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Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.
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Reward responses to food are thought to play an important role in highly palatable food overconsumption. In animal models, food reward responses can be decoupled into unique "liking" (in the moment enjoyment) and "wanting" (motivation/craving) components. However, research on liking and wanting has been hampered by uncertainty regarding whether liking and wanting can be reliably separated in humans. We used factor analysis to test whether ratings of liking and wanting could be empirically separated in women assessed across 49 consecutive days. Female participants (N = 688; ages 15-30) from the Michigan State University Twin Registry reported liking and wanting of foods consumed that day, and wanting of foods not consumed that day, separately for sweets (e.g., cookies), fast food (e.g., French fries), carbohydrates (e.g., bread), and whole foods (fruit, plain chicken) each evening for 49 consecutive days. We examined both average levels and daily levels of liking/wanting across the 49-day period that captured individual differences in liking/wanting over time. Across both types of analyses, liking and wanting for foods that were eaten formed a single factor rather than separate, dissociable factors, while wanting of foods not eaten formed an independent factor. At the daily level, a liking/wanting factor emerged for each individual food category (e.g., liking/wanting sweets), whereas in average analyses, a single factor emerged that collapsed across all food types (i.e., liking/wanting of all foods). Results suggest individuals have difficulty distinguishing between liking and wanting of foods they have eaten on that day but may be able to more reliably separate wanting of foods they have not consumed.
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Preferencias Alimentarias , Motivación , Autoinforme , Humanos , Femenino , Preferencias Alimentarias/psicología , Adulto , Adulto Joven , Adolescente , Análisis Factorial , Recompensa , Michigan , Comida Rápida , Ansia , Sistema de Registros , PlacerRESUMEN
A growing literature links socioeconomic disadvantage and adversity to brain function, including disruptions in reward processing. Less research has examined exposure to community violence (ECV) as a specific adversity related to differences in reward-related brain activation, despite the prevalence of community violence exposure for those living in disadvantaged contexts. The current study tested whether ECV was associated with reward-related ventral striatum (VS) activation after accounting for familial factors associated with differences in reward-related activation (e.g. parenting and family income). Moreover, we tested whether ECV is a mechanism linking socioeconomic disadvantage to reward-related activation in the VS. We utilized data from 444 adolescent twins sampled from birth records and residing in neighborhoods with above-average levels of poverty. ECV was associated with greater reward-related VS activation, and the association remained after accounting for family-level markers of disadvantage. We identified an indirect pathway in which socioeconomic disadvantage predicted greater reward-related activation via greater ECV, over and above family-level adversity. These findings highlight the unique impact of community violence exposure on reward processing and provide a mechanism through which socioeconomic disadvantage may shape brain function.
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Exposición a la Violencia , Imagen por Resonancia Magnética , Características de la Residencia , Recompensa , Adolescente , Niño , Femenino , Humanos , Masculino , Encéfalo/fisiología , Mapeo Encefálico , Exposición a la Violencia/psicología , Exposición a la Violencia/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Pobreza/psicología , Características de la Residencia/estadística & datos numéricos , Disparidades Socioeconómicas en Salud , Factores Socioeconómicos , Estriado Ventral/fisiología , Estriado Ventral/diagnóstico por imagenRESUMEN
One long-standing analytic approach in adoption studies is to examine correlations between features of adoptive homes and outcomes of adopted children (hereafter termed 'measured environment correlations') to illuminate environmental influences on those associations. Although results from such studies have almost uniformly suggested modest environmental influences on adopted children's academic achievement, other work has indicated that adopted children's achievement is routinely higher than that of their reared-apart family members, often substantially so. We sought to understand this discrepancy. We examined academic achievement and literacy-promotive features of the home in 424 yoked adoptive/biological families participating in the Early Growth and Development Study (EGDS; i.e., adopted children, adoptive mothers, birth mothers, and biological siblings of the adopted children remaining in the birth homes) using an exhaustive modeling approach. Results indicated that, as anticipated, adopted children scored up to a full standard deviation higher on standardized achievement tests relative to their birth mothers and reared-apart biological siblings. Moreover, these achievement differences were associated with differences in the literacy-promotive features of the adoptive and birth family homes, despite minimal measured environment correlations within adoptive families. A subsequent simulation study highlighted noise in measured environmental variables as an explanation for the decreased utility of measured environment correlations. We conclude that the field's heavy focus on measured environment correlations within adoptive families may have obscured detection of specific environmental effects on youth outcomes, and that future adoption studies should supplement their measured environment analyses with mean differences between reared-apart relatives.
