risk for PTSD (CRIES≥30). Post-traumatic cognition emerged as an important factor that was associated with PTSD reactions in children. Social support can lessen the impact of a natural disaster by affecting post-traumatic cognition.
Psychiatry Research 02/2011; 189(3):385-91. · 2.52 Impact Factor
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Xiaohong Ma,
Caixia Li,
Huaqing Meng,
Lian Du,
Qiang Wang,
Yingcheng Wang,
Wei Deng,
Xiehe Liu, Xun Hu,
Robin M Murray,
David A Collier,
Tao Li
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ABSTRACT: Rates of cigarette smoking in individuals with schizophrenia well exceed those in the general population and in other mental illnesses. In the present study, we examined the relationship between smoking status, clinical characteristics and cognitive functions in 230 male Chinese schizophrenia patients. They were interviewed by experienced psychiatrists using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (SCID-P). Clinical symptoms were rated using the Positive and Negative Syndrome Scale (PANSS), and the Revised Tolerance Questionnaire (RTQ) used to evaluate the severity of nicotine dependence. Nine neuropsychological tests were used to assess cognitive function. We found that never-smokers had a younger age at examination and earlier onset and longer duration of illness than smokers and ex-smokers. The age of initiation of regular smoking in patients was significantly earlier than their age of illness onset. We found that longer duration of illness was significantly associated with higher RTQ scores. Ex-smokers with schizophrenia performed significantly more poorly on the Stroop C test than smokers. The results imply that smoking may affect cognitive function and illness onset time in patients with schizophrenia.
Psychiatry Research 08/2010; 178(3):461-6. · 2.52 Impact Factor
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ABSTRACT: Schizophrenia patients have a wide range of cognitive deficits. To explore the structure of these deficits and index their psychometric properties in order to define the major separable factors, exploratory factor analysis (EFA) was performed on a series of neuropsychological test results in a sample of Han Chinese first-episode schizophrenia patients, their relatives and controls without mental illness.
The factors derived from the composite sample were tested with confirmatory factor analysis (CFA) in each of the subsamples. The heritability of each factor was estimated by using the mixed linear model in order to determine whether the common factor scores describe the familiarity of the data.
A six-factor model of general mental activity, sort and shift, attention and anti-interference, logical memory, reasoning and problem-solving/executive function, and visual reproduction were extracted and confirmed on EFA and CFA. There was a hierarchy in cognitive performance deficits in relatives depending on their relatedness to probands. Patients performed more poorly than siblings/offspring in general mental activity, sort and shift, attention and anti-interference, logical memory, planning and problem-solving, but not in visual reproduction. The logical memory domain was found to be significantly heritable (h(2)=0.34), and reasoning and problem-solving had a marginal heritability of around 0.19.
Generalized cognitive deficit accounts for the majority of the overall variance of cognitive deficits in schizophrenia. Estimates of heritability were modest. The present results also support the hypothesis that neurocognitive deficits of schizophrenia are familial and could serve as endophenotypes, especially logical memory, which is the most heritable.
Australian and New Zealand Journal of Psychiatry 02/2010; 44(2):109-19. · 2.93 Impact Factor
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Wanjun Guo,
Qiang Wang,
Gongga Lanzi,
Ouzhu Luobu,
Xiaohong Ma,
Yingcheng Wang,
Puo Zhen,
Yulin Ji,
Geng Wei,
Zheng Wang, [......],
Xiaoming Shi,
Chengyin Yan,
Chan He,
Xiehe Liu,
Yuejing Wu,
Hongrong Luo,
David A Collier,
David Ball,
Tao Li, Xun Hu
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ABSTRACT: Associations between alcohol use disorders and polymorphisms of genes influencing ethanol metabolism have been widely reported, but gene-gene and gene-sex interaction studies have rarely been examined. Using a set of samples collected during an epidemiological study of alcohol use disorders AUDs in a Tibetan population in China, we performed a case-control study to investigate the relationship between the functional polymorphisms of genes influencing ethanol metabolism and AUDs. The sample included 383 individuals with an AUDIT score >or=10 and 350 control subjects with the AUDIT score <or=5. All participants were genotyped for ALDH2*1/*2, ADH1B*1/*2, and CYP2E1*c1/c2*. Data were analyzed employing an integrated strategy using MDR, SPSS, and UNPHASED software. The MDR analysis showed that the four-factor model including ADH1B*1/*2, ALDH2*1/*2, and CYP2E1*c1/*c2 polymorphisms, and sex was the most accurate model associated with AUDs with the highest OR 3.299. It also revealed that CYP2E1 *c1/*c2 polymorphism interacted significantly with sex. Independent analysis confirmed that both ADH2*2 and ALDH2*2 allele were significantly associated with AUDs (OR: 0.441 for ADH2*2 and 0.137 for ALDH2*2). CYP2E1*c2 was positively associated with AUDs only in males homozygotic for ALDH2*1 and ADH1B*1 (OR: 2.585). Cumulative association analysis showed the number of protective alleles and genotypes were negatively associated with AUDs. In conclusion, ALDH2*2 and ADH1B*2 alleles were not only independently associated with AUDs but also demonstrated cumulative dosage effects. However the positive association between CYP2E1*c2 allele and AUDs might only exist in males homozygotic for ALDH2*1 and ADH1B*1.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2009; 153B(2):561-9. · 3.70 Impact Factor
