Amygdala responses to threat in violence-exposed children depend on trauma context and maternal caregiving.

Early life adversity (ELA) has been linked with increased arousal responses to threat, including increased amygdala reactivity. Effects of ELA on brain function are well recognized, and emerging evidence suggests that caregivers may influence how environmental stressors impact children's brain function. We investigated the hypothesis that positive interaction between mother and child can buffer against ELA effects on children's neural responses to threat, and related symptoms. N = 53 mother-child pairs (children ages 8-14 years) were recruited from an urban population at high risk for violence exposure. Maternal caregiving was measured using the Parenting Questionnaire and in a cooperation challenge task. Children viewed fearful and neutral face stimuli during functional magnetic resonance imaging. Children who experienced greater violence at home showed amygdala sensitization, whereas children experiencing more school and community violence showed amygdala habituation. Sensitization was in turn linked with externalizing symptoms. However, maternal warmth was associated with a normalization of amygdala sensitization in children, and fewer externalizing behaviors prospectively up to 1 year later. Findings suggested that the effects of violence exposure on threat-related neural circuitry depend on trauma context (inside or outside the home) and that primary caregivers can increase resilience.

Childhood Violence Exposure Predicts High Blood Pressure in Black American Young Adults.

OBJECTIVE: To test the impact of childhood adversity, including community violence exposure, on hypertension risk in Black American young adults to understand what risk factors (eg, prenatal factors, later exposures) and ages of adversity exposure increased hypertension risk. STUDY DESIGN: The study included 396 Black American participants with data from prenatal, birth, and age 7-, 14-, and 19-year visits. At age 19 years, individuals with blood pressure (BP) measures >120 mmHg systolic and/or >80 mmHg diastolic were classified as having high blood pressure (HBP), and those with BP <120/80 mmHg were classified as normal. Associations between prenatal and birth risk factors; childhood adversity at age 7, 14, and 19 years; age 19 body mass index (BMI); and both systolic and diastolic BP at age 19 were tested using logistic regression models. RESULTS: Age 19 BMI was positively associated with systolic and diastolic HBP status at age 19. Controlling for all covariates, community violence exposure at age 7 and 19 years was associated with 2.2-fold (95% CI, 1.242-3.859) and 2.0-fold (95% CI, 1.052-3.664) greater odds of systolic HBP, respectively, at age 19 years. Prenatal risk, birth risk, and other dimensions of childhood adversity were not associated with HBP in this cohort. CONCLUSION: Childhood community violence exposure is a significant risk factor for HBP in young adults. As Black American children typically experience more community violence exposure than other American children, our results suggest that racial disparities in childhood community violence exposure may contribute to racial disparities in adult hypertension burden.

Associations of maternal emotion regulation with child white matter connectivity in Black American mother-child dyads.

Parental emotion regulation plays a major role in parent-child interactions, and in turn, neural plasticity in children, particularly during sensitive developmental periods. However, little is known about how parental emotion dysregulation is associated with variation in children's brain structure, which was the goal of this study. Forty-five Black American mother-child dyads were recruited from an intergenerational trauma study; emotion regulation in mothers and their children (age 8-13 years) was assessed. Diffusion-weighted images were collected in children; deterministic tractography was used to reconstruct pathways of relevance to emotion regulation. Metrics of white matter connectivity [fractional anisotropy (FA), mean diffusivity (MD)] were extracted for pathways. Socio-economic variables were also included in statistical models. Maternal emotion dysregulation was the strongest predictor of child fornix MD (r = .35, p = .001), indicating that more severe emotion dysregulation in mothers corresponded with lower fornix connectivity in children. Maternal impulsivity was a strong predictor of child fornix MD (r = .51, p < .001). Maternal emotion dysregulation may adversely influence connectivity of the child.s fornix, a hippocampal-striatal pathway implicated in reward processes; these associations remained even after accounting for other socio-environmental factors. Dysregulated maternal emotions may uniquely impact children's adaptation to trauma/stress by affecting networks that support appetitive processing.

White matter microstructure in trauma-exposed children: Associations with pubertal stage.

