Article

Neural and psychological characteristics of college students with alcoholic parents differ depending on current alcohol use

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Abstract

A significant proportion of college students are adult children of an alcoholic parent (ACoA), which can confer greater risk of depression, poor self-esteem, alcohol and drug problems, and greater levels of college attrition. However, some ACoA are resilient to these negative outcomes. The goal of this study was to better understand the psychobiological factors that distinguish resilient and vulnerable college-aged ACoAs. To do so, scholastic performance and psychological health were measured in ACoA college students not engaged in hazardous alcohol use (resilient) and those currently engaged in hazardous alcohol use (vulnerable). Neural activity (as measured by functional magnetic resonance imaging) in response to performing working memory and emotion-based tasks were assessed. Furthermore, the frequency of polymorphisms in candidate genes associated with substance use, risk taking and stress reactivity were compared between the two ACoA groups. College ACoAs currently engaged in hazardous alcohol use reported more anxiety, depression and posttraumatic stress symptoms, and increased risky nicotine and marijuana use as compared to ACoAs resistant to problem alcohol use. ACoA college students with current problem alcohol showed greater activity of the middle frontal gyrus and reduced activation of the posterior cingulate in response to visual working memory and emotional processing tasks, which may relate to increased anxiety and problem alcohol and drug behaviors. Furthermore, polymorphisms of cholinergic receptor and the serotonin transporter genes also appear to contribute a role in problem alcohol use in ACoAs. Overall, findings point to several important psychobiological variables that distinguish ACoAs based on their current alcohol use that may be used in the future for early intervention.

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... Being raised by an alcoholic parent confers an increased risk of trauma exposure, not limited to abuse (Mackrill and Hesse, 2011), neglect (Reich et al., 1988;Haverfield and Theiss, 2014) as well as dysfunction in social development and attachment (Reich et al., 1988;Lander et al., 2013). ACoA's are significantly more likely to report difficulties in psychological, cognitive, and social functioning (Haverfield and Theiss, 2014;Klostermann et al., 2011;Brown-Rice et al., 2018), and are 3-4 times more likely to develop a substance use disorder (SUD) in their lifetime (Yoon et al., 2013;Eddie et al., 2015), due to interactions between genetic and environmental factors (Crane, 2019). Trauma exposure can influence mental health outcomes directly (Khoury et al., 2010;Carr et al., 2013) through the alteration of epigenetic factors (Klengel et al., 2014;Kader et al., 2018). ...
... All procedures were approved by the Institutional Review Board of the University of South Dakota. Twenty-nine participants were enrolled in the study from advertisements posted on campus at the University of South Dakota as part of a larger study (Brown-Rice et al., 2018). An initial screening was completed to determine eligibility, which included a score of 6 or more on the Children of Alcoholics Screening Test (CAST (Jones, 1983),), indicating that the participant was more than likely a child of an alcoholic (Brown-Rice et al., 2018), as well as for contraindications to functional magnetic resonance imaging (fMRI) and possible psychotic or psychological symptoms excluding them from testing. ...
... Twenty-nine participants were enrolled in the study from advertisements posted on campus at the University of South Dakota as part of a larger study (Brown-Rice et al., 2018). An initial screening was completed to determine eligibility, which included a score of 6 or more on the Children of Alcoholics Screening Test (CAST (Jones, 1983),), indicating that the participant was more than likely a child of an alcoholic (Brown-Rice et al., 2018), as well as for contraindications to functional magnetic resonance imaging (fMRI) and possible psychotic or psychological symptoms excluding them from testing. ...
Article
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Many Americans are adult children of an alcoholic parent (ACoA), which can confer an increased risk of trauma and hazardous alcohol use, as well as heritable and environmental genetic influence. Psychological health and related neural activity can be influenced by inflammation responses, but it is not clear how these factors interact regarding risk or resilience to hazardous alcohol use. The goals of this study were to better understand the relationships between current alcohol use and inflammation, how these are modified by single nucleotide polymorphisms (SNPs) and/or epigenetic modifications of inflammation-associated genes; and how these alter neural reactivity to emotionally-salient stimuli. To do so, ACoA participants were dichotomized as resilient (not engaged in hazardous alcohol use) or vulnerable (currently engaged in hazardous alcohol use). Measures of blood-oxygen-level-dependent (BOLD) activity within regions of interest (ROIs), SNPs and DNA methylation of specific inflammation regulatory genes, and biological markers of inflammation were compared between these groups. Vulnerable ACoAs exhibited higher plasma C-reactive protein (CRP) and greater BOLD activity in the right hippocampus and ventral anterior cingulate cortex in response to emotional cues as well as reduced methylation of CRP and glucocorticoid-related genes. Path analysis revealed significant relationships between alcohol use, SNPs, DNA methylation of inflammatory-related genes, CRP levels, and BOLD activity to emotional stimuli. Taken together, these findings suggest a complex association related to hazardous alcohol use in ACoAs that may predict current inflammation and neural reactivity to emotional stimuli. A better understanding of these associations could direct the future of individual treatment options.
... Autoaggresiveness is manifested by depressive settings, nonacceptance of themselves, by persistent but suppressed feelings of shame and guilt that find no way out. This range of emotions belongs to the so-called self-conscious emotions associated with perception of oneself, of one's ideas and acts, with self-conception in the interpersonal contacts, and is a regulator of behavior [16,30]. Shame triggers a negative estimation of oneself, while guilt triggers a negative estimation of one's acts. ...
... There exist scattered, separate, nonsystematized data concerning a role of the family in formation of alcohol dependence [1,4,10,[13][14][15]19,[23][24][25][26][27][29][30][31][32][33]. However, all the data converge on the idea about only «alcoholic» and «destructive» families being stable basic markers of the risk for initi- ation and formation of alcohol dependence at young age. ...
... A family (even an «alcoholic» one) is not an exclusively homeostatically closed system. Connections between children and their educators not only influence formation of future interpersonal relationships, but also play a role in appearance of adaptation problems in the offspring [4][5][6][11][12][13][14][15][16][17][18][19][20][21][22][23][27][28][29][30]. ...
Article
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This article is a review of literature data, devoted to the influence of alcohol dependence of parents on the suicidal and personality-psychological characteristics of their offspring. Despite a decline of the incidence of alcohol dependence in the population, in Russia about 15-50% of families can say that they have encountered the problem of an alcoholized parent. Adult children of alcoholics (ACAs) are a fairly extensive, highly autoaggressive stratum of society. This group of people is the most dangerous in terms of the frequency of development in them of various kinds of addictions, as well as the likelihood of committing a suicidal attempt. The purpose of this review was to present modern ideas about the suicidality of adult children of alcoholics, their socio-cultural characteristics, personality and psychological characteristics; to demonstrate the degree of influence of addictive parental figures on the antivitality of offspring and its formation. The analysis of English and Russian literature is carried out. We have convincingly demonstrated that the ACAs represents a group with an elevated, relative to normative population, autoaggressiveness, inclination to parasuicidal patterns, with difficulties in building relationships with the society and finding a place in it. Conclusions were made about the inadequacy of the studies conducted, the lack of accurate data on the transgenerational mechanisms of autoaggressive transmission to offspring, the factors influencing the heterogeneity of the ACAs a population-species group, the need to take into account the gender of both parents and the ACAs themselves.
... The offspring of those with alcoholism were at risk of experiencing the negative effects of parental alcohol dependence [6]. Compared with the children of those without alcoholism, these children had a higher vulnerability to developing "risky drinking" [7] and other negative social and mental outcomes, including mood problems, suicide, school dropout, marital discord, and work and social relationship problems [7][8][9]. "Risky drinking", which was defined as consuming ≥ 5 standard drinks on a single occasion at least monthly [10], might lead to later heavy drinking and had been associated with a 60% increased risk of developing alcoholism, in which complicated genetic factors may play a role [11,12]. ...
... The offspring of those with alcoholism were at risk of experiencing the negative effects of parental alcohol dependence [6]. Compared with the children of those without alcoholism, these children had a higher vulnerability to developing "risky drinking" [7] and other negative social and mental outcomes, including mood problems, suicide, school dropout, marital discord, and work and social relationship problems [7][8][9]. "Risky drinking", which was defined as consuming ≥ 5 standard drinks on a single occasion at least monthly [10], might lead to later heavy drinking and had been associated with a 60% increased risk of developing alcoholism, in which complicated genetic factors may play a role [11,12]. Higher rates of alcoholism had been found in the offspring of an alcoholic twin than in the children of the nonalcoholic twin [13], indicating that when genetic factors were excluded the development of alcoholism in COA might mainly be due to environmental factors. ...
Article
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Objective To determine whether adverse childhood experiences (ACEs) of children of alcoholics (COA) in male were associated with their current “risky drinking”. Methods This case–control study used the Alcohol Use Disorder Identification Test (AUDIT, cutoff is 7) to divide the participants into two groups, a “risky drinking” group (N = 53) and a "non-risky drinking” group (N = 97). Demographic data, Adverse Childhood Experiences-International Questionnaire (ACE-IQ), the Hamilton Anxiety Rating Scale (HAMA), the Hamilton Depression Rating Scale (HAMD) and the Mini-International Neuropsychiatric Interview (MINI) were used for assessment. The specific relationships between ACEs and “risky drinking” were explored. Results Respondents ranged in age from 29.70 ± 6.72 years; 74.5% were females; 94.7% were of Han nationality; 56.7% had a level of education above high school; 12% had no formal or stable job. There was difference in attitude to self-drinking between two groups (P < 0.001). The “risky drinking” group was more likely to have experienced a major depressive episode (P < 0.05), nonalcohol psychoactive substance use disorder (P < 0.01) and bulimia nervosa (P < 0.05), and they also experienced more physical abuse (P < 0.05), community violence (P < 0.001) and collective violence (P < 0.01). In a single factor logistic regression, physical abuse, community violence and collective violence were associated with a two to 11- fold increase in “risky drinking” in the adult COA, and in multiple factor logistic regression, community violence showed a graded relationship with “risky drinking”. Conclusion The childhood adverse experiences contribute to “risky drinking” in COA. This finding in the Chinese context have significant implications for prevention not only in China but in other cultures. There must be greater awareness of the role of ACEs in the perpetuation of alcoholism.
