Objective: The aim of this paper is to review and integrate recent literature on aetiological factors that have been postulated for attention deficit hyperactivity disorder (ADHD).
Method: Recent studies relating to perinatal brain damage, intra-uterine toxic effects, neurochemical, brain imaging and genetic studies are reviewed, and those considered most significant are discussed. Where possible, recent findings are integrated and directions of future research are suggested. Clinical implications are briefly discussed.
Results: Perinatal studies indicate that children with a birth weight under 750 g may be disadvantaged for attentional skills. Magnetic resonance imaging (MRI) and steady state visually evoked potential studies show differences in prefrontal, caudate and parietal areas in ADHD children, suggesting right hemispheric dysfunction. Functional MRI studies hold promise in further elucidating attentional systems in the central nervous system that are involved in ADHD. Genetic studies suggest genes related to dopaminergic systems may be important.
Conclusions: Recent research on ADHD has made considerable advances, particularly in the areas of brain imaging and genetic studies. Genetic studies should provide further aetiological understandings of ADHD, leading to more targeted treatments.
RutterM.Syndromes attributed to ‘minimal brain dysfunction in childhood’. American Journal of Psychiatry1982; 139:21–33.
2.
RutterM.Behavioural studies: questions and findings on the concept of a distinctive syndrome. In: RutterM, ed. Developmental neuropsychiatry. New York: Guilford, 1983:259–279.
3.
FusterJMThe prefrontal cortex, anatomy, physiology and neuropsychology of the frontal lobe. New York: Raven Press, 1989.
4.
GillbergC.Clinical child neuropsychology. Cambridge: Cambridge University Press, 1995:23.
5.
LevyFHayDMcLaughlinMWoodCWaldmanI.Twinsibling differences in parental reports of ADHD, speech, reading and behaviour problems. Journal Child Psychology and Psychiatry1996; 37:569–578.
6.
RooneyRHayDALevyF.Small for gestational age as a predictor of behavioural and learning problems in twins. Journal of Abnormal Psychology (in press).
7.
HackMTaylorHGEibenRSchatschneiderCMeruni-MinichN.School-aged outcomes in children with birth weights under 750 g. New England Journal of Medicine1994; 31:802–803.
8.
MilbergerSBiedermanJFaraoneSChenLJonesJ.Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children?American Journal of Psychiatry1996; 153:1138–1142.
9.
ClarrenSKSmithDWThe fetal alcohol syndrome. New England Journal of Medicine1978; 298:1063–1067.
10.
StreissguthAPBarrHMSampsonPDModerate prenatal alcohol exposure: effects on child IQ and learning problems at age 7 years. Alcoholism, Clinical and Experimental Research1990; 14:662.
11.
NorénJHulthePGillbertC.Analysis of lead and cadmium in deciduous teeth by means of potentiometric stripping analysis. Swedish Dental Journal1987; 11:45–52.
12.
WakschlagLSLaheyBBLoeberRGreenSMGordonRALeventhalBLMaternal smoking during pregnancy and the risk of conduct disorder in boys. Archives of General Psychiatry1997; 54:670–676.
13.
FergussonDMHorwoodLJLynskeyMYEarly dentine lead levels and subsequent cognitive and behavioural development. Journal of Child Psychology and Psychiatry1993; 34:215–227.
14.
NeedlemanHLSchellABellingerDCLevitonLAllrichEDThe long-term effects of exposure to low doses of lead in childhood: an 11 year follow up report. New England Journal of Medicine1990; 322:83–88.
15.
RoweKJRoweKSSynthetic food colouring and behaviours: a dose response effect in a double blind, placebo controlled repeated measures study. Journal of Paediatrics1994; 125:691–698.
16.
ZametkinAJRapoportJLNeurobiology of attention deficit disorder with hyperactivity. Where have we come in 50 years?Journal of the American Academy of Child and Adolescent Psychiatry1987; 26:676–686.
17.
CastellanosFXEliaJKruesiMJCSF monoamine metabolites in boys with ADHD. Psychiatry Research1994; 52:305–316.
18.
McCrackenJTA two-part model of stimulant action on attention deficit hyperactivity disorder. Journal of Neuropsychiatry1991; 3:201–209.
19.
RogenessGAJavorsMAPliszkaSRNeurochemistry and child and adolescent psychiatry. Journal of the American Academy of Child and Adolescent Psychiatry1992; 31:765–781.
20.
GrayJAThe neuropsychology of anxiety. New York: Guilford Press, 1982.
21.
DaughertyTKQuayHCRamosL.Response perseveration induced by methylphenidate in children: preliminary findings. Progress in Neuropsychopharmacology and Biological Psychiatry1993; 6:259–273.
22.
PliszkaSRHatchJPBorchedingSHRogenessAGClassical conditioning in children with attention deficit hyperactivity disorder (ADHD) and anxiety disorders: a test of Quay's model. Journal of Abnormal Child Psychology1993; 21:411–423.
23.
LevyF.The dopamine theory of attention deficit hyperactivity disorder (ADHD). Australian and New Zealand Journal of Psychiatry1991; 25:277–283.
24.
CastellanosFXTowards a pathophysiology of attention deficit/hyperactivity disorder. Clinical Pediatrics1997; 36:381–393.
25.
