Irons, D.E., Iacono, W.G., & McGue, M. (2015). Tests of the effects of adolescent early alcohol exposures on adult outcomes. Addiction, 110(2), 269-278. doi:10.1111/add.12747 PMCID: PMC4459504

FINDINGS: Background covariates unbalanced between those with and without early alcohol exposure were balanced through PS-based weighting, leaving several adult outcomes related to substance use or social functioning remaining significantly associated with early alcohol exposure. Similarly, the within-pair individual-level component of a CTC indicated that early alcohol-exposed twins had higher risk than their non-exposed co-twins for several, but not all, of the same adult outcomes. For example, early alcohol use was associated with an adult index of alcohol use in both PS-weighted (β = 0.57, P < 0.001) and CTC (β = 0.21, P = 0.031) analyses.
CONCLUSIONS: Early alcohol exposures predict adult alcohol problems and related outcomes, despite stringent adjustment for measured and non-measured sources of potential confounding using propensity score and co-twin control. Contrasting the methods indicated that exposure effect estimates from PS application were likely biased by unmeasured confounding factors.

McGue, M., Malone, S.M., Keyes, M.A., & Iacono, W.G. (2014). Parent-offspring similarity for drinking: a longitudinal adoption study. Behavior Genetics, 44(6), 620-628. PMCID: PMC4439100

Abstract: Parent-offspring resemblance for drinking was investigated in a sample of 409 adopted and 208 non-adopted families participating in the Sibling Interaction and Behavior Study (SIBS). Drinking data was available for 1229 offspring, assessed longitudinally up to three times in the age range from 10 to 28 years. A single drinking index was computed from four items measuring quantity, frequency and density of drinking. As expected, the mean drinking index increased with age, was greater in males as compared to females (although not at the younger ages), but did not vary significantly by adoption status. Parent-offspring correlation in drinking did not vary significantly by either offspring or parent gender but did differ significantly by adoption status. In adopted families, the parent-offspring correlation was statistically significant at all ages but decreased for the oldest age group (age 22–28). In non-adopted families, the parent-offspring correlation was statistically significant at all ages and increased in the oldest age group. Findings imply that genetic influences on drinking behavior increase with age while shared family environment influences decline, especially during the transition from late-adolescence to early adulthood.

Hicks, B.M., Durbin, E., Blonigen, D.M., Iacono, W.G., & McGue, M. (2012). Relationship between personality change and the onset and course of alcohol dependence in young adulthood. Addiction, 107, 540-548. PMCID: PMC3275658

Findings: Onset and course of AUD moderated personality change from age 17 to 24. Adolescent onset AUD was associated with greater decreases in behavioral disinhibition. Those with an adolescent onset and persistent course failed to exhibit normative declines in negative emotionality. Desistence was associated with a "recovery" toward psychological maturity in young adulthood, while persistence was associated with continued personality dysfunction. Personality traits at age 11 predicted onset and course of AUD, indicating personality differences were not due to active substance abuse.
Conclusions: Personality differences present prior to initiation of use increase risk for AUD, but the course of AUD affects the rate of personality change during emerging adulthood. Examining the reciprocal effects of personality and AUD within a developmental context is necessary to improve understanding of theory and intervention.

Gogineni, A., King, S.M., Iacono, W.G., McGue, M., etal. (2006). Female Offspring of Alcoholic Individuals: Recent Finding on Alcoholism and Psychopathology Risk: Symposium Presented at the Research Society on Alcoholism, 2004, Vancouver Aruna Gogineni Chair. Alcoholism: Clinical and Experimental Research, 30, 377-387.

In the past decade, significant advances have been made in understanding how genetic and environmental factors contribute to alcoholism and other psychopathology
among children of alcoholic individuals. Potential biopsychosocial markers of risk (e.g., low level of response to alcohol, behavioral undercontrol, and family functioning variables) have been identi.ed and indicate that both individual and environmental variables are highly relevant. Despite these advances, studies have predominantly
focused on examining outcomes among sons of alcoholic individuals, with the consequence that relatively little is known about the risk for alcoholism and other psychopathology among daughters. Effective prevention and treatment strategies are predicated upon further knowledge of these risks among daughters as well as sons. This symposium will present recent .ndings using family, prospective, and cross-sectional research to elucidate the biopsychosocial correlates and the moderators of risk for alcoholism and other psychopathology among daughters from developmental trajectories spanning the periods of childhood, adolescence, and adulthood.
This symposium begins with a presentation by John Kramer in which high-risk daughters’ and sons’ alcohol and drug involvement are compared with respect to their predictors, drawn from demographic, familial, and personal domains. Next, Serena King focuses on the correlates of disinhibited behavior in males and females from adoptive and biological families, with an emphasis on parental alcoholism, genetic versus environmental in.uences, and differences between genders. This talk is followed by a presentation by Kristina Jackson, who examines the predictors of alcohol use disorders among young adults from high-risk and control families, including such factors as family history, negative affect, behavioral undercontrol, and childhood stressors. Finally, Aruna
Gogineni addresses the familial predictors of adult daughters’ alcohol problems and depression, focusing on the effects of maternal versus paternal alcoholism as well as family density of pathology.