... Large numbers of offspring have parents with alcohol dependence, resulting from the high prevalence of alcohol dependence (2). Evidence shows that OPAD have a 2.5-to 4.4-fold increase in the possibility of developing risky drinking (3) and are more likely to have other negative social and mental outcomes (3)(4)(5). Causal associations between offspring drinking and parent alcohol use have even been reported (6,7). ...
... Large numbers of offspring have parents with alcohol dependence, resulting from the high prevalence of alcohol dependence (2). Evidence shows that OPAD have a 2.5-to 4.4-fold increase in the possibility of developing risky drinking (3) and are more likely to have other negative social and mental outcomes (3)(4)(5). Causal associations between offspring drinking and parent alcohol use have even been reported (6,7). In fact, similar to all other factors, parent alcohol use elicits a heterogeneous influence: some offspring remain resilient, but others indulge in drinking. ...
Article
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Aims The aim of this study was to investigate the personality traits, and P300 component in the offspring of parents with alcohol dependence (OPAD) currently engaged in risky drinking and those not engaged in risky drinking, and to further explore the correlates of problematic alcohol use. Methods A case-control study was conducted according to the cutoff of the Alcohol Use Disorder Identification Test (AUDIT). The frequency of the TaqIA polymorphism of the dopamine receptor D2 gene associated with alcohol dependence was compared between the two OPAD groups. Tridimensional Personality Questionnaire (TPQ), The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the MINI-International Neuropsychiatric Interview (M.I.N.I.) were measured or interviewed in OPAD not engaged in risky drinking (resilient; n = 35) and those currently engaged in risky drinking (vulnerable; n = 20). P300 was measured to test the possible electrophysiological differences. The correlates of alcohol use were analyzed. Results Vulnerable OPAD showed higher novelty seeking subscale scores (NS4; 4.45 ± 2.012 vs. 3.31 ± 1.728, P < 0.05) and harm avoidance subscale scores (HA4; 5.3 ± 2.319 vs. 3.66 ± 2.461, P < 0.05) than resilient OPAD, while the total scores of each dimension showed no significant difference. OPAD engaged in risky drinking showed more tobacco use than OPAD resistant to risky drinking. OPAD with risky drinking showed a shorter P300 latency than resilient OPAD on Fz electrodes. AUDIT scores of OPAD were correlated with P300 latency. Conclusions P300 differed between OPAD with and without risky drinking and alcohol use was associated with P300 latency, indicating that P300 may be used in the early detection of vulnerable OPAD and early intervention in the future.
... Regionally thin cortices were also related to greater drinking quantity and frequency and to recent alcohol use (Mashhoon et al., 2014). Research focusing on substance-naive adolescents at baseline corroborates that thinner dorsolateral prefrontal cortex and inferior frontal cortex predicted binge drinking and externalizing symptoms in late adolescence, especially in youth who were FHP (Brumback et al., 2016). ...
... Neuroimaging research supports the existence of specific brain correlates associated with resilience in youth with a family history of AUD. Comparing resilient (non-drinkers) to vulnerable (hazardous drinkers, Table 1) emerging adults (18-25 year-olds) of AUD parents, cross-sectional results showed that the vulnerable group reported emotional distress, risky substance use, and greater activity in the middle frontal gyrus when rating negative emotional pictures compared with their resilient counterparts and showed higher activation of the posterior cingulate cortex during a working memory challenge (Brown-Rice et al., 2018). In another cross-sectional study, blunted nucleus accumbens responsivity was observed during decisionmaking in FHP participants who did not present alcohol use problems, suggesting that this attenuated activity is protective . ...
Chapter
Alcohol use disorder (AUD) is recognized as harmful for the developing brain. Numerous studies have sought environmental and genetic risk factors that predict the development of AUD, but recently identified resilience factors have emerged as protective. This chapter reviews normal processes of brain development in adolescence and emerging adulthood, delineates disturbed growth neurotrajectories related to heavy drinking, and identifies potential endogenous, experiential, and time-linked brain markers of resilience. For example, concurrent high dorsolateral prefrontal activation serving inhibitory control and low nucleus accumbens activation serving reward functions engender positive adaptation and low alcohol use. Also discussed is the role that moderating factors have in promoting risk for or resilience to AUD. Longitudinal research on the effects of all levels of alcohol drinking on the developing brain remains crucial and should be pursued in the context of resilience, which is a promising direction for identifying protective biomarkers against developing AUDs.
... The problem of addictive behavior has been actively studied in the last five years in Russia and in Europe [1][2][3][4][5][6][7][8][9][10]. The popularity of this topic is associated with the very wide prevalence of this disease. ...
... According to the Ministry of Health of the Russian Federation, in Russia, there were over 12 million people with alcohol-addicted parents in 2017. Most of the psychological studies of alcohol addiction are focused on the personality of the patient-the study of their cognitive and emotional features [7,9,11]. However, the characteristics of the patient's family system, the distribution of family roles, the family rules, and the negative emotions experienced by family members can play an important role in the development of alcohol addiction and in the effectiveness of its medical and psychotherapeutic treatment [5,12]. ...
Article
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The relevance of this research is due to the wide prevalence of addictive behavior and the insufficient knowledge of the coping strategies of patients and their families. The purpose of this research was to investigate the resource factors and coping strategies of adults with alcohol-addicted parents and to make recommendations for psychological counseling for these people. The sample consisted of 52 subjects—who were participants in a twelve-step rehabilitation program for adult people whose parents had alcohol addictions—and 50 controls. We used guilt questionnaires (“The Guilt Inventory Questionnaire”, “The Interpersonal Guilt Questionnaire”), quantitative methods for evaluating the coping strategies used by participants (“coping strategies” (Lazarus, Folkman)), and a phenomenological analysis of the interviews with the participants. The results showed that adults with alcohol-addicted parents felt guilty in situations when they took care of somebody because their own parents did not model (and teach them) caretaking behavior. People whose parents were alcohol addicts tend to avoid accepting responsibility for their lives. The resource factors of people with alcohol-addicted parents included keeping a diary, participation in a rehabilitation program, and confidential communication with other people.
... The phenotypes were categorized into four groups based on predicted metabolism: ultra-rapid metabolizer, normalextensive metabolizer, reduced intermediate metabolizer, and poor metabolizers. A more detailed description of these methods may be obtained from previously published research [30]. ...
Article
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This study evaluated the timing, use, and clinical outcomes of the GeneFolio® Pharmacogenomic Panel in a healthcare setting with patients managed by primary care providers or by psychiatrists. Participants were randomized to receive a pharmacogenetics report at four weeks or 12 weeks. After DNA collection and genetic analysis, pharmacists produced a recommendation report which was given to providers at the randomization week. The four-week group decreased depression severity (PHQ-9 and BDI) faster than the 12-week group (p = 0.0196), and psychiatrists’ patients decreased their depression severity faster than primary care patients (PHQ-9 p = 0.0005, BDI p = 0.0218). Mean mental quality of life increased over time (p < 0.0001), but it increased slower for patients taking drugs in the Significant drug-drug-gene interaction category (p = 0.0012). Mental quality of life, depression severity, and clinical outcomes were improved by GeneFolio® pharmacogenomic testing regardless of provider type, with earlier testing improving outcomes sooner.
... The offspring of those with alcoholism are at risk of experiencing the negative effects of parental alcohol dependence 6 . Compared with the children of those without alcoholism, these children have a higher vulnerability to developing "risky drinking" 7 and other negative social and mental outcomes, including mood problems, suicide, school dropout, marital discord, and work and social relationship problems [7][8][9] . "Risky drinking", which is de ned as consuming ≥ 5 standard drinks on a single occasion at least monthly 10 , may lead to later heavy drinking and has been associated with a 60% increased risk of developing alcoholism, in which complicated genetic factors may play a role 11,12 . ...
Preprint
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Objective: To determine whetheradverse childhood experiences (ACEs) of children of alcoholics (COA) were associated with their current “risky drinking”. Methods: This case-control study used the Alcohol Use Disorder Identification Test (AUDIT, cutoff is 7) to divide the participants into two groups, a “risky drinking group" (N=53) and a "non-risky drinking group" (N=97). Demographic data, Adverse Childhood Experiences-International Questionnaire (ACE-IQ), the Hamilton Anxiety Rating Scale (HAMA), the Hamilton Depression Rating Scale (HAMD) and the Mini-International Neuropsychiatric Interview (MINI) were used for assessment. The specific relationships between ACEs and “risky drinking” were explored. Results: Respondents ranged in age from 29.70±6.72 years; 74.5% were females; 94.7% were of Han nationality; 56.7% had a level of education above high school; 12% had no formal or stable job. The “risky drinking” group was more likely to have experienced a major depressive episode (P<0.05), nonalcohol psychoactive substance use disorder and bulimia nervosa (P<0.01), and they also experienced more physical abuse(P<0.05), community violence (P<0.01) and collective violence (P<0.05). In a single factor logistic regression, physical abuse, community violence and collective violence were associated with a two to eleven fold increase in “risky drinking” in the adult COA, and in multiple factor logistic regression, community violence showed a graded relationship with “risky drinking”. Conclusion: The childhood adverse experiences contribute to “risky drinking” in COA. This finding in the Chinese context have significant implications for prevention not only in China but in other cultures. There must be greater awareness of the role of ACEs in the perpetuation of alcoholism.
