ABSTRACT
Women are particularly vulnerable to the effects of psychological trauma and the development of trauma-, stressor-, and anxiety-related mental illnesses such as posttraumatic stress disorder (PTSD). In the current chapter, we examine the female hormonal systems that interact with psychobiological stress response systems to elicit maladaptive behavior and mental disease states in traumatized female populations. In addition, we provide a contemporary translational example of a stress vulnerability genomic profile (coding for pituitary adenylate cyclase-activating polypeptide) that may underlie the specific susceptibilities observed in women. Translational scientific investigations such as those described herein may lead to the identification of risk and resilience factors for PTSD as well as enhanced clinical interventions for treating excessive fear and anxiety.
Subject(s)
Estrogens/metabolism , Neurosecretory Systems/physiopathology , Ovary/metabolism , Stress Disorders, Post-Traumatic/physiopathology , Adult , Animals , Female , Genetic Predisposition to Disease , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiology , Hypothalamo-Hypophyseal System/physiopathology , Male , Neurosecretory Systems/physiology , Pituitary Adenylate Cyclase-Activating Polypeptide/blood , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/physiology , Pituitary-Adrenal System/physiopathology , Polymorphism, Single Nucleotide , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/agonists , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/genetics , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Risk , Sex Factors , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/genetics , Stress Disorders, Post-Traumatic/metabolism , Testis/metabolism , Testosterone/metabolismABSTRACT
Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10-8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.