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Éxito Académico , Niño , Femenino , Adolescente , Humanos , Adopción , Madres , Hermanos , EscolaridadRESUMEN
Prior theoretical and empirical research has highlighted links between positive parenting and the socioeconomic characteristics of the family's neighborhood, but has yet to illuminate the etiologic origins of this association. One possibility is that the various predictors of parenting outlined by Belsky (1984; e.g., characteristics of the child, characteristics of the parent, and contextual influences) may matter more in some neighborhood contexts than in others. To examine this possibility, we conducted etiologic moderation analyses in a sample of 1,030 families of twins (average age 8 years; 51% male, 49% female; racial composition: 82% White, 10% Black, 1% Asian, 1% Indigenous, and 6% multiracial) from the Twin Study of Behavioral and Emotional Development in Children in the Michigan State University Twin Registry. Neighborhood and parenting were assessed using multiple informants and assessment strategies (neighborhood and family informants, administrative data, and videotaped parent-child interactions). Results pointed to strong evidence of etiologic moderation, such that child effects on positive mothering were prominent in neighborhoods with little opportunity and near zero in neighborhoods with ample opportunity. Such findings not only reframe the magnitude of child effects on the parenting they receive as context-dependent, but also indicate that mothers in impoverished neighborhoods may be more responsive to their children's characteristics than mothers in neighborhoods with ample opportunity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Responsabilidad Parental , Características de la Residencia , Humanos , Femenino , Responsabilidad Parental/psicología , Masculino , Niño , Relaciones Madre-Hijo , Gemelos , Factores Socioeconómicos , Características del Vecindario , Adulto , MichiganRESUMEN
Emerging literature links neighborhood disadvantage to altered neural function in regions supporting socioemotional and threat processing. Few studies, however, have examined the proximal mechanisms through which neighborhood disadvantage is associated with neural functioning. In a sample of 7- to 19-year-old twins recruited from disadvantaged neighborhoods (354 families, 708 twins; 54.5% boys; 78.5% White, 13.0% Black, 8.5% other racial/ethnic group membership), we found that exposure to community violence was related to increased amygdala reactivity during socioemotional processing and may be one mechanism linking neighborhood disadvantage to amygdala functioning. Importantly, parenting behavior appeared to modulate these effects, such that high parental nurturance buffered the effect of exposure to community violence on amygdala reactivity. These findings elucidate the potential impact of exposure to community violence on brain function and highlight the role parents can play in protecting youth from the neural effects of exposure to adversity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Exposición a la Violencia , Violencia , Masculino , Adolescente , Humanos , Niño , Adulto Joven , Adulto , Femenino , Violencia/psicología , Amígdala del Cerebelo , Padres , Características de la Residencia , Características del VecindarioRESUMEN
BACKGROUND: Trait-level emotion regulation (ER) difficulties are associated with eating disorders (EDs) transdiagnostically. However, little research has examined whether within-person fluctuations in ER longitudinally predict ED behaviors in daily life or the mechanisms of ER effects. Investigating daily ER could help us better understand why people experience ED behaviors at a given time. We examined whether day-to-day changes in adaptive (e.g., cognitive reappraisal) and maladaptive (e.g., rumination) ER longitudinally predicted core ED behaviors (binge eating, purging, dieting) and whether changes in affect mediated effects. METHOD: Female participants (N = 688) ages 15-30 from the Michigan State University Twin Registry reported their adaptive and maladaptive ER use, negative affect (NA), positive affect (PA), binge eating, purging, and dieting on 49 consecutive days. Using structural equation modeling, we examined whether within-person fluctuations in ER predicted same- and next-day ED behaviors and whether changes in affect mediated longitudinal ER effects. RESULTS: Greater maladaptive ER predicted increased likelihood of same-day binge eating and next-day binge eating and purging. The association between maladaptive ER and next-day binge eating and purging was mediated by increased next-day NA. In contrast, dieting was more closely related to changes in PA. Adaptive ER did not predict reduced likelihood of any ED behavior. CONCLUSIONS: Maladaptive ER may longitudinally increase risk for binge eating and purging by amplifying NA. Interventions focused on decreasing maladaptive ER and subsequent NA might help disrupt binge eating-purging cycles. Conversely, results add to evidence that PA fluctuations may play a unique role in maintaining restrictive behaviors. PUBLIC SIGNIFICANCE: Little is known about how daily changes in emotion regulation may impact disordered eating. We found that maladaptive emotion regulation (e.g., rumination) was associated with a higher likelihood of binge eating and purging on the next day because it predicted increased next-day negative affect. In contrast, dieting was more closely tied to fluctuations in positive affect. Targeting daily emotion regulation and affective processes may help disrupt cycles of disordered eating.