... The other trend in the research with its focus on negative effects of PSU has investigated both shortterm and long-term consequences, and the possible problems which these children are facing personally during youth and adulthood. Mental, emotional and health problems are often more prevalent children and youth with PSU (Brown-Rice et al., 2017;Jääskeläinen, 2016;Staton-Tindall et al., 2013). In childhood, school is often more challenging for children experiencing PSU, resulting in lower school performance, more skipping school days and higher rates of drop-out Hafekost et al., 2017). ...
Thesis
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This PhD-thesis contributes towards a better understanding of problematic parental substance use (PSU) and how it affects the children involved. The thesis is based on three independent papers investigating: 1) the prevalence of PSU in the general population of youth in Denmark, 2) school outcomes and 3) adverse outcomes related with family structure and years living with the parent with a problematic substance use (SU).
... In line with previous studies, college students in this group seemed to use alcohol, along with other substances such as cannabis and tobacco, as a maladaptive coping strategy (Backer-Fulghum et al., 2012;Kenney et al., 2018;Tomaka et al., 2013). It is also important to emphasize that the higher level of family histories of AUD found in this cluster has been associated with several vulnerability factors for alcohol misuse, including genetic liability (Brown-Rice et al., 2018). ...
Article
Aims: Investigation of the relationship between self-esteem and alcohol use among college students has yielded discrepant results. We hypothesized that these discrepancies could originate from a potential heterogeneity of self-esteem patterns among young adult with an alcohol use disorder (AUD). Methods: A community sample of 343 college students was recruited and categorized with or without AUD using the Alcohol Use Disorders Identification Test cut-offs. College students were compared on the dimensions of the Coopersmith Self-Esteem Inventory (CSEI) as well as mood, impulsiveness, alcohol- and other substance-related measures, including drinking motives. Results: A cluster analysis conducted among college students with AUD highlighted two subgroups characterized by contrasting patterns on the CSEI: one group with a high level of self-esteem and low levels of anxiety and depression symptoms and one group with a low level of self-esteem and high levels of impulsiveness, mood symptoms and drinking to cope motives. Conclusion: Findings caution against assuming that AUD is associated with low self-esteem, as reported in previous studies. These results rather emphasize a heterogeneity of self-esteem in college students, showing that high self-esteem was also related to AUD. Implications of these results are major for prevention purposes and clinical practice.
... (2018) alkol bağımlısı olan ve olmayan ebeveyne sahip lise öğrencilerinin nöropsikolojik özelliklerini karşılaştıran çalışmalarında, alkol bağımlısı ebeveyne sahip ergenlerin daha fazla kaygı, depresyon, travma sonrası stres belirtileri ve artmış nikotin ve esrar kullanımı olduğu bildirilmiştir. Ayrıca artan kaygı, alkol ve uyuşturucu davranışlarıyla ilişkili olabilecek frontal lob ve posterior singulat korteks bölgelerinde anormallikler, alkol kullanımı problemlerinde rol oynayan kolinerjik reseptör ve seratonin taşıyıcı genlerde poliformizm saptanmıştır (5). Park ve ark. ...
... Problems in sustaining attention [39] , lack of interest in school, lack of respect for school rules [40] lead adolescents from families with untreated alcoholism to lower achievement in education, or to be less oriented to the future and planning to accomplish their life goals both in personal and professional. The obtained middle group average in the second dis-criminated function (0,457) of adolescents from families with untreated alcoholism leads to the conclusion that the adolescents of this sub-sample tend to: conflicts with peers [13,26] , truancy, running away from home [6,7,23] , suicide attempts [41] , depression and posttraumatic stress symptoms [42] . ...
Article
Growing up with an alcohol-misusing caregiver can be chaotic and damaging for children. Nevertheless, achieving better-than-expected outcomes in the face of adversity is by no means an unusual outcome for those young people. This study presents an understanding of the interactional resilience process between 15 National University of Lesotho undergraduate students and people in their social environment as a result of sharing adverse experiences. An interactional resilience perspective that builds on from the social-ecology and person-in-environment viewpoints on resilience, informed the study. Various in-depth interviews were conducted together with a draw-and-write technique. Findings show that the sharing of similar and diverse adverse experiences between young people raised by alcohol-misusing caregivers and significant people in their social ecology improved their resilience. Given the significance of sharing adverse experiences by the participants, established in this study, support groups (e.g., at schools, churches, community centers) could be very helpful in promoting the resilience of vulnerable young people. Social service practitioners, working with young people growing up in vulnerable environments, should help these young people develop interactive skills including the ability to be more communicative and be more receptive to sharing hard to share experiences with trustworthy people.
Article
Alcohol use is prevalent among undergraduates, however, limited research on drinking among Latinx college students exists. This study examined potential risk and protective factors of alcohol use and consequences. Participants (n = 382) completed multiple measures including alcohol use frequency and the Rutgers Alcohol Problem Index (RAPI). Linear regression models identified predictors of monthly and yearly drinking days and RAPI. Findings indicated that alcohol use frequency was associated with increasing age, parental alcohol use disorder, greater anger, and lower self-efficacy. Alcohol-related consequences were positively associated with anxiety and adverse childhood experiences. Early alcohol prevention and intervention efforts appear warranted.
Article
Resumen Introducción Distintos síntomas de malestar psicológico y los motivos de consumo se han asociado con el consumo de alcohol de los estudiantes universitarios. El aislamiento social, preventivo y obligatorio (ASPO) por la COVID-19 redujo la circulación al mínimo, impactó en la salud mental de los universitarios y generó cambios en diversas conductas, incluido el consumo de alcohol. Objetivos Analizar la relación de síntomas de ansiedad, depresión y estrés y los motivos de consumo con el consumo de alcohol de los estudiantes universitarios argentinos antes y durante los primeros 3 meses del ASPO, así como examinar si los motivos de consumo median la relación entre malestar psicológico y consumo de alcohol. Métodos Completaron una encuesta online 2 muestras de estudiantes, una antes del ASPO (n = 125; media de edad, 23,87 ± 3,27 años; el 73,6% mujeres) y otra durante este (n = 174; 24,32 ± 3,64 años; el 78,2% mujeres). Resultados El consumo de alcohol y los motivos social y de mejora disminuyeron en los estudiantes durante el ASPO. Comparados con el grupo antes del ASPO, las asociaciones del malestar psicológico y los motivos de consumo con el consumo de alcohol fueron más consistentes en el grupo durante el ASPO. En el análisis multivariado, los motivos de afrontamiento explicaron una frecuencia incrementada de consumo de alcohol en los universitarios durante el ASPO. Conclusiones Resulta necesario prestar especial atención a la salud mental de los universitarios que han sufrido cambios en sus rutinas como consecuencia de las restricciones implementadas a partir de la pandemia.
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Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity and is influenced by both environmental and genetic factors. The identification of specific genetic factors and their biological pathways underpinning resilient functioning can help in the identification of common key factors, but heterogeneities in the operationalisation of resilience have hampered advances. We conducted a systematic review of genetic variants associated with resilience to enable the identification of general resilience mechanisms. We adopted broad inclusion criteria for the definition of resilience to capture both human and animal model studies, which use a wide range of resilience definitions and measure very different outcomes. Analyzing 158 studies, we found 71 candidate genes associated with resilience. OPRM1 (Opioid receptor mu 1), NPY (neuropeptide Y), CACNA1C (calcium voltage-gated channel subunit alpha1 C), DCC (deleted in colorectal carcinoma), and FKBP5 (FKBP prolyl isomerase 5) had both animal and human variants associated with resilience, supporting the idea of shared biological pathways. Further, for OPRM1, OXTR (oxytocin receptor), CRHR1 (corticotropin-releasing hormone receptor 1), COMT (catechol-O-methyltransferase), BDNF (brain-derived neurotrophic factor), APOE (apolipoprotein E), and SLC6A4 (solute carrier family 6 member 4), the same allele was associated with resilience across divergent resilience definitions, which suggests these genes may therefore provide a starting point for further research examining commonality in resilience pathways.
Article
Studies on the effects of parental alcoholism on adult children of alcoholics (ACOAs) have been mostly quantitative. To acquire a richer and better understanding of this realm in Malta, while outlining concrete recommendations to further contain this problem, a qualitative study was thus employed. Six participants were selected after meeting all inclusion criteria. Data were analysed following interpretative phenomenological analysis (IPA) guidelines. Semi‐structured interviews were audio‐recorded and transcribed verbatim. Three superordinate themes, namely a) psychosocial impact, b) coping strategies, and c) a sense of identity, were elevated. A number of findings resulting from this study may point at the resilient nature and skills exhibited by ACOAs, who move on to lead successful lives, despite their past hard life. Recommendations for future applications are discussed. Overall, recognition of children of parents who misuse alcohol should be prioritised in service planning to ensure that their needs are not overlooked.