King, S.M., Burt, A., Malone, S.M., McGue, M. & Iacono, W.G. (2005). Etiological Contributions to Heavy Drinking from Late Adolescents to Young Adulthood. Journal of Abnormal Psychology, 114, 587-598.

The authors examined genetic and environmental contributions to stability and change in heavy drinking from late adolescence to young adulthood in a sample of 1,152 twin pairs. In men, heavy drinking was similarly heritable at ages 17 (h2 _ .57) and 20 (h2 _ .39), and its stability owed primarily to common genetic factors. In women, heavy drinking was less heritable than in men at ages 17 (h2 _ .18) and 20 (h2 _ .30) and its stability was primarily due to enduring shared environmental influences. P3 amplitude, an event-related brain potential marker of alcoholism risk, was less predictive of heavy drinking in women than in men, providing further support for the proposition that biological factors have less impact on heavy drinking in young adult women than in young adult men.

Legrand, L.N., Iacono, W.G. & McGue, M. (2005). Predicting Addiction. American Scientist, 93, 140-147.

In 1994, the 45-year-old daughter of Senator and former presidential nominee George McGovern froze to death outside a bar in Madison, Wisconsin. Terry McGovern’s death followed a night of heavy drinking and a lifetime of battling alcohol addiction. The Senator’s middle child had been talented and charismatic, but also rebellious. She started drinking at 13, became pregnant at 15 and experimented with marijuana and LSD in high school. She was sober during much of her 30s but eventually relapsed. By the time she died, Terry had been through many treatment programs and more than 60 detoxifications.
Her story is not unique. Even with strong family support, failure to over-come an addiction is common. Success rates vary by treatment type, severity of the condition and the criteria for success. But typically, fewer than a third of alcoholics are recovered a year or two after treatment. Thus, addiction may be thought of as a chronic, relapsing illness. Like other serious psychiatric conditions, it can cause a lifetime of re-current episodes and treatments.
Given these somber prospects, the best strategy for fighting addiction may be to prevent it in the first place. But warning young people about the dangers of addiction carries little force when many adults drink openly with-out apparent consequences. Would specific warnings for individuals with a strong genetic vulnerability to alcohol-ism be more effective? Senator McGovern became convinced that his daughter possessed such a vulnerability, as other family members also struggled with dependency. Perhaps Terry would have taken a different approach to alcohol, or avoided it altogether, if she had known that something about her biology made drinking particularly dangerous for her.
How can we identify people—at a young enough age to intervene—who have a high, inherent risk of becoming addicted? Does unusual susceptibility arise from differences at the biochemical level? And what social or environmental factors might tip the scales for kids at greatest risk? That is, what kind of parenting, or peer group, or neighbor-hood conditions might encourage—or inhibit—the expression of “addiction” genes? These questions are the focus of our research.

Carlson, S.R., Iacono, W.G. & McGue, M. (2004) P300 Amplitude in Non-Alcoholic Adolescent Twin Pairs Who Become Discordant for Alcoholism as Adults. Psychophysiology, 41, 841-844.

Past reports suggest that reduced P300 amplitude is associated with risk for alcoholism. We examined whether visual P300 amplitude could identify familial risk for alcohol disorders in individuals not known to be at risk at the time P300 was recorded. These individualswere twins from pairswhere neither twin had an alcohol disorder at age 17 but familial risk was established at age 20 when one twin developed an alcohol disorder whereas the other did not. Of special interest was the P300 of the unaffected twin recorded at age 17 when both twins were alcoholism free. We found reduced P300 in the unaffected twin compared to pairs where both members were continuously disorder free. Hence, P300 was reduced in alcohol disorder-free individuals whose twin siblings subsequently developed alcoholism, further supporting reduced P300 amplitude as an endophenotype indexing familial risk for alcoholism.

Elkins, I.J., McGue, M., Malone, S. & Iacono, W.G. (2004). The effect of parental alcohol and drug disorder on adolescent personality. American Journal of Psychiatry, 161, 670-676.

