Effects of Early Life Trauma on Risks for Adult Opioid Use Disorder Are Mediated by Stress and Occur Independent of Depression and Anxiety.

Objectives: Adverse childhood experiences, or early life trauma (ELT), may be a potential risk factor for opioid use disorders (OUDs) that could be further influenced by depression, anxiety, and stress. The prevalence and strength of these associations are largely unknown.

Methods: This study examined the association between current OUD severity and lifetime history of ELT, and the degree to which current depression, anxiety, and stress influenced this association, in persons (n = 310) with at least 1 lifetime exposure to opioids using an online survey.

Adverse childhood experiences and burn pain: a review of biopsychosocial mechanisms that may influence healing.

Adverse childhood experiences (ACEs) affect over half of the adults in the United States and are known to contribute to the development of a wide variety of negative health and behavioral outcomes. The consequences of ACE exposure have been studied in patient populations that include individuals with gynecologic, orthopedic, metabolic, autoimmune, cardiovascular, and gastrointestinal conditions among others. Findings indicate that ACEs not only increase risks for chronic pain but also influence emotional responses to pain in many of these individuals.

Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings.

A robust body of research has shown that traumatic experiences occurring during critical developmental periods of childhood when neuronal plasticity is high increase risks for a spectrum of physical and mental health problems in adulthood, including substance use disorders. However, until recently, relatively few studies had specifically examined the relationships between early life stress (ELS) and opioid use disorder (OUD). Associations with opioid use initiation, injection drug use, overdose, and poor treatment outcome have now been demonstrated.

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.

Comments and controversies: Piecing together the neurobiology of decision-making.

In this paper, we address issues raised by Tierney and Hart (Assessing Complex Cognitive Functioning Requires Multiple Tasks) in response to our recently published findings showing that less advantageous decision-making on the Iowa Gambling Task (IGT) was associated with enhanced right ventral striatal dopamine response to intravenous amphetamine (Oswald et al., 2015). We agree with the overall premise of the paper, which was that decision-making involves multiple components, which may not be tapped by a single measure.

Risky decision-making and ventral striatal dopamine responses to amphetamine: a positron emission tomography [(11)C]raclopride study in healthy adults.

Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered on gambling disorder.

History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine.

Rationale: Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse.

Volunteerism and self-selection bias in human positron emission tomography neuroimaging research.

Scientists have known for decades that persons who volunteer for behavioral research may be different from those who decline participation and that characteristics differentiating volunteers from non-volunteers may vary depending on the nature of the research. There is evidence that volunteer self-selection can impact representativeness of samples in studies involving physically or psychologically stressful procedures, such as electric shocks, sensory isolation, or drug effects. However, the degree to which self-selection influences sample characteristics in "stressful" studies involving positron emission tomography (PET) has not been evaluated.

Impulsivity and chronic stress are associated with amphetamine-induced striatal dopamine release.

A challenging question that continues to plague the field of addiction is why some individuals are more vulnerable for substance use disorders than others. Several important risk factors for substance abuse have been identified in clinical studies, including trait impulsivity and environmental stress. However, the neurobiological mechanisms that underlie the relationships remain poorly understood.

Association of amphetamine-induced striatal dopamine release and cortisol responses to psychological stress.

Preclinical studies have shown that stress and glucocorticoids increase mesolimbic dopamine (DA) and thereby facilitate psychostimulant self-administration. The relationship between stress-induced cortisol and mesolimbic DA responses to psychostimulants has not been studied in humans. To test the hypotheses that glucocorticoid responses to psychological stress are correlated with DA and subjective responses to psychostimulants in humans, 25 healthy adults (18-29 years) completed the Trier Social Stress Test (TSST) and two positron emission tomography (PET) scans with high-specific [11C]raclopride.

Striatal dopamine release and family history of alcoholism.

Background: The offspring of alcohol-dependent individuals are at increased risk for alcoholism. The present study was designed to determine whether mesolimbic dopamine binding potential (BP), dopamine release, stress hormones, and subjective responses to intravenous amphetamine are different in nonalcoholic offspring from families with a history of alcohol dependence [family history positive (FHP)] than in nonalcoholic offspring without a family history of alcohol dependence [family history negative (FHN)].

