Alison Shea

Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females

A history of child maltreatment increases the vulnerability to the development of Major Depressive Disorder (MDD) and/or Posttraumatic Stress Disorder (PTSD), especially in females. Both MDD and PTSD are associated with a dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. Dysregulation of the HPA axis may be an important etiological link between child maltreatment and subsequent psychiatric disorder, yet little is known about the relationship between exposure and outcome. The aim of this review is to explore the role of HPA axis dysregulation in the link between child maltreatment and MDD/PTSD among women. Studies of females with MDD frequently indicate a hyperactivity of the HPA axis, and contribute to our understanding of the underlying mechanisms involved in mood dysregulation. Evidence for HPA axis dysregulation in PTSD is less convincing and suggests that timing of the stressful experience as well as the type of the trauma may influence the outcome. The strongest evidence to date suggesting that the development of the HPA axis may be affected by early life stressful experiences comes from pre-clinical animal studies. Together these studies add to our understanding of the role of the HPA axis in psychiatric disorders in relation to stress. The literature on HPA axis function in both children and adults following child maltreatment further highlights the potential relevance of early stress to later onset of major psychiatric disorders. Such knowledge may also contribute to the development of early interventions targeted at primary prevention.

Cortisol Response to Stress in Female Youths Exposed to Childhood Maltreatment: Results of the Youth Mood Project

BACKGROUND Few studies have examined stress reactivity and its relationship to major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) among maltreated youth. We examined differences between maltreated and control participants in heart rate and cortisol resting and reactivity levels in response to a psychosocial stressor. METHODS We recruited 67 female youths aged 12 to 16 with no prior history of depression from child protection agencies and a control group of 25 youths matched on age and postal code. Child maltreatment was measured with two self-report instruments. Psychiatric status was assessed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. RESULTS Piecewise multilevel growth curve analysis was used to model group differences in resting and reactivity cortisol levels and heart rate in response to the Trier Social Stress Test (TSST). During the resting period, both the maltreated and control groups showed a similar decline in levels of cortisol. During the reactivity phase, youth in the control group showed an increase in cortisol levels following the TSST and a gradual flattening over time; maltreated youth exhibited an attenuated response. This blunted reactivity was not associated with current symptoms of MDD or PTSD. There were no group differences in resting and reactivity levels of heart rate. CONCLUSIONS These findings provide further support for hypothalamic-pituitary-adrenal axis dysregulation among maltreated youth. Since the ability to respond to acute stressors by raising cortisol is important for health, these findings may assist in understanding the vulnerability of maltreated youth to experience physical and mental health problems.

Effects of maternal prenatal stress on offspring development: a commentary

Pregnancy is associated with major physiological changes and adaptation to these changes is crucial for normal fetal development. Heightened emotional stress during pregnancy may interfere with the necessary adaptation and lead to dysregulation of the two major stress response systems: the Hypothalamic–Pituitary–Adrenal (HPA) Axis and the Autonomic Nervous System (ANS). Negative effects on the fetus of such maladaptation have been documented in both animals and humans and range from poor birth outcomes to negative impacts on neurodevelopment, as well as long term emotional and behavioural disturbances. Conversely, it has been hypothesized that low levels of maternal prenatal stress may actually have an adaptive value for the offspring. Investigation of these associations employing physiological markers and repeated measures throughout pregnancy and postpartum of both the mother and the offspring, is required in order to understand the various effects of prenatal stress on the development of the offspring. It is also crucial to explore the possibility of variable periods of vulnerability throughout gestation. The aim of this commentary is to reexamine the current literature on the ill-effects of maternal stress during pregnancy on the offspring and to explore avenues for future treatment and prevention.

The effect of depression, anxiety and early life trauma on the cortisol awakening response during pregnancy: Preliminary results

The purpose of this study was to examine the effects of maternal depression and anxiety on the cortisol awakening response (CAR), a marker of the hypothalamic-pituitary-adrenal (HPA) axis function, during pregnancy. Sixty-six pregnant women were studied between 25 and 33 weeks of gestation and were identified as either Depressed (n=33) or healthy, Control (n=33), based on depression scores and lifetime psychiatric history. Saliva samples were collected (passive drool) upon awakening and at +30 and +60 min thereafter. The CAR was not significantly different between women who were depressed during pregnancy compared to healthy control women. However, women taking antidepressant (AD) medication showed an attenuated CAR (time x AD use interaction, p=0.06). Childhood maltreatment (as measured with the Childhood Trauma Questionnaire) was associated with a lower baseline cortisol concentration explaining 12% of the variance, controlling for wake-up time and AD use. There is a complex interplay of factors involved in the HPA axis regulation of vulnerable women during pregnancy, including depression, anxiety, early life stress and psychotropic medication use, which remain unclear. The CAR may provide important information about the maternal HPA axis during pregnancy and warrants further investigation in larger cohorts.

Fetal Serotonin Reuptake Inhibitor Antidepressant Exposure: Maternal and Fetal Factors

Prenatal serotonin reuptake inhibitor exposure is common and neonatal outcomes vary greatly, often leading to confusion about whether to use or even continue antenatal use of these antidepressants. Importantly, some but not all infants are affected, which raises questions about how maternal drug metabolism contributes to fetal drug exposure. To address this key question, our paper reviews the role of key maternal, fetal, and placental pharmacokinetic, metabolic, and genetic factors that affect the extent of fetal drug exposure. Considering the role of these factors may further our understanding of variables that may assist in optimizing maternal psychopharmacotherapy during pregnancy and neonatal outcomes.

Clinical predictors for diabetes screening in the first year postpartum after gestational diabetes

Background: Postpartum screening for diabetes in women with gestational diabetes (GDM) improves with use of reminder systems. Our primary objective was to identify predictors of diabetes screening in the first year after delivery. Methods: A retrospective study was performed of 556 women with GDM who received outpatient prenatal care between 2007 and 2009. A mailed reminder system was utilized at two sites. Rates of postpartum glucose testing at 6 and 12 months postpartum were measured. Results: Site of care and non-smoking status were identified as the only predictors of postpartum diabetes screening (p<0.001 and p = 0.02, respectively). Rates of OGTT completion at one year (38% vs. 19% p<0.001) were higher in women who attended clinics with postpartum reminders. Conclusions: The site of diabetes care in pregnancy is a major predictor of adherence to diabetes screening postpartum. Health care delivery should be considered in the development of strategies to increase screening rates.

Maternal and Fetal Factors That Influence Prenatal Exposure to Selective Serotonin Reuptake Inhibitor Antidepressants

Prenatal serotonin reuptake inhibitor (SRI) exposure is common and neonatal outcomes vary greatly, often leading to confusion about whether to use or even continue antenatal use of these antidepressants. Importantly, some but not all infants are affected, which raises questions about how maternal drug metabolism contributes to fetal drug exposure. To address this question, this chapter reviews the role of key maternal, fetal, and placental pharmacokinetic, metabolic, and genetic factors that affect the extent of fetal drug exposure. Considering the role of these factors may further our understanding of variables that might assist in optimizing maternal psychopharmacotherapy during pregnancy and neonatal outcomes.