Early life adversity and increased antisocial and depressive tendencies in young adults with family histories of alcohol and other substance use disorders: Findings from the Family Health Patterns project.

Background: Individuals with a family history of alcohol and other substance use disorders (FH+) are several times more likely to develop alcohol problems compared to individuals with no such family histories (FH-). Here we sought to evaluate associations of early life adversity (ELA) with two key risk-related FH+ phenotypic characteristics: increased antisocial and depressive tendencies. Methods: We examined data from 1187 FH+ and FH- young adults (average age 23.6 years old) with and without personal histories of substance use disorders. Antisocial tendencies were evaluated with the Socialization scale of the California Personality Inventory (CPI-So), while depressive tendencies were evaluated with the Beck Depression Inventory II (BDI). Results: In general, being FH+, having a personal substance use disorder history, and experiencing greater levels of ELA were associated with lower CPI-So scores (indicating more antisocial tendencies) and higher BDI scores (indicating more depressive tendencies). Conclusions: These results suggest that ELA is linked to increased antisocial and depressive tendencies observed in FH+ persons. Given that FH+ individuals are disproportionately exposed to ELA, this increased exposure may be a major contributor to these and other risk-related characteristics commonly present in FH+ individuals. Additional studies are needed to evaluate the impact of ELA on risk-related phenotypic characteristics, including prospective studies in early childhood and mechanistic studies evaluating pathways by which ELA exerts its effects on FH phenotypic characteristics.

Baseline associations between biomarkers, cognitive function, and self-regulation indices in the Cognitive and Self-regulatory Mechanisms of Obesity Study.

OBJECTIVE: Understanding how biological, cognitive, and self-regulatory factors are related to obesity, and weight regulation is clearly needed to optimize obesity prevention and treatment. The objective of this investigation was to understand how baseline biological, cognitive, and self-regulatory factors are related to adiposity at the initiation of a behavioral weight loss intervention among treatment-seeking adults with overweight/obesity. METHODS: Participants (N = 107) in the Cognitive and Self-regulatory Mechanisms of Obesity Study (Identifier-NCT02786238) completed a baseline assessment with anthropometric, cardiometabolic, inflammatory, cognitive function, and self-regulation measures as part of a larger on-going trial. Data were analyzed with linear regression. RESULTS: At baseline, body mass index, body fat percentage, and waist circumference (WC) were positively associated with fasting insulin and insulin resistance. Higher WC was related to higher fasting glucose and hemoglobin A1c (HbA1c). Higher glucose and insulin resistance levels were related to lower list sorting working memory. Higher glucose and HbA1c levels were negatively associated with reading scores. Cognitive function and self-regulation indices were unrelated. CONCLUSIONS: In adults with overweight/obesity entering a weight loss treatment study: (1) elevated WC and associated glycemic impairment were negatively associated with cognition, (2) poorer executive function and reading abilities were associated with poorer glycemic control, and (3) objectively measured cognitive functions were unrelated to self-reported/behavioral measures of self-regulation. Such findings increase understanding of the relationships between adiposity, biomarkers, cognition, and self-regulation at treatment initiation and may ultimately inform barriers to successful obesity treatment response.

Cardiovascular Stress Reactivity and Health: Recent Questions and Future Directions.

OBJECTIVE: High cardiovascular reactions to psychological stress are associated with the development of hypertension, systemic atherosclerosis, and cardiovascular disease. However, it has become apparent that low biological stress reactivity also may have serious consequences for health, although less is known about the mechanisms of this. The objectives of this narrative review and opinion article are to summarize and consider where we are now in terms of the usefulness of the reactivity hypothesis and reactivity research, given that both ends of the reactivity spectrum seem to be associated with poor health, and to address some of the key criticisms and future challenges for the research area. METHODS: This review is authored by the members of a panel discussion held at the American Psychosomatic Society meeting in 2019, which included questions such as the following: How do we measure high and low reactivity? Can high reactivity ever indicate better health? Does low or blunted reactivity simply reflect less effort on task challenges? Where does low reactivity originate from, and what is a low reactor? RESULTS: Cardiovascular (and cortisol) stress reactivity are used as a model to demonstrate an increased understanding of the different individual pathways from stress responses to health/disease and show the challenges of how to understand and best use the reconstruction of the long-standing reactivity hypothesis given recent data. CONCLUSIONS: This discussion elucidates the gaps in knowledge and key research issues that still remain to be addressed in this field, and that systematic reviews and meta-analyses continue to be required.

