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1.  A Preliminary Analysis of Interactions Between Genotype, Retrospective ADHD Symptoms, and Initial Reactions to Smoking in a Sample of Young Adults 
Nicotine & Tobacco Research  2011;14(2):229-233.
Introduction:
Initial reactions to cigarettes predict later regular smoking. Symptoms of attention deficit hyperactivity disorder (ADHD) have also been shown to increase smoking risk and may moderate the relationship between genotype and smoking. We conducted an exploratory study to assess whether ADHD symptoms interact with genetic variation to predict self-reported initial reactions to smoking.
Methods:
Participants were a subsample of 1,900 unrelated individuals with genotype data drawn from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. Linear regression was used to examine relationships among self-reported ADHD symptoms, genotype, and self-reported initial reactions to cigarettes (index scores reflecting pleasant and unpleasant reactions).
Results:
Polymorphisms in the DRD2 gene, SLC6A4 gene, and among males, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting pleasant initial reaction to cigarettes. Polymorphisms in the CYP2A6 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting unpleasant initial reaction to cigarettes. No main effect for any of these polymorphisms was observed nor were any interactions with DRD4 and DAT genes.
Conclusions:
These findings suggest that genotypes associated with monoamine neurotransmission interact with ADHD symptoms to influence initial reactions to cigarette smoking. Given that an initial pleasant reaction to cigarettes increases risk for lifetime smoking, these results add to a growing body of literature that suggests that ADHD symptoms increase risk for smoking and should be accounted for in genetic studies of smoking.
doi:10.1093/ntr/ntr125
PMCID: PMC3265740  PMID: 21778150
2.  Adverse childhood events are associated with obesity and disordered eating: Results from a U.S. population-based survey of young adults 
Journal of traumatic stress  2009;22(4):329-333.
We investigated the relationship between childhood abuse and obesity in young adulthood (M age = 22) in a large, U.S., representative sample (N = 15,197). Controlling for demographics and depression, men with a history of childhood sexual abuse (CSA) were at increased risk of overweight and obesity. No association between childhood abuse and obesity or overweight was observed for women in this sample. Higher percentages of skipping meals to loose weight and problematic eating were observed among women with a history of physical abuse. This is the first study to note an association between childhood abuse with obesity and problematic weight management behaviors in a sample of young adults.
doi:10.1002/jts.20421
PMCID: PMC2748336  PMID: 19588510
Child adversity; child maltreatment; obesity; weight management
3.  Interactions between genotype and depressive symptoms on obesity 
Behavior genetics  2009;39(3):296-305.
Background
Depression and Genetic variation in serotonin and monoamine transmission have both been associated with Body Mass Index (BMI), but their interaction effects are not well understood. We examined the interaction between depressive symptoms and functional polymorphisms of serotonin transporter (SLC6A4) and monoamine oxidase A (MAOA) on categories of BMI.
Methods
Participants were from the National Longitudinal Study of Adolescent Health. Multiple logistic regression was used to investigate interactions between candidate genes and depression on risk of obesity (BMI≥30) or overweight + obese combined (BMI≥25).
Results
Males with an MAOA active allele with high depressive symptoms were at decreased risk of obesity (OR, 0.22; 95% CI, 0.06 – 0.78) and overweight + obesity (OR, 0.48; 95% CI, 0.26 – 0.89). No similar effect was observed among females.
Conclusions
These findings highlight that the obesity-depression relationship may vary as a function of gender and genetic polymorphism, and suggest the need for further study.
doi:10.1007/s10519-009-9266-z
PMCID: PMC2884968  PMID: 19337825
4.  Dopamine Polymorphisms and Depressive Symptoms Predict Foods Intake: Results from a Nationally Representative Sample 
Appetite  2011;57(2):339-348.
Depression and variation in dopamine related genes have both independently been associated with food consumption. Depressive symptoms could synergistically interact with genetic variation to influence food intake. We examined the interaction between high depressive symptoms and functional polymorphisms of dopamine transportor (SLC6A3), monoamine oxidase A (MAOA), dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) on intake of high-calorie sweet, high-calorie non-sweet, and low-calorie foods in the National Longitudinal Study of Adolescent Health (Add Health). Multivariate linear regression analyses were used to examine main effects of gene and depression symptoms and their interaction (genotype-by-high depression symptoms) on food categories. Applying a false discovery rate criterion for multiple comparisons indicated a statistically significant interaction for females with high depressive symptoms and the SLC6A3 gene, such that those with the SLC6A3 10/10 allele reported greater intake of high-calorie sweet foods than their counterparts high in depressive symptoms with the SLC6A3 any 9 allele (LS mean 10/10 allele = 2.5, SE = .13; LS mean any 9 allele = 1.8, SE = .13, p<.05). These findings highlight that the relationship between depression and food intake may vary as a function of genetic polymorphism. Further research is needed to confirm these findings.
