Browsing by Author "Anokhin, Andrey"

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    Associations of parent–adolescent closeness with P3 amplitude, frontal theta, and binge drinking among offspring with high risk for alcohol use disorder
    (Wiley, 2023) Pandey, Gayathri; Kuo, Sally I-Chun; Horne-Osipenko, Kristina A.; Pandey, Ashwini K.; Kamarajan, Chella; Saenz de Viteri, Stacey; Kinreich, Sivan; Chorlian, David B.; Kuang, Weipeng; Stephenson, Mallory; Kramer, John; Anokhin, Andrey; Zang, Yong; Kuperman, Samuel; Hesselbrock, Victor; Schuckit, Marc; Dick, Danielle; Chan, Grace; McCutcheon, Vivia V.; Edenberg, Howard; Bucholz, Kathleen K.; Meyers, Jacquelyn L.; Porjesz, Bernice; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background: Parents impact their offspring's brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1256, mean age [SD] = 19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring. Methods: Self-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task. Results: Multivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p = 0.002) and higher FT power (p = 0.01). Closeness with mother was associated with less binge drinking (p = 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father's and mothers' AUD symptoms, socioeconomic status, and offspring impulsivity in the model. Conclusions: Among high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.
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    Density and Dichotomous Family History Measures of Alcohol Use Disorder as Predictors of Behavioral and Neural Phenotypes: A Comparative Study Across Gender and Race/Ethnicity
    (Wiley, 2020-03) Pandey, Gayathri; Seay, Michael J.; Meyers, Jacquelyn L.; Chorlian, David B.; Pandey, Ashwini K.; Kamarajan, Chella; Ehrenberg, Morton; Pitti, Daniel; Kinreich, Sivan; de Viteri, Stacey Subbie-Saenz; Acion, Laura; Anokhin, Andrey; Bauer, Lance; Chan, Grace; Edenberg, Howard; Hesselbrock, Victor; Kuperman, Samuel; McCutcheon, Vivia V.; Bucholz, Kathleen K.; Schuckit, Marc; Porjesz, Bernice; Biochemistry and Molecular Biology, School of Medicine
    Background: Family history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD. Methods: Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM-5 AUD diagnostic information obtained through direct interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM-5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes. Results: Density measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude. Conclusions: Density (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD.
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    Early Sexual Trauma Exposure and Neural Response Inhibition in Adolescence and Young Adults: Trajectories of Frontal Theta Oscillations During a Go/No-Go Task
    (Elsevier, 2019) Meyers, Jacquelyn; McCutcheon, Vivia V.; Pandey, Ashwini K.; Kamarajan, Chella; Subbie, Stacey; Chorlian, David; Salvatore, Jessica; Pandey, Gayathri; Almasy, Laura; Anokhin, Andrey; Bauer, Lance; Bender, Annah; Dick, Danielle M.; Edenberg, Howard J.; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Agrawal, Arpana; Bucholz, Kathleen; Porjesz, Bernice; Biochemistry and Molecular Biology, School of Medicine
    Objective Trauma, particularly when experienced early in life, can alter neurophysiologic and behavioral development, thereby increasing risk for substance use disorders and related psychopathology. However, few studies have empirically examined trauma using well-characterized developmental samples that are followed longitudinally. Method The association of assaultive, non-assaultive, and sexual assaultive experiences before 10 years of age with developmental trajectories of brain function during response inhibition was examined by measuring electrophysiologic theta and delta oscillations during no-go and go conditions in an equal probability go/no-go task. Data were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort, composed of offspring from high-risk and comparison families who were 12 to 22 years old at enrollment, with follow-ups at 2-year intervals since 2004. In addition, other important predictors of neurophysiologic functioning (eg, substance use, impulsivity, and parental alcohol use disorders) were investigated. Moreover, associations of neurophysiologic functioning with alcohol and cannabis use disorder symptom counts and externalizing and internalizing psychopathology were examined. Results Individuals exposed to sexual assaultive trauma before 10 years of age had slower rates of change in developmental trajectories of no-go frontal theta during response inhibition. Importantly, effects remained significant after accounting for exposure to other traumatic exposures, such as parental history of alcohol use disorder and participants’ substance use, but not measures of impulsivity. Further, slower rates of change in no-go frontal theta adolescent and young adult development were associated with increased risk for alcohol use disorder symptoms and internalizing psychopathology, but not for cannabis use disorder symptoms or externalizing psychopathology. Conclusion Childhood sexual assault is associated with atypical frontal neurophysiologic development during response inhibition. This could reflect alterations in frontal lobe development, synaptic pruning, and/or cortical maturation involving neural circuits for inhibitory control. These same areas could be associated with increased risk for young adult alcohol use disorder symptoms and internalizing psychopathology. These findings support the hypothesis that changes in neurocognitive development related to early sexual trauma exposure could increase the risk for mental health and substance use problems in young adulthood.
