Great Smoky Mountains Study Research Articles

Lagged effects of childhood depressive symptoms on adult epigenetic aging.

Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks 'tick faster' (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging. Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent (N = 539 individuals; 1029 assessments) and lagged (N = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging. Concurrent models showed that BMI (r = 0.15, PFDR < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms (b = 1.67 months per symptom, PFDR = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use. Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately 'accelerate' epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.

The biological embedding of social adversity: How adolescent housing insecurity impacts inflammation over time

Background & PurposeAdolescent housing insecurity is a dynamic form of social adversity that impacts child health outcomes worldwide. However, the means by which adolescent housing insecurity may become biologically embedded to influence health outcomes over the life course remain unclear. Therefore, we aimed to utilize life course perspectives and advanced causal inference methods to evaluate the potential for inflammation to contribute to the biological embedding of adolescent housing insecurity. Materials and methodsUsing prospective data from the Great Smoky Mountains Study, we investigated the relationship between adolescent housing insecurity and whole-blood spot samples assayed for C-reactive protein (CRP). Adolescent housing insecurity was created based on annual measures of frequent residential moves, reduced standard of living, forced separation from the home, and foster care. Annual measures of CRP ranged from 0.001 mg/L to 13.6 mg/L (median = 0.427 mg/L) and were log10 transformed to account for positively skewed values. We used g-estimation of structural nested mean models to estimate a series of conditional average causal effects of adolescent housing insecurity on CRP levels from ages 11 to 16 years and interpreted the results within life course frameworks of accumulation, recency, and sensitive periods. Principal ResultsOf the 1,334 participants, 427 [44.3 %] were female. Based on the conditional average causal effect, one exposure to adolescent housing insecurity from ages 11 to 16 years led to a 6.4 % (95 % CI = 0.69 – 12.4) increase in later CRP levels. Exposure at 14 years of age led to a 27.9 % increase in CRP levels at age 15 (95 % CI = 6.5 – 53.5). Recent exposures to adolescent housing insecurity (<3 years) suggested stronger associations with CRP levels than distant exposures (>3 years), but limited statistical power prevented causal conclusions regarding recency effects at the risk of a Type II Error. Major ConclusionsThese findings highlight inflammation—as indicated by increased CRP levels—as one potential mechanism for the biological embedding of adolescent housing insecurity. The results also suggest that adolescent housing insecurity—particularly recent, repeated, and mid-adolescent exposures—may increase the risk of poor health outcomes and should be considered a key intervention target.

Adult Mental Health, Substance Use Disorders, and Functional Outcomes of Children Resilient to Early Adversity.

Some children are unaffected by mental illness despite exposure to childhood adversity. These children are typically considered resilient. The objective of this study was to follow up such resilient children in adulthood to characterize mental health status, substance use, and functional outcomes. The analysis was based on the prospective, representative Great Smoky Mountains Study (N=1,420). Participants were assessed for psychiatric disorders and exposure to adversity with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6,674 observations). In total, 1,266 participants (86.3%) were followed up in adulthood at ages 25 and 30 to assess psychiatric disorders, substance use disorders, and functional outcomes. Seventy-five percent of the sample had met criteria for a psychiatric disorder or displayed subthreshold psychiatric problems by age 16. The number of adverse childhood experiences was strongly associated with childhood psychiatric status. Of children exposed to multiple adversities (N=650), 12.2% (N=63) did not display psychiatric problems. This group meets common definitions of childhood resilience. In adulthood, these individuals showing childhood resilience had greater risk of anxiety (risk ratio=2.9, 95% CI=1.0-9.1) and depressive (risk ratio=4.5, 95% CI=1.1-16.7) disorders, as well as worse physical health (means ratio=0.7, 95% CI=0.5-0.9) and financial or educational functioning (means ratio=0.6, 95% CI=0.5-0.7), compared with individuals exposed to fewer childhood adversities. These individuals showing childhood resilience did not have elevated risk for substance use disorders. Resilience to childhood adversity was uncommon. Individuals who appeared resilient in childhood were at risk for delayed poorer outcomes in adulthood. Public health efforts should prioritize minimizing early adversity exposure over promoting resilience.