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Regulación Emocional , Trastornos de Alimentación y de la Ingestión de Alimentos , Humanos , Femenino , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Regulación Emocional/fisiología , Adulto , Adolescente , Adulto Joven , Afecto/fisiología , Estudios Longitudinales , MichiganRESUMEN
Neighborhood is a key context where children learn to process social information; however, the field has largely overlooked the ways children's individual characteristics might be moderated by neighborhood effects. We examined 1,030 six- to 11-year-olds (48.7% female; 82% White) twin pairs oversampled for neighborhood disadvantage from the Twin Study of Behavioral and Emotional Development in Children. We evaluated neighbor reports (N = 1,880) of neighborhood structural and social characteristics as moderators of genetic and environmental influences on children's social processing. Although there was no evidence of moderation for children's hostile attributions, there was robust evidence that the social and structural characteristics of the neighborhood moderated the genetic and environmental origins of children's positive expectations of aggressive behavior. Specifically, we found that genetic influences on aggressive expectations increased in the presence of neighborhood deprivation and decreased in the presence of protective social processes and availability of resources. Such findings suggest that protective neighborhood social processes may buffer against the development of aggressive expectations during middle childhood by suppressing the expression of genetic influences on those outcomes. In doing so, they suggest that neighborhood social processes may be able to promote youth resilience to neighborhood deprivation "under the skin." (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Trastornos de la Conducta Infantil , Adolescente , Niño , Femenino , Humanos , Masculino , Agresión , Trastornos de la Conducta Infantil/psicología , Cognición , Características de la Residencia , Percepción SocialRESUMEN
BACKGROUND: Childhood anxiety and depression symptoms are potential risk factors for accelerated biological aging. In child and adolescent twins, we tested whether these symptoms were associated with DNA methylation (DNAm) aging, a measure of biological aging. METHODS: 276 twins (135 pairs, 6 singletons) had DNAm assayed from saliva in middle childhood (mean = 7.8 years). Residuals of five different DNAm age estimates regressed on chronological age were used to indicate accelerated aging. Anxiety and depression symptoms were assessed in middle childhood and early adolescence using the Child Behavior Checklist. Mixed effect regression was used to examine potential relationships between anxiety or depression symptoms, and accelerated DNAm age. MZ twin difference analysis was then utilized to determine if associations were environmentally-driven or due to genetic or shared-environment confounding. RESULTS: Anxiety and depression symptoms were not associated with accelerated DNAm aging in middle childhood. In early adolescence, only the Wu clock was significant and indicated that each one symptom increase in anxiety symptoms had an associated age acceleration of 0.03 years (~0.4 months; p = 0.019). MZ twin difference analysis revealed non-significant within-pair effects, suggesting genetic and shared environmental influences. LIMITATIONS: Sample is predominantly male and white. Generalizability to other populations may be limited. CONCLUSION: Accelerated DNAm aging of the Wu clock in middle childhood is associated with anxiety, but not depression, symptoms in early adolescence. Further, this association may be the result of shared genetic and environmental influences. Accelerated DNAm aging may serve as an early risk factor or predictor of later anxiety symptoms.
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Envejecimiento , Depresión , Humanos , Masculino , Adolescente , Niño , Recién Nacido , Femenino , Depresión/epidemiología , Depresión/genética , Envejecimiento/genética , Ansiedad/epidemiología , Ansiedad/genética , Metilación de ADN , Epigénesis GenéticaRESUMEN
BACKGROUND: Increased reactivity to response conflict and errors, processes governed by the dorsal anterior cingulate cortex (dACC), have both been implicated in anxiety. Anxiety is also more common in females than males. Importantly, natural changes in ovarian hormones levels are related to fluctuations in anxiety symptoms in healthy and clinical populations, and ovarian hormones likely modulate prefrontal cortex structure and function. No studies, however, have examined the role of fluctuating ovarian hormones in the association between anxiety and cognitive control across the menstrual cycle. METHODS: In this multimodal proof-of-concept study, naturally cycling females (N = 30 twins from 14 complete twin pairs and 2 participants whose co-twin was not in the final sample; age 18-29) provided saliva samples to assay for estradiol and progesterone and completed the Penn State Worry Questionnaire for 35 consecutive days. At two time points, during projected pre-ovulatory and post-ovulatory phases, they also completed the Flanker task while undergoing functional magnetic resonance imaging to probe cognitive control-related dACC activity. Multilevel modeling was used to examine within- and between-person effects of hormones and worry on cognitive-control indices. RESULTS: On days when estradiol and progesterone were low relative to a female's own average (i.e., within-subjects effect), worry was associated with greater flanker interference. In females with higher estradiol and progesterone levels compared to other females (i.e., between-subject effects), worry was associated with less error-related dACC activity, irrespective of the day that dACC activity was assessed. CONCLUSION: Findings suggest a protective effect of ovarian hormones on the link between worry and cognitive control. Associations between worry and conflict-monitoring were sensitive to daily hormonal fluctuations (within-person states), whereas associations between worry and error-monitoring were sensitive to mean hormone levels (between-person traits), suggesting that ovarian hormones are critical to consider in studies examining associations between anxiety and cognitive control in females.
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Ansiedad , Progesterona , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Cognición , Estradiol , Ciclo Menstrual/fisiología , Prueba de Estudio ConceptualRESUMEN
OBJECTIVE: This study investigates eating pathology in transgender and gender non-conforming (TGNC) youth compared to a community-based sample and individuals with eating disorders (EDs). METHOD: Participants (ages 13-21 years) included TGNC youth from a paediatric gender clinic (N = 97), a demographically matched community-based sample of cisgender males (N = 97) and cisgender females (N = 97), and treatment-seeking patients with EDs (N = 112). The Eating Disorder Examination Questionnaire (EDE-Q) was used to assess ED cognitions and behaviours. RESULTS: Transgender and gender non-conforming participants reported significantly higher EDE-Q global scores compared to the cisgender samples, but significantly lower than the ED sample. Transgender and gender non-conforming individuals reported a higher likelihood of objective binge episodes (OBEs) than the cisgender groups, albeit lower than youth with EDs. A substantial proportion of TGNC participants scored in elevated ranges on the EDE-Q global score (35% ≥ score of 3, 17% ≥ score of 4), significantly higher than cisgender males (0% ≥ score of 3, 0% ≥ score of 4) and females (9% ≥ score of 3, 3% ≥ score of 4). CONCLUSIONS: Findings indicate that TGNC youth exhibit increased ED cognitions and OBEs compared to cisgender samples, highlighting the need for screening and addressing ED symptoms in this population.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Personas Transgénero , Masculino , Femenino , Niño , Humanos , Adolescente , Encuestas y Cuestionarios , Identidad de Género , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiologíaRESUMEN
BACKGROUND: Some preliminary research suggests higher rates of gastrointestinal disease in individuals with eating disorders (EDs). However, research is limited, and it remains unknown what etiologic factors account for observed associations. This was the first study to examine how EDs and dimensional ED symptoms (e.g. body dissatisfaction, binge eating) are phenotypically and etiologically associated with gastrointestinal disease in a large, population-based twin sample. METHODS: Adult female (N = 2980) and male (N = 2903) twins from the Michigan State University Twin Registry reported whether they had a lifetime ED (anorexia nervosa, bulimia nervosa, or binge-eating disorder) and completed a measure of dimensional ED symptoms. We coded the presence/absence of lifetime gastrointestinal disease (e.g. inflammatory bowel disease) based on responses to questions regarding chronic illnesses and medications. We first examined whether twins with gastrointestinal disease had higher rates of EDs and ED symptoms, then used correlated factors twin models to investigate genetic and environmental contributions to the overlap between disorders. RESULTS: Twins with gastrointestinal disease had significantly greater dimensional ED symptoms (ß = 0.21, p < 0.001) and odds of a lifetime ED (OR 2.90, p = 0.001), regardless of sex. Shared genetic factors fully accounted for the overlap between disorders, with no significant sex differences in etiologic associations. CONCLUSIONS: Comorbidity between EDs and gastrointestinal disease may be explained by overlap in genetic influences, potentially including inflammatory genes implicated in both types of disorders. Screening for gastrointestinal disease in people with EDs, and EDs in those with gastrointestinal disease, is warranted.
