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Pregnancy, delivery and infancy complications and attention deficit hyperactivity disorder: Issues of gene-environment interaction

  • Sharon Milberger
    Affiliations
    Pediatric Psychopharmacology Unit, Massachusetts General Hospital Boston, Massachusetts, USA

    Harvard Institute of Psychiatric Epidemiology and Genetics Boston, Massachusetts, USA
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  • Joseph Biederman
    Correspondence
    Address reprint requests to Dr. Joseph Biederman, Pediatric Psychopharmacology, ACC-725, Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114.
    Affiliations
    Pediatric Psychopharmacology Unit, Massachusetts General Hospital Boston, Massachusetts, USA

    Harvard Institute of Psychiatric Epidemiology and Genetics Boston, Massachusetts, USA
    Search for articles by this author
  • Stephen V. Faraone
    Affiliations
    Pediatric Psychopharmacology Unit, Massachusetts General Hospital Boston, Massachusetts, USA

    Harvard Institute of Psychiatric Epidemiology and Genetics Boston, Massachusetts, USA

    Harvard Schools of Medicine and Public Health, Boston Massachusetts, USA
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  • Jessica Guite
    Affiliations
    Pediatric Psychopharmacology Unit, Massachusetts General Hospital Boston, Massachusetts, USA
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  • Ming T. Tsuang
    Affiliations
    Harvard Institute of Psychiatric Epidemiology and Genetics Boston, Massachusetts, USA

    Harvard Schools of Medicine and Public Health, Boston Massachusetts, USA
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      This paper is only available as a PDF. To read, Please Download here.
      We evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit hyperactivity disorder (ADHD) and addressed issues of comorbidity and familiarity by testing multiple hypotheses. Subjects were 6–17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120) and their first-degree biologic relatives. Information on PDICs was obtained from mothers in a standardized manner blind to the proband's clinical status. Using linear and logistic regression models, a positive association was found between ADHD and PDICs in the probands. Additionally, PDICs were associated with the correlates of ADHD (i.e., impaired cognitive functioning and poor school performance). Moreover, it was those specific complications that reflect chronic exposure, such as maternal bleeding, smoking, family problems, and illicit drug use during pregnancy that accounted for these findings. No interaction between genetic factors and PDICs were found. Our findings add to the literature supporting an association between ADHD and PDICs. Our results may help clinicians focus on particular complications rather than the wide range of possible perinatal complications.

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      References

        • Anderson JC
        • Williams S
        • McGee R
        • Silva PA
        DSM-III disorders in preadolescent children: Prevalence in a large sample from the general population.
        Arch Gen Psychiatry. 1987; 44: 69-76
        • Biederman J
        • Faraone SV
        • Keenan K
        • Benjamin J
        • Krifcher B
        • Moore C
        • Sprich S
        • Ugaglia K
        • Jellinek MS
        • Steingard R
        • Spencer T
        • Norman D
        • Kolodny R
        • Kraus I
        • Perrin J
        • Keller MB
        • Tsuang MT
        Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder (ADHD): Patterns of comorbidity in probands and relatives in psychiatrically and pediatrically referred samples.
        Arch Gen Psychiatry. 1992; 49: 728-738
        • Biederman J
        • Faraone SV
        • Keenan K
        • Knee D
        • Tsuang MT
        Family-genetic and psychosocial risk factors in DSM-III attention deficit disorder.
        J Am Acad Child and Adolesc Psychiatry. 1990; 29: 526-533
        • Biederman J
        • Faraone SV
        • Keenen K
        • Tsuang MT
        Evidence of familial association between attention deficit disorder and major affective disorders.
        Arch Gen Psychiatry. 1991; 48: 633-642
        • Biederman J
        • Munir K
        • Knee D
        • Habelow W
        • Armentano M
        • Autor S
        • Hoge SK
        • Waternaux C
        A family study of patients with attention deficit disorder and normal controls.
        J Psychiatr Res. 1986; 20: 263-274
        • Biederman J
        • Rosenbaum JF
        • Hirshfeld DR
        • Faraone SV
        • Bolduc EA
        • Gersten M
        • Meminger SR
        • Kagan J
        • Snidman N
        • Reznick JS
        Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders.
        Arch Gen Psychiatry. 1990; 47: 21-26
        • Bird HR
        • Canino G
        • Rubio-Stipec M
        • Gould MS
        • Ribera J
        • Sesman M
        • Woodbury M
        • Huertas-Goldman S
        • Pagan A
        • Sanchez-Lacay A
        • Moscoso M
        Estimates of the prevalence of childhood maladjustment in a community survey in Puerto Rico.
        Arch Gen Psychiatry. 1988; 45: 1120-1126
      1. Breslau N, DelDotto J, Brown G, Kumar S, Ezhuthachan S, Hufnagle K, Peterson E (in press): A gradient relationship between low birth weight and IQ at 6 years of age. Arch Pediatr Adolesc Med.