Associations Between Configurations of Childhood Adversity and Adult Mental Health Disorder Outcomes.

The life course perspective and cumulative inequality theory suggest that childhood adversity, occurring during a sensitive period of the life course, can have long-term consequences for adult mental health and well-being. Yet, the long-term influence of adversity on adult outcomes may depend on both the features of adverse childhood experiences (e.g., the number, type, and co-occurrence of adversities) as well as the outcome assessed. Using latent class analysis applied to several waves of prospective data from the Great Smoky Mountain Study (GSMS; N=1,420) we identify subpopulations that are similar in their adversity experiences before age 18. We then predict adult internalizing and substance use disorder diagnoses by adversity experience. Results reveal five distinct classes of adversity, with unique risks for specific diagnoses in adulthood.

Violent Experiences and Patterns of Firearm Ownership From Childhood to Young Adulthood

Young adults in their 20s are at high relative risk for self- and other-directed firearm injury, but little is known about gun access patterns for this group. To describe the longitudinal patterns of firearm access from childhood to young adulthood and to estimate whether violence experienced as a child or as an adult is associated with gun ownership in young adulthood. The Great Smoky Mountains Study included participants from 11 contiguous, mostly rural counties in the Southeastern US. The first wave was completed in 1993 and the most recent in 2019. Periodic survey data were gathered in adolescence through participants' late 20s. In 2023, adjusted Poisson regression with incident rate ratios (IRRs) and 95% CIs were used to estimate associations between violence and gun ownership in young adulthood in 3 age cohorts from the original sample. Violent experiences in childhood (bullying, sexual and physical abuse, violent events, witnessing trauma, physical violence between parents, and school/neighborhood dangerousness) or adulthood (physical and sexual assault). Initiating gun ownership was defined as no gun access or ownership in childhood followed by gun ownership at age 25 or 30 years. Maintaining gun ownership was defined as reporting gun access or ownership in at least 1 survey in childhood and ownership at age 25 or 30 years. Among 1260 participants (679 [54%] male; ages 9, 11, and 13 years), gun access or ownership was more common in childhood (women: 366 [63%]; men: 517 [76%]) than in adulthood (women: 207 [36%]; men: 370 [54%]). The most common longitudinal pattern was consistent access or ownership from childhood to adulthood (373 [35%]) followed by having access or ownership in childhood only (408 [32%]). Most of the violent exposures evaluated were not significantly associated with the outcomes. Being bullied at school was common and was associated with reduced ownership initiation (IRR, 0.76; 95% CI, 0.61-0.94). Witnessing a violent event was significantly associated with increased probability of becoming a gun owner in adulthood (IRR, 1.24; 95% CI, 1.03-1.49). In this cohort study, gun ownership and access were transitory, even in a geographic area where gun culture is strong. Early adulthood-when the prevalence of gun ownership was relatively low-may represent an opportune time for clinicians and communities to provide education on the risks associated with firearm access, as well as strategies for risk mitigation.

Intergenerational Effects of a Family Cash Transfer on the Home Environment

A natural experiment that provided income supplements to families has been associated with beneficial outcomes for children that persisted into adulthood. The children in this study are now adults, and many are parents. The study builds on the longitudinal, representative Great Smoky Mountains study conducted from 1993 to 2020. At follow-up in their late 30s, 1,094 of the 1,348 living participants (81.2%) were assessed. Of these participants (67.6%), 739 were parents. A tribe in the area implemented a cash transfer program of approximately $5,000 annually per person to every tribal member based on the profits received from operating a casino. Ten aspects of the home environment of participants were assessed (eg, family chaos, substance use, and food insecurity) as well as a composite measure across all home environment indicators. The proposed analyses were preregistered (https://osf.io/ex638). Of the 739 parents assessed, 192 (26.0%) were American Indians. Parents whose families received cash transfers during childhood did not differ from parents whose families did not receive cash transfers on any of the home environment indicators or the composite measure. At the same time, there was little evidence of elevated risk for participants in either group in measures of parental mental health, substance use, and violence. A family cash transfer in childhood that had long-term effects on individual functioning did not impact the home environment of participants who became parents. Rather, parents in both groups were providing home environments generally conducive to their children's growth and development. Intergenerational Effects of a Family Cash Transfer on the Home Environment; https://osf.io/; ex638.

