Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?

Ruben D. Baler, Nora D. Volkow, Joanna S. Fowler, Helene Benveniste

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development - but not during adult life - is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke-induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalJournal of Psychiatry and Neuroscience
Issue number3
StatePublished - May 2008
Externally publishedYes


  • Conduct disorder
  • Maternal-fetal exchange
  • Monoamine oxidase
  • Smoking


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