Meta-Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol Exposure?

Leah Wetherill, Tatiana Foroud, Charles Goodlett

Research output: Contribution to journalArticlepeer-review


Background: Externalizing disorders are heritable precursors to alcohol dependence, common in children of alcoholics (COA), and in children with prenatal alcohol exposure (PAE). Pregnancies involving alcohol exposure sufficient to affect the fetus may involve women with genetic risk for alcohol dependence. We hypothesized that known PAE will increase the odds of having an externalizing disorder compared to COA. Methods: The odds ratios of 3 externalizing disorders (attention-deficit hyperactivity disorder [ADHD], conduct disorder [CD], and oppositional defiant disorder [ODD]) were obtained for 2 domains: (i) PAE and (ii) COA, by estimating the logged odds ratio (LOR) for each study. Permutation tests were implemented to compare LORs for PAE versus COA studies within each disorder, including PAE versus an alcohol dependent (AD) mother and PAE versus an AD father. Results: In PAE studies, the odds of ADHD and CD were elevated. Rates of all 3 disorders were elevated in COA studies. Permutation tests revealed that the mean LOR for ADHD was significantly higher in PAE studies compared to: COA (p = 0.01), AD mother (p < 0.05), and AD father (p = 0.03). No differences were found for ODD (p = 0.09) or CD (p = 0.21). Conclusions: These results provide compelling evidence of an increased risk of ADHD in those with PAE beyond that due to parental alcohol dependence or a genetic liability, consistent with a unique etiology most likely due to direct alcohol exposure during prenatal development.

Original languageEnglish (US)
Pages (from-to)162-172
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Issue number1
StatePublished - Jan 2018


  • Attention-Deficit Hyperactivity Disorder
  • Children of Alcoholics
  • Externalizing Disorders
  • Genetics
  • Prenatal Alcohol Exposure

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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