- Email: [email protected]
Amgydalocortical connectivity at rest is associated with increased reactivity to social threat, ACTH, and future ethanol self-administration
208
Abstracts / Alcohol 60 (2017) 203e243
of North Carolina, Chapel Hill, NC, USA; University of Missouri, Columbia, MO, USA Recently there has been interest in the emergence of a subclinical syndrome of mood disturbance associated with the evolution of the clinical course of alcohol use disorders (AUDs) that has been labeled by Koob and colleagues the “dark side” of addiction. The present study sought to operationalize a “dark side” phenotype using items from a standard assessment instrument (the semi structured assessment for the genetics of alcoholism (SSAGA)), estimate its prevalence in individuals with AUDs, determine its co-morbidity with other psychiatric disorders, and test its heritability and association with genetic sequence variants in three different epidemiological samples. Data were available from three studies comprising 2,355 individuals with AUDs: 1) A Native American sample (NA: n ¼ 612), 2) A Mexican American sample (MA: n ¼ 295) and a EuroAmerican sample (EA: n ¼ 1448). Fifty percent of the sample reported “dark side” symptoms and it was significantly more common in those with DSM-5 severe AUD. A logistic regression revealed that the severity of the AUD, neuroticism, and a life time history of affective disorders explained most of the variance in “dark side” symptoms. The heritability of the two dark side symptoms ranged between 5 and 50%. A genome wide significant association was found between SNPs in several potassium voltage gated ion channels (KCNC2, KCNJ6) and dark side symptoms in the EA and NA samples. These studies suggest that “dark side” symptoms are common in those with AUD, are associated with internalizing traits and has a genetic component (supported by AA10201, DA 030976). S21 AMGYDALOCORTICAL CONNECTIVITY AT REST IS ASSOCIATED WITH INCREASED REACTIVITY TO SOCIAL THREAT, ACTH, AND FUTURE ETHANOL SELF-ADMINISTRATION Megan N. McClintick, Damien Fair, Christopher Kroenke, Kathleen A. Grant. Oregon Health & Science University, Beaverton, OR, USA Aggression and anxiety are linked to heavier alcohol use and these phenotypes are associated with dysregulated corticolimbic circuitry and HPA function. Prior to ethanol self-administration, male and female rhesus macaques underwent the Human Intruder Test to assess aggressive and anxious behavior and MRI imaging to assess resting state functional connectivity (rsFC) between the amygdala and prefrontal cortex. Basal cortisol and ACTH were also assayed. After induction of ethanol self-administration with a schedule-induced polydipsia procedure, 4% w/v ethanol access was available for 22 hours/day. Longer durations of aggressive (rs ¼ 0.65, p ¼ 0.040) and anxious (rs ¼ 0.61, p ¼ 0.047) behavior at baseline positively associated with higher future ethanol intake. Circulating cortisol was higher in high anxiety and aggression animals (27.4 v. 20.4; t6 ¼ -2.7, p ¼ 0.037; 28.8 v. 21.3, t9 ¼ 2.4, p ¼ 0.039). High aggression subjects exhibited stronger positive rsFC between BA and dlPFC (0.06 v. 0.04, t9 ¼ 5.1, p ¼ 0.0007), while heavy drinkers exhibited stronger positive baseline rsFC between CeA and dlPFC (0.11 v. 0.04, t10 ¼ 4.8, p ¼ 0.0007). Circulating ACTH was associated with higher positive rsFC between LA and dlPFC (rs ¼ 0.84, p ¼ 0.0013) and CeA and OFC (rs ¼ 0.84, p ¼ 0.0013). Overall, the data suggest that monkeys with anxious and/or aggressive temperaments are predisposed to drink heavily. While higher levels of aggression, heavy drinking and circulating stress hormones were all associated with stronger positive dysregulated amygdalocortical connectivity, each associated with specific amygdalar seeds. S22 PREVENTION OF UNDERAGE DRINKING AND ALCOHOL USE DISORDERS IN NATIVE AMERICAN ADOLESCENTS: INFLUENCE OF STRESS AND DARK SIDE SYMPTOMS D. Gilder, R. Moore, J. Geisler, D. Calac, J. Luna, C. Ehlers. The Scripps Research Institute, La Jolla, CA, USA American Indian adolescents have the highest prevalence of drinking, alcohol use disorder, and suicide. A major risk factor for these is early onset of drinking. This study evaluated 300 American Indian adolescents, ages 13e17, for factors associated with age of first drink <14 years. Decreased