Neurobiological mechanisms of early life adversity, blunted stress reactivity and risk for addiction.

Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA) affects brain structure and function and results in blunted stress axis reactivity. In this review, we focus on the underlying neurobiological mechanisms associated with a blunted response to stress, ELA, and risk for addictive disorders. ELA and blunted reactivity are accompanied by unstable mood regulation, impulsive behaviors, and reduced cognitive function. Neuroimaging studies reveal cortical and subcortical changes in persons exposed to ELA and those who have a genetic disposition for addiction. We propose a model in which blunted stress reactivity may be a marker of risk for addiction through an altered motivational and behavioral reactivity to stress that contribute to disinhibited behavioral reactivity and impulsivity leading in turn to increased vulnerability for substance use. Evidence supporting this hypothesis in the context of substance use initiation, maintenance, and risk for relapse is presented. The effects of ELA on persons at risk for addiction may lead to early experimentation with drugs of abuse. Early adoption of drug intake may alter neuroregulation in such vulnerable persons leading to a permanent dysregulation of motivational responses consistent with dependence. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Addiction resistance to alcohol: What about heavy drinkers who avoid alcohol problems?

BACKGROUND: Some individuals are resistant to alcohol use disorders despite high levels of intake. Addiction Resistance (AR) measures the disparity between alcohol consumption and alcohol use disorder (AUD) symptoms, such that some persons exhibit few (AUD) symptoms despite higher intake. The validity of the concept and the factors contributing to AR are not well understood. The aim of this study was to predict AR based on variables related to risk for addiction that are measured in the Family Health Patterns Project. METHOD: Participants were healthy young adults (n = 1122) with and without a family history of alcohol and other substance use disorders who were given measures of mood stability and risk-taking tendencies, and were interviewed to determine alcohol intake, AUD symptoms, and other substance use disorders (SUD). AR was calculated using maximal lifetime alcohol intake and number of AUD symptoms. RESULTS: A principal components analysis was run with varimax rotation, which yielded three components: Component 1 indexed behavioral and mood regulation, Component 2 encompassed family and environmental factors, and Component 3 included cognitive factors. A multiple regression analysis revealed that Component 1 and Component 2 were predictive of AR whereas Component 3 was not. DISCUSSION: Individuals who reported greater emotional stability, norm adherence, risk avoidance, and fewer family members with substance use disorders were more resistant to AUD despite higher alcohol intake. These findings suggest that AUD risk and resistance may represent different points of the same continuum.

Working memory reflects vulnerability to early life adversity as a risk factor for substance use disorder in the FKBP5 cortisol cochaperone polymorphism, rs9296158.

Early life adversity (ELA) negatively affects health behaviors in adulthood, but pathways from ELA exposure to behavioral outcomes are poorly understood. ELA in childhood and adolescence may translate into adult outcomes by way of modified glucocorticoid signaling. The cortisol cotransporter, FKBP5 has a G-to-A substitution (rs9296158) that hinders cortisol trafficking within target cells, and this impaired glucocorticoid signaling may shape the long-term response to ELA. We used performance on the Stroop test to assess working memory in 546 healthy young adults who had experienced 0, 1, or > 1 forms of ELA in childhood and adolescence and were genotyped for the FKBP5 rs9296158 G-to-A polymorphism. We observed a robust Gene x Environment interaction (F = 9.49, p < .0001) in which increased ELA exposure led to progressively greater Stroop interference in persons carrying AG and AA genotypes of FKBP5 with no such effect in GG carriers. Further work is needed to explore the modification of cognitive function resulting from ELA. Impairments in working memory illustrate how ELA may use glucocorticoid pathways to influence working memory with potential implications for decision-making and risky behavior including substance use disorders.

Early-Life Adversity and Blunted Stress Reactivity as Predictors of Alcohol and Drug use in Persons With COMT (rs4680) Val158Met Genotypes.