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ABSTRACT: The aim of this study was to investigate the relationship between polymorphisms in the PRODH and COMT genes and selected neurocognitive functions. Six SNPs in PRODH and two SNPs in COMT were genotyped in 167 first-episode schizophrenic families who had been assessed by a set of 14 neuropsychological tests. Neuropsychological measures were selected as quantitative traits for association analysis. The haplotype of SNPs PRODH 1945T/C and PRODH 1852G/A was associated with impaired performance on the Tower of Hanoi, a problem-solving task mainly reflecting planning capacity. There was no significant evidence for association with any other neuropsychological traits for other SNPs or haplotypes of paired SNPs in the two genes. This study takes previous findings of association between PRODH and schizophrenia further by associating variation within the gene with performance on a neurocognitive trait characteristic of the illness. It fails to confirm previous reports of an association between COMT and cognitive function.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2008; 147B(5):654-7. · 3.70 Impact Factor
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Xiaohong Ma,
Jinhua Sun,
Jing Yao,
Qiang Wang, Xun Hu,
Wei Deng,
Xueli Sun,
Xiehe Liu,
Robin M Murray,
David A Collier,
Tao Li
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ABSTRACT: Previous studies have suggested that catechol-O-methyltransferase (COMT), proline dehydrogenase (PRODH), and brain-derived neurotrophic factor (BDNF) genes are possible susceptibility genes for schizophrenia. We hypothesized that these genes are also associated with schizotypal traits, which are heritable and related to schizophrenia. We genotyped five single nucleotide polymorphism (SNPs) from the COMT, PRODH and BDNF genes, and performed a series of association analyses between alleles, genotypes or haplotypes, and quantitative schizotypal trait scores derived from the Schizotypal Personality Questionnaire (SPQ), in 465 Chinese healthy subjects. We found that 'years of education' was a major influence on seven out of nine schizotypal components, three schizotypal factors and the total SPQ scores. Molecular genetic analysis of COMT, PRODH and BDNF genes showed no significant effects of any variants on schizotypal components or factors of SPQ after correction for multiple testing, although there were weak association between COMT Val158Met (rs4680G/A) and the odd speech subscale (allele-wise, P=0.04; genotype-wise, P=0.049), between COMT Val158Met (rs4680G/A) and the suspiciousness subscale (genotype-wise, P=0.024), and between BDNF Val66Met and the Factor 2 interpersonal measure (genotype-wise, P=0.027) before correction. Furthermore, we found SNP Val158Met (rs4680) of the COMT gene significantly influenced the scores of some of schizotypal traits including total SPQ score, the disorganization factor and the constricted affect subscale in male subjects only. However, the effect was in the opposite direction of an earlier association with the SPQ reported by Avramopoulos et al. [Avramopoulos, D., Stefanis, N.C., Hantoumi, I., Smyrnis, N., Evdokimidis, I., Stefanis, C.N., 2002. Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Molecular Psychiatry 7, 706-711]. We conclude that SNP Val158Met (rs4680) in the COMT gene may be associated with some schizotypal traits in male subjects, but our results are not conclusive.
Psychiatry Research 10/2007; 153(1):7-15. · 2.52 Impact Factor
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Psychiatric Genetics 09/2007; 17(4):247-8. · 2.58 Impact Factor
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Elena Cellini,
Benedetta Nacmias,
Maria Brecelj-Anderluh,
Ana Badía-Casanovas,
Laura Bellodi,
Claudette Boni,
Daniela Di Bella,
Xavier Estivill,
Fernando Fernandez-Aranda,
Christine Foulon, [......],
Radovan Komel,
Carlo Maria Rotella,
Marta Ribases,
Valdo Ricca,
Lucia Romo,
Martina Tomori,
Janet Treasure,
Gudrun Wagner,
David A Collier,
Sandro Sorbi
Psychiatric Genetics 05/2006; 16(2):51-2. · 2.58 Impact Factor
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Marta Ribasés,
Mònica Gratacòs,
Fernando Fernández-Aranda,
Laura Bellodi,
Claudette Boni,
Marija Anderluh,
Maria Cristina Cavallini,
Elena Cellini,
Daniela Di Bella,
Stefano Erzegovesi, [......],
Radovan Komel,
Benedetta Nacmias,
Helmut Remschmidt,
Valdo Ricca,
Sandro Sorbi,
Martina Tomori,
Gudrun Wagner,
Janet Treasure,
David A Collier,
Xavier Estivill
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[hide abstract]
ABSTRACT: Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.
European Journal of HumanGenetics 05/2005; 13(4):428-34. · 4.40 Impact Factor
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ABSTRACT: Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. This study employs an association approach to examine the genetic underpinning of methamphetamine (MAMP) use and MAMP-induced psychosis.
A total of 416 MAMP abusers from a hospital and a detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis.