Puberty represents a critical period in maturation during which major changes in neural architecture emerge; these changes are shaped, in part, by environmental experiences, including exposure to psychological trauma. However, little is known about how trauma exposure affects white matter microstructure across pubertal stages. This was the goal of the present cross-sectional study. Forty-one male and female African-American children between ages 8-13 were recruited as part of a study of developmental trauma and received assessments of trauma exposure, including violence, and pubertal development as well as diffusion tensor imaging (DTI). Significant interactions of pubertal stage and violent trauma exposure were observed in association with a marker of white matter integrity (mean diffusivity, MD) in the corpus callosum, cingulum bundle and uncinate fasciculus. Greater violent trauma exposure was associated with lower MD in the hippocampal cingulum and uncinate fasciculus in girls, but not boys. These data from a sample of trauma-exposed children may reflect a pattern of accelerated maturation in pathways that are critical for emotion regulation as well as attention and memory processes. It appears that fronto-limbic and callosal connections are particularly sensitive to the effects of violent trauma, revealing a potential pathway through which trauma creates vulnerability for later psychiatric and neurological disorders.

Puberty drives fear learning during adolescence.

Risk for adverse outcomes, including the onset of mental illness, increases during adolescence. This increase may be linked to both new exposures, such as violence at home or in the community, or to physiological changes driven by puberty. There are significant sex differences in adolescent risk, for instance, anxiety disorders are significantly more prevalent in girls than boys. Fear learning is linked to mental health and may develop during adolescence, but the role of puberty in adolescent-specific change has not yet been systematically evaluated. We conducted a longitudinal study of fear learning that tested fear-potentiated startle (FPS) in 78 children (40 girls) aged 8-16 years. Participants completed two to three visits that included a differential fear conditioning task and self-report of both pubertal status and violence exposure. We tested for effects of sex, pubertal status, and violence exposure on FPS over time with latent growth curve models. We also examined the association between FPS and later anxiety symptoms. We found significant changes in FPS to the threat cue, but not the safety cue, across visits. Higher pubertal status was significantly associated with increased FPS to threat cues at each visit, whereas sex and violence exposure were not. FPS to threat during the baseline visit also predicted later anxiety symptoms. These findings suggest that puberty drives increased fear response to threat cues similarly for girls and boys, and that this effect may not be significantly impacted by individual differences in violence exposure during early adolescence.

Increased activation of the fear neurocircuitry in children exposed to violence.

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8- to 14-year-old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long-term costs or consequences of these adaptations are largely unknown and an area for future investigations.

Emotion effects on memory from childhood through adulthood: Consistent enhancement and adult gender differences.

Emotion typically enhances memory. This "canonical" emotional memory enhancement (EME) effect has been extensively studied in adults, but its developmental trajectory is unclear. The handful of developmental studies that have manipulated emotion at encoding and then tested subsequent memory have yielded mixed results. To identify whether development change in EME occurs across middle childhood, adolescence, and early adulthood, we examined EME in 206 8- to 30-year-olds, using the same stimuli, paradigm, and analyses for all participants. At encoding, participants saw negative, neutral, and positive pictures while completing an incidental task. Two weeks later, participants completed a recognition memory test. We calculated negative-neutral and positive-neutral memory difference scores for each participant and then tested whether EME was predicted by age or gender. Negative pictures were remembered better than neutral pictures; the magnitude of this difference diminished in older male participants but not in older female ones. Positive pictures were also remembered better than neutral pictures, but this EME effect was small and did not change significantly with age or by gender. We also examined whether subjective ratings of stimulus emotion changed with age or between genders, and we report small differences. These results suggest that emotion effects on recognition memory are apparent by middle childhood and remain consistent across adolescence and early adulthood for girls and women, whereas emotion elicitation and EME effects diminish slightly with age for boys and men. These findings enrich both the EME literature specifically and what is known about emotion-cognition interactions across middle childhood, adolescence, and early adulthood more generally.

Prospective Measurement of Skin Conductance Response during Trauma Interview Predicts Future PTSD Severity in Trauma Exposed Children.

Previous cross-sectional studies have shown that sympathetic nervous system (SNS) arousal is positively associated with posttraumatic stress disorder (PTSD) symptoms in children with trauma exposure. One of the ways that SNS activity is measured is through skin conductance response (SCR), which has been shown to predict future PTSD severity in adults. In this study, we explored the utility of a novel, low-cost mobile SCR device, eSense, to predict future PTSD symptom severity in trauma exposed children. We recruited children (N=43, age 9 years at initial visit) for a longitudinal study in which SCR was recorded at baseline visit, and PTSD symptoms were assessed two years later. Results indicated an interaction between SCR and trauma exposure, such that children with lower trauma exposure who demonstrated greater SCR reported higher PTSD severity two years later. This association remained significant even after controlling for baseline PTSD symptoms. Children with higher levels of trauma exposure did not show this association, potentially due to ceiling effects of PTSD symptoms. Together these findings suggest the utility of SCR as a biomarker for predicting trauma related disorders in children, and that it may be a valuable tool in clinical interventions targeting sympathetic arousal.

