BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the rela...BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.展开更多
Brain-derived neurotrophic factor is the most prevalent member of the nerve growth factor family.Since its discovery in 1978,this enigmatic molecule has spawned more than 27,000 publications,most of which are focused ...Brain-derived neurotrophic factor is the most prevalent member of the nerve growth factor family.Since its discovery in 1978,this enigmatic molecule has spawned more than 27,000 publications,most of which are focused on neurological disorders.Brain-derived neurotrophic factor is indispensable during embryogenesis and postnatally for the normal development and function of both the central and peripheral nervous systems.It is becoming increasingly clear,however,that brain-derived neurotrophic factor likewise plays crucial roles in a variety of other biological functions independently of sympathetic or parasympathetic involvement.Brain-derived neurotrophic factor is also increasingly recognized as a sophisticated environmental sensor and master coordinator of whole organismal physiology.To that point,we recently found that a common nonsynonymous(Val66→Met)single nucleotide polymorphism in the brain-derived neurotrophic factor gene(rs6265)not only substantially alters basal cardiac transcriptomics in mice but subtly influences heart gene expression and function differentially in males and females.In addition to a short description of recent results from associative neuropsychiatric studies,this review provides an eclectic assortment of research reports that support a modulatory role for rs6265 including and beyond the central nervous system.展开更多
The val66met polymorphism of the bdnf gene, which is associated with compromised brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and impaired learning, may increase one’s susceptibil...The val66met polymorphism of the bdnf gene, which is associated with compromised brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and impaired learning, may increase one’s susceptibility to stress- and anxiety-related disorders. Indeed, previous work has reported greater anxiety-related behaviors and impairments of fear conditioning and extinction in individuals who carry the met allele that results from this polymorphism. Nevertheless, findings in this area of research have been equivocal. Thus, we examined the influence of the val66met polymorphism on fear conditioning, extinction, and extinction memory testing. One hundred and twenty healthy participants completed differential fear conditioning in a fear-potentiated startle paradigm, followed by extinction and extinction memory testing 24 and 48 hr later, respectively. Participants were genotyped for the val66met polymorphism and divided into met allele carriers and non-carriers. Results revealed that, although both met-carriers and non-carriers developed conditioned fear, met-carriers exhibited significantly weaker fear acquisition than non-carriers. This difference persisted throughout extinction and extinction memory testing and, during these last two days of testing, was primarily evident in females. These results are consistent with previous work demonstrating that this polymorphism is associated with impaired amygdala-dependent fear learning and extend such findings by demonstrating that females may be more sensitive to such effects.展开更多
<strong>Background:</strong> In the treatment of morbid obesity bariatric surgery has become the method of choice. Dopamine is the primary modulator of the brain’s reward system and plays an essential rol...<strong>Background:</strong> In the treatment of morbid obesity bariatric surgery has become the method of choice. Dopamine is the primary modulator of the brain’s reward system and plays an essential role in the regulation of food intake. The role of dopamine is well documented in weight regulation and food intake in both animal models and humans. Still, the role of dopamine has not been well studied for weight loss. Catechol-O-methyltransferase (COMT) degrades catecholamines and estrogens are both known to be important risk factors for cardiovascular diseases and consequently obesity. The gene coding for COMT contains a Val108/158Met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence weight loss in obese patients, who previously underwent gastric banding surgery. In obesity research, it is known that women tend to lose more weight than men, and weight before surgery might also affect the outcome of weight loss efforts. Several studies have shown that physical activity (PA) plays an important role in maintaining weight as well as in both non-surgical and surgical weight loss. Therefore, we examined whether gender, age, weight before surgery and PA are good predictor variables for the outcome of surgical weight loss. <strong>Methods:</strong> One to six years after bariatric surgery 74 adults underwent a semi-structured interview. In a second step data on the post-surgical PA level were collected with the Moorehead-Ardelt Quality of Life Questionnaire. Finally, mouth swabs were used for genotyping. <strong>Results:</strong> 54 women and 20 men were enrolled between January 2004 and September 2009. Short-term EWL in the mid-activity genotype dopamine group (GA) was significantly higher (p = 0.007) than was short-term EWL in the low-activity genotype dopamine group (AA) or in the high-activity genotype dopamine group (GG). However, there were no significant differences between the COMT groups with respect to long-term EWL. Long-term we determined that EWL is significantly positively influenced by PA and negatively by gender. The effect of EWL was more pronounced in female than in male subjects. <strong>Conclusion:</strong> Various individual genotypes of the COMT polymorphism (Val108/158Met) make an impact only on short-term EWL, but not on long-term EWL. However, gender and PA proved to be good surgical weight loss predictors for long-term EWL.展开更多
Previous investigations suggest association between obesity and Ala16Val MnSOD gene polymorphism. The V allele produces enzyme which not catalyze the superoxide anion efficiently as occurs with A allele. As obesity is...Previous investigations suggest association between obesity and Ala16Val MnSOD gene polymorphism. The V allele produces enzyme which not catalyze the superoxide anion efficiently as occurs with A allele. As obesity is related to development of other metabolic disorders we performed a study that analyzed the effect of interaction between Ala16Val MnSOD polymorphism and obesity on lipid, oxidative and inflammatory biomarkers of adult subjects. The study enrolled 161 volunteers as categorized in six groups with different genotypes: Obeses with different genotypes (AAO, VVO and AVO) and nonobese (AANO, VVNO and AVNO). In general the group AANO presented lower values whereas VVO presented higher values of biomarkers analyzed. These results suggest that oxidative metabolism influenced by genetic status could to minimize or maximize the obesity effects on lipid, oxidative and inflammatory biomarkers that are also implicated in the genesis of important dysfunctions and diseases as atherosclerosis, diabetes 2 and cardiovascular morbidities.展开更多
基金Supported by the National Natural Science Foundation of China,No.81971250 and No.82171501Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202335Early Psychosis Cohort Program of Beijing Anding Hospital,No.ADDL-03.