Article
Background. People with alcohol-addicted parents are at risk of psychoactive addictions, co-dependency, and suicidal behavior. Most studies of these people are aimed at confirming the inevitability of the impact of negative childhood experiences on their lives, and thus do not seek to identify resource factors which would allow them to overcome the negative emotions they experienced. Objective. The purpose of this study was to create a model of resource factors which would allow people with alcohol-addicted parents to overcome the negative emotions they experienced. Design. The participants were 58 healthy individuals (17 men and 41 women; M=25.2; SD=4.4) whose parents were alcohol addicts (they were participants in the 12-step recovery program "Adult Children of Alcoholics"), and 50 healthy individuals (15 men and 35 women, M=24.2; SD=3.7) whose parents were not alcohol addicts. The participants completed the questionnaires "Interpersonal Guilt," "Family Emotional Communication," and "Coping Strategies," and were interviewed on the resource factors which allowed them to overcome negative emotions. We used the content analysis of the interviews and latent variable modeling to analyze the questionnaires. Results. The model of resource factors (CFI=0.895, RMSEA=0.064) showed that the rules set by the parental dysfunctional family (the taboo on the expressing emotions, and external well-being) were associated with being unable to recognize current negative emotions and with avoiding problems. The ability to recognize negative emotions was connected with the participant’s willingness to accept responsibility for his/her life. The resource factors which allowed these subjects to overcome their negative emotions included: communication with relatives and friends; keeping a diary of emotions; and participating in recovery programs. Conclusion. Our model of resource factors explains the mechanism connecting dysfunctional family rules with the resource factors and negative emotions experienced by people with alcohol-addicted parents.
Article
Relevance. The term “family pain” is used in family psychotherapy to refer to the emotional state of dysfunctional family members. Research on this phenomenon in dysfunctional alcoholic families can expand the understanding of the family system and allow us to formulate the goals of psychotherapy with such families. Objective. To investigate the “family pain” experienced by adult children of alcoholics. Methods. The sample consisted of 52 people who were in a recovery program for adult children of alcoholics (ACA), and 50 controls. We implemented a phenomenological analysis of ACA groups, a content analysis of images of “family pain”, and factor analysis of the characteristics of “family pain”. Results. The study showed significant differences between the images of “family pain” experienced by adults who were raised and still live in alcoholic families, by those whose parents were alcoholics and had died by the time of the survey, and by those whose parents were not alcoholics. People who live with their alcoholic parents describe “family pain” as a familiar, long process with effects on the whole family. The experience of “family pain” includes anger, shame, and self-pity. People whose parents were alcoholics and have died describe “family pain” as a feeling of guilt towards their parents and a process of experiencing their parents’ death. The control group had difficulty describing “family pain”, or described it as a process of experiencing their parents’ death. Conclusions. Representations of “family pain” are associated with the subjective meaning of family dysfunction for the participant and the experience of negative emotions in the family.
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Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.
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Objective: This article provides an overview of the scientific literature pertaining to the effects of alcohol on neural correlates of cognitive and emotional functioning, including reward processing and cue-reactivity, in adolescence and young adulthood. Method: Peer-reviewed, original research articles that included a neuroimaging assessment of alcohol effects on subsequent cognitive or emotional processing in adolescent or young adult samples were searched (through November 2018) and summarized in the review. Results: Cross-sectional studies provided early evidence of alcohol-related differences in neural processing across a number of cognitive domains. Longitudinal studies have identified neural abnormalities that predate drinking within most domains of cognitive functioning, while a few neural alterations have been observed within the domains of visual working memory, inhibitory control, reward processing, and cue-reactivity that appear to be related to the neurotoxic effect of alcohol use during adolescence. In contrast, neural correlates of emotion functioning appear to be relatively stable to the effects of alcohol. Conclusions: Larger prospective studies are greatly needed to disentangle premorbid factors from neural consequences associated with drinking, and to detect subsets of youth who may be particularly vulnerable to alcohol's effects on cognitive and emotional functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Manuscript number PSY_2018_998 Title Self-esteem in college students with alcohol use disorder is related to divergent clinical patterns: evidence from a cluster analysis Article type Full Length Article Abstract Investigation of the relationship between self-esteem and alcohol use among college students have yielded discrepant results, with some studies highlighting a negative relationship between self-esteem and alcohol-related measures, and others supporting either the opposite pattern or no relationship at all. We hypothesized that these discrepancies could originate from a potential heterogeneity of self-esteem patterns among young adult with an alcohol use disorder (AUD). To test this hypothesis, 343 community college students were recruited and were categorized on AUD using the Alcohol Use Disorders Identification Test cutoffs. They were compared on the dimensions of the Coopersmith Self-Esteem Inventory (CSEI) as well as mood, alcohol-and other substance-related measures, including drinking motives. Comparison of the two groups on the CSEI dimensions revealed lower self-esteem for the AUD group, but the pattern was not clear-cut. Accordingly, the cluster analysis carried out to investigate the heterogeneity within the AUD group highlighted two subgroups characterized by contrasted patterns on self-esteem, several alcohol related measures, anxiety and depression symptoms. These findings caution against assuming that AUD among college students is associated with a single pattern and, in line with recent studies, emphasize its heterogeneity. Implications of these results for clinical practice and prevention interventions are discussed. Abstract.docx [Abstract] Gierski_Self_Esteem_and_College_AUD.docx [Manuscript File]
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Background: Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The GranadΣp study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andalusia (South Spain), being one of its main objectives to identify genetic and environmental risk factors for MDD and other major psychiatric disorders. In this study, we focused on the possible association of 91 candidate single nucleotide polymorphisms (SNPs) with MDD. Methods: A total of 711 community-based individuals participated in the GranadΣp study. All individuals were extensively assessed for clinical, psychological, sociodemographic, life style, and other environmental variables. A biological sample was also collected for subsequent genetic analyses in 91 candidate SNPs for MDD. DSM-IV diagnosis of MDD was used as the outcome variable. Logistic regression analysis assuming an additive genetic model was performed to test the association between MDD and the genetic data. The experiment-wide significance threshold adjusted with the SNP spectral decomposition method provided a maximum P-value (8×10−3) required to identify an association. Haplotype analyses were also performed. Results: One SNP (rs623580) located in the tryptophan hydroxylase 1 gene (TPH1; chromosome 11), one intergenic variant (rs9526236) upstream of the 5-hydroxytryptamine receptor 2A gene (HTR2A; chromosome 13), and five polymorphisms (rs17689966, rs173365, rs7209436, rs110402, and rs242924) located in the corticotropin-releasing hormone receptor 1 gene (CRHR1; chromosome 17), all showed suggestive trends for association with MDD (P,0.05). Within CRHR1 gene, the TATGA haplotype combination was found to increase significantly the risk for MDD with an odds ratio =1.68 (95% CI: 1.16–2.42, P=0.006). Conclusion: Although limited, perhaps due to insufficient sample size power, our results seem to support the notion that the hypothalamic–pituitary–adrenal and serotonergic systems are likely to be involved in the genetic susceptibility for MDD. Future studies, including larger samples, should be addressed for further validation and replication of the present findings.
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SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been extensively examined as a risk factor for alcohol dependence (AD). More recently, variability in the transporter gene was identified to be a potential moderator of treatment response to serotonergic medications such as ondansetron and sertraline. There is an insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S) allele and a 16-repeat long (L) allele. The S allele has often been associated with AD. By contrast, the L allele has been associated with pharmacological responsiveness in some individuals with AD. Differences in clinical phenotype may determine the utility of the 5-HTTLPR polymorphism as a moderator of pharmacological interventions for AD. We review the AD typology and disease onset in the context of pharmacogenetic and genomic studies that examine the utility of 5-HTTLPR in improving treatment outcomes. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.
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Numerous brain lesion and functional neuroimaging studies have suggested that the dorsolateral and frontopolar prefrontal regions are involved in complex cognitive processes subserving thought and memory. However, previously proposed functional subdivisions of prefrontal function have concentrated predominantly on posterior prefrontal cortex, including the dorsolateral, ventral, and medial regions. Far less consideration has been given to characterizing the psychological processes mediated by the frontopolar cortex. Here we review published neuroimaging studies of reasoning and episodic memory, two domains in which the frontopolar cortex has been frequently activated. The results suggest that dorsolateral prefrontal cortex is involved when externally generated information is being evaluated, whereas the frontopolar cortex becomes recruited when internally generated information needs to be evaluated. A hierarchical model of prefrontal function is proposed in which dorsolateral and frontopolar regions are serially recruited as a reasoning or memory task requires evaluation of internally generated information.
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Cluster-extent based thresholding is currently the most popular method for multiple comparisons correction of statistical maps in neuroimaging studies, due to its high sensitivity to weak and diffuse signals. However, cluster-extent based thresholding provides low spatial specificity; researchers can only infer that there is signal somewhere within a significant cluster and cannot make inferences about the statistical significance of specific locations within the cluster. This poses a particular problem when one uses a liberal cluster-defining primary threshold (i.e., higher p-values), which often produces large clusters spanning multiple anatomical regions. In such cases, it is impossible to reliably infer which anatomical regions show true effects. From a survey of 814 functional Magnetic Resonance Imaging (fMRI) studies published in 2010 and 2011, we show that the use of liberal primary thresholds (e.g., p<.01) is endemic, and that the largest determinant of the primary threshold level is the default option in the software used. We illustrate the problems with liberal primary thresholds using an fMRI dataset from our laboratory (N=33), and present simulations demonstrating the detrimental effects of liberal primary thresholds on false positives, localization, and interpretation of fMRI findings. To avoid these pitfalls, we recommend several analysis and reporting procedures, including 1) setting primary p<.001 as a lower limit default; 2) using more stringent primary thresholds or voxel-wise correction methods for highly powered studies; and 3) adopting reporting practices that make the level of spatial precision transparent to readers. We also suggest alternative and supplementary analysis methods.