Resting heart rate associations with violence exposure and posttraumatic stress symptoms: sex differences in children.

BACKGROUND: Traumatic events experienced in childhood can lead to increased risk of cardiovascular disorders in adulthood. Black Americans are disproportionately affected, as they are at increased risk for experiencing childhood trauma and cardiovascular diseases in adulthood. One of the hypothesized mechanisms of this association is through long-lasting dysregulation of the autonomic nervous system, a hallmark physiological biomarker of posttraumatic stress disorder (PTSD), which is twice as prevalent in women compared to men. METHODS: Ninety-one, majority Black American children, aged 9 were recruited to be a part of our longitudinal study of child development at research centers in Atlanta, GA and Detroit, MI. Resting HR was measured through a electrocardiogram (ECG) recording using the Biopac MP150. Self-report measures of violence exposure and PTSD symptoms were administered by research staff. RESULTS: Children with more violence exposure reported increased PTSS as well as lower resting HR. Regression analysis showed evidence of sex modifying this relationship, (B = -0.64, p < 0.05), such that the association between resting HR and PTSS was stronger in girls than in boys. In our exploratory analysis with standard clinical cutoffs of resting HR, the normative HR group was found to significantly moderate the relationship between violence exposure and PTSS in boys, (B = -2.14, p < 0.01), but not girls (B = -0.94, p = 0.27). CONCLUSION: In our sample of primarily Black urban children, we found that violence exposure was associated with slower, more adult-like HR, that girls showed greater PTSS associated with slower HR while boys did not, and that girls with lower than normative HR showed significantly higher PTSS compared to girls with normative HR. Our sample's demonstration of psychological consequences in addition to the physiological implications could provide new information about a psychobiological sequelae of violence exposure.

Experiencing traumatic events in childhood can lead to increased risk of heart disease in adulthood. One of the ways this might happen is through long-lasting changes of the autonomic nervous system. This system is dysregulated in posttraumatic stress disorder (PTSD), which is twice as common in women compared to men. We explored whether resting heart rate (HR), a measure of autonomic functioning was associated with violence exposure in children, and whether this relationship was different in boys and girls. We also explored whether categorizing our sample into resting HR groups based off standardized norms for HR predicted differing relationships between violence exposure and posttraumatic stress symptoms (PTSS). Because childhood trauma and heart disease impact Black Americans at greater rates, we recruited our sample of 92 nine-year-old children from research centers in Atlanta, GA and Detroit, MI. We measured their resting HR, exposure to violence, and PTSS. We found that violence exposure was associated with lower HR overall, that girls showed greater PTSS associated with lower HR when compared to boys, and that boys with lower than normative HR showed a stronger association between violence exposure and PTSS compared to boys with normative HR. Future studies should examine potential mechanisms underlying this sex difference to best understand the long-term cardiovascular consequences for sex-related health disparities. Specifically, longitudinal studies may be able to help researchers understand how reduced HR during adolescents might lead to future cardiovascular disease and psychopathology.

Getting Better with Age? A Review of Psychophysiological Studies of Fear Extinction Learning Across Development.

A critical developmental task is learning what constitutes reliable threat and safety signals in the environment. In humans, atypical fear learning processes are implicated in many mental health conditions, particularly fear and anxiety disorders, pointing to the potential for laboratory measures of fear learning to facilitate early identification of at-risk individuals. This chapter reviews studies of fear learning and extinction learning that incorporate peripheral measures of psychophysiological response and include a developmental sample. Broadly, these studies indicate substantial consistency in differential learning and extinction across development, as assessed with multiple paradigms, across physiological indices. Importantly, though, response coherence across measures (e.g., physiological, neural, and behavioral) was inconsistent across studies. There was also less consistency in results from studies that probed associations between anxiety and fear learning processes. These mixed findings highlight the need for additional examination of when and why there is variability, both across development and in relation to individual differences factors, including mental health, childhood adversity, and sex. In addition, there remains a need for studies that test for developmental change in extinction recall learning and whether stimulus type impacts learning across development. Longitudinal studies designed to address these questions could provide novel insight into the developmental trajectory of fear learning and extinction.

