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.

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 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.

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.

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.

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.

Implementing brief cognitive behavioral therapy in primary care: A pilot study.

Effective implementation strategies are needed to improve the adoption of evidence-based psychotherapy in primary care settings. This study provides pilot data on the test of an implementation strategy conducted as part of a multisite randomized controlled trial examining a brief cognitive-behavioral therapy versus usual care for medically ill patients in primary care, using a hybrid (type II) effectiveness/implementation design. The implementation strategy was multifaceted and included (1) modular-based online clinician training, (2) treatment fidelity auditing with expert feedback, and (3) internal and external facilitation to provide ongoing consultation and support of practice. Outcomes included descriptive and qualitative data on the feasibility and acceptability of the implementation strategy, as well as initial indicators of clinician adoption and treatment fidelity. Results suggest that a comprehensive implementation strategy to improve clinician adoption of a brief cognitive-behavioral therapy in primary care is feasible and effective for reaching high levels of adoption and fidelity.

Differential impact of serotonin transporter activity on temperament and behavior in persons with a family history of alcoholism in the Oklahoma Family Health Patterns Project.

BACKGROUND: Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+). METHODS: We tested 314 healthy young adults (23.5 years of age, 57% female; 193 FH- and 121 FH+) enrolled in the Oklahoma Family Health Patterns project, a study of alcoholism risk in relation to temperament and behavioral dyscontrol. Dysphoria was assessed using the Eysenck neuroticism and Beck depression scales, and Cloninger's Tridimensional Personality Questionnaire. Risk taking was assessed with the Iowa Gambling Task (IGT) and Balloon Analogue Response Task (BART). All subjects were genotyped for a functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4). RESULTS: FH+ subjects with the gain-of-function 5-HTTLPR genotype scored higher in neuroticism, harm avoidance, and symptoms of depression (p-values ≤ 0.03). No effect of 5-HTTLPR genotype was seen in FH-. FH+ carriers of the gain-of-function 5-HTTLPR genotype played to minimize their frequency of losses in the IGT, whereas FH- carriers played a balanced strategy (p < 0.003). No 5-HTTLPR effects were seen in the BART. Results were unaffected by sex, education, drug use, and antisocial characteristics. CONCLUSIONS: The functional 5-HTTLPR polymorphism predicted significant variation in negative moods and poorer affect regulation in FH+ persons, with possible consequences for behavior, as seen in a simulated gambling task. This pattern may contribute to a drinking pattern that is compensatory for such affective tendencies.

Treatment of posttraumatic stress disorder at the end-of-life: application of the Stepwise Psychosocial Palliative Care model.

OBJECTIVES: Feldman (2011) has proposed a new approach to the treatment of posttraumatic stress disorder (PTSD) in individuals at the end-of-life known as Stepwise Psychosocial Palliative Care (SPPC). This approach helps to compensate for the disadvantages of existing PTSD interventions with regard to treating patients with life-limiting and terminal illnesses by employing a palliative care philosophy. The model relies on cognitive and behavioral techniques drawn from evidence-based approaches to PTSD, deploying them in a stage-wise manner designed to allow for interventions to track with patents' needs and prognoses. Because this model is relatively new, we seek to explore issues related to its implementation in the complex settings in which providers encounter patients at the end-of-life. We also seek to provide concrete guidance to providers regarding the management of PTSD at the end-of-life in diverse palliative care settings. METHODS: We examine three specific cases in which the SPPC model was utilized, highlighting particular treatment challenges and strategies. These case studies provide information regarding the SPPC model's application to patients in two distinct palliative care settings-a palliative care consult team and an inpatient palliative care unit. RESULTS: The SPPC model's stage-wise approach allows for its flexible use given a variety of constraints related to setting and patient issues. SIGNIFICANCE OF RESULTS: The SPPC model provides an alternative to existing psychosocial treatments for PTSD that may be more appropriate for patients at the end of life.

Integrating care coordination home telehealth and home based primary care in rural Oklahoma: a pilot study.

The purpose of this program was to evaluate the benefits of integrating VA Care Coordination Home Telehealth and Telemental health within HBPC. A case study design was used to determine quality assurance and quality improvement of incorporating additional home telehealth equipment within Home Based Primary Care (HBPC). Veterans with complex medical conditions and their caregivers living in rural Oklahoma were enrolled. Veterans received the same care other HBPC patients received with the addition of home telehealth equipment. Members from the interdisciplinary treatment team were certified to use the telehealth equipment. Veterans and their caregivers were trained on use of the equipment in their homes. Standard HBPC program measures were used to assess the program success. Assessments from all disciplines on the HBPC team were at baseline, 3, and 6 months, and participants provided satisfaction and interview data to assess the benefits of integrating technology into standard care delivery within an HBPC program. Six veterans were enrolled (mean age = 72 yrs) with a range of physical health conditions including: chronic obstructive pulmonary disease, cerebrovascular accident, spinal cord injury, diabetes, hypertension, and syncope. Primary mental health conditions included depression, dementia, anxiety, and PTSD. Scores on the Mini-Mental State Examination ranged from 18 to 30. Over a 6-month period, case studies indicated improvements in strength, social functioning, decreased caregiver burden, and compliance with treatment plan. This integration of CCHT and HBPC served previously underserved rural veterans having complex medical conditions and appears both feasible and clinically beneficial to veterans and their caregivers.

Early life adversity contributes to impaired cognition and impulsive behavior: studies from the Oklahoma Family Health Patterns Project.