parental monitoring, lack of involvement with the father, living with only one parent, and ever having a boyfriend/girlfriend were associated with early initiation of drinking. Eight percent had DSM-IV alcohol dependence; half of these had dark side symptoms. Suicidal ideation was associated with conduct disorder and alcohol dependence. Sixty youth participated in a 1.5-hour session of Motivational Interviewing (MI) compared to PsychoEducation (PE) designed to prevent or reduce underage drinking. For drinkers, participation in MI or PE was associated at follow-up with less frequent drinking (p ¼ 0.039), fewer drinks per drinking occasion (p ¼ 0.004), fewer maximum drinks (p ¼ 0.004), and fewer problems with underachieving in school (p ¼ 0.004), lying (p ¼ 0.004), defiance with parents (p ¼ 0.004), spending time with people who smoke, drink, or use drugs (p ¼ 0.004), using alcohol (p ¼ 0.004), using drugs (p ¼ 0.048), and tagging/wearing gang clothing (p ¼ 0.03). In the MI group, males reported fewer drinks per occasion (p ¼ 0.041) and females reported less depression (p ¼ 0.011). In the non-drinking group, 6 participants (17%) had initiated drinking at follow-up. These studies suggest that targeting underage drinking using MI may reduce the development of drinking, associated behavioral problems, and dark side symptoms associated with drinking in youth and may be an important factor in reducing youth suicide (supported by AA10201; AA023755).
Symposium VI Chronic pain and alcohol dependence. Chair: Igor Spigelman, Ph.D.
S24 PHYSICAL PAIN IN ALCOHOL-DEPENDENT PATIENTS ENTERING TREATMENT e PREVALENCE AND RISK OF POST-TREATMENT RELAPSE Marcin Wojnar, Andrzej Jakubczyk, Maciej Kopera, Anna Klimkiewicz, Aleksandra Krasowska, Mark A. Ilgen, Frederic C. Blow, Amy Bohnert, Kirk J. Brower. Medical University of Warsaw, Warsaw, Poland; University of Michigan, Ann Arbor, MI, USA Background: Chronic pain and harmful alcohol use commonly co-exist, however, it is not clear how presence of pain may impact risk of relapse in alcoholism. The purpose of the study was to characterize pain in a group of alcohol-dependent individuals entering treatment programs and to examine if changes in pain before and after the treatment influences risk of post-treatment relapse. Methods: A sample of 366 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, social functioning, childhood abuse, severity of alcohol and sleep problems, level of pain, impulsivity and general psychopathology. After completing treatment program patients were followed up for 12 month; alcohol use and pain severity were evaluated. Results: 34% of individuals reported moderate or greater physical pain before the treatment. At the follow-up assessment, 30% of patients confirmed relapse. Comparing to baseline pain levels, 49% of subjects reported increased severity of pain, 29% e comparable levels, and 22% declared decreased pain after treatment. There was a significant association between the decrease in level of pain and the lower risk of relapse. In multivariate analysis, a decrease in pain level was associated with a lower likelihood of relapse (OR ¼ 0.159) even when controlled for other factors associated with relapse. Conclusions: Physical pain is a prevalent and potentially impairing experience in adults seeking treatment for alcohol dependence. The study indicates that decreases in pain level following treatment for alcohol dependence are associated with, and may contribute to, a lower risk of alcohol relapse. S25 CONVERGENCE OF CENTRAL PAIN AND STRESS SIGNALING IN ALCOHOL DEPENDENCE Scott Edwards Ph.D. LSU Health Sciences Center, New Orleans, LA, USA A key feature of severe alcohol use disorder (AUD) is the emergence of negative affective states that can influence the motivational properties of alcohol. Pain represents one such negative emotional state hypothesized to drive AUD severity, and this relationship is particularly concerning since there are few effective treatments for either chronic pain or AUD.
