Nicole R. Nugent

Initial urinary epinephrine and cortisol levels predict acute PTSD symptoms in child trauma victims

BACKGROUND Previous research examining biological correlates of posttraumatic stress disorder (PTSD) in children has suggested that children with chronic PTSD have altered levels of catecholamines and cortisol compared to similarly traumatized children who do not meet diagnostic criteria. The present study extended these findings by examining whether urinary hormone levels collected soon after a trauma were related to subsequent acute PTSD symptoms in child trauma victims. METHODS Initial 12-h urine samples were collected from 82 children aged 8-18 admitted to a Level 1 trauma center. Collection was begun immediately upon admission, and samples were assayed for levels of catecholamines and cortisol. PTSD and depressive symptomatology were assessed 6 weeks following the accident. RESULTS Initial urinary cortisol levels were significantly correlated with subsequent acute PTSD symptoms (r=0.31). After removing the variance associated with demographic variables and depressive symptoms, urinary cortisol and epinephrine levels continued to predict a significant percentage (7-10%) of the variance in 6-week PTSD symptoms. Examination of boys and girls separately suggested that significance was primarily driven by the strength of the relationships between hormone levels and acute PTSD symptoms in boys. CONCLUSIONS The present findings suggest that high initial urinary cortisol and epinephrine levels immediately following a traumatic event may be associated with increased risk for the development of subsequent acute PTSD symptoms, especially in boys.

Gene–environment interactions: early life stress and risk for depressive and anxiety disorders

RationalePrior reviews have examined how stress, broadly defined, interacts with genetic diathesis in the pathogenesis of internalizing (i.e., depressive and anxiety) disorders. Recent findings have suggested a unique role for early life stress (ELS) in the development of internalizing disorders, contributing to the rapid proliferation of research in this area.ObjectiveThis paper critically reviews studies in humans examining gene–environment interaction (GxE) effects of ELS on the risk for depression and anxiety, primarily from a candidate gene perspective. Major methodological challenges that are unique to such studies are considered.ResultsThe majority of published studies have focused on candidates that regulate the serotonin system, especially the serotonin transporter. More recent work has addressed interactions of ELS with candidates from the hypothalamic-pituitary-adrenal axis and neurotrophin system. Available studies vary greatly with respect to definitions of ELS, examination of gene–gene interactions, consideration of gender effects, and attention to analytic limitations.ConclusionsOverall, there is support for GxE effects of ELS on the risk for depressive and anxiety outcomes. Future studies of ELS in this context will require careful attention to methodologic considerations. Such studies would benefit from more systematic assessment of positive environmental factors (e.g., social support) and greater utilization of developmentally sensitive paradigms.

Genetics of Post-Traumatic Stress Disorder: Review and Recommendations for Genome-Wide Association Studies

Post-traumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder that constitutes a major health care burden. Despite evidence supporting a genetic predisposition to PTSD, the precise genetic loci remain unclear. Herein we review the current state and limitations of genetic research on PTSD. Although recent years have seen an exponential increase in the number of studies examining the influence of candidate genes on PTSD diagnosis and symptomatology, most studies have been characterized by relatively low rates of PTSD, with apparent inconsistencies in gene associations linked to marked differences in methodology. We further discuss how current advances in the genetics field can be applied to studies of PTSD, emphasizing the need to adapt a genome-wide approach that facilitates discovery rather than hypothesis testing. Genome-wide association studies offer the best opportunity to identify novel “true” risk variants for the disorder that in turn has the potential to inform our understanding of PTSD etiology.

Genetics of PTSD: Fear Conditioning as a Model for Future Research.

In the last decade, the number of publications in psychiatric genetics has nearly tripled but little attention has been paid to the role of genetic factors in the etiology of posttraumatic stress disorder (PTSD). The present review summarizes the current state of genetic research on PTSD. First, we outline information regarding genetic influences provided by family investigations and by twin studies. Second, we propose the fear-conditioning model of PTSD as a framework for the nomination of candidate genes that may be related to the disorder. Third, we review lines of evidence from three neurobiological systems involved in fear conditioning, and we summarize published investigations of genetic variants studied in association with PTSD in these three systems. Finally, we review gene-by-environment interaction research, a promising novel approach to genetic research in PTSD.