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Gamma-Aminobutyric Acid (GABA) is a major inhibitory neurotransmitter in mammalian brain. GABA receptor subunit genes are involved in a number of complex disorders including substance abuse. No associated variants on the commonly-studied GABA receptor genes have been unequivocally identified as directly functional or pathogenic in genetic association studies of addictions. We hypothesize that meta-analysis can increase the statistical power to identify the association signals. To reconcile the conflicting associations with substance dependence traits, we performed a meta-analysis of the GABA receptor genes (GABRB2, GABRA6, GABRA1, and GABRG2 on chromosome 5q and GABRA2 on chromosome 4p12) using genotype data from 4739 cases of alcohol, heroin, opioid, or methamphetamine dependence and 4924 controls. Then, we combined these candidate gene association literature data with two additional samples with alcohol dependence (AD), including 1691 cases and 1712 controls from the Study of Addiction: Genetics and Environment (SAGE), and 2644 cases and 494 controls from our own study. We found strong associations between GABRA2 and AD (P=9 × 10(-6) and odds ratio (OR) 95% confidence interval (CI)=1.27 (1.15, 1.4) for rs567926, P=4 × 10(-5) and OR=1.21 (1.1, 1.32) for rs279858), and between GABRG2 and both dependence on alcohol and dependence on heroin (P=0.0005 and OR=1.22 (1.09, 1.37) for rs211014). Significant association was also observed between GABRA6 rs3219151 and AD. The GABRA2 rs279858 association was observed in the SAGE datasets with a combined P of 9 × 10(-6) (OR=1.17 (1.09, 1.26)). When all of these datasets, including our samples, were meta-analyzed, associations of both GABRA2 SNPs remained (for rs567926, P=7 × 10(-5) (OR=1.18 (1.09, 1.29)) in all the studies, and P=8 × 10(-6) (OR=1.25 (1.13, 1.38)) in Europeans; for rs279858, P=5 × 10(-6) (OR=1.18 (1.1, 1.26)) in Europeans). The selected threshold of Bonferroni correction for multiple comparisons was 0.007. We report here an extensive meta-analysis between the five GABA receptor candidate genes and substance abuse. Our findings suggest the involvement of the GABA receptor genes, minimally, GABRA2 in the pathogenesis of alcohol dependence. Further replications with larger samples are warranted.Neuropsychopharmacology accepted article preview online, 18 October 2013; doi:10.1038/npp.2013.291.
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Stress increases drug craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, drug cue and neutral conditions in matched CG (N=5) and CC (N=8) subgroups. We found greater stress-induced craving (P=0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.
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This article presents an examination of college student drinking motives from a self-determination perspective. We predicted positive associations between controlled orientation (a chronic orientation toward pressures and experiencing a lack of choice in one's behaviors), and drinking as a means of regulating affect (enhancement and coping motives) and social approval (social rewards and conformity motives). Contingent self-esteem involves deriving self-worth from meeting expectations and was expected to mediate the relation between controlled orientation and drinking motives, which were in turn expected to predict alcohol consumption and related consequences. College students' (N = 204) controlled orientation, contingent self-esteem, motives for drinking, and patterns of alcohol use were assessed. Mediation analyses provided support for our theoretical framework. Results suggest that “controlled” individuals drink to regulate affect and social approval in part because they have a greater tendency to base self-worth on contingencies.
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Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter.
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Alcohol use literature has linked heavy episodic alcohol use and academic consequences, but has not examined the influence of such use on student engagement. This study uses survey data from over 40,000 students at 28 selective private colleges and universities to examine the connection between heavy episodic alcohol use and engagement. The strongest negative effects of heavy episodic drinking are on student–faculty interaction, with these effects most common at research universities and less common at coed colleges and women's colleges.
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Rationale Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to “Go” trials that carried no need for inhibition [Inh > Go]. Results FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149–158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759–1770, 2011), with FHP being less sensitive to alcohol’s effects.
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This paper explored the relationships between parental alcoholism, sense of belonging, resilience, and depressive symptoms among Koreans in the U.S. Data from 206 Koreans (Mean age = 28.4 years; 59.8% females) living in a Midwestern state were collected in 2009, using a web-based survey, which included Children of Alcoholic Screening Test, Sense of Belonging Instrument, Connor-Davidson Resilience Scale, and Beck Depression Inventory-II. Path analysis results revealed sense of belonging as the most powerful, and resilience as the second important factor, resisting depressive symptoms associated with parental alcoholism. Implications for practice and research and study limitations are discussed. The study's limitations are noted.
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Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter implicated in regulating substance-use disorder (SUD) acquisition, maintenance, and recovery. During the past several years, an abundance of research has begun discovering and describing specific 5-HT genetic polymorphisms associated with SUDs. Genetic variations in the 5-HT system, such as SLC6A4, HTR1B, HTR2A, HTR2C, HTR3 (HTR3A, HTR3B, HTR3C, HTR3D, and HTR3E), likely play a role contributing to SUD patient heterogeneity. The 5-HT transporter-linked polymorphic region S allele, located in SLC6A4, has now been modestly associated with alcohol dependence in two large meta-analyses. Additional 5-HT genes may also play a role but have not been extensively investigated. A limited number of SUD treatment studies have included 5-HT gene variation as moderating treatment outcomes, but the results have been equivocal. Future research on 5-HT addiction genetics should adopt whole-genome sequencing technology, utilize large study samples, and collect data from multiple ethnic groups. Together, these methods will build on the work already conducted with the aim of utilizing 5-HT genetics in SUD treatment settings.
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BACKGROUND: Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence.Method In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.09, p=0.002] but there was no association with depression (p=0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97-1.09, p=0.34) or depression (OR 1.02, 95% CI 0.95-1.09, p=0.62) among smokers. CONCLUSIONS: As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.
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Children of alcoholics (COAs) are at elevated risk to develop alcohol and other substance use disorders. The neurobiological underpinnings of this heightened vulnerability are presently not well understood. This study investigated whether, in humans, COAs have different functioning of the mesolimbic reward circuitry beyond previous substance use confounds and examined potential group differences in neural response in relation to alcohol use and behavioral risk. We studied 20 18- to 22-year-old COAs and 20 controls, developmentally well characterized for substance use and selected to match on sex, age, IQ, lifetime substance use and associated problems, and precursive (ages 12-14 years) externalizing behavioral risk. None met criteria for Diagnostic and Statistical Manual of Mental Disorders IV diagnosis. Neural responses to anticipation of reward and loss were assessed using functional magnetic resonance imaging during a monetary incentive delay task. Overall, COAs showed reduced ventral striatum activation during anticipation of monetary reward and loss compared with controls. However, additional analysis revealed that blunted nucleus accumbens (NAcc) response was only observed in COAs who have not demonstrated any problem drinking behavior. In addition, uniquely in COAs, NAcc activation was positively correlated with precursive externalizing risk, as well as current and lifetime alcohol consumption. These findings suggest a multilevel developmental process whereby lower precursive behavioral risk appears protective of later problem alcohol use in COAs, which is further associated with a blunted NAcc response to incentive anticipation, potentially reflecting a resilience mechanism. Moreover, the results suggest that a close association between motivational responses, alcohol consumption, and behavioral risk may underlie addiction vulnerability in COAs.
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This paper examined whether adult children of alcoholics (ACOAs) would report more depressive mood symptoms as compared to non-ACOAs, whether coping behaviors differed as a function of ACOA status, and whether specific coping behaviors were related to depressive mood symptoms in ACOAs. Participants were 136 college students categorized as ACOAs and 436 college students categorized as non-ACOAs as determined by scores on the Children of Alcoholics Screening Test (CAST; J.W.Jones, 1983 The children of alcoholics screening test: test manual. Chicago: Camelot). As compared to non-ACOAs, ACOAs reported significantly more symptoms of depressive mood as measured by the Profile of Mood States (POMS; McNair, Lorr, and Droppleman, 1992 POMS manual: profile of mood states. San Diego, CA: Edits). On the COPE Inventory (Carver, Scheier, and Weintraub, 1989 Assessing coping strategies: a theoretically based approach. Journal of Personality and Social Psychology, 56:267-283), ACOAs reported higher use of the following coping strategies: Behavior Disengagement, Denial, Focus on and Venting of Emotions, Humor, and Substance Use. For both the ACOA and non-ACOA groups, the use of Positive Reinterpretation and Growth and the use of Planning were significantly associated with fewer depressive symptoms, whereas Mental Disengagement, Focus on and Venting of Emotions, Denial, Behavior Disengagement, Substance Use, and Suppression of Competing Activities were associated with higher depressive mood scores.
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The Adult Children of Alcoholics Trauma Inventory (ACATI) registers variations in the recalled experience of growing up with problem drinkers. The ACATI includes measures of the duration and severity of parental alcohol-use-related problems, the drinking parents' behavior when intoxicated and sober, physical, psychological, and sexual abuse, and environmental factors. The ACATI correlated well with the Family Tree Questionnaire and showed excellent 14-day test-retest reliability for most variables. The test-retest was carried out in 2009 at a counseling service for young adults from families with alcohol-use-related problems in Denmark (N = 49).
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A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been reported to confer relative risk for phenotypes (depression/anxiety) and endophenotypes (amygdala reactivity). In this report, we identify and characterize three rare 5-HTTLPR alleles not previously described in the human literature. The three novel alleles were identified while genotyping 5-HTTLPR in a family-based attention deficit hyperactivity disorder clinical population. Two of the novel alleles are longer than the common 16-repeat long (L) allele (17 and 18 repeats) and the third is significantly smaller than the 14-repeat short (S) allele (11 repeats). The sequence and genetic architecture of each novel allele is described in detail. We report a significant decrease in the expression between the XL₁₇ (17r) allele and the L(A) (16r) allele. The XS₁₁ (11r) allele showed similar expression with the S (14r) allele. A 1.8-fold increase in expression was observed with the L(A)(16r) allele compared with the L(G) (16r) allele, which replicates results from earlier 5-HTTLPR expression experiments. In addition, transcription factor binding site (TFBS) analysis was performed using MatInspector (Genomatix) that showed the presence or absence of different putative TFBSs between the novel alleles and the common L (16r) and S (14r) alleles. The identification of rare variants and elucidation of their functional impact could potentially lead to understanding the contribution that the rare variant may have on the inheritance/susceptibility of multifactorial common diseases.