        • Buka S
        • Tsuang M
        • Lipsitt L
        Pregnancy/delivery complications and psychiatric diagnosis: A prospective study.
        Arch Gen Psychiatry. 1993; 50: 151-156
        • Buka SL
        • Goldstein JM
        • Tsuang MT
        Measurement of fetal events in schizophrenia research.
        American Psychological Association, Washington, DC1989
        • Buka SL
        • Lipsitt LP
        • Tsuang MT
        Birth complications and psychological deviancy: A 25-year prospective inquiry.
        Acta Paediatr Jpn. 1988; 30: 537-546
        • Cantwell DP
        Psychiatric illness in the families of hyperactive children.
        Arch Gen Psychiatry. 1972; 27: 414-417
        • Chandola C
        • Robling M
        • Peters T
        • Melville-Thomas G
        • McGuffin P
        Pre- and perinatal factors and the risk of subsequent referral for hyperactivity.
        Child Psychol Psychiatry. 1992; 33: 1077-1090
        • Colletti LF
        Relationship between pregnancy and birth complications and the later development of learning disabilities.
        J Learning Disabilities. 1979; 12: 659-663
        • Conners CK
        Controlled trial of methylphenidate in preschool children with minimal brain dysfunction.
        Int J Mental Health. 1975; 4: 61-74
        • Deutsch CK
        • Swanson JM
        • Bruell JH
        • Cantwell DP
        • Weinberg F
        • Baren M
        Overrepresentation of adoptees in children with the attention deficit disorder.
        Behav Genet. 1982; 12: 231-238
        • Duane DD
        The medical and neurological diagnostic process.
        Child Adolesc Psychiatr Clinics of North America. 1993; 2: 283-293
        • Faraone S
        • Biederman J
        Is attention deficit hyperactivity disorder familial?.
        Harvard Rev Psychiatry. 1994; 1: 271-287
        • Faraone S
        • Biederman J
        • Chen WJ
        • Krifcher B
        • Keenan K
        • Moore C
        • Sprich S
        • Tsuang M
        Segregation analysis of attention deficit hyperactivity disorder: Evidence for single gene transmission.
        Psychiatr Genet. 1992; 2: 257-275
        • Faraone S
        • Biederman J
        • Krifcher Lehman B
        • Keenan K
        • Norman D
        • Seidman L
        • Kolodny R
        • Kraus I
        • Perrin J
        • Chen W
        Evidence for the independent familial transmission of attention deficit hyperactivity disorder and learning disabilities: Results from a family genetic study.
        Am J Psychiatry. 1993; 150: 891-895
        • Faraone SV
        • Biederman J
        • Keenan K
        • Tsuang MT
        Separation of DSM-III attention deficit disorder and conduct disorder: Evidence from a family-genetic study of American child psychiatric patients.
        Psychol Med. 1991; 21: 109-121
        • Faraone SV
        • Biederman J
        • Krifcher Lehman B
        • Spencer T
        • Norman D
        • Seidman L
        • Kraus I
        • Perrin J
        • Chen W
        • Tsuang MT
        Intellectual performance and school failure in children with attention deficit hyperactivity disorder and in their siblings.
        J Abnorm Psychol. 1993; 102: 616-623
        • Gershon ES
        • Hamovit J
        • Guroff JJ
        • Dibble E
        • Leckman JF
        • Sceery W
        • Targum SD
        • Nurnberg Jr., JI
        • Goldin LR
        • Bunney Jr., WE
        A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control probands.
        Arch Gen Psychiatry. 1982; 39: 1157-1167
        • Gilmore JV
        • Gilmore EC
        Gilmore Oral Reading Test.
        in: Harcourt, Brace & World, Inc., San Francisco, CA1968: 1-29
        • Goodman R
        • Stevenson J
        A twin study of hyperactivity I: An examination of hyperactivity scores and categories derived from Rutter teacher and parent questionnaires.
        J Child Psychol Psychiatry. 1989; 30: 671-689
        • Hartsough CS
        • Lambert NM
        Medical factors in hyperactive and normal children: Prenatal, developmental, and health history findings.
        Am J Orthopsychiatry. 1985; 55: 191-201
        • Herjanic B
        • Campbell W
        Differentiating psychiatrically disturbed children on the basis of a structured interview.
        J Abnorm Child Psychol. 1977; 5: 127-134
        • Herjanic B
        • Reich W
        Development of a structured psychiatric interview for children: Agreement between child and parent on individual symptoms.
        J Abnorm Child Psychol. 1982; 10: 307-324
        • Hollingshead AB
        Four factor index of social status.
        Yale University Press, New York1975
        • Hosmer DW
        • Lemeshow S
        Applied Logistic Regression.
        in: John Wiley & Sons, Inc., New Haven1989: 307
        • Jastak JF
        • Jastak S
