Despite calls to incorporate population science into neuroimaging research, most studies recruit small, non-representative samples. Here, we examine whether sample composition influences age-related variation in global measurements of gray matter volume, thickness, and surface area. We apply sample weights to structural brain imaging data from a community-based sample of children aged 3-18 (N = 1162) to create a "weighted sample" that approximates the distribution of socioeconomic status, race/ethnicity, and sex in the U.S. Census. We compare associations between age and brain structure in this weighted sample to estimates from the original sample with no sample weights applied (i.e., unweighted). Compared to the unweighted sample, we observe earlier maturation of cortical and sub-cortical structures, and patterns of brain maturation that better reflect known developmental trajectories in the weighted sample. Our empirical demonstration of bias introduced by non-representative sampling in this neuroimaging cohort suggests that sample composition may influence understanding of fundamental neural processes.The influence of sample composition on human neuroimaging results is unknown. Here, the authors weight a large, community-based sample to better reflect the US population and describe how applying these sample weights changes conclusions about age-related variation in brain structure.
BACKGROUND: Earlier age of pubertal maturation in females is associated with increased risk for mental health problems in adolescence, compared with on-time or later maturation. However, most investigations of pubertal timing and mental health consider risk for individual disorders and fail to account for comorbidity. A latent-modeling approach using a large, nationally representative sample could better explain the transdiagnostic nature of the consequences of early-onset puberty. METHODS: Data on age of menarche and mental disorders were drawn from a population-representative sample of adolescents (n=4925), ages 13-17. Confirmatory factor analysis was used to fit four latent disorder categories: distress, eating, and externalizing, and fear disorders. Timing of menarche included those with earlier (age<=10, age 11) and later age of onset (age 13, 14+), relative to those with average timing of menarche (age 12). Associations between timing of menarche and latent disorders were estimated in a structural equation model (SEM), adjusted for age, income, race, parent marital status, BMI, and childhood adversity. RESULTS: The measurement model evidenced acceptable fit (CFI=0.91; RMSEA=0.02). Onset of menarche before age 11 was significantly associated with distress disorders (coefficient=0.096; p\textless0.0001), fear disorders (coefficient=0.09; p\textless0.0001), and externalizing disorders (coefficient=0.039; p=0.049) as compared to on-time or late menarche. No residual associations of early menarche with individual disorders over and above the latent disorders were observed. CONCLUSION: The latent modeling approach illuminated meaningful transdiagnostic psychiatric associations with early timing of menarche. Biological processes initiated at puberty can influence cognitive and affective processes as well as social relationships for adolescents. Under developmentally normative conditions, these changes may be adaptive. However, for those out of sync with their peers, researchers and clinicians should recognize the potential for these processes to influence liability to a broad array of psychopathological consequences in adolescence.
OBJECTIVE: Exposure to violence and other forms of potentially traumatic events (PTEs) are common among youths with externalizing psychopathology. These associations likely reflect both heightened risk for the onset of externalizing problems in youth exposed to PTEs and elevated risk for experiencing PTEs among youth with externalizing disorders. In this study, we disaggregate the associations between exposure to PTEs and externalizing disorder onset in a population-representative sample of adolescents. METHOD: We analyzed data from 13- to 18-year-old participants in the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A) (N = 6,379). Weighted survival models estimated hazard ratios (HRs) for onset of oppositional defiant disorder (ODD), conduct disorder (CD), and substance use disorders (SUDs) associated with PTEs, and for exposure to PTEs associated with prior-onset externalizing disorders. Multiplicative interaction terms tested for effect modification by sex, race/ethnicity, and household income. RESULTS: All types of PTEs were associated with higher risk for SUD (HRs = 1.29-2.21), whereas only interpersonal violence (HR = 2.49) was associated with onset of CD and only among females. No associations were observed for ODD. Conversely, ODD and CD were associated with elevated risk for later exposure to interpersonal violence and other/nondisclosed events (HRs = 1.45-1.75). CONCLUSION: Externalizing disorders that typically begin in adolescence, including SUDs and CD, are more likely to emerge in adolescents with prior trauma. ODD onset, in contrast, is unrelated to trauma exposure but is associated with elevated risk of experiencing trauma later in development. CD and interpersonal violence exposure exhibit reciprocal associations. These findings have implications for interventions targeting externalizing and trauma-related psychopathology.