文摘BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.
基金supported by a Kentucky INBRE IDeA grant (P20GM103436)(to CLG)a New Investigator Start-up Grant from Ogden College of Science (to CLG)the WKU Ogden College of Science (to CLG)
文摘Brain-derived neurotrophic factor is the most prevalent member of the nerve growth factor family.Since its discovery in 1978,this enigmatic molecule has spawned more than 27,000 publications,most of which are focused on neurological disorders.Brain-derived neurotrophic factor is indispensable during embryogenesis and postnatally for the normal development and function of both the central and peripheral nervous systems.It is becoming increasingly clear,however,that brain-derived neurotrophic factor likewise plays crucial roles in a variety of other biological functions independently of sympathetic or parasympathetic involvement.Brain-derived neurotrophic factor is also increasingly recognized as a sophisticated environmental sensor and master coordinator of whole organismal physiology.To that point,we recently found that a common nonsynonymous(Val66→Met)single nucleotide polymorphism in the brain-derived neurotrophic factor gene(rs6265)not only substantially alters basal cardiac transcriptomics in mice but subtly influences heart gene expression and function differentially in males and females.In addition to a short description of recent results from associative neuropsychiatric studies,this review provides an eclectic assortment of research reports that support a modulatory role for rs6265 including and beyond the central nervous system.
文摘The val66met polymorphism of the bdnf gene, which is associated with compromised brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and impaired learning, may increase one’s susceptibility to stress- and anxiety-related disorders. Indeed, previous work has reported greater anxiety-related behaviors and impairments of fear conditioning and extinction in individuals who carry the met allele that results from this polymorphism. Nevertheless, findings in this area of research have been equivocal. Thus, we examined the influence of the val66met polymorphism on fear conditioning, extinction, and extinction memory testing. One hundred and twenty healthy participants completed differential fear conditioning in a fear-potentiated startle paradigm, followed by extinction and extinction memory testing 24 and 48 hr later, respectively. Participants were genotyped for the val66met polymorphism and divided into met allele carriers and non-carriers. Results revealed that, although both met-carriers and non-carriers developed conditioned fear, met-carriers exhibited significantly weaker fear acquisition than non-carriers. This difference persisted throughout extinction and extinction memory testing and, during these last two days of testing, was primarily evident in females. These results are consistent with previous work demonstrating that this polymorphism is associated with impaired amygdala-dependent fear learning and extend such findings by demonstrating that females may be more sensitive to such effects.
文摘<strong>Background:</strong> In the treatment of morbid obesity bariatric surgery has become the method of choice. Dopamine is the primary modulator of the brain’s reward system and plays an essential role in the regulation of food intake. The role of dopamine is well documented in weight regulation and food intake in both animal models and humans. Still, the role of dopamine has not been well studied for weight loss. Catechol-O-methyltransferase (COMT) degrades catecholamines and estrogens are both known to be important risk factors for cardiovascular diseases and consequently obesity. The gene coding for COMT contains a Val108/158Met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence weight loss in obese patients, who previously underwent gastric banding surgery. In obesity research, it is known that women tend to lose more weight than men, and weight before surgery might also affect the outcome of weight loss efforts. Several studies have shown that physical activity (PA) plays an important role in maintaining weight as well as in both non-surgical and surgical weight loss. Therefore, we examined whether gender, age, weight before surgery and PA are good predictor variables for the outcome of surgical weight loss. <strong>Methods:</strong> One to six years after bariatric surgery 74 adults underwent a semi-structured interview. In a second step data on the post-surgical PA level were collected with the Moorehead-Ardelt Quality of Life Questionnaire. Finally, mouth swabs were used for genotyping. <strong>Results:</strong> 54 women and 20 men were enrolled between January 2004 and September 2009. Short-term EWL in the mid-activity genotype dopamine group (GA) was significantly higher (p = 0.007) than was short-term EWL in the low-activity genotype dopamine group (AA) or in the high-activity genotype dopamine group (GG). However, there were no significant differences between the COMT groups with respect to long-term EWL. Long-term we determined that EWL is significantly positively influenced by PA and negatively by gender. The effect of EWL was more pronounced in female than in male subjects. <strong>Conclusion:</strong> Various individual genotypes of the COMT polymorphism (Val108/158Met) make an impact only on short-term EWL, but not on long-term EWL. However, gender and PA proved to be good surgical weight loss predictors for long-term EWL.
文摘Previous investigations suggest association between obesity and Ala16Val MnSOD gene polymorphism. The V allele produces enzyme which not catalyze the superoxide anion efficiently as occurs with A allele. As obesity is related to development of other metabolic disorders we performed a study that analyzed the effect of interaction between Ala16Val MnSOD polymorphism and obesity on lipid, oxidative and inflammatory biomarkers of adult subjects. The study enrolled 161 volunteers as categorized in six groups with different genotypes: Obeses with different genotypes (AAO, VVO and AVO) and nonobese (AANO, VVNO and AVNO). In general the group AANO presented lower values whereas VVO presented higher values of biomarkers analyzed. These results suggest that oxidative metabolism influenced by genetic status could to minimize or maximize the obesity effects on lipid, oxidative and inflammatory biomarkers that are also implicated in the genesis of important dysfunctions and diseases as atherosclerosis, diabetes 2 and cardiovascular morbidities.