Abstracts / Alcohol 60 (2017) 203e243
of North Carolina, Chapel Hill, NC, USA; University of Missouri, Columbia, MO, USA Recently there has been interest in the emergence of a subclinical syndrome of mood disturbance associated with the evolution of the clinical course of alcohol use disorders (AUDs) that has been labeled by Koob and colleagues the “dark side” of addiction. The present study sought to operationalize a “dark side” phenotype using items from a standard assessment instrument (the semi structured assessment for the genetics of alcoholism (SSAGA)), estimate its prevalence in individuals with AUDs, determine its co-morbidity with other psychiatric disorders, and test its heritability and association with genetic sequence variants in three different epidemiological samples. Data were available from three studies comprising 2,355 individuals with AUDs: 1) A Native American sample (NA: n ¼ 612), 2) A Mexican American sample (MA: n ¼ 295) and a EuroAmerican sample (EA: n ¼ 1448). Fifty percent of the sample reported “dark side” symptoms and it was significantly more common in those with DSM-5 severe AUD. A logistic regression revealed that the severity of the AUD, neuroticism, and a life time history of affective disorders explained most of the variance in “dark side” symptoms. The heritability of the two dark side symptoms ranged between 5 and 50%. A genome wide significant association was found between SNPs in several potassium voltage gated ion channels (KCNC2, KCNJ6) and dark side symptoms in the EA and NA samples. These studies suggest that “dark side” symptoms are common in those with AUD, are associated with internalizing traits and has a genetic component (supported by AA10201, DA 030976). S21 AMGYDALOCORTICAL CONNECTIVITY AT REST IS ASSOCIATED WITH INCREASED REACTIVITY TO SOCIAL THREAT, ACTH, AND FUTURE ETHANOL SELF-ADMINISTRATION Megan N. McClintick, Damien Fair, Christopher Kroenke, Kathleen A. Grant. Oregon Health & Science University, Beaverton, OR, USA Aggression and anxiety are linked to heavier alcohol use and these phenotypes are associated with dysregulated corticolimbic circuitry and HPA function. Prior to ethanol self-administration, male and female rhesus macaques underwent the Human Intruder Test to assess aggressive and anxious behavior and MRI imaging to assess resting state functional connectivity (rsFC) between the amygdala and prefrontal cortex. Basal cortisol and ACTH were also assayed. After induction of ethanol self-administration with a schedule-induced polydipsia procedure, 4% w/v ethanol access was available for 22 hours/day. Longer durations of aggressive (rs ¼ 0.65, p ¼ 0.040) and anxious (rs ¼ 0.61, p ¼ 0.047) behavior at baseline positively associated with higher future ethanol intake. Circulating cortisol was higher in high anxiety and aggression animals (27.4 v. 20.4; t6 ¼ -2.7, p ¼ 0.037; 28.8 v. 21.3, t9 ¼ 2.4, p ¼ 0.039). High aggression subjects exhibited stronger positive rsFC between BA and dlPFC (0.06 v. 0.04, t9 ¼ 5.1, p ¼ 0.0007), while heavy drinkers exhibited stronger positive baseline rsFC between CeA and dlPFC (0.11 v. 0.04, t10 ¼ 4.8, p ¼ 0.0007). Circulating ACTH was associated with higher positive rsFC between LA and dlPFC (rs ¼ 0.84, p ¼ 0.0013) and CeA and OFC (rs ¼ 0.84, p ¼ 0.0013). Overall, the data suggest that monkeys with anxious and/or aggressive temperaments are predisposed to drink heavily. While higher levels of aggression, heavy drinking and circulating stress hormones were all associated with stronger positive dysregulated amygdalocortical connectivity, each associated with specific amygdalar seeds. S22 PREVENTION OF UNDERAGE DRINKING AND ALCOHOL USE DISORDERS IN NATIVE AMERICAN ADOLESCENTS: INFLUENCE OF STRESS AND DARK SIDE SYMPTOMS D. Gilder, R. Moore, J. Geisler, D. Calac, J. Luna, C. Ehlers. The Scripps Research Institute, La Jolla, CA, USA American Indian adolescents have the highest prevalence of drinking, alcohol use disorder, and suicide. A major risk factor for these is early onset of drinking. This study evaluated 300 American Indian adolescents, ages 13e17, for factors associated with age of first drink <14 years. Decreased