Gene-Environment Interaction in Posttraumatic Stress Disorder: An Update

The authors provide a detailed review of the extant gene-environment interaction (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They begin with a discussion of why PTSD is uniquely fitting for the innovative framework of GxE methodology, followed by a review of the heritability and main effect molecular genetics studies of PTSD. Next, they discuss the six GxE investigations to date on PTSD. They end with a discussion of future directions and significance of this research, with an emphasis on the expansion of psychosocial factors that may be fitting environmental variables for inclusion in this new research area. The authors posit that GxE research is vital to elucidating risk and resilience following exposure to a potentially traumatic event.

The efficacy of early propranolol administration at reducing PTSD symptoms in pediatric injury patients: A pilot study

Initial research supports the use of propranolol to prevent posttraumatic stress disorder (PTSD); research has not examined pharmacological prevention for children. Twenty-nine injury patients (ages 10-18 years old) at risk for PTSD were randomized to a double-blind 10-day trial of propranolol or placebo initiated within 12 hours postadmission. Six-week PTSD symptoms and heart rate were assessed. Although intent-to-treat analyses revealed no group differences, findings supported a significant interaction between gender and treatment in medication-adherent participants, Delta R(2) = .21. Whereas girls receiving propranolol reported more PTSD symptoms relative to girls receiving placebo, Delta R(2) = .44, boys receiving propranolol showed a nonsignificant trend toward fewer PTSD symptoms than boys receiving placebo, Delta R(2) = .32. Findings inform gender differences regarding pharmacological PTSD prevention in youth.

Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

Flexibility and Negative Affect: Examining the Associations of Explanatory Flexibility and Coping Flexibility to Each Other and to Depression and Anxiety

Recent research on vulnerabilities to depression and anxiety has begun to de-emphasize cognitive content in favor of the responsiveness of the individual to variations in situational context in arriving at explanations of events (explanatory flexibility) or attempts to cope with negative events (coping flexibility). The present study integrates these promising avenues of conceptualization by assessing the respective contributions of explanatory and coping flexibility to current levels of depression and anxiety symptoms. Results of structural equation modeling support a model of partial mediation in which both explanatory flexibility and coping flexibility independently contribute to the prediction of latent negative affect, with coping flexibility partially mediating the influence of explanatory flexibility.

Genetic determinants of depression: recent findings and future directions.

Learning ObjectivesAfter participating in this activity, learners should be better able to: 1. Evaluate current evidence regarding the genetic determinants of depression 2. Assess findings from studies of gene-environment interaction 3. Identify challenges to gene discovery in depression AbstractDepression is one of the most prevalent, disabling, and costly mental health conditions in the United States and also worldwide. One promising avenue for preventing depression and informing its clinical treatment lies in uncovering the genetic and environmental determinants of the disorder as well as their interaction (G×E). The overarching goal of this review article is to translate recent findings from studies of genetic association and G×E related to depression, particularly for readers without in-depth knowledge of genetics or genetic methods. The review is organized into three major sections. In the first, we summarize what is currently known about the genetic determinants of depression, focusing on findings from genome-wide association studies (GWAS). In the second section, we review findings from studies of G×E, which seek to simultaneously examine the role of genes and exposure to specific environments or experiences in the etiology of depression. In the third section, we describe the challenges to genetic discovery in depression and promising strategies for future progress.

Sexual Abuse and Sexual Risk Behavior: Beyond the Impact of Psychiatric Problems

OBJECTIVE This study examined the association between sexual abuse (SA) and sex risk in girls and boys placed in alternative and therapeutic school settings while controlling for psychiatric problems. METHOD Adolescents were recruited from alternative and therapeutic schools. Youth completed audio computer-assisted self-interviews assessing childhood abuse, sexual behaviors, sexual attitudes, and psychiatric symptoms. RESULTS Of the 162 youth with available data, 23% reported a moderate or severe SA history. After controlling for gender and the presence of a psychiatric diagnosis, youth with a SA history were significantly more likely to have engaged in sex, had sex in the last 90 days, and engaged in unprotected sex. Adolescents with a history of SA also endorsed fewer advantages of using condoms. CONCLUSIONS SA is uniquely associated with sexual behavior and attitudes even when adjusting for the presence of a psychiatric diagnosis. These data have implications for interventions for those with SA histories.