Heterotypic continuity, whereby individuals transition from one disorder to another, is common; however, longitudinal studies examining transdiagnostic predictors of heterotypic continuity are lacking. The current study examined whether trauma exposure during childhood (maltreatment) and adulthood (interpersonal and non-interpersonal trauma) is associated with heterotypic continuity in a national sample. Men and women (N = 34,653) who participated in Waves 1 (2001-2002) and 2 (2004-2005) of the National Survey of Alcohol and Related Conditions (NESARC) completed face-to-face interviews about trauma exposure and psychopathology. Risk ratios and population attributable risk proportions (PARPs) quantified the effects of childhood maltreatment and interpersonal and non-interpersonal trauma exposure between Waves 1 and 2 on risk for incident disorders and transitions between specific types of disorders. Twenty percent of respondents reported a Wave 2 incident disorder. Those with any Wave 1 disorder were at increased risk of incident mood (RR range = 1.2-2.1) and anxiety (RR = 1.5-2.7) disorders at Wave 2. Child maltreatment and interpersonal trauma exposure since Wave 1 were associated with roughly 50% of the risk for disorder transitions (RR range = 1.2-2.7); non-interpersonal trauma was associated with 30% of the risk for disorder transitions (RR range = 1.0-1.7). Findings suggest that new onset disorders were common in U.S. adults and trauma exposure explained a large proportion of disorder incidence as well as progression from one disorder to another. Universal prevention efforts that begin early in life, rather than those targeted at specific disorders, would be fruitful for reducing the burden of population mental health and preventing a cascade of mental disorders over the life course.
BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.
Background Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. Method A sample of 136 children (aged 6–30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners’ offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Results Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Conclusions Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.
BACKGROUND: Evidence suggests that impulsive aggression and explosive anger are common among individuals with anxiety disorders; yet, the influence of intermittent explosive disorder (IED) on the onset, course, consequences, and patterns of comorbidity among those with anxiety disorders is unknown. METHODS: Data were drawn from the National Comorbidity Survey Replication (N = 9,282) and Adolescent Supplement (N = 9,632), nationally representative surveys conducted between 2001 and 2004. Diagnoses were based on structured lay-administered interviews. Lifetime diagnoses were assessed with structured instruments. Outcomes included comorbidity, functional and role impairment, and treatment utilization. RESULTS: Adolescents with a lifetime anxiety disorder had a higher prevalence of a lifetime anger attacks (68.5%) and IED (22.9%) than adolescents without a lifetime anxiety disorder (48.6 and 7.8%, respectively), especially social phobia and panic disorders. Similar elevation was found for adults. Age of onset and course of anxiety disorders did not differ by IED. Severe functional impairment associated with anxiety was higher among adolescents (39.3%) and adults (45.7%) with IED than those without IED (29.2 and 28.2%, respectively). Comorbidity for all other disorders was elevated. However, individuals with anxiety disorders and IED were no more likely to use treatment services than those with anxiety disorders without IED. CONCLUSIONS: Individuals with IED concomitant to anxiety disorder, especially social phobia and panic, are at marked risk for worse functional impairment and a higher burden of comorbidity, but onset and course of anxiety disorder do not differ, and those with anxiety and IED are no more likely to utilize treatment services. Assessment, identification, and specialized treatment of anger in the context of anxiety disorders are critical to reducing burden.