parental monitoring, lack of involvement with the father, living with only one parent, and ever having a boyfriend/girlfriend were associated with early initiation of drinking. Eight percent had DSM-IV alcohol dependence; half of these had dark side symptoms. Suicidal ideation was associated with conduct disorder and alcohol dependence. Sixty youth participated in a 1.5-hour session of Motivational Interviewing (MI) compared to PsychoEducation (PE) designed to prevent or reduce underage drinking. For drinkers, participation in MI or PE was associated at follow-up with less frequent drinking (p ¼ 0.039), fewer drinks per drinking occasion (p ¼ 0.004), fewer maximum drinks (p ¼ 0.004), and fewer problems with underachieving in school (p ¼ 0.004), lying (p ¼ 0.004), defiance with parents (p ¼ 0.004), spending time with people who smoke, drink, or use drugs (p ¼ 0.004), using alcohol (p ¼ 0.004), using drugs (p ¼ 0.048), and tagging/wearing gang clothing (p ¼ 0.03). In the MI group, males reported fewer drinks per occasion (p ¼ 0.041) and females reported less depression (p ¼ 0.011). In the non-drinking group, 6 participants (17%) had initiated drinking at follow-up. These studies suggest that targeting underage drinking using MI may reduce the development of drinking, associated behavioral problems, and dark side symptoms associated with drinking in youth and may be an important factor in reducing youth suicide (supported by AA10201; AA023755).
Symposium VI Chronic pain and alcohol dependence. Chair: Igor Spigelman, Ph.D.
S24 PHYSICAL PAIN IN ALCOHOL-DEPENDENT PATIENTS ENTERING TREATMENT e PREVALENCE AND RISK OF POST-TREATMENT RELAPSE Marcin Wojnar, Andrzej Jakubczyk, Maciej Kopera, Anna Klimkiewicz, Aleksandra Krasowska, Mark A. Ilgen, Frederic C. Blow, Amy Bohnert, Kirk J. Brower. Medical University of Warsaw, Warsaw, Poland; University of Michigan, Ann Arbor, MI, USA Background: Chronic pain and harmful alcohol use commonly co-exist, however, it is not clear how presence of pain may impact risk of relapse in alcoholism. The purpose of the study was to characterize pain in a group of alcohol-dependent individuals entering treatment programs and to examine if changes in pain before and after the treatment influences risk of post-treatment relapse. Methods: A sample of 366 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, social functioning, childhood abuse, severity of alcohol and sleep problems, level of pain, impulsivity and general psychopathology. After completing treatment program patients were followed up for 12 month; alcohol use and pain severity were evaluated. Results: 34% of individuals reported moderate or greater physical pain before the treatment. At the follow-up assessment, 30% of patients confirmed relapse. Comparing to baseline pain levels, 49% of subjects reported increased severity of pain, 29% e comparable levels, and 22% declared decreased pain after treatment. There was a significant association between the decrease in level of pain and the lower risk of relapse. In multivariate analysis, a decrease in pain level was associated with a lower likelihood of relapse (OR ¼ 0.159) even when controlled for other factors associated with relapse. Conclusions: Physical pain is a prevalent and potentially impairing experience in adults seeking treatment for alcohol dependence. The study indicates that decreases in pain level following treatment for alcohol dependence are associated with, and may contribute to, a lower risk of alcohol relapse. S25 CONVERGENCE OF CENTRAL PAIN AND STRESS SIGNALING IN ALCOHOL DEPENDENCE Scott Edwards Ph.D. LSU Health Sciences Center, New Orleans, LA, USA A key feature of severe alcohol use disorder (AUD) is the emergence of negative affective states that can influence the motivational properties of alcohol. Pain represents one such negative emotional state hypothesized to drive AUD severity, and this relationship is particularly concerning since there are few effective treatments for either chronic pain or AUD.