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Depressive symptoms are common among individuals with alcohol use disorders and impact treatment outcome. Substantial overlap exists among the neurobiological systems proposed in the pathophysiology of depressive and alcohol use disorders; however, specific genetic effects contributing to risk for depressive comorbidity remain poorly understood. This study examines the association of depressive symptom scores for lifetime depression (the sum of DSM-IV major depression co-endorsed criteria for lifetime depression) with markers in 120 candidate genes in 554 alcohol-dependent individuals. The candidate genes code for molecules involved in dopamine, serotonin, glutamate, gamma-aminobutyric acid (GABA), and opioid neurotransmission, cell signaling, pharmacokinetics, stress biology, and behavioral control. Analyses were conducted at the single marker level with experimentwise permutation to control for multiple testing. Results revealed nominal associations for markers in 20 genes. Following experimentwise permutation, markers in the corticotropin-releasing hormone-binding protein (CRHBP) the μ-opioid receptor (OPRM1) and the β1 subunit of GABA A (GABA(A)) receptors (GABRB1) met or exceeded the significance threshold. None of the markers associated with depressive symptom scores were significantly associated with alcohol dependence symptom scores. These findings suggest potential risk genes for depressive symptoms in alcohol-dependent individuals.
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Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P < 2.3 × 10−4) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P < 0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P = 8.2 × 10−7), consumed alcohol on more occasions (P = 2.7 × 10−6), had a higher maximum number of alcoholic drinks in a single day (P = 2.7 × 10−6) and a higher overall alcohol consumption (P = 8.9 × 10−8) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P = 4.7 × 10−5) and suggestive associations (P < 0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes.
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There is shared genetic risk for dependence on multiple substances, and the nicotinic receptor gene cluster on chromosome 15 harbors multiple polymorphisms that associate to this risk. Here, we report the results of an association study with 21 SNPs genotyped across the CHRNA5, CHRNA3, and CHRNB4 loci on chromosome 15q25.1. The sample consists of a discovery set (N=1858) of European-American and African-American (AA) families, ascertained on the basis of a sibling pair with cocaine and/or opioid dependence, and a case-control replication sample (N=3388) collected for association studies of alcohol, cocaine, and opioid dependence. We tested the SNPs for association with lifetime cocaine, opioid, nicotine, and alcohol dependence. We replicated several previous findings, including associations between rs16969968 and nicotine dependence (P=0.002) and cocaine dependence (P=0.02), with opposite risk alleles for each substance. We observed these associations in AAs, which is a novel finding. The strongest association signal in either sample was between rs684513 in CHRNA5 and cocaine dependence (OR=1.43, P=0.0004) in the AA replication set. We also observed two SNPs associated with alcohol dependence, that is, rs615470 in CHRNA5 (OR=0.77, P=0.0006) and rs578776 (OR=0.78, P=0.001). The associations between CD and rs684513, AD and rs615470, and AD and rs578776 remained significant after a permutation-based correction for multiple testing. These data reinforce the importance of variation in the chromosome 15 nicotinic receptor subunit gene cluster for risk of dependence on multiple substances, although the direction of the effects may vary across substances.
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Objective: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. Method: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. Results: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. Conclusions: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.
Article
Background and objectives: Genetic studies have revealed a significant association between variants in nicotinic acetylcholine receptor (CHRN) genes and smoking cessation, but the results are inconsistent. In this study, we aimed to examine the relationship between single nucleotide polymorphisms (SNPs) in seven CHRN genes and smoking cessation in a Chinese rural population. Methods: Participants were recruited from 17 villages of 3 counties in Shandong, China. DNA was extracted from the blood samples. Thirty-two SNPs in seven CHRN genes were genotyped. Logistic regression was used to explore the relationship between single SNP and smoking cessation. Pearson's χ(2) test was performed to test the association between haplotype and smoking cessation. Results: Rs578776 (in CHRNA3), rs660652 (in CHRNA3), and rs588765 (in CHRNA5) were significantly related to smoking cessation. Two haplotypes were associated with smoking cessation. Conclusions: This study confirmed the association between CHRN genes and smoking cessation in the Chinese rural population. Scientific significance: Our findings provide confirmatory support to the role of CHRN genes to the etiology of smoking cessation in the Chinese rural population. (Am J Addict 2016;XX:1-4).
Article
Relapse is a common clinical problem in individuals with substance dependence. Previous studies have implicated a multifactorial process underlying relapse; however, the contribution of specific neural substrates has not yet been examined. To determine whether results from functional magnetic resonance imaging (fMRI) shortly after drug cessation could predict relapse in stimulant-dependent individuals. Treatment-seeking methamphetamine-dependent males (N = 46) underwent fMRI 3 to 4 weeks after cessation of drug use. Of the 40 subjects who were followed up a median of 370 days, 18 relapsed and 22 did not. Blood oxygen level-dependent fMRI activation during a simple 2-choice prediction task. The fMRI activation patterns in right insular, posterior cingulate, and temporal cortex obtained early in recovery correctly predicted 20 of 22 subjects who did not relapse and 17 of 18 subjects who did. A Cox regression analysis revealed that the combination of right middle frontal gyrus, middle temporal gyrus, and posterior cingulate activation best predicted the time to relapse. To our knowledge, this is the first investigation to show that fMRI can be used to predict relapse in substance-dependent individuals.
Article
Background and AimsTwin and family studies suggest that genetic influences are shared across substances of abuse. However, despite evidence of heritability, genome-wide association and candidate gene studies have indicated numerous markers of limited effects, suggesting that much of the heritability remains missing. We estimated (1) the aggregate effect of common single nucleotide polymorphisms (SNPs) on multiple indicators of comorbid drug problems that are typically employed across community and population-based samples, and (2) the genetic covariance across these measures.Participants2596 unrelated subjects from the “Study of Addiction: Genetics and Environment” provided information on alcohol, tobacco, cocaine, cannabis, and other illicit substance dependence. Phenotypic measures included: (1) a factor score based on DSM-IV drug dependence diagnoses (DD), (2) a factor score based on problem use (PU; i.e., 1+ DSM-IV symptoms), and (3) dependence vulnerability (DV; a ratio of DSM-IV symptoms to the number of substances used).FindingsUnivariate and bivariate Genome-wide complex trait analyses of this selected sample indicated that common SNPs explained 25-36% of the variance across measures, with DD and DV having the largest effects [h2SNP (CI) = 0.36 (0.11-0.62) and 0.33(0.07-0.58), respectively; PU =0.25 (-0.01-0.51)]. Genetic effects were shared across the three phenotypic measures of comorbid drug problems (rSNP; rDD-PU =0.92 (0.76-1.00), rDD-DV =0.97 (0.87-1.00), and rPU-DV =0.96 (0.82-1.00)).Conclusion At least 20% of the variance in the generalized vulnerability to substance dependence is attributable to common single nucleotide polymorphisms. The additive effect of common single nucleotide polymorphisms is shared across important indicators of comorbid drug problems. This article is protected by copyright. All rights reserved.
Article
Posttraumatic stress disorder (PTSD) represents a debilitating psychiatric condition that is affecting the lives of many returning veterans. PTSD and alcohol use and dependence are highly comorbid. The purpose of this study was to understand the functional mechanisms between PTSD and alcohol use and problems. Specifically, the role of negative urgency and emotional intelligence were investigated as vulnerability and resiliency factors, respectively. This study utilized experience sampling to test associations between PTSD symptoms and alcohol use and related problems in a sample of 90 OIF/OEF veterans. Participants completed 8 brief questionnaires daily for 2 weeks on palmtop computers. Elevations in PTSD symptoms during the day were associated with subsequent increases in alcohol use and associated problems that night. PTSD symptoms were associated with greater problems above and beyond the effect of drinking level at both the within- and between- person level. Emotional intelligence was associated with lower negative urgency, fewer PTSD symptoms, and less alcohol use and associated problems. The effects of emotional intelligence were primarily indirect via negative urgency and the effects of negative urgency on alcohol use and problems were indirect via its positive association with PTSD symptoms. Hypothesized cross-level effects of emotional intelligence and negative urgency were not supported. The findings suggest a functional association between PTSD symptoms and alcohol consumption. The association between PTSD symptoms and alcohol consumption is consistent with a self-medication model. However, the significant associations between PTSD symptoms and alcohol problems, after controlling for use level, suggest a broader role of dysregulation. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Article
Patients with schizophrenia often show abnormal social interactions, which may explain their social exclusion behaviors. This study aimed to elucidate patients' brain responses to social rejection in an interactive situation. Fifteen patients with schizophrenia and 16 healthy controls participated in the functional magnetic resonance imaging experiment with the virtual handshake task, in which socially interacting contents such as acceptance and refusal of handshaking were implemented. Responses to the refusal versus acceptance conditions were evaluated and compared between the two groups. Controls revealed higher activity in the refusal condition compared to the acceptance condition in the right superior temporal sulcus, whereas patients showed higher activity in the prefrontal regions, including the frontopolar cortex. In patients, contrast activities of the right superior temporal sulcus were inversely correlated with the severity of schizophrenic symptoms, whereas contrast activities of the left frontopolar cortex were positively correlated with the current anxiety scores. The superior temporal sulcus hypoactivity and frontopolar hyperactivity of patients with schizophrenia in social rejection situations may suggest the presence of mentalizing deficits in negative social situations and inefficient processes of socially aberrant stimuli, respectively. These abnormalities may be one of the neural bases of distorted or paranoid beliefs in schizophrenia.
Article
Background Previously identified resting functional connectivity (FC) differences in individuals with stimulant use disorder (SUD) suggest an imbalance in neural regions that mediate behavioral aspects relevant to addiction such as emotion regulation and reward processing. There is a need to further investigate these differences across time between those that relapse and those that do not. This is the first longitudinal study of recently abstinent SUD (SUD-RA) that identifies specific FC changes in subsequent relapsers (vs abstainers). We hypothesized that (1) subsequent relapsers (vs abstainers) will show lower FC of emotion regulation regions and higher FC of reward processing regions and (2) FC differences would be more evident across time. Methods We examined resting FC in 18 SUD-RAs (8 females, age: M = 22.05 ± 2.64) and 15 non-substance abusing controls (NSAC; 5 females, age: M = 24.21 ± 5.76) at Time 1 (abstinent ∼5 weeks). Fourteen NSAC and 12 SUD-RAs were re-examined at Time 2 (abstinent ∼13 weeks). With seed-based FC measures, we examined FC differences between SUD-RAs that abstained or relapsed over the subsequent 6 months. RESULTS: Relapsers (vs abstainers) had higher FC between (1) nucleus accumbens (NAcc) and left frontopolar cortex (FPC), (2) NAcc and posterior cingulate gyrus and (3) subgenual anterior cingulate and left FPC at Time 1. Relapsers (vs abstainers) showed larger reduction in FC strength within these regions across time. Conclusions Resting FC reduction found in relapsers (vs. abstainers) from five to thirteen weeks of abstinence may be a biological marker of relapse vulnerability. These preliminary findings require replication with larger sample sizes.
Article
The present investigation examined the role of gender, family history of alcohol and drug use disorders, temperament, childhood behavior problems, and adult psychopathology, on adult alcohol use disorder (AUD) severity. Structural equation modeling was used to examine multiple etiological pathways to adult alcohol use disorder (AUD) severity. Participants included 335 treatment-seeking males and females with current or lifetime DSM-III-R alcohol dependence (96%) or abuse (4%) enrolled in one of five treatment outcome studies. Extensive assessment at treatment entry used a mixture of retrospective and current self-report. Results identified two significant paths associated with a latent factor of adult alcohol use disorder severity at entry to treatment. In Path 1, male gender and family history of drug use disorder predicted greater childhood behavior problems, which predicted antisocial personality disorder (ASPD), borderline personality disorder (BPD), and anxiety disorders (ADs), with anxiety disorders leading directly to alcohol use disorder severity. In Path 2, family history of alcohol use disorder predicted difficult temperament in childhood, which predicted borderline personality disorder, major depressive disorder (MDD) and anxiety disorders; both major depressive disorder and anxiety disorders in turn predicted alcohol use disorder severity at treatment entry. The present findings build on the literature on heterogeneity in developmental risk processes leading to the expression of adult alcohol use disorder symptomology among patients presenting for alcohol use disorder treatment.
Article
The risk for drug addiction is partially heritable. Genes of the dopamine system are likely candidates to harbour risk variants, as dopamine neurotransmission is involved in mediating the rewarding effects of drugs of abuse. One functional single nucleotide polymorphism in dopamine receptor D2 (DRD2), rs1076560, is involved in regulating splicing of the gene and alters the ratio of DRD2 isoforms located pre- and postsynaptically. rs1076560 has been previously associated with cocaine abuse and we set out to confirm this association in a sample of European American (EA) (n = 336) and African American (AA) (n = 1034) cocaine addicts and EA (n = 656) and AA (n = 668) controls. We also analysed the role of rs1076560 in opioid dependence by genotyping EA (n = 1041) and AA (n = 284) opioid addicts. rs1076560 was found to be nominally associated with opioid dependence in EAs (p = 0.02, OR = 1.27) and AAs (p = 0.03, OR = 1.43). When both opioid-addicted ancestral samples were combined, rs1076560 was significantly associated with increased risk for drug dependence (p = 0.0038, OR = 1.29). This association remained significant after correction for multiple testing. No association was found with cocaine dependence. These data demonstrate the importance of dopamine gene variants in the risk for opioid dependence and highlight a functional polymorphism that warrants further study.
Article
Although parental alcohol use disorder (AUD) increases risk for alcohol problems in offspring, no studies have evaluated the odds of AUD in offspring based on the number of biological parents with AUD (0, 1, or 2) in a population-based national sample. The purpose of this study was to investigate the relationship between the number of AUD parents and prevalence of AUD in offspring. This study utilized data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, which assessed AUD using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (main outcome variable). We analyzed the sample (n = 40,374) to investigate the effect of the number of AUD parents on lifetime AUD in offspring. In a subgroup analysis, gender differences were examined. 22% of adults in the United States had at least 1 biological parent with AUD. Compared with offspring of non-AUD parents, offspring of 1 AUD parent had a 2.5-fold increase (AOR = 2.51; 95% CI, 2.38-2.66) and offspring of 2 AUD parents had a 4.4-fold increase (AOR = 4.44; 95% CI, 3.93-5.02) in the odds of lifetime AUD. Each additional AUD parent increased the odds of AUD in offspring in an additive pattern. Female offspring were more vulnerable to the impact of parental AUD than male offspring (OR = 1.17 in offspring of 1 AUD parent; OR = 1.48 in offspring of 2 AUD parents). Offspring of AUD parents had heightened odds of lifetime AUD, with an additive parental effect. Awareness of this risk can be useful for clinicians to educate individuals with AUD parents about prevention and intervention.
Article
Altered behavioral performance and brain activation during spatial working memory (SWM) tasks have been demonstrated in individuals with an alcohol use disorder (AUD). It is possible that alterations in processing during SWM may be present prior to initiation of heavy alcohol use in adolescents with a family history of AUDs (family history positive [FHP]) and therefore represent a premorbid neural phenotype that could increase risk for developing an AUD. The goal of our study was to investigate group differences in brain activation during a SWM task between FHP adolescents and adolescents with no family history of AUDs (family history negative [FHN]), as well as examine the relationship between brain activation and individual differences in family history density (FHD) of AUDs. Eighteen FHP and 16 gender and age-matched FHN participants completed a SWM and vigilance task while undergoing a functional magnetic resonance imaging (fMRI) scan. There were no group differences in task performance. The FHN group demonstrated expected greater activation during the SWM than vigilance condition in the right middle frontal gyrus and dorsolateral prefrontal cortex, whereas the FHP group demonstrated comparable brain activation for both the more demanding and simple task conditions. Additionally, FHD was associated with greater activation of the right superior parietal cortex and less activation of the right cerebellum during the SWM task, but not during the vigilance task. Results suggest FHP adolescents demonstrate alterations in activation of prefrontal regions that are related more generally to the maintenance of top-down cognitive control and alterations in parietal and cerebellar regions that are specific to SWM. Alterations in top-down cognitive control may be a general risk factor for FHP adolescents, whereas SWM-specific alterations are seen as a function of family history loading.
Article
Background: Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. Methods: Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. Results: Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 μl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. Conclusions: Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.
Article
Background: Differences in fronto-striatal connectivity in problem substance users have suggested reduced influence of cognitive regions on reward-salience regions. Youth with a family history of alcoholism (FH+) have disrupted ventral striatal processing compared with controls with no familial risk (FH-). As sensation-seeking represents an additional vulnerability factor, we hypothesized that functional connectivity during reward anticipation would differ by family history, and would mediate the relationship between sensation-seeking and drinking in high-risk subjects. Methods: Seventy 18-22 year olds (49 FH+/21 FH-) performed a monetary incentive delay task during functional magnetic resonance imaging. Group connectivity differences for incentive (reward/loss) vs. neutral conditions were evaluated with psychophysiological interaction (PPI) analysis, seeded in nucleus accumbens (NAcc). Indirect effects of sensation-seeking on drinking volume through accumbens connectivity were tested. Results: NAcc connectivity with paracentral lobule/precuneus and sensorimotor areas was decreased for FH- vs. increased for FH+ during incentive anticipation. In FH+, task-related functional coupling between left NAcc and supplementary sensorimotor area (SSMA) and right precuneus correlated positively with sensation-seeking and drinking volume and mediated their relationship. In FH-, left NAcc-SSMA connectivity correlated negatively with sensation-seeking but was not related to drinking. Conclusions: These results suggest preexisting differences in accumbens reward-related functional connectivity in high-risk subjects. NAcc coupling with SSMA, involved in attention and motor networks, and precuneus, a default mode structure, appear to mediate sensation-seeking's effect on drinking in those most at-risk. Differences in accumbens connectivity with attention/motor/default networks, rather than control systems, may influence the reward system's role in vulnerability for substance abuse.
Article
This study examined executive functioning in college aged adult children of alcoholics (ACOAs; n = 84) and non-ACOAs (188). We examined whether characteristics of the family environment and family responsibility in one’s family of origin were associated with executive functioning above the contribution of ACOA status. ACOAs reported more difficulty regulating behavior related to executive functioning but comparable metacognitive abilities to non-ACOAs. Family environment contributed to behavioral and metacognitive regulation above the contribution of group (ACOA/non-ACOA). These findings suggest that ACOAs may be at greater risk for experiencing difficulty in higher order processes related to behavioral regulation. For both ACOA and non-ACOA college students, one’s family of origin environment appears related to higher order processes, suggesting the need for interventions aimed at improving executive functioning for vulnerable students.
Article
The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e, > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.