BACKGROUND: Risk for alcoholism may be enhanced by exposure to early-life adversity (ELA) in persons with genetic vulnerabilities. We examined ELA in the presence of a common variant of the gene for the enzyme catechol-O-methyltransferase (COMT, Val158Met, rs4680) in relation to cortisol reactivity, the onset of early drinking, and experimentation with drugs. METHODS: Saliva cortisol reactivity to speech and mental arithmetic stress was measured in 480 healthy young adults (23.5 years of age, 50% females) who experienced either 0, 1, or ≥ 2 forms of ELA during childhood and adolescence, provided information on use of alcohol and recreational drugs, and were genotyped for the Val158Met polymorphism. RESULTS: ELA led to progressively smaller cortisol responses in the Met/Met and Val/Met allele groups but to progressively larger responses in Val homozygotes, F = 3.29, p = 0.011. ELA independently predicted earlier age at first drink, F = 14.2, p < 0.0001, with a larger effect in Met-allele carriers, F = 13.95, p < 0.00001, and a smaller effect in Val homozygotes, F = 4.14, p = 0.02. Similar effects were seen in recreational drug use. Cortisol reactivity was unrelated to drinking behavior or drug experimentation. CONCLUSIONS: ELA leads to blunted stress reactivity and, independently, contributes to potentially risky drinking and drug-use behaviors in persons carrying 1 or 2 copies of the COMT 158Met allele. The results reinforce the impact of early experience on the stress axis and on risky behaviors, and they point to the 158Met allele as conveying a vulnerability to the early environment.

Cortisol stress reactivity in women, diurnal variations, and hormonal contraceptives: studies from the Family Health Patterns Project.

Women have smaller cortisol responses to psychological stress than men do, and women taking hormonal contraceptives (HC+) have smaller responses than HC- women. Cortisol secretion undergoes substantial diurnal variation, with elevated levels in the morning and lower levels in the afternoon, and these variations are accompanied by differences in response to acute stress. However, the impact of HC use on these diurnal relationships has not been examined. We tested saliva cortisol values in 744 healthy young adults, 351 men and 393 women, 254 HC- and 139 HC+, who were assigned to morning (9:00 am) or afternoon (1:00 pm) test sessions that were held both on a rest day and on a stress day that included public speaking and mental arithmetic challenges. Saliva cortisol responses to stress were largest in men and progressively smaller in HC- and in HC+ women (F = 23.26, p < .0001). In the morning test sessions, HC+ women had significantly elevated rest day cortisol levels (t = 5.99, p ≪ .0001, Cohen's d = 0.95) along with a complete absence of response on the stress day. In the afternoon sessions, both HC+ and HC- women had normal rest-day cortisol levels and normal responses to the stressors. Heart rates at rest and during stress did not vary by time of day or HC status. Cortisol stress responses in HC+ women are absent in the morning and normal in size by early afternoon. Studies of stress reactivity should account for time of day in evaluating cortisol responses in women using hormonal contraceptives.

The role of genetics in stress effects on health and addiction.

Advances in stress research have yielded new insights into how stress exposure, in combination with genetics, can contribute to poor health outcomes. We review these topics with a special emphasis on early life stress and vulnerability to addiction. The direct effects of stress and our compensatory responses can modify our physiology and behavior during future stress episodes. These consequences can influence health, including an increased propensity for addiction. The relation between stress and health is not uniform across individuals. Some people succumb to stress-related disorders while others are resilient. Specific genetic polymorphisms affect how an individual appraises and responds to stress, potentially mediating the impact of stress on health. These genetic vulnerabilities can influence responses to the external environment, shape motivated behavior, and have an impact on health throughout life.

Blunted stress reactivity reveals vulnerability to early life adversity in young adults with a family history of alcoholism.

BACKGROUND AND AIMS: People with blunted stress reactivity have poor impulse control and also show increased risk for alcoholism. Exposure to early life adversity (ELA) contributes to blunted reactivity, but individual differences in susceptibility to ELA are not well understood. This study aimed to determine whether exposure to ELA has a greater impact on stress reactivity in young adults with a family history of alcoholism (FH+) compared with young adults with no family history of alcoholism (FH-). DESIGN: Observational study using linear modeling. SETTING: Oklahoma, USA. PARTICIPANTS: Seven hundred and nine young adults (398 females) recruited through community advertisement. MEASUREMENTS: We obtained heart rates and cortisol levels in subjects while undergoing public speaking and mental arithmetic stress compared with a resting control day (1418 test sessions). ELA was quantified as 0, 1 or > 1 adverse events experienced by age 15 years. FH+ people had one or two parents with an alcohol use disorder, and FH- controls had no such history for two generations. FINDINGS: Increasing levels of ELA predicted progressive blunting of cortisol and heart rate reactivity for the whole sample (Fs = 4.57 and 4.70, Ps ≤ 0.011), but examination by FH status showed that the effect of ELA was significant only among FH+ (Fs ≥ 3.5, Ps < 0.05) and absent in FH- (Ps > 0.40). This difference in ELA impact was not explained by the cortisol diurnal cycle or subjective evaluation of the stressors. CONCLUSIONS: People with a family history of alcoholism appear to be vulnerable, in terms of changes to physiological stress response, to the impact of exposure to early life adversity while people with no family history of alcoholism appear to be resilient. Blunted stress reactivity may reflect differential vulnerability to early life adversity in young adults with a family history of alcoholism.

Early life adversity and increased delay discounting: Findings from the Family Health Patterns project.

Increased discounting (devaluing) of delayed rewards is associated with nearly all types of substance use disorders (SUDs) and is also present in individuals with family histories of SUDs. Early life adversity (ELA) likely contributes to these findings as it is common in both individuals with SUDs and their children and is linked to increased delay discounting and other neurocognitive impairments in human and animal studies. Here we examined data from 1192 healthy young adults (average age 23.6 years old) with (SUDs+) and without (SUDs-) histories of SUDs and with (FH+) and without (FH-) family histories of SUDs. A 2-way ANOVA was conducted to examine the effects of SUDs (SUDs-, SUDs+) and FH (FH-, FH+) on delay discounting followed by an examination of the effects of adding ELA to the model. First, we replicated findings that SUDs+ and FH+ participants had increased rates of delay discounting. After taking ELA into account, the effect of SUDs and FH on delay discounting were both reduced but still significant. The association of ELA and delay discounting was similar in magnitude among both SUDs+ and SUDs- participants and FH+ and FH- participants; those with higher levels of ELA had increased delay discounting. Collectively, these findings indicate that increased ELA is closely associated with the increased delay discounting seen in SUDs+ and FH+ individuals and suggests ELA may be contributing to the increased delay discounting seen in these populations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project.

Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA. We administered 50 mg of naltrexone or placebo to 72 healthy women (23 years of age) in a double-blind crossover study and observed deviations in cortisol secretion from placebo over the next 180 minutes. ELA was assessed by reported exposure to physical and sexual abuse or neglect and low socioeconomic status and scored as Low, Medium, or High (0, 1-2, and 3+). The ELA groups all had identical placebo-day cortisol secretion, indicating normal basal regulation of the hypothalamic-pituitary-adrenocortical axis. Cortisol rises to naltrexone were largest in the Low-ELA group and strongly blunted in the High-ELA group (F = 3.51, p = 0.035), indicating a lack of opioid function in women with high degrees of ELA. The Low-ELA women reported dysphoric responses to naltrexone (F = 4.05, p = .022) indicating a mild opioid withdrawal, an effect that was absent in the High-ELA group. Women exposed to ELA have blunted cortisol responses to naltrexone, indicating reduced opioid regulation of the stress axis. Central opioid changes may be one pathway linking ELA to blunted stress reactivity in adulthood.

Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments.

Obesity is a global epidemic, yet successful interventions are rare. Up to 60% of people fail to achieve clinically meaningful, short-term weight loss (5-10% of start weight), whereas up to 72% are unsuccessful at achieving long-term weight loss (5-10% loss for ≥5years). Understanding how biological, cognitive, and self-regulatory factors work together to promote or to impede weight loss is clearly needed to optimize obesity treatment. This paper describes the methodology of the Cognitive and Self-regulatory Mechanisms of Obesity Study (the COSMOS trial). COSMOS is the first randomized controlled trial to investigate how changes in multiple biopsychosocial and cognitive factors relate to weight loss and one another across two weight loss treatments. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits and poorer self-regulation, 2) Evaluate pre- to post-treatment change across time to assess individual differences in biomarkers, cognition, and self-regulation, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in outcomes (e.g., greater weight loss and less weight regain, improvements in biomarkers, cognition, and self-regulation), than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. The results of COSMOS will provide critical information about how dysregulation in biomarkers, cognition, and/or self-regulation is related to weight loss and whether weight loss treatments are differentially associated with these factors. This information will be used to identify promising treatment targets that are informed by biological, cognitive, and self-regulatory factors in order to advance obesity treatment.

Defining the phenotype of young adults with family histories of alcohol and other substance use disorders: Studies from the family health patterns project.

Individuals with a family history of alcohol and other drug use disorders (FH+) are at increased risk for developing substance use disorders themselves relative to those with no such histories (FH-). Here we sought to identify key characteristics associated with FH+ status and alcohol and other drug use disorder status in a large cohort of FH+ and FH- young adults. We conducted principal component analyses on demographic, temperament, and cognitive measures differentiating 506 FH+ and 528 FH- young adults. Three principal components were identified, and these component scores were then used to predict the odds of being FH+ and the odds of having an alcohol or other drug use disorder. Component 1 consisted of measures indexing internalizing traits, with higher component scores indicating greater depressive, anxious, and emotional instability tendencies. Component 2 consisted of measures of externalizing traits as well as exposure to early life adversity (ELA), with higher scores indicating less impulse control, more antisocial behavior, and greater ELA exposure. Component 3 consisted of estimated intelligence, delay discounting, and demographic characteristics, with higher scores indicating lower estimated intelligence, greater discounting of delayed rewards, less education, and lower childhood socioeconomic status. For each 1-point increase in the Component 1, 2, and 3 scores, the odds of being classified FH+ increased by 2%, 8%, and 4%, respectively. Similar findings were observed when individuals with alcohol or other drug use disorders were removed from the analyses. Finally, greater Component 2 scores were also associated with increased odds of having an alcohol or other drug use disorder. Collectively, these findings provide a more comprehensive understanding of the FH+ phenotype in young adults and help form a basis for further studies on biological mechanisms underlying risk for substance use disorders. The present findings also provide further support for a prominent role of ELA in promoting risk for problem alcohol and other drug use.

Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress.

OBJECTIVE: Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA). METHODS: We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism. RESULTS: Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure. CONCLUSIONS: Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.

The behavioural, cognitive, and neural corollaries of blunted cardiovascular and cortisol reactions to acute psychological stress.

Recent research shows that blunted cardiovascular and cortisol reactions to acute psychological stress are associated with adverse behavioural and health outcomes: depression, obesity, bulimia, and addictions. These outcomes may reflect suboptimal functioning of the brain's fronto-limbic systems that are needed to regulate motivated behaviour in the face of challenge. In support of this, brain imaging data demonstrate fronto-limbic hypoactivation during acute stress exposure. Those demonstrating blunted reactions also show impairments of motivation, including lower cognitive ability, more rapid cognitive decline, and poorer performance on motivation-dependent tests of lung function. Persons exhibiting blunted stress reactivity display well established temperament characteristics, including neuroticism and impulsivity, characteristic of various behavioural disorders. Notably, the outcomes related to blunted stress reactivity are similar to those that define Reward Deficiency Syndrome. Accordingly, some individuals may be characterised by a broad failure in cardiovascular and cortisol responding to both stress and reward, reflecting fronto-limbic dysregulation. Finally, we proffer a model of blunted stress reactivity, its antecedents and sequelae, and identify future research priorities.

Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project.

Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling. FKBP5 expression is upregulated by cortisol exposure during stressful episodes, with greater upregulation seen in A-allele carriers. As such, FKBP5 expression and GR function may be environmentally sensitive in A-allele carriers and therefore suitable for the study of gene-by-environment (G × E) interactions. Compared with FKBP5, GG homozygotes (N=118), A-allele carriers (N = 132) without psychiatric morbidity had progressively worse performance on the Stroop color-word task with increasing levels of ELA exposure (Genotype × ELA, F=5.14, P=0.007), indicating a G × E interaction on working memory in early adulthood. In addition, heart rate response to mental stress was diminished overall in AA/AG-allele carriers (F=5.15, P=0.024). Diminished working memory and attenuated autonomic responses to stress are both associated with risk for alcoholism and other substance use disorders. The present data suggest that FKBP5 in the GR pathway may be a point of vulnerability to ELA, as seen in this group of non-traumatized young adults. FKBP5 is accordingly a potential target for more extensive studies of the impact of ELA on health and health behaviors in adulthood.

Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.

Differences in stress reactivity may affect long-term health outcomes, but there is little information on how these differences arise. The stress axis is regulated by, in part, the endogenous opioid, beta-endorphin, acting on mu-opioid receptors. Persons carrying one or two copies of the G allele of the mu-opioid receptor gene (OPRM1 A118G) may have higher receptor binding for beta-endorphin compared with AA homozygotes that may contribute to individual differences in cortisol reactivity to stress, leading to a relative blunting of cortisol stress reactivity in G allele genotypes. We measured cortisol in 251 young adults (69 GA/GG vs 182 AA genotypes) exposed to mental arithmetic plus public speaking stress relative to a resting control day. Women had smaller cortisol responses than men (F=10.2, p=0.002), and women with GA or GG genotypes (N=39) had an absence of cortisol response relative to AA carriers (N=110) (F=18.4, p<0.0001). Male genotypes had no such difference in response (F=0.29). Cortisol response following mu-opioid receptor blockade using naltrexone in 119 of these subjects unmasked a greater tonic opioid inhibition of cortisol secretion in women (N=64), consistent with their blunted stress reactivity. Compared with men, women may have cortisol stress responses that are more heavily regulated by endogenous opioid mechanisms, and the OPRM1 GA/GG genotypes may affect females differentially relative to males. Diminished cortisol responses to stress may have consequences for health behaviors in women with GA/GG genotypes.

Can exaggerated stress reactivity and prolonged recovery predict negative health outcomes? The case of cardiovascular disease.

Researchers and laypersons have long argued that stress is bad for health, particularly when responses are large, prolonged, and frequent. By extension, individuals who have the largest and the most prolonged responses are assumed to have worse outcomes than do less reactive persons. Research in animals has been supportive of the connection between stress and poor health, but evidence in humans has been slow to accumulate. The current issue of Psychosomatic Medicine presents a meta-analysis of 33 studies of delayed recovery from stress and its association with poor cardiovascular disease outcomes and all-cause mortality. The analysis supports the contention that slower recovery to baseline after exercise or psychological stress may predict earlier death due to all causes. This finding raises questions for psychosomatic theories of disease and points the direction for further study of how or whether to incorporate reactivity measures into standard risk profiles.

Risk factors for alcoholism in the Oklahoma Family Health Patterns project: impact of early life adversity and family history on affect regulation and personality.

AIM: This study examined the impact of early lifetime adversity (ELA) on affect regulation and personality in persons with family history (FH+) and without (FH-) a family history of alcoholism. We examined the impact of early life adversity in healthy young adults, 18-30 years of age enrolled in a long-term study on risk for alcohol and other substance abuse. METHODS: ELA was assessed by a composite score of low socioeconomic status and personal experience of physical or sexual abuse and/or separation from parents before age 16, resulting in a score of 0, 1-2, or >3 adverse events. Unstable affect regulation and personality variables were obtained via self-report measures. RESULTS: Higher ELA scores were seen in FH+ (χ(2)=109.2, p<0.0001) and in women (χ(2)=17.82, p=0.0019). Although higher ELA predicted less emotional stability and more behavioral undercontrol, further analysis including both FH and ELA showed that FH+ persons are prone to poor affect regulation, negative moods, and have risky drinking and drug abuse tendencies independent of ELA level. ELA predicts reduced stress reactivity and poorer cognitive control over impulsive behaviors as shown elsewhere. CONCLUSIONS: The present work shows that FH+ have poor mood regulation and antisocial characteristics. The greater prevalence of ELA in FH+ persons indicates that life experience and FH+ work in tandem to result in risky patterns of alcohol and drug experimentation to elevate risk for alcoholism. Further studies of genetic and environmental contributions to alcoholism are called for.