The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Robert D. Levitan - One of the best experts on this subject based on the ideXlab platform.
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A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children.
Journal of child psychology and psychiatry and allied disciplines, 2016Co-Authors: Robert D. Levitan, Patrícia Pelufo Silveira, James L. Kennedy, Pauline W. Jansen, Barbara Wendland, Henning Tiemeier, Vincent W. V. Jaddoe, Leslie Atkinson, Alison S. Fleming, Marla B. SokolowskiAbstract:Background Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk. Method The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed. Results In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort. Conclusions Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results.
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A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa
Neuropsychopharmacology, 2010Co-Authors: Robert D. Levitan, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, James L. KennedyAbstract:We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene–environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season × DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring -birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall -birth/7R+ group exhibited the highest BMI values ( N =17: mean maximal BMI=28.2 kg/m^2 (SE 0.9) vs 25.2 kg/ m^2 (SE 0.3) for all other probands combined ( N =171); p =0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs ‘other’ group (29.9 vs 8.8%, respectively, p =0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.
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A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.
The International journal of eating disorders, 2008Co-Authors: Allan S. Kaplan, Robert D. Levitan, Caroline Davis, Subi Tharmalingam, Zeynep Yilmaz, James L. KennedyAbstract:The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN. We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the Dopamine-4 Receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype. In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups. These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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A Birth-Season/DRD4 Gene Interaction Predicts Weight Gain and Obesity in Women with Seasonal Affective Disorder: A Seasonal Thrifty Phenotype Hypothesis
Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F=4.42, df=8, 173, p
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A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.
James L. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children.
Journal of child psychology and psychiatry and allied disciplines, 2016Co-Authors: Robert D. Levitan, Patrícia Pelufo Silveira, James L. Kennedy, Pauline W. Jansen, Barbara Wendland, Henning Tiemeier, Vincent W. V. Jaddoe, Leslie Atkinson, Alison S. Fleming, Marla B. SokolowskiAbstract:Background Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk. Method The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed. Results In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort. Conclusions Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results.
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Association between the seven-repeat allele of the Dopamine-4 Receptor gene (DRD4) and spontaneous food intake in pre-school children.
Appetite, 2013Co-Authors: Patrícia Pelufo Silveira, Caroline Davis, A.k. Portella, James L. Kennedy, Hélène Gaudreau, Meir Steiner, Claudio N. Soares, Stephen G. Matthews, Marla B. Sokolowski, Laurette DubéAbstract:Background: Studies in adults show associations between the hypofunctional seven-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), increased eating behaviour and/or obesity, particularly in females. We examined whether 7R is associated with total caloric intake and/or food choices in pre-schoolers. Methods: 150 four-year-old children taking part in a birth cohort study in Canada were administered a snack test meal in a laboratory setting. Mothers also filled out a food frequency questionnaire to address childrens’ habitual food consumption. Total caloric and individual macronutrient intakes during the snack meal and specific types of foods as reported in the food diaries were compared across 7R allele carriers vs. non-carriers, using current BMI as a co-variate. Results: We found significant sex by genotype interactions for fat and protein intake during the snack test. Post hoc testing revealed that in girls, but not boys, 7R carriers ate more fat and protein than did non-carriers. Based on the food diaries, across both sexes, 7R carriers consumed more portions of ice cream and less vegetables, eggs, nuts and whole bread, suggesting a less healthy pattern of habitual food consumption. Conclusion: The 7R allele of DRD4 influences macronutrient intakes and specific food choices as early as four years of age. The specific pattern of results further suggests that prior associations between the 7R allele and adult overeating/obesity may originate in food choices observable in the preschool years. Longitudinal follow-up of these children will help establish the relevance of these findings for obesity risk and prevention.
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A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa
Neuropsychopharmacology, 2010Co-Authors: Robert D. Levitan, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, James L. KennedyAbstract:We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene–environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season × DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring -birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall -birth/7R+ group exhibited the highest BMI values ( N =17: mean maximal BMI=28.2 kg/m^2 (SE 0.9) vs 25.2 kg/ m^2 (SE 0.3) for all other probands combined ( N =171); p =0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs ‘other’ group (29.9 vs 8.8%, respectively, p =0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.
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A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.
The International journal of eating disorders, 2008Co-Authors: Allan S. Kaplan, Robert D. Levitan, Caroline Davis, Subi Tharmalingam, Zeynep Yilmaz, James L. KennedyAbstract:The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN. We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the Dopamine-4 Receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype. In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups. These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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A Birth-Season/DRD4 Gene Interaction Predicts Weight Gain and Obesity in Women with Seasonal Affective Disorder: A Seasonal Thrifty Phenotype Hypothesis
Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F=4.42, df=8, 173, p
Caroline Davis - One of the best experts on this subject based on the ideXlab platform.
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Association between the seven-repeat allele of the Dopamine-4 Receptor gene (DRD4) and spontaneous food intake in pre-school children.
Appetite, 2013Co-Authors: Patrícia Pelufo Silveira, Caroline Davis, A.k. Portella, James L. Kennedy, Hélène Gaudreau, Meir Steiner, Claudio N. Soares, Stephen G. Matthews, Marla B. Sokolowski, Laurette DubéAbstract:Background: Studies in adults show associations between the hypofunctional seven-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), increased eating behaviour and/or obesity, particularly in females. We examined whether 7R is associated with total caloric intake and/or food choices in pre-schoolers. Methods: 150 four-year-old children taking part in a birth cohort study in Canada were administered a snack test meal in a laboratory setting. Mothers also filled out a food frequency questionnaire to address childrens’ habitual food consumption. Total caloric and individual macronutrient intakes during the snack meal and specific types of foods as reported in the food diaries were compared across 7R allele carriers vs. non-carriers, using current BMI as a co-variate. Results: We found significant sex by genotype interactions for fat and protein intake during the snack test. Post hoc testing revealed that in girls, but not boys, 7R carriers ate more fat and protein than did non-carriers. Based on the food diaries, across both sexes, 7R carriers consumed more portions of ice cream and less vegetables, eggs, nuts and whole bread, suggesting a less healthy pattern of habitual food consumption. Conclusion: The 7R allele of DRD4 influences macronutrient intakes and specific food choices as early as four years of age. The specific pattern of results further suggests that prior associations between the 7R allele and adult overeating/obesity may originate in food choices observable in the preschool years. Longitudinal follow-up of these children will help establish the relevance of these findings for obesity risk and prevention.
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A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa
Neuropsychopharmacology, 2010Co-Authors: Robert D. Levitan, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, James L. KennedyAbstract:We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene–environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season × DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring -birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall -birth/7R+ group exhibited the highest BMI values ( N =17: mean maximal BMI=28.2 kg/m^2 (SE 0.9) vs 25.2 kg/ m^2 (SE 0.3) for all other probands combined ( N =171); p =0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs ‘other’ group (29.9 vs 8.8%, respectively, p =0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.
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A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.
The International journal of eating disorders, 2008Co-Authors: Allan S. Kaplan, Robert D. Levitan, Caroline Davis, Subi Tharmalingam, Zeynep Yilmaz, James L. KennedyAbstract:The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN. We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the Dopamine-4 Receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype. In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups. These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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A Birth-Season/DRD4 Gene Interaction Predicts Weight Gain and Obesity in Women with Seasonal Affective Disorder: A Seasonal Thrifty Phenotype Hypothesis
Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F=4.42, df=8, 173, p
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A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.
Allan S. Kaplan - One of the best experts on this subject based on the ideXlab platform.
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A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa
Neuropsychopharmacology, 2010Co-Authors: Robert D. Levitan, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, James L. KennedyAbstract:We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene–environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season × DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring -birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall -birth/7R+ group exhibited the highest BMI values ( N =17: mean maximal BMI=28.2 kg/m^2 (SE 0.9) vs 25.2 kg/ m^2 (SE 0.3) for all other probands combined ( N =171); p =0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs ‘other’ group (29.9 vs 8.8%, respectively, p =0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.
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A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.
The International journal of eating disorders, 2008Co-Authors: Allan S. Kaplan, Robert D. Levitan, Caroline Davis, Subi Tharmalingam, Zeynep Yilmaz, James L. KennedyAbstract:The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN. We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the Dopamine-4 Receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype. In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups. These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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A Birth-Season/DRD4 Gene Interaction Predicts Weight Gain and Obesity in Women with Seasonal Affective Disorder: A Seasonal Thrifty Phenotype Hypothesis
Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F=4.42, df=8, 173, p
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A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.
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The Dopamine-4 Receptor gene associated with binge eating and weight gain in women with seasonal affective disorder: an evolutionary perspective.
