Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study.

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans.

Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder.

Background: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL).

Adiposity, aldosterone and plasma renin activity among African Americans: The Jackson Heart Study.

Objective: To analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort.

Methods: Cross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models.

Results: A 1-SD higher BMI was associated with a 4.

Associations of Cardiometabolic Multimorbidity With All-Cause and Coronary Heart Disease Mortality Among Black Adults in the Jackson Heart Study.

Importance: A combination of diabetes, coronary heart disease (CHD), and stroke has multiplicative all-cause mortality risk compared with any individual morbidity in White populations, but there is a lack of studies in Black populations in the US.

Objective: To examine the association of cardiometabolic multimorbidity (diabetes, stroke, and CHD) individually and collectively with all-cause and CHD mortality.

Design, Setting, And Participants: This cohort study included Black adults in the Jackson Heart Study followed over a median of 15 years.

Methylomic and transcriptomic predictors of one-month exposure to cortisol in healthy individuals.

Allostatic load (AL) refers to the cumulative "wear and tear" on an organism throughout its lifetime. One of the primary contributing factors to AL is prolonged exposure to stress or its primary catabolic agent cortisol. Chronic exposure to stress or cortisol is associated with numerous diseases, including cardiovascular disease, metabolic disorders, and psychiatric disorders.

Cross-species Association Between Telomere Length and Glucocorticoid Exposure.

Context: Chronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to accelerated aging; however, while the link between chronic GC exposure and disease onset is well established, the underpinning mechanisms are not clear.

Objective: We explored the potential nexus between GCs or stress exposure and telomere length.

Association of Serum Aldosterone and Plasma Renin Activity With Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

Background: The renin-angiotensin-aldosterone system (RAAS) is an important driver of blood pressure (BP), but the association of the RAAS with ambulatory BP (ABP) and ABP monitoring phenotypes among African Americans has not been assessed.

Methods: ABP and ABP monitoring phenotypes were assessed in 912 Jackson Heart Study participants with aldosterone and plasma renin activity (PRA). Multivariable linear and logistic regression analyses were used to analyze the association of aldosterone and PRA with clinic, awake, and asleep systolic BP and diastolic BP (DBP) and ABP monitoring phenotypes, adjusting for important confounders.

Changes in Hemodynamic Response Function Resulting From Chronic Alcohol Consumption.

Background: Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known.

Methods: Participants with AUD and controls (CTL) received structural, functional, and vascular scans.

The Relationship of Varenicline Agonism of α4β2 Nicotinic Acetylcholine Receptors and Nicotine-Induced Dopamine Release in Nicotine-Dependent Humans.

Introduction: Cigarette smoking continues to be one of the most important behavioral causes of morbidity and mortality in the world. Varenicline, an α4β2 nicotinic acetylcholine receptor (nAChR) partial agonist, has been shown to increase smoking quit rates compared with nicotine-based products. This human laboratory, double-blind, placebo-controlled study examined varenicline and placebo effects on α4β2-nAChRs occupancy, nicotine-induced change in [11C]raclopride non-displaceable binding potential (BPND), and behavioral measures of cigarette smoking, nicotine craving, and withdrawal.

A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure.

As genomes of a wider variety of animals become available, there is an increasing need for tools that can capture dynamic epigenetic changes in these animal models. The rat is one particular model animal where an epigenetic tool can complement many pharmacological and behavioral studies to provide insightful mechanistic information. To this end, we adapted the SureSelect Target Capture System (referred to as Methyl-Seq) for the rat, which can assess DNA methylation levels across the rat genome.

DNA methylation and sex-specific expression of FKBP5 as correlates of one-month bedtime cortisol levels in healthy individuals.

Chronic exposure to cortisol is associated with cardiovascular, metabolic, and psychiatric disorders. Although cortisol can be readily measured from peripheral sources such as blood, urine, or saliva, multiple samplings spanning several days to weeks are necessary to reliably assess chronic cortisol exposure levels (referred to as cortisol load). Although cortisol levels in hair have been proposed as a measure of cortisol load, measurement is cumbersome and many people are not candidates due to short hair length and use of hair dyes.

Type 2 diabetes and cardiometabolic risk may be associated with increase in DNA methylation of .

Background: Subclinical hypercortisolism and hypothalamic-pituitary-adrenal (HPA) axis dysfunction are associated with type 2 diabetes (T2DM), cardiovascular disease, and metabolic dysfunction. Intronic methylation of has been implicated as a potential indicator of chronic cortisol exposure. Our overall objective in this study was to determine the association of chronic cortisol exposure, measured via percent methylation of at intron 2, with percent glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-cholesterol), waist circumference (WC), and body mass index (BMI), in a clinic-based sample of 43 individuals with T2DM.

Sex differences in the ACTH and cortisol response to pharmacological probes are stressor-specific and occur regardless of alcohol dependence history.