Children who have experienced environmental adversity-such as abuse, neglect, or poverty-are more likely to develop physical and mental health problems, perform poorly at school, and have difficulties in social relationships than children who have not encountered adversity. What is less clear is how and why adverse early experiences exert such a profound influence on children's development. Identifying developmental processes that are disrupted by adverse early environments is the key to developing better intervention strategies for children who have experienced adversity. Yet, much existing research relies on a cumulative risk approach that is unlikely to reveal these mechanisms. This approach tallies the number of distinct adversities experienced to create a risk score. This risk score fails to distinguish between distinct types of environmental experience, implicitly assuming that very different experiences influence development through the same underlying mechanisms. We advance an alternative model. This novel approach conceptualizes adversity along distinct dimensions, emphasizes the central role of learning mechanisms, and distinguishes between different forms of adversity that might influence learning in distinct ways. A key advantage of this approach is that learning mechanisms provide clear targets for interventions aimed at preventing negative developmental outcomes in children who have experienced adversity.
Alterations in physiological reactivity to stress are argued to be central mechanisms linking adverse childhood environmental experiences to internalizing and externalizing psychopathology. Childhood trauma exposure may influence physiological reactivity to stress in distinct ways from other forms of childhood adversity. This study applied a novel theoretical model to investigate the impact of childhood trauma on cardiovascular stress reactivity - the biopsychosocial model of challenge and threat. This model suggests that inefficient cardiovascular responses to stress - a threat as opposed to challenge profile - are characterized by blunted cardiac output (CO) reactivity and increased vascular resistance. We examined whether childhood trauma exposure predicted an indicator of the threat profile of cardiovascular reactivity and whether such a pattern was associated with adolescent psychopathology in a population-representative sample of 488 adolescents (M=16.17years old, 49.2% boys) in the TRacking Adolescents' Individual Lives Survey (TRAILS). Exposure to trauma was associated with both internalizing and externalizing symptoms and a pattern of cardiovascular reactivity consistent with the threat profile, including blunted CO reactivity during a social stress task. Blunted CO reactivity, in turn, was positively associated with externalizing, but not internalizing symptoms and mediated the link between trauma and externalizing psychopathology. None of these associations varied by gender. The biopsychosocial model of challenge and threat provides a novel theoretical framework for understanding disruptions in physiological reactivity to stress following childhood trauma exposure, revealing a potential pathway linking such exposure with externalizing problems in adolescents.
OBJECTIVE: Childhood trauma is associated with hypertension in adults. It is unknown whether childhood trauma predicts elevated blood pressure earlier in development. We investigated whether the trauma of child abuse was associated with blood pressure in adolescents. METHODS: The sample included 145 adolescents aged 13-17 years, 40% with exposure to child abuse. The mean age of participants was 14.93 years (SD = 1.33); 58% were female. The majority self-identified as non-Hispanic White (43%), with the remainder identifying as non-Hispanic Black (17%), Hispanic (17%), or other/mixed race (23%). We used established age/sex/height-specific cutoffs to determine the prevalence of prehypertension and hypertension in the sample. We used two-sample t tests to examine associations of abuse with resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and blood pressure reactivity to the Trier Social Stress Test and a frustration task. We used linear regression to adjust for potential confounders including sociodemographic variables, body mass index, smoking, and psychopathology. RESULTS: Mean resting SBP and DBP were 114.07 mmHg and 61.35 mmHg in those with a history of abuse and 111.39 mmHg and 56.89 mmHg in those without a history of abuse. This difference was significant for DBP only. Twelve percent of participants met criteria for prehypertension or hypertension based on resting blood pressure values; this did not differ between those with and without an abuse history. Child abuse was associated with lower DBP and SBP reactivity to laboratory stress tasks and reduced DBP reactivity to frustration. These associations were robust to adjustment for potential confounders. CONCLUSIONS: Child abuse is associated with higher resting DBP and blunted DBP and SBP reactivity to laboratory stress in adolescence. These findings suggest a potential pathway by which child abuse leads to hypertension.
BACKGROUND: Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. METHODS: Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p \textless .05 with a false discovery rate correction. RESULTS: Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. CONCLUSIONS: Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility.
OBJECTIVES: Exposure to violence is associated with chronic physical conditions in adults. Although violence exposure is common among youths, it is unknown whether violence is associated with chronic physical conditions in childhood and adolescence. We examined the associations of violence exposure with chronic physical conditions in a population-representative sample of US adolescents and determined whether associations were explained by co-occurring mental disorders. METHODS: Data were drawn from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A), a national cross-sectional survey of 6,483 adolescents (ages 13-17). Lifetime exposure to violence; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition mood, anxiety, and substance disorders; and self-reported arthritis, frequent headaches, back or neck problems, other chronic pain, asthma, and allergies were assessed. RESULTS: One in 4 (24.99%) adolescents reported exposure to violence. Violence exposure was associated with elevated odds of back/neck pain, headaches, chronic pain, allergies, and asthma (odds ratio [OR], 1.5-2.1; 95% confidence interval [CI], 1.1-3.5) after adjustment for sociodemographics, socioeconomic status, and lifetime mental disorders. Regarding new onsets, violence exposure was associated with greater hazard for subsequent first-onset only of back/neck pain (hazard ratio, 1.9; 95% CI, 1.2-3.0) and headaches (hazard ratio, 1.4; 95% CI, 1.1-1.8), and these associations were explained by early-onset mental disorders. CONCLUSIONS: Childhood violence exposure is associated with chronic physical conditions that emerge early in the life course, although associations are stronger for prevalent than incident conditions. Violence exposure predicts incident pain conditions only, and these associations are explained by mental disorders that begin after violence exposure. Interventions and policies aimed at preventing violence and detecting and treating early-onset mental disorders have the potential to reduce morbidity, mortality, and health disparities beginning early in development.
Child maltreatment is a robust risk factor for internalizing and externalizing psychopathology in children and adolescents. We examined the role of disruptions in emotion regulation processes as a developmental mechanism linking child maltreatment to the onset of multiple forms of psychopathology in adolescents. Specifically, we examined whether child maltreatment was associated with emotional reactivity and maladaptive cognitive and behavioral responses to distress, including rumination and impulsive behaviors, in two separate samples. We additionally investigated whether each of these components of emotion regulation were associated with internalizing and externalizing psychopathology and mediated the association between child maltreatment and psychopathology. Study 1 included a sample of 167 adolescents recruited based on exposure to physical, sexual, or emotional abuse. Study 2 included a sample of 439 adolescents in a community-based cohort study followed prospectively for 5 years. In both samples, child maltreatment was associated with higher levels of internalizing psychopathology, elevated emotional reactivity, and greater habitual engagement in rumination and impulsive responses to distress. In Study 2, emotional reactivity and maladaptive responses to distress mediated the association between child maltreatment and both internalizing and externalizing psychopathology. These findings provide converging evidence for the role of emotion regulation deficits as a transdiagnostic developmental pathway linking child maltreatment with multiple forms of psychopathology.
OBJECTIVE: Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. METHOD: Data were drawn from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A), which included adolescents aged 13 to 18 years (N = 9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. RESULTS: Exposure to any PTE before age 11 years was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR = 1.80), other drugs (RR = 1.90), and multiple drugs (RR = 1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. CONCLUSION: Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention. The results also highlight that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events.
Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development.
Generalized anxiety disorder (GAD) and unipolar depressive disorders (UDD) have been shown to differ from each other in dimensions of affective functioning despite their high rates of comorbidity. We showed emotional film clips to a community sample (n = 170) with GAD, GAD with secondary UDD, or no diagnosis. Groups had comparable subjective responses to the clips, but the GAD group had significantly lower heart rate variability (HRV) during fear and after sadness, compared to controls. While HRV in the GAD and control groups rose in response to the sadness and happiness clips, it returned to baseline levels afterwards in the GAD group, potentially indicating lesser ability to sustain attention on emotional stimuli. HRV in the GAD + UDD group changed only in response to sadness, but was otherwise unvarying between timepoints. Though preliminary, these findings suggest comorbid UDD as a potential moderator of emotional responding in GAD.
Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.
Early-life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on the following: 1) the distinction between specific versus general aspects of ELA with regard to the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; 2) the importance of timing in the critical phases of exposure to ELA; and 3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as a mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multisystem processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.