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Anorexia Nerviosa , Trastorno por Atracón , Bulimia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Enfermedades Gastrointestinales , Adulto , Humanos , Femenino , Masculino , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/genética , Bulimia Nerviosa/epidemiología , Bulimia Nerviosa/genética , Bulimia Nerviosa/diagnóstico , Anorexia Nerviosa/genética , Trastorno por Atracón/genética , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/genéticaRESUMEN
The misconception that eating disorders are conditions of affluence has shaped research and public understanding for decades. Here, we highlight links between socioeconomic disadvantage and eating disorder risk. With prevailing stereotypes discredited, we argue that considering disadvantage as a key eating disorder risk factor will advance science and reduce disparities.
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Trastornos de Alimentación y de la Ingestión de Alimentos , HumanosRESUMEN
Parenting behaviors are among the most robust predictors of youth resilience to adversity. Critically, however, very few studies examining these effects have been genetically-informed, and none have considered parenting as an etiologic moderator of resilience. What's more, despite the multidimensionality of resilience, extant etiologic literature has largely focused on a single domain. The current study sought to fill these respective gaps in the literature by examining whether and how parental nurturance shapes the etiology of academic, social, and psychological resilience, respectively. We employed a unique sample of twins (N = 426 pairs; ages 6-11) exposed to moderate-to-severe levels of environmental adversity (i.e., family poverty, neighborhood poverty, community violence) from the Twin Study of Behavioral and Emotional Development in Children. As expected, parental nurturance was positively correlated with all forms of resilience. Extended univariate genotype-by-environment interaction models revealed that parental nurturance significantly moderated genetic influences on all three domains of resilience (academic resilience A1= -0.53, psychological resilience A1= -1.22, social resilience A1= -0.63; all p < .05), such that as parental nurturance increased, genetic influences on youth resilience decreased. Put another way, children experiencing high levels of parental nurturance were more resilient to disadvantage, regardless of their genetic predisposition towards resilience. In the absence of nurturing parenting, however, genetic influences played an outsized role in the origins of resilience. Such findings indicate that parental nurturance may serve as a malleable protective factor that increases youth resilience regardless of genetic influences.
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Resiliencia Psicológica , Niño , Humanos , Adolescente , Conducta Social , Responsabilidad Parental/psicología , Padres , Relaciones Padres-HijoRESUMEN
Although extant cross-sectional data suggest that parents have experienced numerous challenges (e.g., homeschooling, caregiver burden) and mental health consequences during the COVID-19 pandemic, longitudinal data are needed to confirm mental health changes relative to pre-pandemic levels and identify which specific pandemic-related changes most highly predict mental health during the pandemic. In two longitudinal subsamples (N = 299 and N = 175), we assessed change in anxiety, depression, and stress before and during the pandemic and whether the accumulation of pandemic-related changes predicted observed mental health changes. On average, parents reported increased depression and anxiety, but no significant changes in reported stress. Moreover, increased interpersonal conflict, difficulty managing work and caregiving responsibilities, and increased economic challenges were the types of pandemic-related changes that most strongly predicted worse mental health, highlighting that juggling caregiving responsibilities and economic concerns, along with the pandemic's impact on interpersonal family relationships are key predictors of worsening parental mental illness symptoms.
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Family poverty has been associated with altered brain structure, function, and connectivity in youth. However, few studies have examined how disadvantage within the broader neighborhood may influence functional brain network organization. The present study leveraged a longitudinal community sample of 538 twins living in low-income neighborhoods to evaluate the prospective association between exposure to neighborhood poverty during childhood (6-10 y) with functional network architecture during adolescence (8-19 y). Using resting-state and task-based fMRI, we generated two latent measures that captured intrinsic brain organization across the whole-brain and network levels - network segregation and network segregation-integration balance. While age was positively associated with network segregation and network balance overall across the sample, these associations were moderated by exposure to neighborhood poverty. Specifically, these positive associations were observed only in youth from more, but not less, disadvantaged neighborhoods. Moreover, greater exposure to neighborhood poverty predicted reduced network segregation and network balance in early, but not middle or late, adolescence. These effects were detected both across the whole-brain system as well as specific functional networks, including fronto-parietal, default mode, salience, and subcortical systems. These findings indicate that where children live may exert long-reaching effects on the organization and development of the adolescent brain.