Intergenerational Transmission of Depression: Examining the Roles of Racism and Trauma Among Black Mothers and Youth.

OBJECTIVE: Racism is a multifaceted system of oppression that disproportionately harms Black mothers and children across the lifespan. Despite reliable evidence that racism is associated with worse mental health outcomes (eg, increased depressive symptoms), less is known about potential intergenerational effects of Black mothers' experiences of racism on children's mental health, as well as how traumatic experiences influence these pathways. In this cross-sectional quantitative study, we aimed (1) to replicate the finding that maternal experiences of racism are associated with both maternal and child depression; (2) to identify whether maternal experiences of racism are indirectly associated with child depression via the effect of maternal depression; and (3) to test whether the indirect effect of racism on child depression via maternal depression is conditioned on maternal trauma. METHOD: Black mothers and their children (N = 148 dyads) were recruited from an urban hospital and were interviewed about their experiences of racism, trauma, and mental health symptoms. The mothers' average age was 35.16 years (SD = 8.75) and the children's average age was 10.03 years (SD = 1.51). RESULTS: First, we found that maternal experiences of racism were associated with more severe maternal depression (r = 0.37, p < .01) as well as more severe child depression (r = 0.19, p = .02). Second, we found that maternal experiences of racism were indirectly associated with child depression through the effect of maternal depression (ab = 0.76, 95% CI = 0.26, 1.37). Third, we found that maternal trauma exposure moderated this indirect effect such that, at relatively lower levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was nonsignificant (ωlow = -0.05, 95% CI = -0.50, 0.45), whereas at relatively higher levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was statistically significant (ωhigh= .65, 95% CI = 0.21, 1.15). CONCLUSION: These findings suggest that the indirect effect of maternal experiences of racism on child depression through the effect of maternal depression depends on the degree of maternal trauma exposure. This study advances the literature by shedding light on key processes that can explain the intergenerational effects of racism as well as contextual factors that can exacerbate racism's downstream consequences across generations.

The role of specific emotion dysregulation facets in the association between child violence exposure and psychopathology.

OBJECTIVE: African Americans living in low-income urban environments are disproportionately exposed to violence compared to other racial groups. Child exposure to community violence is linked to adverse psychological outcomes, including externalizing and internalizing behaviors. Emotion dysregulation may be one psychological process through which externalizing and internalizing behaviors develop in the context of childhood violence exposure. However, limited research exists on how different aspects of emotion dysregulation are affected by community violence exposure in children. METHOD: The present study examined whether violence exposure was indirectly associated with externalizing and internalizing behaviors via facets of emotion dysregulation in a sample of 94 African American mother-child dyads. Mothers and children completed measures to assess child community violence exposure, externalizing and internalizing behaviors, and emotion dysregulation (anger, sadness, and worry dysregulation). RESULTS: Results indicated that maternal report of child community violence exposure was indirectly associated with externalizing behaviors via anger dysregulation and internalizing behaviors via worry dysregulation. Child report of community violence exposure was also indirectly associated with externalizing behavior via anger dysregulation; however, there were no significant associations with internalizing behavior. CONCLUSIONS: These findings suggest that certain components of emotion dysregulation serve as an indirect pathway of influence for community violence exposure on child behavior, and the pathways differ between externalizing and internalizing behavior outcomes. Emotion dysregulation may serve as an important potential treatment target in reducing long-term risks associated with violence exposure in urban communities of color. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intergenerational transmission of risk for PTSD symptoms in African American children: The roles of maternal and child emotion dysregulation.