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    ERRATUM: Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans
    (Wiley, 2019-11) Wetherill, Leah; Lai, Dongbing; Johnson, Emma C.; Anokhin, Andrey; Bauer, Lance; Bucholz, Kathleen K.; Dick, Danielle M.; Hariri, Ahmad R.; Hesselbrock, Victor; Kamarajan, Chella; Kramer, John; Kuperman, Samuel; Meyers, Jacquelyn L.; Nurnberger, John I., Jr.; Schuckit, Marc; Scott, Denise M.; Taylor, Robert E.; Tischfield, Jay; Porjesz, Bernice; Goate, Alison M.; Edenberg, Howard J.; Foroud, Tatiana; Bogdan, Ryan; Agrawal, Arpana; Medical and Molecular Genetics, School of Medicine
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    A GABRA2 Polymorphism Improves a Model for Prediction of Drinking Initiation
    (Elsevier, 2017-09) Kuperman, Samuel; Chan, Grace; Kramer, John; Wetherill, Leah; Acion, Laura; Edenberg, Howard J.; Foroud, Tatiana M.; Nurnberger, John, Jr.; Agrawal, Arpana; Anokhin, Andrey; Brooks, Andrew; Hesselbrock, Victor; Hesselbrock, Michie; Schuckit, Marc; Tischfield, Jay; Liu, Xiangtao; Department of Biochemistry & Molecular Biology, IU School of Medicine
    Background Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model's ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking. Methods A subsample of 674 adolescents (ages 14–17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics. Results The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype. Conclusions The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.
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    Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans
    (Wiley, 2019-05-19) Wetherill, Leah; Lai, Dongbing; Johnson, Emma C.; Anokhin, Andrey; Bauer, Lance; Bucholz, Kathleen K.; Dick, Danielle M.; Hariri, Ahmad R.; Hesselbrock, Victor; Kamarajan, Chella; Kramer, John; Kuperman, Samuel; Meyers, Jacquelyn L.; Nurnberger, John I.; Schuckit, Marc; Scott, Denise M.; Taylor, Robert E.; Tischfield, Jay; Porjesz, Bernice; Goate, Alison M.; Edenberg, Howard J.; Foroud, Tatiana; Bogdan, Ryan; Agrawal, Arpana; Medical and Molecular Genetics, School of Medicine
    Genetic influences on alcohol and drug dependence partially overlap, however specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7,291 European-Americans (EA; 2,927 cases) and 3,132 African-Americans (AA: 1,315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h2 in EA=0.60, AA=0.37). The AA GWAS identified 3 regions with genome-wide significant (GWS; p<5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA+AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and 4 sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk.
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    Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts
    (American Psychiatric Association, 2022) Mallard, Travis T.; Savage, Jeanne E.; Johnson, Emma C.; Huang, Yuye; Edwards, Alexis C.; Hottenga, Jouke J.; Grotzinger, Andrew D.; Gustavson, Daniel E.; Jennings, Mariela V.; Anokhin, Andrey; Dick, Danielle M.; Edenberg, Howard J.; Kramer, John R.; Lai, Dongbing; Meyers, Jacquelyn L.; Pandey, Ashwini K.; Harden, Kathryn Paige; Nivard, Michel G.; de Geus, Eco J. C.; Boomsma, Dorret I.; Agrawal, Arpana; Davis, Lea K.; Clarke, Toni-Kim; Palmer, Abraham A.; Sanchez-Roige, Sandra; Biochemistry and Molecular Biology, School of Medicine
    Objective: Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT. Methods: To explore these unexpected differences in genetic correlations, the authors conducted the first item-level and the largest GWAS of AUDIT items (N=160,824) and applied a multivariate framework to mitigate previous biases. Results: The authors identified novel patterns of similarity (and dissimilarity) among the AUDIT items and found evidence of a correlated two-factor structure at the genetic level ("consumption" and "problems," rg=0.80). Moreover, by applying empirically derived weights to each of the AUDIT items, the authors constructed an aggregate measure of alcohol consumption that was strongly associated with alcohol dependence (rg=0.67), moderately associated with several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, the authors identified novel genetic associations between alcohol consumption, alcohol misuse, and health. Conclusions: This work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.
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    Mapping Pathways by which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay between Externalizing Polygenic Risk Scores, Parental Knowledge, and Peer Substance Use
    (Springer, 2021) Kuo, Sally I-Chun; Salvatore, Jessica E.; Barr, Peter B.; Aliev, Fazil; Anokhin, Andrey; Bucholz, Kathleen K.; Chan, Grace; Edenberg, Howard J.; Hesselbrock, Victor; Kamarajan, Chella; Kramer, John R.; Lai, Dongbing; Mallard, Travis T.; Nurnberger, John I., Jr.; Pandey, Gayathri; Plawecki, Martin H.; Sanchez-Roige, Sandra; Waldman, Irwin; Palmer, Abraham A.; Externalizing Consortium; Dick, Danielle M.; Biochemistry and Molecular Biology, School of Medicine
    Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene-environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; Mage = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene-environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.