BACKGROUND: Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism. METHODS: We tested 386 healthy young adults (18 to 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop color-word task, and a delay discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards. Body mass index (BMI) was examined as an early indicator of altered health behavior. RESULTS: Greater levels of adversity predicted higher Stroop interference scores (F = 3.07, p = 0.048), faster discounting of delayed rewards (F = 3.79, p = 0.024), lower Shipley mental age scores (F = 4.01, p = 0.019), and higher BMIs in those with a family history of alcoholism (F = 3.40, p = 0.035). These effects were not explained by age, sex, race, education, or depression. CONCLUSIONS: The results indicate a long-term impact of stressful life experience on cognitive function, impulsive behaviors, and early health indicators that may contribute to risk in persons with a family history of alcoholism.

Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design.

BACKGROUND: Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. METHODS: This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. CONCLUSIONS: Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. TRIAL REGISTRATION: NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772.

Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.

Naltrexone evokes a cortisol response through its blockade of central opioid receptors on the hypothalamic-pituitary-adrenocortical axis (HPA). The magnitude of this cortisol response may be useful as a probe for central opioid activity in different groups of subjects. Accordingly, the present study examined the effect of opioid blockade on the HPA in 70 women and 58 men with (N=41) and without (N=87) a family history of alcoholism, using a randomized, placebo-controlled, double blind administration of oral naltrexone (50mg). Saliva cortisol was sampled at baseline prior to placebo or naltrexone and again every 30 min over the next 180 min. Women had significantly larger cortisol responses to naltrexone than did the men, F=6.88, p<0.0001. There were no significant differences in cortisol response between groups differing in family history of alcoholism, F=0.65, p>0.69. The present results confirm that women have much greater central opioid restraint on the HPA than men do and that this endogenous restraint is unmasked by opioid blockade. However the results provide no evidence of a differential central opioid tonus in persons with a family history of alcoholism at this dose of naltrexone. The cortisol response to naltrexone may be a useful probe for central opioid activity in women and to a lesser degree in men.

Lifetime adversity leads to blunted stress axis reactivity: studies from the Oklahoma Family Health Patterns Project.

BACKGROUND: Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease; however, little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity. METHODS: We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events, including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months before age 15). RESULTS: Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events) (F values = 5.79 and 8.11, p values < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure. CONCLUSIONS: The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.

Greater discounting of delayed rewards in young adults with family histories of alcohol and drug use disorders: studies from the Oklahoma family health patterns project.

BACKGROUND: Increased discounting of delayed rewards may be a premorbid characteristic and possible risk factor for alcohol and other drug use disorders; however, previous studies have found no or minimal differences in delay discounting in individuals at risk for substance use disorders based on family history. It is possible that increased delay discounting may be more closely associated with antisocial traits, evident in a subset of individuals with positive family histories of alcohol and drug use disorders, and that previous studies were underpowered for detecting subtle to modest overall group differences. METHODS: In this study, we compared 143 young adults with family histories of alcohol and other drug use disorders (FH+) and 155 young adults with no such histories (FH-) on delay discounting and subsequently examined how delay discounting was related to antisocial traits and other selected psychological and demographic variables. RESULTS: The FH+ group discounted delayed rewards more than the FH- group. Subsequent analyses revealed that increased delay discounting was correlated with having more parents and grandparents with alcohol and drug use disorders, more antisocial traits, more depressive tendencies and lower IQs, and lower income. After controlling for all these relationships, more antisocial traits and lower IQ still predicted greater delay discounting, and subsequent analysis revealed that the greater delay discounting in the FH+ group was mediated by this group's greater number of individuals with antisocial traits. CONCLUSION: FH+ individuals who discount delayed rewards more may be at increased risk for developing alcohol and other drug use disorders; however, additional descriptive studies and longitudinal studies are needed.

Multidisciplinary cognitive-behavioral therapy training for the veterans affairs primary care setting.

OBJECTIVE: Current research highlights the need to embed evidence-based psychotherapies such as cognitive-behavioral therapy (CBT) within primary care settings. Few studies have examined CBT training procedures, and no studies have examined the impact of CBT training in the primary care setting. The current study sought to describe and assess the feasibility and effectiveness of a focused CBT training program for a diverse sample of primary care mental health providers in the Department of Veterans Affairs (VA). METHOD: A multidisciplinary group of 28 mental health clinicians from 6 VA medical centers and 15 community-based outpatient clinics received an intensive 1½-day CBT workshop, held in Houston, Texas, in May 2008, including didactic presentations, expert modeling, and small-group role plays. CBT experts also provided biweekly follow-up group telephone consultation calls for participants over 12 weeks to aid in development of CBT skills. Participant program evaluation surveys and self-reported CBT knowledge, ability, and utilization were measured preworkshop, postworkshop, and 3 months postworkshop. Analyses compared mean change scores at baseline to those at 3-month follow-up. Wilcoxon signed rank tests were completed, and Cohen d effect-size calculations were also computed. RESULTS: Statistical analyses found that participant self-reported CBT knowledge (P < .01, effect size [ES] = 0.49) was significantly improved postworkshop and maintained at 3-month follow-up. Self-reported abilities were also improved (P = .07, ES = 0.40). The potency of the training experience appeared to be enhanced by the multimodal nature of the program. CONCLUSION: Although challenges exist, focused and intensive training in CBT appears feasible for multidisciplinary mental health practitioners in the primary care setting.