Does MAOA increase susceptibility to prenatal stress in young children?
We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure.



Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences.



Concurrent stress exposure predicted DB in children (β=0.310, p=0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA×PSE×sex on DB (β=0.813, p=0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β=0.774, p=0.015), and as a function of PTE, controlling for PSE (β=0.362, p=0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β=-0.133, p=0.561) nor PTE (β=-0.144; p=0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r=-0.240, p=0.013).



Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression.
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N Saint Clair, 19(th) Floor, Chicago, IL, 60611, USA; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL, 60611, USA. Electronic address: suena.massey@northwestern.edu.
Suena H
SH
Massey
Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA. Electronic address: ahatch8@uic.edu.
Amalia E
AE
Hatcher
Department of Psychology, University of Arizona, 1503 E University Blvd., P.O.Box 210068, Tucson, AZ 85721, USA. Electronic address: cclark4@unl.edu.
Caron A C
CAC
Clark
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL, 60611, USA. Electronic address: james-l-burns@northwestern.edu.
James L
JL
Burns
Section on Development and Affective Neuroscience, NIMH Intramural Research Program, 15K North Drive, MSC-2670, Bethesda, MD 20892-2670, USA. Electronic address: pined@mail.nih.gov.
Daniel S
DS
Pine
Department of Medicine, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA. Electronic address: askol@uchicago.edu.
Andrew D
AD
Skol
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N Saint Clair, 19(th) Floor, Chicago, IL, 60611, USA; Department of Psychology, Northwestern University, Swift Hall 102, 2029 Sheridan Road, Evanston, IL60208, USA. Electronic address: daniel.mroczek@northwestern.edu.
Daniel K
DK
Mroczek
Department of Psychology, University of Arizona, 1503 E University Blvd., P.O.Box 210068, Tucson, AZ 85721, USA; Department of Psychiatry, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85721, USA; Office for Research & Economic Development, University of Nebraska-Lincoln, USA. Electronic address: kespy@email.arizona.edu.
Kimberly A
KA
Espy
Laboratory of Neurogenetics, NIAAA Intramural Research Program, National Institutes of Health, 5625 Fishers Lane, Room 3S-32:MSC 9412, Bethesda, MD 20892-9412, USA. Electronic address: davidgoldman@mail.nih.gov.
David
D
Goldman
Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA. Electronic address: ecook@psych.uic.edu.
Edwin
E
Cook
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL, 60611, USA; Institute for Policy Research, Northwestern University, 2040 Sheridan Road, Evanston, IL 60208, USA; Institute for Innovations in Developmental Sciences, Northwestern University, 633 N Saint Clair, 19th Floor, Chicago, IL, 60611, USA. Electronic address: lauriew@northwestern.edu.
Lauren S
LS
Wakschlag
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D000066553:Problem Behavior; D011446:Prospective Studies; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics*; D000073869:Tobacco Smoking / Q000009:adverse effects; D055815:Young Adult
D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
Disruptive behavior; Early adversity; Gene×environment interaction; Monoamine oxidase A; Pregnancy smoking; Sex differences