Women and men differ in their risk for developing stress-related conditions such as alcohol use and anxiety disorders and there are gender differences in the typical sequence in which these disorders co-occur. However, the neural systems underlying these gender-biased psychopathologies and clinical course modifiers in humans are poorly understood and may involve both central and peripheral mechanisms regulating the limbic-hypothalamic-pituitary-adrenal axis. In the present randomized, double blind, placebo-controlled, triple-dummy crossover study, we juxtaposed a centrally-acting, citalopram (2 mg/unit BMI) neuroendocrine stimulation test with a peripherally-acting, dexamethasone (Dex) (1.

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia.

Background: The α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition.

Methods: We expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia.

Early Life Stress as a Predictor of Co-Occurring Alcohol Use Disorder and Post-Traumatic Stress Disorder.

During the critical developmental periods of childhood when neural plasticity is high, exposure to early life stress (ELS) or trauma may lead to enduring changes in physiological stress systems and enhanced vulnerability for psychopathological conditions such as post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) in adulthood. Clinical and preclinical studies have sought to understand the possible mechanisms linking ELS, PTSD, and AUD. Preclinical studies have employed animal models of stress to recapitulate PTSD-like behavioral deficits and alcohol dependence, providing a basic framework for identifying common physiological mechanisms that may underlie these disorders.

Detecting Deception in Our Research Participants: Are Your Participants Who You Think They Are?

There is increasing awareness of the potential negative impacts of participant deception on research, including possibly undermining reliability and reproducibility of study findings. These deceptive individuals set their personal interests above the rules of study participation, thereby jeopardizing data quality as well as placing themselves and others at risk. The costs of participant deception are numerous.

Aldosterone, Renin, Cardiovascular Events, and All-Cause Mortality Among African Americans: The Jackson Heart Study.

Objectives: This study examined the association of aldosterone and plasma renin activity (PRA) with incident cardiovascular disease (CVD), using a composite endpoint of coronary heart disease, stroke, and/or heart failure and mortality among African Americans in the Jackson Heart Study.

Background: There is a paucity of data for the association of aldosterone and PRA with incident CVD or all-cause mortality among community-dwelling African Americans.

Methods: A total of 4,985 African American adults, 21 to 94 years of age, were followed for 12 years.

Differential effects of perceived stress on alcohol consumption in moderate versus heavy drinking HIV-infected women.

Objective: To examine the association between perceived stress and subsequent alcohol use in women living with HIV.

Methods: Women (n=338) receiving HIV care between April 2006 and July 2010 who enrolled in either a brief intervention for hazardous drinking or a cohort of non-hazardous drinkers completed a 90-day drinking and drug use history, and completed stress, depression and anxiety measures at 0, 6, and 12 months. We examined the association between perceived stress at months 0 or 6 and measures of quantity and frequency of alcohol use in months 3-6 and 9-12, respectively.

Genome-wide Methyl-Seq analysis of blood-brain targets of glucocorticoid exposure.

Chronic exposure to glucocorticoids (GCs) can lead to psychiatric complications through epigenetic mechanisms such as DNA methylation (DNAm). We sought to determine whether epigenetic changes in a peripheral tissue can serve as a surrogate for those in a relatively inaccessible tissue such as the brain. DNA extracted from the hippocampus and blood of mice treated with GCs or vehicle solution was assayed using a genome-wide DNAm platform (Methyl-Seq) to identify differentially methylated regions (DMRs) induced by GC treatment.

A paradigm for examining stress effects on alcohol-motivated behaviors in participants with alcohol use disorder.

Although epidemiological research has shown an increase in drinking following stressors and trauma, limited paradigms have been validated to study the relationship between stress and drinking in the human laboratory. The current study developed a progressive ratio (PR) operant procedure to examine the effects of psychosocial stress on alcohol craving and several alcohol-motivated behaviors in persons with alcohol use disorder. Current heavy, nontreatment-seeking drinkers (N = 30) were media-recruited and completed a comprehensive assessment of recent drinking, mood and health.

Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.

Background: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers.

Methods: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.

Anxiety, Anxiety Sensitivity, and Perceived Stress as Predictors of Recent Drinking, Alcohol Craving, and Social Stress Response in Heavy Drinkers.

Background: Stress and anxiety are widely considered to be causally related to alcohol craving and consumption, as well as development and maintenance of alcohol use disorder (AUD). However, numerous preclinical and human studies examining effects of stress or anxiety on alcohol use and alcohol-related problems have been equivocal. This study examined relationships between scores on self-report anxiety, anxiety sensitivity, and stress measures and frequency and intensity of recent drinking, alcohol craving during early withdrawal, as well as laboratory measures of alcohol craving and stress reactivity among heavy drinkers with AUD.

The Prevalence and Specificity of Depression Diagnosis in a Clinic-Based Population of Adults With Type 2 Diabetes Mellitus.

Objective: To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes.

Methods: We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder.