Dorthie Cross

Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans

Cigarette smoking is an environmental risk factor for many chronic diseases, and disease risk can often be managed by smoking control. Smoking can induce cellular and molecular changes, including epigenetic modification, but the short- and long-term epigenetic modifications caused by cigarette smoking at the gene level have not been well understood. Recent studies have identified smoking-related DNA methylation (DNAm) sites in Caucasians. To determine whether the same DNAm sites associate with smoking in African Americans, and to identify novel smoking-related DNAm sites, we conducted a methylome-wide association study of cigarette smoking using a discovery sample of 972 African Americans, and a replication sample of 239 African Americans with two array-based methods. Among 15 DNAm sites significantly associated with smoking after correction for multiple testing in our discovery sample, 5 DNAm sites are replicated in an independent cohort, and 14 sites in the replication sample have effects in the same direction as in the discovery sample. The top two smoking-related DNAm sites in F2RL3 (factor II receptor-like 3) and GPR15 (G-protein-coupled receptor 15) observed in African Americans are consistent with previous findings in Caucasians. The associations between the replicated DNAm sites and smoking remain significant after adjusting for genetic background. Despite the distinct genetic background between African Americans and Caucasians, the DNAm from the two ethnic groups shares common associations with cigarette smoking, which suggests a common molecular mechanism of epigenetic modification influenced by environmental exposure.

Perceived neighborhood disorder, community cohesion, and PTSD symptoms among low-income African Americans in an urban health setting.

Studies have established a link between contextual factors, such as neighborhood and community environments, and psychopathology. Although these factors have been shown to affect the expression of symptoms of depression and other disorders, little evidence exists of a link between contextual factors and posttraumatic stress disorder (PTSD). The current study tested the relationships among perceived neighborhood disorder (a measure of self-reported perceptions of the physical environment), community cohesion (a measure of perceived social ties), and self-reported PTSD symptoms while controlling for previous trauma exposure in a low-income, urban, African American population. Regression analyses indicated that both neighborhood disorder and community cohesion are related to PTSD symptoms after controlling for trauma exposure. Community cohesion, however, was found to be a partial mediator of the relationship between neighborhood disorder and PTSD symptoms.

PAC1 receptor (ADCYAP1R1) genotype is associated with dark-enhanced startle in children

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a regulator of stress response across species.1 Within limbic brain circuits, PACAP signaling coordinates normal physiological stress reactions. PACAP and corticotrophin-releasing hormone work together in the bed nucleus of the stria terminalis (BNST) to modulate anxiety-like behavior.1 We have recently shown that PACAP and a single-nucleotide polymorphism (SNP) of its PAC1 receptor (PAC1R) may be critical mediators of response to psychological trauma. We also reported that this PAC1R gene polymorphism is associated with increased dark-enhanced startle (DES) in adult females but not males with posttraumatic stress disorder (PTSD). We believe these sex differences are because of the location of the PAC1R SNP (rs2267735) in an estrogen response element.2 DES is a known marker of anxiety in adults and children,3–5 and has been shown to be BNST dependent, indicating the potential role of PACAP in increasing DES. We recently found that children of abused mothers show elevated DES.6 Using a sample of children of traumatized mothers, we have extended this research by examining effects of the PAC1R polymorphism on the DES response in these previously non-genotyped children. Based on our study with adults, we hypothesized that genotype would interact with sex to increase DES in girls but not boys. However, we found that the same gene polymorphism associated with PTSD risk in adult females is also associated with increased DES in both male and female children.