None of the three markers we studied were associated with predisposition to psychosis among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the seven-repeat allele of DRD4 than normal controls.
Chance fluctuations in the frequency of rare alleles and ascertainment differences in the case and control samples cannot be ruled out. Therefore, further studies of the seven-repeat allele in MAMP abusers and controls should be performed before an association can be established.
Psychiatric Genetics 01/2005; 14(4):223-6. · 2.58 Impact Factor
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Marta Ribas|[eacute]|s,
M|[ograve]|nica Gratac|[ograve]|s,
Fernando Fern|[aacute]|ndez-Aranda,
Laura Bellodi,
Claudette Boni,
Marija Anderluh,
Maria Cristina Cavallini,
Elena Cellini,
Daniela Di Bella,
Stefano Erzegovesi, [......],
Radovan Komel,
Benedetta Nacmias,
Helmut Remschmidt,
Valdo Ricca,
Sandro Sorbi,
Martina Tomori,
Gudrun Wagner,
Janet Treasure,
David A Collier,
Xavier Estivill
[show abstract]
[hide abstract]
ABSTRACT: Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case–control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.Keywords: eating disorders, BDNF, anorexia
European Journal of HumanGenetics 12/2004; 13(4):428-434. · 4.40 Impact Factor
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ABSTRACT: To investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine.
One hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA).
No association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03).
The results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 11/2004; 21(5):479-81.
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ABSTRACT: We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2004; 129B(1):120-4. · 3.70 Impact Factor
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Tao Li,
Xiaohong Ma,
Pak C Sham,
Xueli Sun, Xun Hu,
Qiang Wang,
Huaqing Meng,
Wei Deng,
Xiehe Liu,
Robin M Murray,
David A Collier
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ABSTRACT: Haploinsufficiency for or mutation in at least one gene from the velocardiofacial syndrome (VCFS) region at chromosome 22q11 is implicated in psychosis. Linkage disequilibrium mapping of the region in patients identified a segment containing two genes, proline dehydrogenase (PRODH) and DGCR6, as candidates [Liu et al., 2002a] and by analysis of additional polymorphisms the PRODH gene was associated with schizophrenia in adult and early onset patients. In the present study we provide additional evidence in support of genetic association between PRODH and schizophrenia in a Chinese population. We analyzed the PRODH gene in a samples of schizophrenic patients and their families from Sichuan, SW China consisting of 528 family trios and sibling pairs. We genotyped six SNPs, PRODH*1195C-->T, PRODH*1482C-->T, PRODH*1483A-->G, PRODH*1766A-->G, PRODH*1852G-->A PRODH*1945T-->C, two of which (PRODH*1483A-->G and PRODH*1852G-->A) have not been previously reported. We found association with schizophrenia for two haplotypes consisting of PRODH*1945T-->C and PRODH*1852G-->A (Global P = 0.006), and PRODH*1852G-->A and PRODH*1766A-->G (Global P = 0.01) which include one of the newly identified markers. After six-fold Bonferroni correction for multiple testing the PRODH*1945T-C/PRODH*1852G-A haplotypes remained significant. This is a sub-haplotype of the PRODH haplotype previously associated with schizophrenia and it also maps to the 3' region of the gene, indicating that this is the region most likely to contain the underlying risk alleles. Overall this finding supports a role for the PRODH locus in schizophrenia.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2004; 129B(1):13-5. · 3.70 Impact Factor
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Marta Ribasés,
Mònica Gratacòs,
Fernando Fernández-Aranda,
Laura Bellodi,
Claudette Boni,
Marija Anderluh,
Maria Cristina Cavallini,
Elena Cellini,
Daniela Di Bella,
Stefano Erzegovesi, [......],
Amélie Kipman,
Radovan Komel,
Benedetta Nacmias,
Helmut Remschmidt,
Valdo Ricca,
Sandro Sorbi,
Gudrun Wagner,
Janet Treasure,
David A Collier,
Xavier Estivill
[show abstract]
[hide abstract]
ABSTRACT: Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.
Human Molecular Genetics 07/2004; 13(12):1205-12. · 7.64 Impact Factor
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ABSTRACT: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterised by multiple motor and phonic tics, which wax and wane. Recently, evidence has accumulated supporting the role of autoimmune mechanisms in the aetiology of GTS, suggesting that it is within the paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) spectrum of childhood neurobehavioural disorders. An immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) has been suggested in this syndrome. In this study, we investigate the association of three microsatellite polymorphisms (MOGa, MOGb, MOGc) in the gene for MOG with GTS in 197 family trios collected from southwest China. Linkage disequilibrium between these three markers was observed with the strongest between MOGa and MOGc (D' = 0.541, P = 0.000). We did not find overall significant evidence for distorted transmission of any of these three markers of MOG gene in GTS, although we observed a weak preferential transmission of the 148 bp allele of MOGc (chi(2) = 4.000, P = 0.046) which did not survive correction for multiple testing. Our results suggest that there is no association between the MOG gene polymorphisms we tested and GTS.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2004; 124B(1):76-80. · 3.70 Impact Factor