LouHCHenriksonLBruhnPBernerHNielsenJBStriatal dysfunction in attention deficit and hyperkinetic disorder. Archives of Neurology1989; 46:48–52.
26.
ZametkinAJNordahlTEGrossMCerebral glucose metabolism in adults with hyperactivity of child-based onset. New England Journal of Medicine1990; 323:1361–1366.
27.
SilbersteinRBFarrowMLevyFPipingasABHayDJarmanR.Functional brain electrical activity mapping in normal children and those with attention deficit hyperactivity disorder. Archives of General Psychiatry1997 (in press).
28.
HyndGWHernKLNoveyESAttention deficit hyperactivity disorder and asymmetry of the caudate nucleus. Journal of Child Neurology1993; 89:339–347.
29.
HyndGWSemrud-ClikemanMLorysARNoveyESEliopulosDLyytinenH.Corpus callosum morphology in attention-deficit-hyperactivity disorder: morphometric analysis of MRI. Journal of Learning Disabilities1991; 24:141–146.
30.
CastellanosFXGieddNJEckburgPQuantitative morphology of the caudate nucleus in attention-deficit hyperactivity disorder. American Journal of Psychiatry1994; 151:1791–1796.
31.
CastellanosFXGieddNJMarshWLQuantitative brain magnetic resonance imaging in ADHD. Archives of General Psychiatry1996; 53:607–616.
32.
CaseyBJCastellanosFXGieddJNImplication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry1997; 36:374–383.
33.
PardoJVFoxPTRaicheMELocalisation of a human system for sustained attention by positron emission tomography. Nature1991; 349:61–64.
34.
HeilmanKMKytjaKSVoellerMDMadlauSEA possible pathophysiologic subtrate of attention deficit hyperactivity disorder. Journal of Child Neurology1991; 6(Suppl.):374–379.
35.
BiedermanJFaraoneSVKeenanK.Further evidence for family–genetic risk factors in attention deficit hyperactivity disorder. Archives of General Psychiatry1992; 49:728–738.
36.
MorrisonJRStewartMAThe psychiatric status of the legal families of adopted hyperactive children. Archives of General Psychiatry1971; 28:189–195.
37.
LopezREHyperactivity in twins. Canadian Psychiatric Association Journal1965; 10:421–426.
38.
WillermanL.Activity level and hyperactivity in twins. Child Development1973; 44:286–293.
39.
GoodmanRStevensonJ.A twin study of hyperactivity II. The aetiological role of genes, family relationships and perinatal adversity. Journal of Child Psychology and Psychiatry1989; 30:691–709.
40.
GillisJJGilgerJWPenningtonBFDefriesJCAttention deficit disorder in reading disabled twins: evidence for a genetic aetiology. Journal of Abnormal Child Psychology1992; 20:303–315.
41.
GilgerJWPenningtonBFde FriesJCA twin study of the aetiology of comorbidity: attention deficit hyperactivity disorder and dyslexia. Journal of the American Academy of Child and Adolescent Psychiatry1991; 31:343–348.
42.
StevensonJ.Evidence for a genetic aetiology in hyperactivity in children. Behaviour Genetics1992; 22:337–344.
43.
EdelbrockCRendleRPlominRThompsonLAA twin study of competence and problem behaviour in childhood and early adolescence. Journal of Child Psychology and Psychiatry.1995; 36:775–785.
44.
LevyFHayDMcLaughlinMWoodCWaldmanI.Twinsibling differences in parental reports of ADHD, speech, reading and behaviour problems. Journal of Child Psychology and Psychiatry1996; 37:569–578.
45.
LevyFHayDAMcStephenMWoodCWaldmanI.ADHD: a category or a continuum? Genetic analysis of a large-scale twin study. Journal of the American Academy of Child and Adolescent Psychiatry1997; 36:737–744.
46.
BenjaminJLiLPattersonCGreenbergBDMurphyDLHamerDHPopulation and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics1996; 1281–1284.
47.
EbsteinEBNovickOUmanskyRDopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nature Genetics1996; 12:78–80.
48.
MalhotraAKVirkkunenMRooneyWEggertMGoldmanD.The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Molecular Psychiatry1996; 1:388–391.
49.
la HosteGJSwansonJMWigalSBDopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Molecular Psychiatry1996; 1:121–124.
50.
HausserPZametkinAJMartinexPAttention deficit hyperactivity disorder in people with generalised resistance to thyroid hormone. New England Journal of Medicine1993; 328:997–1001.
51.
ComingsDEComingsBGMuhlemanDThe dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. Journal of the American Medical Association1991; 266:1793–1800.
52.
CookEGSteinMAKrasowskiDAssociation of attention deficit disorder and the dopamine transporter gene. American Journal of Human Genetics1995; 56:993–998.
53.
PlominR.The Emanuel Miller memorial lecture 1993: genetic research and identification of environmental influences. Journal of Child Psychology and Psychiatry1994; 35:817–834.
54.
WilkinsonLSThe nature of interactions involving prefrontal and striatal dopamine systems. Journal of Psychopharmacology1997; 11:107–114.
55.
MastermanDLCummingsTLFrontal–subcortical circuits: the anatomic basis of executive, social and motivated behaviours. Journal of Psychopharmcology1997; 11:107–114.