Article
Background : Research has indicated a close relationship between the P3 event-related potential and the dopamine D2 receptor A1 allele in individuals at high risk for alcoholism. Other research has suggested an association between the dopamine D2 receptor A1 allele and sensation-seeking. In this study, we further examined the relationships between the P3, the A1 allele, and sensation-seeking in a sample of nonalcoholic adult children of alcoholics. Methods: Participants (n= 57; range, 19–30 years; 41 women), who performed a visual novelty oddball task to elicit the P3, were asked to fill in personality questionnaires, including Zuckerman's Sensation-Seeking Scale, and were classified according to the presence of the dopamine D2 receptor A1 allele. The effects of sex, age, and socioeconomic status were assessed to determine whether these variables affected the relations between the P3, the A1 allele, and sensation-seeking. Results: A small P3 amplitude was associated with high sensation-seeking, particularly with high disinhibition. The presence of the A1 allele was also associated with high disinhibition, but only in men. By contrast, P3 amplitudes and latencies were not associated with the presence of the A1 allele. Conclusions: Although a small P3 amplitude, high sensation-seeking, and the presence of the A1 allele were all associated with alcoholism risk, these findings indicate that these three characteristics together do not reflect a common risk factor in alcoholism.
Article
Suicide among older people, especially men, is a significant problem. In this study the applicability of the compensatory, the risk-protective, the challenge, and the protective-protective models of resiliency for the prediction of suicidal ideation from depression (the risk factor) and sense of belonging to the community (the protective factor) was investigated. A total of 351 retired Australians (130 males and 221 females), with a mean age of 71.31 years (SD = 7.99), completed the Zung Depression Scale, the suicide subscale of the General Health Questionnaire, and the Sense of Belonging Instrument. When sense of belonging (psychological) was the protective factor, results indicated support for the risk-protective model for men and women, and for the compensatory model for women only. In contrast, when sense of belonging (antecedents) was the protective factor, support was evident for the compensatory model for men and women, and for the challenge model for women only. Results indicate that interventions should be developed to enhance sense of belonging among aging adults.
Article
Experimental designs for event-related functional magnetic resonance imaging can be characterized by both their detection power, a measure of the ability to detect an activation, and their estimation efficiency, a measure of the ability to estimate the shape of the hemodynamic response. Randomized designs offer maximum estimation efficiency but poor detection power, while block designs offer good detection power at the cost of minimum estimation efficiency. Periodic single-trial designs are poor by both criteria. We present here a theoretical model of the relation between estimation efficiency and detection power and show that the observed trade-off between efficiency and power is fundamental. Using the model, we explore the properties of semirandom designs that offer intermediate trade-offs between efficiency and power. These designs can simultaneously achieve the estimation efficiency of randomized designs and the detection power of block designs at the cost of increasing the length of an experiment by less than a factor of 2. Experimental designs can also be characterized by their predictability, a measure of the ability to circumvent confounds such as habituation and anticipation. We examine the relation between detection power, estimation efficiency, and predictability and show that small increases in predictability can offer significant gains in detection power with only a minor decrease in estimation efficiency.
Article
Adolescents with a family history of alcoholism (FHP) are at risk for developing an alcohol use disorder (AUD), and some studies indicate that FHP individuals show deficits in executive functioning. The ability to make adaptive decisions is one aspect of successful executive functioning that is often measured during risk-taking tasks; however, this behavior has not been examined in FHP youth. As impaired decision-making could predispose FHP youth to make poor choices related to alcohol use, the current study examined the neural substrates of risk-taking in FHP adolescents and their family history negative (FHN) peers. Thirty-one (18 FHP, 13 FHN) youth between 13 and 15 years old were included in this study. All youth had used little to no alcohol prior to study involvement. Functional magnetic resonance imaging was used to examine the neural substrates of risk-taking during the Wheel of Fortune (WOF) decision-making task (Ernst et al., 2004) in FHP and FHN youth. FHP youth did not differ from FHN youth in risk-taking behavior, but showed less brain response during risky decision-making in right dorsolateral prefrontal cortex and right cerebellar regions compared with FHN peers. Despite no behavioral differences on the WOF decision-making task, FHP youth exhibited atypical neural response during risk-taking compared with FHN peers. Atypical brain activity, in regions implicated in executive functioning could lead to reduced cognitive control, which may result in risky choices regarding alcohol use. This could help explain the higher rates of AUDs seen in FHP adolescents. Further examination of risky behavior and associated brain response over the course of adolescence is necessary to characterize the vulnerabilities of FHP youth in the absence of alcohol abuse.
Article
Posttraumatic stress disorder (PTSD) has been linked to numerous negative outcomes in persons living with HIV (PLH) and there is evidence that PTSD symptoms may play a role in maintaining alcohol use problems. The opioid receptor mu-1 (OPRM1) gene may play a role in both PTSD and alcohol use. We examined the association between PTSD and drinking motives as well as variation in the OPRM1 as a predictor of both PTSD and drinking motives in a sample of 201 PLH reporting recent binge drinking. Self-reported PTSD symptom severity was significantly associated with drinking motives for coping, enhancement, and socialization. OPRM1 variation was associated with decreased PTSD symptom severity as well as enhancement motives for drinking.
Article
Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD. Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility. We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009). Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.
Article
We examined the association between serotonin transporter (5HTTLPR) genotype (SS vs SL vs LL) and sertraline treatment outcome in posttraumatic stress disorder (PTSD). Outpatients (n=330) with PTSD underwent 5HTTLPR genotyping. All patients received sertraline (100 mg/day) for 12 weeks. Patients were assessed using the Clinician-Administered PTSD Scale (CAPS) and other instruments. Patients and rater were blind to the genotyping results. The primary outcome was completer sample CAPS improvement at 12 weeks. Response was defined as ≥30% improvement in CAPS total score with a CGI-I score of 1 or 2. The discontinuation rate was 31.5%. Adverse events led to drop out in 18.1%, 15.3%, and 5.9% of SS, SL, and LL patients, respectively (P=0.038). Among completers, there were 95, 43, and 88 patients with the SS, SL, and LL genotypes, respectively. At endpoint, CAPS total scores improved by 26% vs 46%, respectively, in SS and SL vs LL patients (P<0.001); much of this improvement (15% vs 31% in SS and SL vs LL patients, respectively; P<0.001) was apparent by week 4. The findings were largely similar for the other outcome measures. The response rate was 0%, 0%, and 47.7% in the SS, SL, and LL groups, respectively (P<0.001). We administered a fixed dose of sertraline. For sociopolitical reasons, we planned a completer analysis only. Relative to the SS and SL 5HTTLPR genotypes, the LL genotype is associated with greater responsiveness of PTSD to sertraline (100mg/day) and with lower drop out due to adverse events. The S allele is associated with a striking specificity for treatment nonresponse, as defined in this study.
Article
A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.
Article
The human serotonin receptor 1B (HRT1B) plays an important role in regulating serotonin release. Previous research has suggested that the genetic variation of the HTR1B gene may confer susceptibility to alcoholism or some subtypes of alcohol dependence, but the evidence has been inconsistent. The aim of the present study is to examine whether polymorphic variants of the HTR1B gene are associated with alcohol dependence subtypes or drinking-related behaviors in Chinese Han population. Alcohol-dependent (AD) male patients (n=135) and controls (n=143) were genotyped for two polymorphisms: A161T in the promoter region and the synonymous variation G861C in the coding region of HTR1B. The results showed that the A161T polymorphism was associated with alcohol dependence (T vs. A allele: p=0.002; OR=2.18, 95% CI: 1.32-3.60). This association was strengthened in those with positive family history (OR=3.12, 95% CI: 1.71-5.70) and/or early onset (OR=4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was also significantly associated with age of onset of alcoholism (p=0.001). Furthermore, there was a significant difference of haplotypic frequencies between patients and controls (χ(2)=14.84, df=3, p=0.002), with one common haplotype AG of being significantly underrepresented among the patient group compared to the control group (34% vs. 47.7%, permutation p=0.0034; OR=0.56; 95% CI: 0.39-0.79). These findings confirm HTR1B as a susceptibility gene for alcohol dependence in the sample of Chinese Han population. The HTR1B A-161T polymorphism may be particularly valuable as a functional genetic marker for alcoholism and merits additional study.
Article
Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.
Article
Relationships among adult children of alcoholics (ACOAs) and parent and peer relations and depressive mood were examined among 136 ACOAs and 436 non-ACOAs. As compared to non-ACOAs, ACOAs reported less positive relationships to mothers, fathers, and peers, and more depressive mood; however, more positive relationships to parents and peers significantly reduced the strength of the association between ACOA categorization and depressive mood. Examination of data from ACOAs alone revealed that maternal alcoholism was related to less positive relationships to their mothers and to their peers; however, paternal alcoholism did not predict the quality of the relationship to fathers, mothers, or peers. Attachment to parents and peers and the gender of the alcohol-abusing parent were associated with depressive symptoms among ACOAs.
Article
This study was intended to assess the extent to which the low-expression alleles of the serotonin transporter gene promoter predict poor response to cognitive behavior therapy in patients with posttraumatic stress disorder (PTSD). Forty-five patients with PTSD underwent an 8-week exposure-based cognitive behavior therapy program and provided mouth swabs or saliva samples to extract genomic DNA and classify individuals according to four allelic forms (S(A), S(G), L(A), L(G)) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in PTSD severity following treatment (n = 45) and 6 months later (n = 42). After controlling for pretreatment PTSD severity and number of treatment sessions, the 5-HTTLPR low-expression genotype group (S or L(G) allele carriers) displayed more severe PTSD 6 months following treatment relative to other patients. This study suggests a genetic contribution to treatment outcome following cognitive behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PTSD.