OBJECTIVE: Emotion dysregulation is a transdiagnostic risk factor for many mental health disorders and develops in the context of early trauma exposure. Research suggests intergenerational risk associated with trauma exposure and posttraumatic stress disorder (PTSD), such that maternal trauma experiences and related symptoms can negatively impact child outcomes across development. The goals of the present study were to examine child and mother correlates of child PTSD symptoms and the unique roles of child and maternal emotion dysregulation in understanding child PTSD symptoms. METHOD: Subjects included 105 African American mother-child dyads from an urban hospital serving primarily low-income minority individuals. RESULTS: Correlational results showed that child trauma exposure, child emotion dysregulation, maternal depressive symptoms, maternal emotion dysregulation, and potential for maternal child abuse all were significantly associated with child PTSD symptoms (ps < 0.05). Hierarchical linear regression models revealed that child trauma exposure, maternal depression, and maternal abuse potential accounted for 29% of the variance in child PTSD symptoms (p < 0.001). Both child emotion dysregulation (Rchange² = 0.14, p < .001) and maternal emotion dysregulation (Rchange² = 0.04, p < .05) were significantly associated with child PTSD symptoms independent of other risk factors and potential for maternal abuse was no longer a significant predictor. CONCLUSIONS: These results suggest that maternal emotion dysregulation may be an important factor in influencing their child's PTSD symptoms above and beyond child-specific variables. Both maternal and child emotion dysregulation could be valuable treatment targets for improving maternal mental health and parenting behaviors and bolstering child health outcomes, thus reducing intergenerational transmission of risk associated with trauma. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intergenerational effects of maternal PTSD: Roles of parenting stress and child sex.

OBJECTIVES: Parental posttraumatic stress disorder (PTSD) increases children's risk for emotional and behavioral problems. We examined parenting stress and parenting behavior quality as mediators of the relation between maternal PTSD and problematic child behaviors in a sample at high risk for trauma exposure. We also examined whether child sex moderated this association. METHOD: Participants were 141 African American mother-child dyads (children aged 8-12). Mothers reported PTSD severity, parenting stress, and child behavior (externalizing, internalizing, and emotional self-control). Parenting behavior quality (accounting for factors including parental warmth and engagement) was assessed from an observational parent-child interaction task. RESULTS: Parenting stress, but not observed parenting behavior quality, mediated the relation between maternal PTSD severity and child behaviors. Child sex moderated this association, such that the effect was stronger for girls. CONCLUSIONS: Maternal PTSD may be associated with negative child behavior outcomes, and this relation appears to be mediated by increased parenting stress. Stress-reducing interventions for parents with PTSD could improve child outcomes, especially for girls. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Developmental Timing of Trauma in Women Predicts Unique Extracellular Vesicle Proteome Signatures.

BACKGROUND: Exposure to traumatic events is a risk factor for negative physical and mental health outcomes. However, the underlying biological mechanisms that perpetuate these lasting effects are not known. METHODS: We investigated the impact and timing of sexual trauma, a specific type of interpersonal violence, experienced during key developmental windows of childhood, adolescence, or adulthood on adult health outcomes and associated biomarkers, including circulating cell-free mitochondrial DNA levels and extracellular vesicles (EVs), in a predominantly Black cohort of women (N = 101). RESULTS: Significant changes in both biomarkers examined, circulating cell-free mitochondrial DNA levels and EV proteome, were specific to developmental timing of sexual trauma. Specifically, we identified a large number of keratin-related proteins from EVs unique to the adolescent sexual trauma group. Remarkably, the majority of these keratin proteins belong to a 17q21 gene cluster, which suggests a potential local epigenetic regulatory mechanism altered by adolescent trauma to impact keratinocyte EV secretion or its protein cargo. These results, along with changes in fear-potentiated startle and skin conductance detected in these women, suggest that sexual violence experienced during the specific developmental window of adolescence may involve unique programming of the skin, the body's largest stress organ. CONCLUSIONS: Together, these descriptive studies provide novel insight into distinct biological processes altered by trauma experienced during specific developmental windows. Future studies will be required to mechanistically link these biological processes to health outcomes.

Associations between children's trauma-related sequelae and skin conductance captured through mobile technology.

Although many children experience trauma, few receive diagnoses and subsequent care despite experiencing trauma-related sequelae. At age nine (M = 9.11), children (N = 62; female = 46.4%) who predominantly identified as Black (78.7%) were enrolled in this first study examining how skin conductance as captured by mobile technology, eSense, related to children's traumatic experiences and trauma-related symptoms. Skin conductance measures were associated with degree of trauma exposure and PTSD hyperarousal symptoms. These findings suggest that physiological responses in addition to self-report measures may be easily used to assess children's trauma exposure and symptoms. Given eSense's ease-of-use, this technology could assist clinics and research institutions assess children's trauma-related needs.

Sex-Specific Associations Between Trauma Exposure, Pubertal Timing, and Anxiety in Black Children.