doi:10.1016/j.appet.2011.05.325
PMCID: PMC3156384  PMID: 21672565
Adolescent; Diet; Dopamine; Depression
5.  Association between Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms and obesity and hypertension in early adulthood: A population-based study 
Objective
To examine associations between attention-deficit/hyperactivity disorder (ADHD) symptoms, obesity and hypertension in young adults in a large population-based cohort.
Design, Setting, and Participants
The study population consisted of 15,197 respondents from the National Longitudinal Study of Adolescent Health, a nationally representative sample of adolescents followed from 1995 – 2009 in the United States. Multinomial logistic and logistic models examined the odds of overweight, obesity, and hypertension in adulthood in relation to retrospectively reported ADHD symptoms. Latent curve modeling was used to assess the association between symptoms and naturally occurring changes in body mass index (BMI) from adolescence to adulthood.
Results
Linear association was identified between the number of inattentive (IN) and hyperactive/impulsive (HI) symptoms and waist-circumference, BMI, diastolic blood pressure, and systolic blood pressure (all ps for trend < .05). Controlling for demographic variables, physical activity, alcohol use, smoking, and depressive symptoms, those with 3 or more HI or IN symptoms had the highest odds of obesity (HI 3+ OR, 1.50; 95% CI, 1.22-2.83; IN 3+ OR, 1.21; 95% CI, 1.02-1.44) compared to those with no HI or IN symptoms. HI symptoms at the 3+ level were significantly associated with a higher OR of hypertension (HI 3+ OR, 1.24; 95% CI 1.01-1.51; HI continuous OR, 1.04; 95% CI 1.00-1.09), but associations were non-significant when models were adjusted for BMI. Latent growth modeling results indicated that compared to those reporting no HI or IN symptoms, those reporting more 3 or symptoms had higher initial levels of BMI during adolescence. Only HI symptoms were associated with change in BMI.
Conclusion
Self-reported ADHD symptoms were associated with adult BMI and change in BMI from adolescence to adulthood, providing further evidence of a link between ADHD symptoms and obesity.
doi:10.1038/ijo.2010.214
PMCID: PMC3391591  PMID: 20975727
attention-deficit/hyperactivity disorder; obesity; hypertension; young adult; risk factors
6.  Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements 
Epigenetics  2012;7(7):735-746.
Depressed mood in pregnancy has been linked to low birth weight (LBW, < 2,500 g), a risk factor for adult-onset chronic diseases in offspring. We examined maternal depressed mood in relation to birth weight and evaluated the role of DNA methylation at regulatory sequences of imprinted genes in this association. We measured depressed mood among 922 pregnant women using the CES-D scale and obtained birth weight data from hospital records. Using bisulfite pyrosequencing of cord blood DNA from 508 infants, we measured methylation at differentially methylated regions (DMRs) regulating imprinted genes IGF2/H19, DLK1/MEG3, MEST, PEG3, PEG10/SGCE, NNAT and PLAGL1. Multiple regression models were used to examine the relationship between depressed mood, birth weight and DMR methylation levels. Depressed mood was associated with a more that 3-fold higher risk of LBW, after adjusting for delivery mode, parity, education, cigarette smoking, folic acid use and preterm birth. The association may be more pronounced in offspring of black women and female infants. Compared with infants of women without depressed mood, infants born to women with severe depressed mood had a 2.4% higher methylation at the MEG3 DMR. Whereas LBW infants had 1.6% lower methylation at the IGF2 DMR, high birth weight (> 4,500 g) infants had 5.9% higher methylation at the PLAGL1 DMR compared with normal birth weight infants. Our findings confirm that severe maternal depressed mood in pregnancy is associated with LBW, and that MEG3 and IGF2 plasticity may play important roles.
doi:10.4161/epi.20734
PMCID: PMC3414394  PMID: 22677950
depression; DNA Methylation; epigenetics; fetal growth retardation; health status disparities; low birth weight
7.  The Roles of Posttraumatic Stress Disorder and Major Depressive Disorder in Childhood Traumatic Stress and Weight Problems among Women 
Journal of Traumatic Stress  2010;23(6):785-763.