Methylome-wide association study of anxiety disorders.

Anxiety Disorders (ANX) such as panic disorder, generalized anxiety disorder, and phobias, are highly prevalent conditions that are moderately heritable. Evidence suggests that DNA methylation may play a role, as it is involved in critical adaptations to changing environments. Applying an enrichment-based sequencing approach covering nearly 28 million autosomal CpG sites, we conducted a methylome-wide association study (MWAS) of lifetime ANX in 1132 participants (618 cases/514 controls) from the Netherlands Study of Depression and Anxiety. Using epigenomic deconvolution, we performed MWAS for the main cell types in blood: granulocytes, T-cells, B-cells and monocytes. Cell-type specific analyses identified 280 and 82 methylome-wide significant associations (q-value < 0.1) in monocytes and granulocytes, respectively. Our top finding in monocytes was located in ZNF823 on chromosome 19 (p = 1.38 × 10-10) previously associated with schizophrenia. We observed significant overlap (p < 1 × 10-06) with the same direction of effect in monocytes (210 sites), T-cells (135 sites), and B-cells (727 sites) between this Discovery MWAS signal and a comparable replication dataset from the Great Smoky Mountains Study (N = 433). Overlapping Discovery-Replication MWAS signal was enriched for findings from published GWAS of ANX, major depression, and post-traumatic stress disorder. In monocytes, two specific sites in the FZR1 gene showed significant replication after Bonferroni correction with an additional 15 nominally replicated sites in monocytes and 4 in T-cells. FZR1 regulates neurogenesis in the hippocampus, and its knockout leads to impairments in associative fear memory and long-term potentiation in mice. In the largest and most extensive methylome-wide study of ANX, we identified replicable methylation sites located in genes of potential relevance for brain mechanisms of psychiatric conditions.

Prospective Associations of Childhood Housing Insecurity With Anxiety and Depression Symptoms During Childhood and Adulthood

Childhood housing insecurity has dramatically increased in the US in recent decades, but whether an association with adverse mental health outcomes exists after adjusting for repeated measures of childhood poverty is unclear. To test whether childhood housing insecurity is associated with later anxiety and depression symptoms after adjusting for time-varying measures of childhood poverty. This prospective cohort study included individuals aged 9, 11, and 13 years at baseline from the Great Smoky Mountains Study in western North Carolina. Participants were assessed up to 11 times from January 1993 to December 2015. Data were analyzed from October 2021 to October 2022. Participants and their parents reported social factors annually when participants were 9 to 16 years of age. A comprehensive measure of childhood housing insecurity was constructed based on frequent residential moves, reduced standard of living, forced separation from home, and foster care status. Between ages 9 and 16 years, the Child and Adolescent Psychiatric Assessment was used up to 7 times to evaluate childhood anxiety and depression symptoms. Adult anxiety and depression symptoms were assessed at ages 19, 21, 26, and 30 years using the Young Adult Psychiatric Assessment. Of the 1339 participants (mean [SD] age, 11.3 [1.63] years), 739 (55.2%; 51.1% weighted) were male; 1203 individuals assessed up to 30 years of age were included in the adulthood outcome analyses. Standardized mean (SD) baseline anxiety and depression symptom scores were higher among children who experienced housing insecurity than among those who never experienced housing insecurity (anxiety: 0.49 [1.15] vs 0.22 [1.02]; depression: 0.20 [1.08] vs -0.06 [0.82]). Individuals who experienced childhood housing insecurity had higher anxiety symptom scores (fixed effects: standardized mean difference [SMD], 0.21; 95% CI, 0.12-0.30; random effects: SMD, 0.25; 95% CI, 0.15-0.35) and higher depression symptom scores (fixed effects: SMD, 0.18; 95% CI, 0.09-0.28; random effects: SMD, 0.26; 95% CI, 0.14-0.37) during childhood. In adulthood, childhood housing insecurity was associated with higher depression symptom scores (SMD, 0.11; 95% CI, 0.00-0.21). In this cohort study, housing insecurity was associated with anxiety and depression during childhood and with depression during adulthood. Because housing insecurity is a modifiable, policy-relevant factor associated with psychopathology, these results suggest that social policies that support secure housing may be an important prevention strategy.

