Abstract
Twin, family and adoption studies have led to a solid understanding of the contribution of both genetic and environmental factors to the development of attention deficit/hyperactivity disorder (ADHD). We review recent studies under consideration of both methodological aspects and relevant findings. Heritability estimates in the range of 0.6 - 0.8 surpass those for most other child and adolescent psychiatric disorders. First degree relatives have elevated rates for ADHD, affective disorders, conduct disorders and substance abuse and dependency. The ADHD subtype of the index patient does not predict the subtype of other family members affected with ADHD; hence non-genetic factors seemingly account for this intrafamilial variability. Because the familial rates for ADHD are not higher in families of female in comparison to male index patients, there is no indication that the genetic loading is higher in affected females. Recently, rater effects have been discussed broadly: Whereas the heritability estimates are uniformly high independent of the informant (mother, father, teacher), the correlations between quantitatively rated symptoms are low between different informants. Knowledge of the formal genetic aspects of ADHD is a prerequisite for understanding the results of recent molecular genetic studies.
Zusammenfassung
Zwillings-, Familien- und Adoptionsstudien haben zu einem fundierten Verständnis des Anteils genetischer und Umweltfaktoren an der Entstehung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) beigetragen. In diesem Übersichtsartikel sind die wichtigsten rezenten Studien zusammengefasst, wobei methodische Aspekte ebenso ausführlich wie die Ergebnisse formalgenetischer Studien dargestellt werden. Die Erblichkeitsschätzungen für ADHS übersteigen mit 0,6 bis 0,8 die der meisten anderen kinder- und jugendpsychiatrischen Störungen. Verwandte ersten Grades weisen neben ADHS gehäuft affektive Störungen, Störungen des Sozialverhaltens und Substanzmissbrauch und -abhängigkeit auf. Der ADHS-Subtyp des Indexpatienten prädiziert nicht den Subtyp von Verwandten mit ADHS; offenbar sind nicht-genetische Faktoren für die Subtypausbildung verantwortlich. Da in Familien von Mädchen mit ADHS nicht mehr Angehörige betroffen sind als in solchen von männlichen Indexpatienten, spricht dies gegen die Annahme einer höheren genetischen Belastung bei betroffenen weiblichen Individuen. In den letzten Jahren hat der so genannte Rater-Effekt viel Beachtung gefunden. Hiernach sind die hohen Heritabilitätsschätzungen relativ unabhängig davon, ob die Symptome über Mutter, Vater oder Lehrer(in) erhoben werden. Jedoch sind die Korrelationen zwischen quantitativen Angaben dieser Beobachter niedrig. Die Kenntnis der formalgenetischen Aspekte der ADHS stellt eine wichtige Voraussetzung für die Durchführung bzw. Interpretation molekulargenetischer Studien dar.
Literatur
1 Remschmidt H, Schmidt M. Multiaxiales Klassifikationsschema für psychische Störungen des Kindes- und Jugendalters nach ICD-10 der WHO. Bern: Hans Huber 1996
2 American Psychiatric Association .DSM-IV Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Washington, DC: APA 1994
3
Lalonde J, Turgay A, Hudson J I.
Attention-deficit hyperactivity disorder subtypes and comorbid disruptive behaviour disorders in a child and adolescent mental health clinic.
Can J Psychiatry.
1998;
43
623-628
4
Eaves L, Rutter M, Silberg J L, Shillady L, Maes H, Pickles A.
Genetic and environmental causes of covariation in interview assessments of disruptive behavior in child and adolescent twins.
Behav Genet.
2000;
30
321-334
5
Hauser P, Zametkin A J, Martinez P, Vitiello B, Matochik J A, Mixson A J, Weintraub B D.
Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone.
N Engl J Med.
1993;
328
997-1001
6
Levy F, Hay D, McLaughlin M, Wood C, Waldman I.
Twin sibling differences in parental reports of ADHD, speech, reading and behaviour problems.
J Child Psychol Psychiatry.
1996;
37
569-578
7
Mick E, Biederman J, Prince J, Fischer M J, Faraone S V.
Impact of low birth weight on attention-deficit hyperactivity disorder.
J Dev Behav Pediatr.
2002;
23
16-22
8
Goodman R, Stevenson J.
A twin study of hyperactivity-II: The aetiological role of genes, family relationships and perinatal activity.
J Child Psychol Psychiatry.
1989;
30
691-709
9
Lopez R E.
Hyperactivity in twins.
Canadian Psychiatric Association Journal.
1965;
10
421-426
10
Gillis J J, Gilger J W, Pennington B F, Fries J C De.
Attention deficit disorders in reading disabled twins: evidence for a genetic aetiology.
Abnorm Child Psychol.
1992;
20
303-315
11
Willerman L.
Activity level and hyperactivity in twins.
Child Dev.
1973;
44
288-293
12
Nadder T S, Silberg J L, Eaves L J, Maes H H, Meyer J M.
Genetic effects on ADHD symptomatology in 7- to 13-year-old twins: results from a telephone survey.
Behav Genet..
1998;
28
83-99
13
Thapar A, Harrington R, McGuffin P.
Examining the comorbidity of ADHD-related problems using a twin study design.
Br J Psychiatry.
2001;
179
224-229
14
Eaves L J, Silberg J L, Meyer J M, Maes H H, Simonoff E, Pickles A, Rutter M, Neale M C, Reynolds C A, Erikson M T, Heath A C, Loeber R, Truett K R, Hewitt J.