Objective: The relationship of parental alcohol or drug diagnosis to offspring personality was examined in a population based sample of 17-year-old twins (568 girls and 479 boys) participating in the Minnesota Twin Family Study. Whether offspring personality characteristics 1) are specific to the type of substance use disorder in parents (alcohol versus drug) and 2) are found in high-risk offspring without substance use disorders as well as in offspring with substance use disorders was investigated.
Method: Personality was assessed with the Multidimensional Personality Questionnaire; substance use disorders were assessed in person through diagnostic interviews.
Results: In both male and female offspring, parental history of alcohol dependence was associated with greater negative emotionality, aggression, stress reaction, and alienation but lower wellbeing; parental history of drug disorders was associated with lower constraint, control, harm avoidance, and traditionalism but higher social potency. Excluding offspring with a substance use disorder had virtually no effect on the statistical significance of these findings.
Conclusions: In contrast to findings in some adult samples, personality characteristics associated with a family history of substance use disorders are found even in adolescent offspring who have not yet developed these disorders themselves, suggesting that personality might be one indicator of familial risk for substance use disorders during this developmental stage. Personality profiles of offspring of parents with substance use disorders also show some diagnostic specificity, with constraint associated with parental drug abuse and negative emotionality with parental alcoholism.
(Am J Psychiatry 2004; 161:670–676)

Krueger, R.F., Nichol, P.E., Hicks, B.M., Markon, K.E., Patrick, C.J., Iacono, W.G. & McGue, M. (2004). Using Latent Trait Modeling to Conceptualize an Alcohol Continuum. Psychological Assessment, 16, 107-119.

Recent research points toward the viability of conceptualizing alcohol problems as arrayed along a continuum. Nevertheless, modern statistical techniques designed to scale multiple problems along a continuum (latent trait modeling; LTM) have rarely been applied to alcohol problems. This study applies LTM methods to data on 110 problems reported during in-person interviews of 1,348 middle-aged men (mean age _ 43) from the general population. The results revealed a continuum of severity linking the 110 problems, ranging from heavy and abusive drinking, through tolerance and withdrawal, to serious complications of alcoholism. These results indicate that alcohol problems can be arrayed along a dimension of severity and emphasize the relevance of LTM to informing the conceptualization and assessment of alcohol problems.

Carlson, S.R., Iacono, W.G., & McGue, M. (2002). P300 Amplitude in Adolescent Twins Discordant for Alcohol Use Disorders. Biological Psychology, 61, 203-227.

The sons of alcoholics have repeatedly been found to have reduced P300 amplitude. Further, quantitative behavioral genetic and molecular genetic studies indicating a genetic influence on P300 amplitude have fueled speculation that this component may be a biological vulnerability marker for alcoholism. To further explore this possibility, we examined P300 in adolescent twin pairs from an epidemiological sample who were (a) discordant for alcohol abuse/dependence, (b) concordant for alcohol abuse/dependence, or (c) concordant for the absence of alcohol abuse/dependence and other relevant disorders. For discordant pairs, the alcohol abusing/dependent twins’ amplitude did not differ from that of non-alcoholic cotwins. Pairs free of psychopathology had greater amplitudes than both alcoholism discordant and concordant pairs. P300 amplitude was more similar in monozygotic than dizygotic discordant pairs, suggesting a genetic influence on P300 amplitude in this group. The findings are consistent with P300 amplitude being a marker of vulnerability to alcohol use disorders.
©2002 Elsevier Science B.V. All rights reserved.

Holdcraft, L.C., & Iacono, W.G. (2002). Cohort effects on Gender Differences in Alcohol Dependence. Addiction, 97, 1025-1036.

Aims: The present study investigated the presence of cohort effects on gender differences in the course, severity and symptomatology of DSM-III-R alcohol dependence in a community-based sample.
Design: A comparison of substance-related variables among men and women divided into two groups based on the median birth year of the sample was conducted.
Participants: Participants were 468 men and 132 women with life-time alcohol dependence, the vast majority of whom were born between 1941 and 1960.
Measurements: Substance use and DSM-III-R substance use disorders were assessed by a structured interview administered in person.
Findings: Individuals born after 1951 had higher rates of alcohol dependence. Among individuals with alcohol dependence, those born after 1951 had an earlier onset and longer duration of alcohol-related problems. Significant interactions indicated that these effects were stronger for women than men.
Conclusions: Risk for alcohol dependence appears to be rising in younger generations, and particularly for younger women, making them an important target group for prevention and treatment programs.



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