In this study, symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) were modeled as intervening variables in the relationship between childhood traumatic stress and weight outcomes in civilian women in the United States. Of the 148 participants, 72 had current PTSD, 64 had current MDD, and 32 had neither disorder. In separate single indirect effect models, there were significant indirect effects of both PTSD and depressive symptoms on body mass index and waist-hip ratio. When models included both PTSD and depressive symptoms, an indirect effect of PTSD symptoms was evident in the relationship between childhood traumatic stress and waist-hip ratio. PTSD may play a particularly important role in the development of central adiposity.
doi:10.1002/jts.20584
PMCID: PMC3308146  PMID: 21171140
8.  Parent-child relationship of directly measured physical activity 
Background
Studies on parent-child correlations of physical activity have been mixed. Few studies have examined concurrent temporal patterns of physical activity and sedentary behaviors in parents and children using direct measures. The purpose of this study was to examine parent-child activity correlations by gender, day of week, and time of day, using accelerometers - a method for direct assessment of physical activity.
Methods
Accelerometers were used to assess physical activity and sedentary time in 45 fathers, 45 mothers and their children (23 boys, 22 girls, mean age 9.9 years) over the course of 4 days (Thursday - Sunday). Participants were instructed to wear accelerometers for 24 hours per day. Data from accelerometers were aggregated into waking hours on weekdays and weekends (6:00 am to midnight) and weekday after-school hours (3:00 - 7:00 pm).
Results
Across the 4 days, the mean minutes per day of moderate-to-vigorous physical activity (MVPA) for fathers was 30.0 (s.d. = 17.3), for mothers was 30.1 (s.d. = 20.1) and for children was 145.47 (s.d. = 51.64). Mothers' and fathers' minutes of MVPA and minutes of sedentary time were positively correlated with child physical activity and sedentary time (all ps < .05, with the exception of mothers' and children's sedentary time on weekdays from 6 am to 12 am). Multivariate linear regression analyses resulted in significant effects between parents and children for MVPA across all time segments. For sedentary activity, significant associations were observed only between father and child on the weekend. Sedentary activity of parents and children were not related for other time segments. Models examining the associations of one or two parents with high levels of MVPA or sedentary time indicated a dose response increase in child activity relative to parent.
Conclusions
Greater parental MVPA was associated with increased child MVPA. In addition, having two parents with higher levels of MVPA was associated with greater levels of activity in children. Sedentary time in children was not as strongly correlated with that of their parents. Findings lend support to the notion that to increase childhood activity levels it may be fruitful to improve physical activity among parents.
doi:10.1186/1479-5868-8-17
PMCID: PMC3062578  PMID: 21385455
9.  Genes implicated in serotonergic and dopaminergic functioning predict BMI categories 
Obesity (Silver Spring, Md.)  2008;16(2):348-355.
Objective
This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4), and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined.
Research Methods and Procedures
Participants were a subsample of individuals from The National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI > 25) with normal weight (BMI = 18.5–24.9) as a referent. Linear regression models were used examine change in BMI from adolescence to young adulthood.
Results
Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter VNTR among males and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for males overall, and for White and Hispanic males specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood.
Discussion
Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance.
doi:10.1038/oby.2007.65
PMCID: PMC2919156  PMID: 18239643
Adolescents; Genetic Epidemiology; Serotonin; Neuro Transmitter
10.  Weight, Dietary Behavior, and Physical Activity in Childhood and Adolescence: Implications for Adult Cancer Risk 
Obesity Facts  2009;2(3):179-186.
Summary
Lifestyle factors related to energy balance, including weight, dietary behavior and physical activity, are as-sociated with cancer risk. The period of childhood and growth into adolescence and early adulthood may re-present a ‘cumulative risk’ for later adult-onset cancers. We review a number of epidemiologic studies that have examined associations among childhood and adolescent body size, diet, and physical activity with adult cancer risk. These studies suggest that unhealthy behaviors that develop early in life and persist over time may increase the risk of some cancer types, such as premenopausal breast, ovarian, endometrial, colon and renal cancer, adversely affect cancer-related morbidities, and increase mortality. Continued research is needed to further determine and refine how timing and degree of such exposures in early childhood and adolescence relate to adult cancer risk. Presently, sufficient evidence suggests a continued need for stronger primary prevention in cancer and obesity research via modified lifestyle behaviors earlier in the developmental spectrum, i.e. during childhood and adolescence.
doi:10.1159/000220605
PMCID: PMC2924235  PMID: 20054223
Children; Weight; Diet; Physical activity; Cancer; Obesity; Tracking
11.  Association Between Trauma Exposure and Smoking in a Population-Based Sample of Young Adults 
Purpose
To evaluate the relationship between smoking and trauma exposure in a population-based, longitudinal sample. Contrary to current smoking trends in the general population, recent findings indicate continued high smoking rates in trauma-exposed samples.
Methods
A nationally representative sample of 15,197 adolescents was followed from 1995 (mean age=15.6) to 2002 (mean age=22) as part of 3 waves of The National Longitudinal Study of Adolescent Health (Add Health). We examined the relation between self-reported trauma exposure and smoking behaviors (lifetime regular, current regular), nicotine dependence (Fagerström Test of Nicotine Dependence (FTND)), number of cigarettes per day, and age of onset of regular smoking.
Results
Controlling for demographics and depressive symptoms, exposure to traumatic events yielded a significant increase in the odds of lifetime regular smoking. Nicotine dependence and cigarettes smoked per day was also significantly related to exposure to Childhood Physical and Sexual Abuse. Decreased age of regular smoking onset was seen for those reporting Childhood Physical Abuse and Childhood Sexual Abuse.
Conclusions
Exposure to traumatic life events during childhood and young adulthood increases the risk of smoking, highlighting the need to prevent and treat tobacco use in this vulnerable population.
doi:10.1016/j.jadohealth.2007.08.029
PMCID: PMC2675188  PMID: 18295135
Traumatic Stress; Smoking; Nicotine Dependence; Adolescent; Depression
12.  Dietary essential fatty acids and gender-specific behavioral responses in cranially irradiated rats 
Specific memory deficits, reduced intellectual processing speed, and a variety of social and behavioral problems have been implicated as long-term effects of cranial radiation therapy (CRT). These deficits are thought to be related to changes in brain cytology and structure associated with microvascular aberrations. N-3 fatty acids may serve as protectants in pediatric patients who receive CRT for brain tumors. Timed-pregnant rat dams were fed one of four diets that were identical in all respects, except for their essential fatty acid content. The dams were placed on these diets at the beginning of the third trimester of gestation and their pups remained on them throughout the study. The rats’ behavioral response as judged by acoustic startle response (ASR) and neurocognitive response (performance in a radial maze, RM) were evaluated in relation to diet, gender, and CRT. The following hypotheses were tested: (1) female rats will show greater CRT-induced neurocognitive and behavioral deficits; (2) dietary n-3 fatty acids will diminish CRT-induced neurocognitive and behavioral deficits; (3) gender-specific differences would be dampened by n-3 fatty acids in the diet. All three hypotheses were partially supported. These findings are discussed in light of the potential neuroprotective effects of n-3 fatty acids.
PMCID: PMC2671816  PMID: 19412484
cranial radiation therapy; learning and memory; fatty acid; omega-3; radial arm maze; acoustic startle test
13.  Understanding the Phenotypic Structure of Adult Retrospective ADHD Symptoms During Childhood in the United States 
Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous disorder, and the phenotypic structure comprising inattentive and hyperactive-impulsive type symptoms has been the focus of a growing body of recent research. Methodological studies are needed to better characterize phenotypes to advance research as well as clinical practice. A large U.S. population-based sample of young adults (N = 14,307, aged 17–28 years, 52.8% female) retrospectively reported their experiences of childhood ADHD symptoms. Factor analysis, latent class analysis, and factor mixture modeling of ADHD symptoms were compared to determine which underlying structure best fit the data. Fit statistics as well as substantive criteria compared models within and across model subtypes. Analyses supported a two-factor two-class structure for both male and female subjects. The two latent factors represented inattentive and hyperactive-impulsive symptom dimensions. The two latent classes divided people into a smaller affected class and a larger unaffected class. Individuals who reported having been diagnosed with ADHD were more likely to be in the affected class (OR male subjects = 4.03, 95% CI [2.65, 6.13]; OR female subjects = 5.65, 95% CI [3.15, 10.10]). This work aids in the understanding of ADHD symptomatology within the population; a majority of people experience very low symptom severity, whereas a minority of people experience high symptom severity. Within this high symptom group, however, variability in symptom experiences exists. Empirical models can be helpful in clarifying ADHD phenotypic structure that has the potential to advance research on the etiology and consequences of ADHD symptoms.
doi:10.1080/15374416.2012.654465
PMCID: PMC3354630  PMID: 22394329

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