Biological psychiatry, 2004Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Pierandrea Muglia, Bronwyn Mackenzie, Subi Tharmalingam, Sidney H. KennedyAbstract:We recently described a preliminary association between the hypofunctional seven-repeat allele of the Dopamine-4 Receptor gene (DRD4) and increased maximal lifetime body mass index in women with seasonal affective disorder (SAD). In this study, we examined whether binge eating behavior mediated this putative association. The study sample consisted of 131 women with winter SAD who reported increased intake of high-carbohydrate/high-fat foods during depressive episodes. We compared rates of binge eating behavior in the two genotypic groups defined by the presence or absence of the seven-repeat allele of DRD4. Consistent with our working hypothesis, the proportion of binge eaters was significantly greater in probands with the seven-repeat allele (18 of 46, 39.1%) than in probands without this allele (14 of 85, 16.5%) [chi(2)(1)= 8.32, p = .004; odds ratio = 3.25, 95% confidence interval 1.43, 7.41]. Pending replication in other samples, these results point to a genetic factor that could help in the early identification and treatment of women at higher risk for seasonal weight gain associated with binge eating behavior. At a theoretic level, the current results suggest a novel link between evolutionary models of seasonal weight gain on the one hand and the DRD4 gene on the other.
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A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa
Neuropsychopharmacology, 2010Co-Authors: Robert D. Levitan, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, James L. KennedyAbstract:We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the Dopamine-4 Receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene–environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season × DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring -birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall -birth/7R+ group exhibited the highest BMI values ( N =17: mean maximal BMI=28.2 kg/m^2 (SE 0.9) vs 25.2 kg/ m^2 (SE 0.3) for all other probands combined ( N =171); p =0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs ‘other’ group (29.9 vs 8.8%, respectively, p =0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.
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A Birth-Season/DRD4 Gene Interaction Predicts Weight Gain and Obesity in Women with Seasonal Affective Disorder: A Seasonal Thrifty Phenotype Hypothesis
Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F=4.42, df=8, 173, p
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A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2006Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Bronwyn Mackenzie, Subi Tharmalingam, James L. KennedyAbstract:We have recently described an association between the hypofunctional 7-repeat allele (7R) of the Dopamine-4 Receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.
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The Dopamine-4 Receptor gene associated with binge eating and weight gain in women with seasonal affective disorder: an evolutionary perspective.
Biological psychiatry, 2004Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Pierandrea Muglia, Bronwyn Mackenzie, Subi Tharmalingam, Sidney H. KennedyAbstract:We recently described a preliminary association between the hypofunctional seven-repeat allele of the Dopamine-4 Receptor gene (DRD4) and increased maximal lifetime body mass index in women with seasonal affective disorder (SAD). In this study, we examined whether binge eating behavior mediated this putative association. The study sample consisted of 131 women with winter SAD who reported increased intake of high-carbohydrate/high-fat foods during depressive episodes. We compared rates of binge eating behavior in the two genotypic groups defined by the presence or absence of the seven-repeat allele of DRD4. Consistent with our working hypothesis, the proportion of binge eaters was significantly greater in probands with the seven-repeat allele (18 of 46, 39.1%) than in probands without this allele (14 of 85, 16.5%) [chi(2)(1)= 8.32, p = .004; odds ratio = 3.25, 95% confidence interval 1.43, 7.41]. Pending replication in other samples, these results point to a genetic factor that could help in the early identification and treatment of women at higher risk for seasonal weight gain associated with binge eating behavior. At a theoretic level, the current results suggest a novel link between evolutionary models of seasonal weight gain on the one hand and the DRD4 gene on the other.
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the Dopamine 4 Receptor gene associated with binge eating and weight gain in women with seasonal affective disorder an evolutionary perspective
Biological Psychiatry, 2004Co-Authors: Robert D. Levitan, Mario Masellis, Vincenzo S. Basile, Raymond W. Lam, Allan S. Kaplan, Caroline Davis, Pierandrea Muglia, Bronwyn Mackenzie, Subi Tharmalingam, Sidney H. KennedyAbstract:Background We recently described a preliminary association between the hypofunctional seven-repeat allele of the Dopamine-4 Receptor gene (DRD4) and increased maximal lifetime body mass index in women with seasonal affective disorder (SAD). In this study, we examined whether binge eating behavior mediated this putative association. Methods The study sample consisted of 131 women with winter SAD who reported increased intake of high-carbohydrate/high-fat foods during depressive episodes. We compared rates of binge eating behavior in the two genotypic groups defined by the presence or absence of the seven-repeat allele of DRD4. Results Consistent with our working hypothesis, the proportion of binge eaters was significantly greater in probands with the seven-repeat allele (18 of 46, 39.1%) than in probands without this allele (14 of 85, 16.5%) [χ2(1)= 8.32, p = .004; odds ratio = 3.25, 95% confidence interval 1.43, 7.41]. Conclusions Pending replication in other samples, these results point to a genetic factor that could help in the early identification and treatment of women at higher risk for seasonal weight gain associated with binge eating behavior. At a theoretic level, the current results suggest a novel link between evolutionary models of seasonal weight gain on the one hand and the DRD4 gene on the other.