PTSD, emotion dysregulation, and dissociative symptoms in a highly traumatized sample

Exposure to multiple traumas has been shown to result in many negative mental health outcomes, including posttraumatic stress disorder (PTSD). Dissociation, which involves disruptions in memory, identity, and perceptions, may be a component of PTSD, particularly among individuals who have experienced childhood trauma. Emotion regulation difficulties are also strongly associated with childhood trauma and emotion dysregulation may be a particularly important factor to consider in the development and maintenance of dissociative symptoms. The goal of the present study was to determine whether emotion dysregulation mediated the relationship between PTSD symptoms and dissociation in a sample of 154 (80% female, 97% African-American) adults recruited from a public, urban hospital. PTSD was measured using the Clinician Administered PTSD Scale, emotion dysregulation was measured using the Difficulties in Emotion Regulation Scale, and dissociation was measured using the Multiscale Dissociation Inventory. A linear regression analysis showed that both PTSD and emotion dysregulation were statistically significant predictors of dissociation even after controlling for trauma exposure. Alexithymia and an inability to use emotion regulation strategies in particular were predictive of dissociation above and beyond other predictor variables. Using bootstrapping techniques, we found that overall emotion dyregulation partially mediated the effect of PTSD symptoms on dissociative symptoms. Our results suggest that emotion dysregulation may be important in understanding the relation between PTSD and dissociative symptoms. Treatment approaches may consider a focus on training in emotional understanding and the development of adaptive regulation strategies as a way to address dissociative symptoms in PTSD patients.

Emotional Dysregulation and Negative Affect Mediate the Relationship Between Maternal History of Child Maltreatment and Maternal Child Abuse Potential

Risk for committing child abuse is frequently attributed to an intergenerational “cycle of violence” through which abuse as a child increases risk for committing abuse as a parent. While this hypothesis has support, more research is needed to understand the factors that account for this pattern of risk. Given literature suggesting that adults with a history of child maltreatment have increased risk for a wide range of psychopathology, this study examined the role of two behavioral endophenotypes, emotional dysregulation and negative affect, in the association between maternal experiences of childhood maltreatment and maternal child abuse potential among 83 low-income, primarily African-American mothers of elementary school age children. Results indicate that a mother’s experience of abuse as a child predicts later risk for abusive parenting as measured by child abuse potential scores. However, our data also indicate that the relationship between maternal experience of child abuse and later child abuse potential is mediated by maternal emotional dysregulation and negative affect.

Emotion dysregulation as a mediator between childhood emotional abuse and current depression in a low-income African-American sample

Abuse and neglect in childhood are well-established risk factors for later psychopathology. Past research has suggested that childhood emotional abuse may be particularly harmful to psychological development. The current cross-sectional study employed multiple regression techniques to assess the effects of childhood trauma on adulthood depression and emotion dysregulation in a large sample of mostly low-income African Americans recruited in an urban hospital. Bootstrap analyses were used to test emotion dysregulation as a potential mediator between emotional abuse in childhood and current depression. Childhood emotional abuse significantly predicted depressive symptoms even when accounting for all other childhood trauma types, and we found support for a complementary mediation of this relationship by emotion dysregulation. Our findings highlight the importance of emotion dysregulation and childhood emotional abuse in relation to adult depression. Moving forward, clinicians should consider the particular importance of emotional abuse in the development of depression, and future research should seek to identify mechanisms through which emotional abuse increases risk for depression and emotion dysregulation.

Childhood trauma, PTSD, and problematic alcohol and substance use in low-income, African-American men and women

Previous studies demonstrate that PTSD mediates the relationship between childhood trauma and alcohol and substance use disorders and that PTSD and alcohol/substance use comorbidity is greater in men than in women. We sought to replicate and extend these findings in a predominantly low-income, African-American sample recruited from a public hospital. We administered measures of childhood trauma, PTSD symptoms, problematic alcohol use, and problematic substance use to 803 men and 2084 women. We examined rates of comorbidity in men and women. Next, two bootstrap analyses were used to test whether PTSD is a mediator between childhood trauma and problematic alcohol use and between childhood trauma and problematic substance use. Finally, two bootstrap analyses were used to test whether gender would moderate the indirect effect of PTSD in both the alcohol and substance use models. Results showed that although men and women reported similar overall PTSD symptom frequency, men were more likely than women to report PTSD comorbid with alcohol and/or substance use problems. In addition, PTSD partially mediated the relationship between childhood trauma and problematic alcohol use and between childhood trauma and problematic substance use. The indirect effects of PTSD on the relationship between childhood trauma and problematic alcohol use and between childhood trauma and problematic substance use were greater in men. This study demonstrates the important interplay of gender, childhood trauma, PTSD, and alcohol and substance use. Mental health providers should consider childhood trauma histories and diagnostic comorbidities when treatment planning.

Childhood trauma, PTSD, and psychosis: Findings from a highly traumatized, minority sample☆

Trauma, especially early life trauma, is a risk factor for the development of both posttraumatic stress disorder and psychosis. The goal of the present study was to determine specific associations between exposure to childhood abuse, PTSD symptoms, and current psychotic disorder. Subjects were recruited from a public, urban hospital (N = 328, >90% African American). Psychotic disorders were measured using the MINI International Neuropsychiatric Interview, PTSD was measured using the Clinician Administered PTSD Scale, child abuse was measured with the Childhood Trauma Questionnaire, and lifetime trauma exposure was measured with the Traumatic Events Inventory. Logistic regression analyses showed that both child abuse and current PTSD were statistically significant predictors of psychotic disorder beyond the effects of lifetime trauma load. When PTSD symptom clusters were examined, avoidance and numbing symptoms showed unique association with psychotic disorder independent of demographic variables and trauma exposure. Using bootstrapping techniques, we found a full indirect effect of PTSD on the association between child abuse and, suggesting a particularly important role of PTSD symptoms in relation to psychotic disorder in the presence of early life trauma. Because this is a cross-sectional study, continued research is needed to determine causality of such models. Identifying co-occurring psychosis and PTSD, particularly in populations with high levels of trauma exposure, is critical and will likely aid in more successful treatment interventions.

Personality subtypes of adolescents who attempt suicide.

Abstract Research suggests that personality pathology is shared among a considerable portion of adolescents presenting suicidal behavior. Furthermore, heterogeneity of personality within this population suggests a need to tease apart different types of attempters. The goal of this study was to identify the personality subtypes of adolescents who attempt suicide. We analyzed data on 266 adolescents, ages 13 to 18 years, with a history of at least one suicide attempt who were selected by treating clinicians for having at least some degree of personality problems. We used a Q-factor analysis to identify subtypes based on the Shedler-Westen Assessment Procedure-II for Adolescents (a 200-item measure of personality pathology used by clinically experienced observers). We derived six subtypes: Externalizing, Internalizing, Emotionally dysregulated, High functioning, Narcissistic, and Immature. The subtypes differed on measures of adaptive functioning, axis I and II pathology, and etiology. Adolescents who attempt suicide constitute a heterogeneous group, and they vary meaningfully on a measure of personality pathology. Interventions targeting suicidal behaviors in adolescents should consider individual differences.

Maternal buffering of fear-potentiated startle in children and adolescents with trauma exposure

ABSTRACT Parental availability influences fear expression and learning across species, but the effect of maternal buffering on fear learning in humans is unknown. Here we investigated the effect of maternal availability during fear conditioning in a group of children (ages 8–10) and adolescents (ages 11–13) from a low-income population with a range of trauma exposure. Acoustic startle response data were collected to measure fear-potentiated startle (FPS) in 104 participants. A total of 62 participants were tested with the mother available and 42 when the mother was not in the testing room. We observed that maternal availability during fear conditioning interacted with age to affect FPS discrimination between CS+ and CS–. In line with previous findings suggesting an absence of maternal buffering in adolescents, fear discrimination was affected by maternal availability only in children. Second, we observed that the effect of maternal buffering on FPS discrimination in children was not influenced by maternally reported warmth. In conclusion, we demonstrated that maternal availability improved discrimination in children, regardless of the quality of the relationship. Adolescents discriminated irrespective of maternal status, suggesting that childhood may be a sensitive period for environmental influences on key processes such as learning of danger and safety signals.