Methods: Participants were 41 healthy men and women (11 FHP, 30 FHN; age range 18-29).

Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity.

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.

Sex differences in striatal dopamine release in healthy adults.

Background: Sex differences in addictive disorders have been described. Preclinical studies have implicated the striatal dopamine system in these differences, but human studies have yet to substantiate these findings.

Methods: Using positron emission tomography (PET) scans with high-specific-activity [11C] raclopride and a reference tissue approach, we compared baseline striatal dopamine binding potential (BP) and dopamine release in men and women following amphetamine and placebo challenges.

Hormonal responses to psychological stress and family history of alcoholism.

The present study was designed to determine whether stress hormones and subjective responses to a psychological stressor were different in nonalcoholic offspring from families with a history of alcohol dependence (family history positive, FHP) than in nonalcoholic offspring without a family history of alcohol dependence (family history negative, FHN). Forty-five healthy subjects (17 FHP, 28 FHN), between the ages of 18 and 29 years, completed the Trier Social Stress Test (TSST). The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic.

Relationship between cortisol responses to stress and personality.

Although there is growing evidence of links between the cortisol stress response and personality, the nature of the relationships and the underlying mechanisms require further clarification. The purpose of this study was to examine associations between personality traits and cortisol responses to stress using the Revised NEO Personality Inventory five-factor model of personality. In total, 68 healthy adults, aged 18-30 years, completed the personality assessment and underwent a laboratory psychological stress test that consisted of a 5 min speech and 5-min of mental arithmetic.

The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress.

A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase beta-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.

Hormone responses to social stress in abstinent alcohol-dependent subjects and social drinkers with no history of alcohol dependence.

Background: Previous studies have described blunted stress hormone responses after pharmacological activation of the hypothalamic-pituitary-adrenal (HPA) axis in sober alcoholics. The aim of the present study was to compare ACTH, cortisol, and prolactin responses to a psychological stressor in abstinent alcohol-dependent subjects matched to healthy control subjects.

Methods: Individuals who met DSM-IV diagnostic criteria for a history of alcohol dependence but not for other axis I disorders were included in the study (n = 18; mean duration of abstinence +/- SEM, 3.

Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine.

There is evidence that stress and glucocorticoids alter drug self-administration and mesolimbic dopamine (DA) activity in preclinical models. The primary purpose of this study was to test the hypothesis that glucocorticoids are associated with psychostimulant reinforcement and DA release in humans. In total, 16 healthy adults, ages 18-27 years, underwent two consecutive 90-min PET studies with high specific activity [11C]raclopride.

Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary-adrenal axis responses to naloxone: a preliminary report.

Background: A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered mu-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric conditions. We hypothesized that subjects homozygous for the low-activity allele would have greater hypothalamic-pituitary-adrenal axis responses to opioid blockade than subjects with the high-activity allele.

Comparison of HPA axis hormonal responses to naloxone vs psychologically-induced stress.

Although the naloxone challenge has been used to draw inferences about the dynamics of the stress response, this procedure has never actually been compared "head to head" with a psychological stressor. In the present study, we asked 14 healthy volunteers to complete the naloxone challenge and the Trier Social Stress Test in an outpatient GCRC laboratory setting so that the degree of correspondence between the two procedures could be examined. Findings indicated that subjects who had greater ACTH responses to naloxone also had greater ACTH responses to the psychologically-induced stressor.

The cyclic AMP/protein kinase A signal transduction pathway modulates tolerance to sedative and hypothermic effects of ethanol.

Background: An expanding body of literature indicates the important role of the cAMP/PKA signaling pathway in establishing initial sensitivity to alcohol as well as being involved in certain forms of tolerance to ethanol. The use of mice with heterozygous inactivation of the Gnas gene encoding Gsalpha allowed us to explore the relationship between tolerance to ethanol and cAMP/PKA signaling.

Methods: Mice with the targeted disruption of one Gsalpha allele were compared with wild-type littermates in their initial sensitivity to ethanol-induced sedation and hypothermia and then monitored for the development of tolerance during two subsequent bouts of intoxication.