The HOME-21: A revised measure of the home environment for the 21st century tested in two independent samples.

For decades, the Home Observation for Measurement of the Environment (HOME) has been the most widely used measure of children's home environments. This report provides a revised version of the HOME-Short Form, the HOME-21, reflecting historical changes in family composition and caregiver roles, norms about the acceptability of different forms of discipline, and children's digital environments. Using data from two samples of parents of children ages 0-17 (Fast Track [FT], N = 553, age = 33.8, 49.2% female, 48.1% Black, 51.9% White/other; Great Smoky Mountains Study [GSMS], N = 722, age = 37.2, 54.7% female, 67.6% White, 6.6% Black, 25.8% American Indian), we assess the utility of the HOME-21 with descriptive statistics and correlations with a range of demographic, family context, parenting, and child adjustment measures. Higher HOME-21 scores were correlated with obtaining a high school diploma or equivalency diploma (in GSMS only), having 4 or more years of college, and household income. HOME-21 was also correlated with having a more favorable family context indexed by fewer stressful life events (in FT only), less household food insecurity, lower household chaos, and more perceived social support. Higher HOME-21 scores were correlated with better parenting in the form of parental acceptance, positive parenting, warm involvement, appropriate and consistent discipline, verbal discussion, less physical aggression, and greater parental self-efficacy. Higher HOME-21 scores were correlated with better child adjustment in terms of fewer emotional and conduct problems, less hyperactivity, and more prosocial behavior. The HOME-21 has utility for use in future studies of children's home environments in the 21st century. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Identifying adolescents at risk for depression: Assessment of a global prediction model in the Great Smoky Mountains Study

The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) has been externally assessed in samples from four continents, but North America is lacking. Our aim here was to evaluate the performance of the IDEA-RS in predicting future onset of Major Depressive Disorder (MDD) in an adolescent population-based sample in the United States of America - the Great Smoky Mountains Study (GSMS). We applied the intercept and weights of the original IDEA-RS model developed in Brazil to generate individual probabilities for each participant of the GSMS at age 15 (N = 1029). We then evaluated the performance of such predictions against the diagnosis of MDD at age 19 using simple, case-mix corrected and refitted models. Furthermore, we compared how prioritizing the information provided by parents or by adolescents affected performance. The IDEA-RS exhibited a C-statistic of 0.63 (95% CI 0.53–0.74) to predict MDD in the GSMS when applying uncorrected weights. Case-mix corrected and refitted models enhanced performance to 0.69 and 0.67, respectively. No significant difference was found in performance by prioritizing the reports of adolescents or their parents. The IDEA-RS was able to parse out adolescents at risk for a later onset of depression in the GSMS cohort with above chance discrimination. The IDEA-RS has now showed above-chance performance in five continents.

Impact of dimensions of early adversity on adult health and functioning: A 2-decade, longitudinal study.

Recent neurodevelopmental and evolutionary theories offer strong theoretical rationales and some empirical evidence to support the importance of specific dimensions of early adversity. However, studies have often been limited by omission of other adversity dimensions, singular outcomes, and short follow up durations. 1,420 participants in the community, Great Smoky Mountains Study, were assessed up to eight times between age 9 and 16 for four dimensions of early adversity: Threat, Material Deprivation, Unpredictability, and Loss (as well as a Cumulative Adversity measure). Participants were followed up to four times in adulthood (ages 19, 21, 25, and 30) to measure psychiatric disorders, substance disorder, and "real-world" functioning. Every childhood adversity dimension was associated with multiple adult psychiatric, substance, or functional outcomes when tested simultaneously in a multivariable analysis that accounted for other childhood adversities. There was evidence of differential impact of dimensions of adversity exposure on proximal outcomes (e.g., material deprivation and IQ) and even on distal outcomes (e.g., threat and emotional functioning). There were similar levels of prediction between the best set of individual adversity scales and a single cumulative adversity measure when considering distal outcomes. All dimensions of childhood adversity have lasting, pleiotropic effects, on adult health and functioning, but these dimensions may act via distinct proximal pathways.

Childhood loneliness as a specific risk factor for adult psychiatric disorders.

Loneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood. This study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6674 observations; 1993-2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes. Both self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status. Childhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness - even in childhood - might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.

Longitudinal associations of trauma exposure with disordered eating: Lessons from the Great Smoky Mountains Study

ABSTRACT Disordered eating is prevalent among trauma survivors, yet little is known about mechanisms underlying this relation. We explored cross-sectional and longitudinal associations of trauma exposure and posttraumatic stress disorder symptoms (PTSD) with disordered eating among 1,420 community-based youth participating in the Great Smoky Mountain Study. Participants were interviewed about trauma exposure, PTSD symptoms, and disordered eating at regular intervals throughout childhood, adolescence, and early adulthood. Our findings confirmed associations of all forms of trauma exposure (violent, sexual, and other) with disordered eating symptoms in childhood and adulthood, although the pattern of results varied by disordered eating symptom and trauma exposure type. Only non-sexual, non-violent trauma exposure in childhood had significant associations with any disordered eating symptoms in adulthood. Within childhood, trauma exposures but not PTSD symptoms showed significant longitudinal associations with bulimia nervosa symptoms and sustained appetite changes and preoccupation with eating. In adulthood, PTSD symptoms but not trauma exposures showed significant longitudinal associations only with bulimia nervosa symptoms. The association of specific PTSD clusters on bulimia nervosa symptoms was significant for reexperiencing, whereas hyperarousal symptoms trended toward significance. The impact of trauma exposures on disordered eating may vary by developmental period.

Depression in childhood may increase vulnerability to opioid euphoria in young adulthood

Researchers have found that childhood depression as well as tobacco use were associated with later opioid use in general, weekly opioid use, and heroin use. The cohort study, based on the Great Smoky Mountains Study (GSMS), concluded that children with chronic depression may take opioids to alleviate the physical symptoms — including pain — that often accompany depression. While depression may not be an evident cause of such symptoms, these complaints may lead to unnecessary opioid prescriptions, and the child's first exposure to opioid‐associated euphoria. Childhood somatic complaints — and elevated inflammation and injury — were associated with progression from any to weekly non‐heroin opioid use.

Depression in childhood may increase vulnerability to opioid euphoria in young adulthood

Researchers have found that childhood depression as well as tobacco use were associated with later opioid use in general, weekly opioid use, and heroin use. The cohort study, based on the Great Smoky Mountains Study (GSMS), concluded that children with chronic depression may take opioids to alleviate the physical symptoms — including pain — that often accompany depression. While depression may not be an evident cause of such symptoms, these complaints may lead to unnecessary opioid prescriptions, and the child's first exposure to opioid‐associated euphoria. Childhood somatic complaints — and elevated inflammation and injury — were associated with progression from any to weekly non‐heroin opioid use.

Depression in childhood may increase vulnerability to opioid euphoria

Researchers have found that childhood depression as well as tobacco use were associated with later opioid use in general, weekly opioid use and heroin use. The cohort study, “Prevalence and Childhood Precursors of Opioid Use in the Early Decades of Life,” based on the Great Smoky Mountains Study (GSMS), concluded that children with chronic depression may take opioids to alleviate the physical symptoms — including pain — that often accompany depression. While depression may not be an evident cause of such symptoms, these complaints may lead to unnecessary opioid prescriptions and the child's first exposure to opioid‐associated euphoria. Childhood somatic complaints — and elevated inflammation and injury — were associated with progression from any to weekly nonheroin opioid use.

Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences

The impact of adolescent cannabis use is a pressing public health question owing to the high rates of use and links to negative outcomes. This study considered the association between problematic adolescent cannabis use and methylation. Using an enrichment-based sequencing approach, a methylome-wide association study (MWAS) was performed of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, MWASs were performed for the main cell types in blood: granulocytes, T cells, B cells, and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use. Whole-blood analyses identified 45 significant CpGs, and cell type-specific analyses yielded 32 additional CpGs not identified in the whole-blood MWAS. Significant overlap was observed between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T cells and monocytes overlapped with findings from an MWAS of psychosis conducted in brain tissue. In one of the first methylome-wide association studies of adolescent cannabis use, several methylation sites located in genes of importance for potentially relevant brain functions were identified. These findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development and inflammation response as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects.

Depression and tobacco use in childhood increases opioid use

Researchers have found that childhood depression as well as tobacco use were associated with later opioid use in general, weekly opioid use and heroin use. The cohort study, based on the Great Smoky Mountains Study (GSMS), concluded that children with chronic depression may take opioids to alleviate the physical symptoms — including pain — that often accompany depression. While depression may not be an evident cause of such symptoms, these complaints may lead to unnecessary opioid prescriptions, and the child's first exposure to opioid‐associated euphoria. Childhood somatic complaints — and elevated inflammation and injury — were associated with progression from any to weekly nonheroin opioid use.

Early life trauma - review of clinical and neurobiological studies.

Psychological trauma is a significant risk factor for physical and mental health development distortion. This paper presents the results of longitudinal epidemiological surveys and naturalistic observations. It also reviews the results of the most important neurobiological findings in the field of impact of early life trauma on cognitive and emotional development, and the structure and functions of the brain. Trauma is defined as subjective experiences that overwhelm a person's ability to maintain psychophysical integrity. During the stage of neurodevelopment, various life adversities, such as emotional and sensory deprivation, abandonment and neglect by caregivers as well as physical or emotional violence and sexual abuse overwhelm the physiological and mental capacity of a child and impact their cognitive, emotional and social development, adversely influencing adulthood functioning. Symptoms of abused children can evolve and change with time, from moderate signs of distress to more complex symptoms and organized disorders. The most important longitudinal studies, such as the Lives Across Time Study, Minnesota Study, Adverse Childhood Experiences Study, The Great Smoky Mountains Study, and the English and Romanian Adoptee Study are discussed in the paper. The lifelong influences of early adversities on brain structures like the corpus callosum, hippocampus, the amygdaloid nuclei, ventral striatum and cerebral cortex has been described. The variability of the sensitivity of specific brain regions, based on different rates of maturation, has also been discussed. This review integrates and summarizes the basic knowledge about the impact and neurobiological consequences of early traumatic adversities.

Journal Digest: Sertraline &amp; Depression; Cognitive Therapy &amp; Pregnancy; Clozaphine &amp; Schizofrenia; Despair &amp; Negative outcome; LGBTQ Teens &amp; Bullying; Exposure Therapy &amp; Drug Craving

Journal Digest: Sertraline &amp; Depression; Cognitive Therapy &amp; Pregnancy; Clozaphine &amp; Schizofrenia; Despair &amp; Negative outcome; LGBTQ Teens &amp; Bullying; Exposure Therapy &amp; Drug Craving