        The Wide Range Achievement Test-Revised.
        Jastak Associates, New York1985
        • Kleinbaum D
        • Kupper L
        • Muller K
        Applied Regression Analysis and Other Multivariable Methods.
        PWS-Kent Publishing Company, Wilmington, Delaware1988
        • Kline J
        • Stein Z
        • Susser M
        Conception to birth: Epidemiology of prenatal development, 14.
        Oxford University Press, Boston1989
        • Leckman JF
        • Dolnansky ES
        • Hardin MT
        • Clubb M
        • Walkup JT
        • Stevenson J
        • Pauls DL
        Perinatal factors in the expression of tourette's syndrome; An exploratory study.
        J Am Acad Child Adolesc Psychiatry. 1990; 29: 220-226
        • Lewis DO
        • Shanok SS
        A comparison of the medical histories of incarcerated delinquent children and a matched sample of non-delinquent children.
        Child Psychiatry Hum Dev. 1979; 9: 210-214
        • Lilienfeld AM
        • Pasamanick B
        • Rogers M
        Relationship between pregnancy experience and the development of certain neuropsychiatric disorders in childhood.
        Am J Public Health. 1955; 45: 637-643
        • McGee R
        • Williams S
        • Silva PA
        Background characteristics of aggressive, hyperactive and aggressive-hyperactive boys.
        J Am Acad Child Adolesc Psychiatry. 1984; 23: 280-284
        • McNeil TF
        • Kaij L
        Obstetric factors in the development of schizophrenia: Complications in the births of preschizophrenics and in reproduction by schizophrenic parents.
        in: Wynne LC The nature of schizophrenia. Wiley, New York1978: 401-429
        • Minde K
        • Webb G
        • Sykes D
        Studies on the hyperactive child. VI. Prenatal and paranatal factors associated with hyperactivity.
        Dev Med Child Neurol. 1968; 10: 355-363
        • Morrison J
        Adult psychiatric disorders in parents of hyperactive children.
        Am J Psychiatry. 1980; 137: 825-827
        • Morrison JR
        • Stewart MA
        A family study of the hyperactive child syndrome.
        Biol Psychiatry. 1971; 3: 189-195
        • Orvaschel H
        • Puig-Antich J
        Kiddie-SADS, patient version.
        1987
        • Pasamanick B
        • Rogers ME
        • Lilienfeld AM
        Pregnancy experience and the development of behavior disorder in children.
        Am J Psychiatry. 1956; 112: 613-618
        • Sattler JM
        Assessment of children's intelligence.
        in: Jerome M. Sattler, New York1988: 995
        • Schmidt MH
        • Esser G
        • Allehoff W
        • Geisel B
        • Laucht M
        • Woerner W
        Evaluating the significance of minimal brain dysfunction - Results of an epidemiologic study.
        J Child Psychol Psychiatry. 1987; 28: 803-821
        • Semrud-Clikeman MS
        • Biederman J
        • Sprich S
        • Krifcher B
        • Norman D
        • Faraone S
        Comorbidity between ADHD and learning disability: A review and report in a clinically referred sample.
        J Am Acad Child Adolesc Psychiatry. 1992; 31: 439-448
        • Spitzer RL
        • W J.B.W.
        • Gibbon M
        • First MB
        The Structured clinical interview for DSM-III-R (SCID) I. History, rationale, and description.
        Arch Gen Psychiatry. 1992; 49: 624
        • Sprich-Buckminster S
        • Biederman J
        • Milberger S
        • Faraone S
        • Krifcher Lehman B
        Are perinatal complications relevant to the manifestation of ADD?.
        J Am Acad Child Adolesc Psychiatry. 1993; 32: 1032-1037
        • Stewart MA
        • deBlois CS
        • Cummings C
        Psychiatric disorder in the parents of hyperactive boys and those with conduct disorder.
        J Child Psychol Psychiatry. 1980; 21: 283-292
        • Wechsler D
        Manual for the Wechsler Intelligence Scale for Children-Revised. Psychological Corporation, San Diego1974
        • Weissman MM
        • Gershon ES
        • Kidd KK
        • Prusoff BA
        • Leckman JF
        • Dibble E
        • Hamovit J
        • Thompson WD
        • Pauls DL
        • Guroff JJ
        Psychiatric disorders in the relatives of probands with affective disorders.
        Arch Gen Psychiatry. 1984; 41: 13-21
        • Welner Z
        • Welner A
        • Stewart M
        • Palkes H
        • Wish E
        A controlled study of siblings of hyperactive children.
        J Nerv Ment Disorders. 1977; 165: 110-117
        • Wenar C
        The reliability of developmental histories: Summary and evaluation of evidence.
        Psychosom Med. 1963; 25: 505-509
        • Werner EE
        • Bierman JM
        • French FE
        The children of Kauai: A longitudinal study from the prenatal period to age ten.
        University of Hawaii Press, New York1971