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Encéfalo , Pobreza , Niño , Humanos , Adolescente , Características de la Residencia , Imagen por Resonancia MagnéticaRESUMEN
Background: Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. Methods: Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal resting-state functional magnetic resonance imaging scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (n = 79). Independent component analysis was used to define frontal and limbic regions of interest. Results: Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. Conclusions: Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.
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Despite early-life disadvantage (ELD) in humans being a highly heterogenous construct, it consistently predicts negative neurobehavioral outcomes. The numerous environmental contributors and neural mechanisms underlying ELD remain unclear, though. We used a laboratory rat model to evaluate the effects of limited resources and/or heavy metal exposure on mothers and their adult male and female offspring. Dams and litters were chronically exposed to restricted (1-cm deep) or ample (4-cm deep) home cage bedding postpartum, with or without lead acetate (0.1%) in their drinking water from insemination through 1-week postweaning. Restricted-bedding mothers showed more pup-directed behaviors and behavioral fragmentation, while lead-exposed mothers showed more nestbuilding. Restricted bedding-raised male offspring showed higher anxiety and aggression. Either restricted bedding or lead exposure impaired goal-directed performance in a reinforcer devaluation task in females, whereas restricted bedding alone disrupted it in males. Lead exposure, but not limited bedding, also reduced sucrose reward sensitivity in a progressive ratio task in females. D1 and D2 receptor mRNA in the medial prefrontal cortex and nucleus accumbens (NAc) were each affected by the early-life treatments and differently between the sexes. Most notably, adult males (but not females) exposed to both early-life treatments had greatly increased D1 receptor mRNA in the NAc core. These results illuminate neural mechanisms through which ELD threatens neurobehavioral development and highlight forebrain dopamine as a factor.
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Dopamina , Receptores Dopaminérgicos , Ratas , Animales , Humanos , Masculino , Femenino , Dopamina/metabolismo , Receptores Dopaminérgicos/metabolismo , Plomo/metabolismo , Plomo/farmacología , Núcleo Accumbens/metabolismo , Ansiedad , Agresión , Recompensa , ARN Mensajero/metabolismoRESUMEN
The heritability of eating disorder (ED) symptoms increases dramatically across gonadarche in girls. Past studies suggest these developmental differences could be due to pubertal activation of estrogen, but findings have been limited to only one ED symptom (i.e., binge eating). The current study examined whether estrogen contributes to gonadarcheal differences in genetic influences on overall levels of ED symptoms as well as key cognitive symptoms (i.e., weight/shape concerns) that are present across all EDs and are early risk factors for eating pathology. Given that binge eating frequently co-occurs with all of these symptoms, analyses also examined whether estrogen effects exist for overall levels of ED symptoms and body weight/shape concerns after accounting for the known effects of estrogen on genetic risk for binge eating. Participants included 964 female twins (ages 8-16) from the Michigan State University Twin Registry. Overall levels of ED symptoms were assessed with the Minnesota Eating Behavior Survey (MEBS) total score. Weight/shape concerns were assessed with a latent factor modeled using subscales from the MEBS and the Eating Disorder Examination Questionnaire. Estradiol levels were assessed with saliva samples. Twin moderation models were used to examine whether genetic influences on overall levels of ED symptoms and weight/shape concerns differed significantly across estradiol levels. Although initial models suggested modest differences in genetic influences on overall levels of ED symptoms across estradiol levels, these effects were eliminated when binge eating was accounted for in the models. In addition, weight/shape concerns did not show significant moderation of genetic influences by estradiol in models with or without binge eating. Taken together, results are significant in suggesting that individual differences in estradiol levels during gonadarche have a unique and specific impact on genetic risk for binge eating, while other etiologic factors must contribute to increased heritability of cognitive ED symptoms during this key developmental period in girls.