Recent research has linked early life stress (ELS), such as trauma exposure, with early puberty. Early puberty has also been identified as a risk factor for poor mental health outcomes. However, these two paths have primarily been examined independently. In addition, more studies have examined these associations in girls than boys, and findings for boys remain mixed. We hypothesized that early puberty (relative to peers) would be positively associated with both prior trauma exposure and concurrent anxiety symptoms. We anticipated that these associations might differ by sex. We tested these hypotheses within a cross-sectional sample of 133 8- to 13-year-old Black girls and boys with trauma exposure. The association between trauma and accelerated pubertal timing was sex-specific: it was positive for girls and negative for boys. We stratified subsequent analyses by sex. Regression analyses indicated that early puberty relative to peers predicted more anxiety symptoms for girls but not boys, after accounting for trauma exposure. A statistical mediation analysis indicated that, for girls, the positive association between trauma exposure and anxiety was partially mediated by pubertal timing. These results indicate that trauma exposure may have sex-specific effects on pubertal timing and anxiety risk in Black children. We also found that, for girls, trauma may increase risk for adverse outcomes by prompting earlier puberty, which is linked to higher anxiety. These findings are consistent with cascading effects of trauma across development, and highlight the need for further study of sex-specific mechanisms.

A legacy of fear: Physiological evidence for intergenerational effects of trauma exposure on fear and safety signal learning among African Americans.

OBJECTIVE: To determine the influence of maternal trauma and posttraumatic stress disorder (PTSD) symptoms on children's physiological response to threat and safety signals during a fear conditioning task in trauma-exposed mothers and children. METHOD: Participants were African American mother-child dyads (N = 137; children aged 8-13 years). Mothers' trauma history and PTSD symptoms were assessed; Latent Class Analysis (LCA) was conducted from these measures to identify distinct classes. Children reported violence exposure and completed a differential fear conditioning task using fear-potentiated startle (FPS) responses to conditioned danger (CS+) and safety (CS-) signals. RESULTS: Four classes of maternal trauma history and PTSD symptoms emerged: 1) Lower Trauma, 2) Moderate Trauma, 3) High Sexual Abuse, and 4) High Trauma and PTSD Symptoms. Children's FPS to CS + and CS- were tested with maternal class as the between-subjects factor. FPS to the danger signal was not significantly different across maternal classes, but FPS to safety (CS-) was significantly higher for the Lower Trauma and High Trauma and PTSD Symptoms classes than either the Moderate Trauma or the High Sexual Abuse classes. CONCLUSIONS: Results indicate that maternal trauma impacts children's ability to modulate fear responses in the presence of a safety signal, independent of the children's own trauma exposure. To our knowledge, this is the first study to demonstrate that children's fear inhibition is impacted by maternal trauma exposure. Prior studies have linked fear inhibition to mental health outcomes, highlighting the need to understand intergenerational modulation of fear learning and physiology.

Impact of ADCYAP1R1 genotype on longitudinal fear conditioning in children: interaction with trauma and sex.

Dysregulated fear conditioned responses have been associated with PTSD in adults, with increased fear-potentiated startle (FPS) serving as a potential intermediate phenotype for PTSD risk. This phenotype has also been associated with stress-related ADCYAP1R1 gene variants in adult women. However, FPS and genotype have not yet been examined during development. The aim of this study was to examine developmental changes in fear conditioning, and to see whether these changes were impacted by genotype and trauma. Differential fear conditioning using FPS was tested in n = 63 children ages 8-13 at two visits (V1, V2) 1 year apart. Startle response was measured using electromyograph recordings of the eyeblink muscle. The rs2267735 SNP of the ADCYAP1R1 gene was extracted from genome-wide (GWAS) analyses. Trauma exposure was assessed using the Violence Exposure Scale-Revised (VEX-R). We found significant Visit by Genotype interactions, with CC genotype increasing FPS from V1 to V2. At V2 there was a Genotype by Violence interaction, with higher FPS in the CC vs G allele groups among those with higher violence exposure (F = 17.46, p = 0.0002). Females with the CC genotype had higher FPS compared to G allele females (F = 12.09, p = 0.002); there were no effects of genotype in males. This study showed Gene × Environment × Development and Gene × Sex effects of ADCYAP1R1 in a high-risk pediatric population. Those with the CC genotype and high levels of violence exposure, as well as females with the CC genotype, showed the greatest conditioned fear responses in adolescence.