Genetic and developmental psychopathology: 2. The main effects of genes and environment on behavioural problems in the Virginia twin study of adolescent development.
J Child Psychol and Psychiatry.
1997;
38
965-980
15
Gilger J W, Pennington B F, Fries J C De.
A twin study of the etiology of comorbidity: attention-deficit hyperactivity disorder and dyslexia.
J Am Acad Child Adolesc Psychiatry.
1992;
31
343-348
16
Martin N, Scourfield J, McGuffin P.
Observer effects and heritability of childhood attention-deficit hyperactivity disorder symptoms.
Br J Psychiatry.
2002;
180
260-265
17
Sherman D K, McGue M K, Iacono W G.
Twin concordance for attention deficit hyperactivity disorder: a comparison of teachers' and mothers' reports.
Am J Psychiatry.
1997;
154
532-535
18
Coolidge F L, Thede L L, Young S E.
Heritability and the comorbidity of attention deficit hyperactivity disorder with behavioral disorders and executive function deficits: a preliminary investigation.
Dev Neuropsychol.
2000;
17
273-287
19
Levy F, Hay D A, McStephen M, Wood C, Waldman I.
Attention-deficit hyperactivity disorder: a category or a continuum? Genetic analysis of a large-scale twin study.
J Am Acad Child Adolesc Psychiatry.
1997;
36
737-744
20
Sherman D K, Iacono W G, McGue M.
Attention-deficit hyperactivity disorder dimensions: A twin study of inattention and impulsivity- hyperactivity.
J Am Acad Child Adolesc Psychiatry.
1997;
36
745-753
21 Plomin R, Fries J De, McClearn G E. Behavioral Genetics. San Francisco: Freeman 1980
22
Arnold L E.
Sex differences in ADHD: conference summary.
J Abnorm Child Psychol.
1996;
24
555-569
23
Gaub M, Carlson C L.
Gender differences in ADHD: a meta-analysis and critical review.
J Am Acad Child Adolesc Psychiatry.
1997;
36
1036-1045
24
Safer D J, Krager J M.
A survey of medication treatment for hyperactive/inattentive students.
JAMA.
1988;
260
2256-2258
25
Wilens T E, Biederman J.
The stimulants.
Psychiatr Clin North Am.
1992;
15
191-222
26
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
27
Neuman R J, Todd R D, Heath A C, Reich W, Hudziak J J, Bucholz K K, Madden P A, Begleiter H, Porjesz B, Kuperman S, Hesselbrock V, Reich T.
Evaluation of ADHD typology in three contrasting samples: a latent class approach.
J Am Acad Child Adolesc Psychiatry.
1999;
38 (1)
25-33
28
Hewitt J K, Silberg J L, Rutter M, Simonoff E, Meyer J M, Maes H, Pickles A, Neale M C, Loeber R, Erickson M T, Kendler K S, Heath A C, Truett K R, Reynolds C A, Eaves L J.
Genetics and developmental psychopathology: 1. Phenotypic assessment in the Virginia Twin Study of Adolescent Behavioral Development.
J Child Psychol Psychiatry.
1997;
38
943-963
29
Todd R D, Rasmussen E R, Neuman R J, Reich W, Hudziak J J, Bucholz K K, Madden P A, Heath A.
Familiality and heritability of subtypes of attention deficit hyperactivity disorder in a population sample of adolescent female twins.
Am J Psychiatry.
2001;
158
1891-1898
30
Todd R D, Sitdhiraksa N, Reich W, J T, Joyner C, Heath A, Neuman R.
Discrimination of DSM-IV Latent class Attention-Deficit/Hyperactivity Disorder subtypes by educational and cognitive performance in a population-based sample of child and adolescent twins.
J Am Acad Child Adolesc Psychiatry.
2002;
41
820-828
31
Thapar A, Holmes J, Poiulton K, Harrington R.
Genetic basis of attention deficit and hyperactivity.
Br J Psychiatry.
1999;
174
105-111
32
Biederman J, Faraone S V, Keenan K, Benjamin J, Krifcher B, Moore C, Sprich-Buckminster S, Ugaglia K, Jellinek M S, Steingard R. et al .
Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples.
Arch Gen Psychiatry.
1992;
49
728-738
33
Faraone S V, Biederman J, Mennin D, Wozniak J, Spencer T.
Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype?.
J Am Acad Child Adolesc Psychiatry.
1997;
36
1378-1387; discussion 1387 - 1390
34
Faraone S V, Biederman J, Friedman D.
Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: a family study perspective.
J Am Acad Child Adolesc Psychiatry.
2000;
39
300-307
35
Epstein J N, Conners C K, Erhardt D, Arnold L E, Hechtman L, Hinshaw S P, Hoza B, Newcorn J H, Swanson J M, Vitiello B.
Familial aggregation of ADHD characteristics.
J Abnorm Child Psychol.
2000;
28
585-594
36 McGuffin P, Owen M J, O'Donovan M C, Thapar A, Gottesman L L. Seminars in Psychiatric Genetics 1994. London: Gaskell
37
Bradley J DD, Golden C J.
Biological contributions to the presentation and understanding of attention-deficit/hyperactivity disorder: a review.
Clin Psychol Rev.
2001;
21
907-929
38
Smalley S, McGough J J, Del'Homme M, NewDelman J, Gordon E, Kim T, Liu A, McCracken J.
Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry.
2000;
39
1135-1143
39
Sprich S, Biederman J, Crawford M H, Mundy E, Faraone S V.
Adoptive and biological families of children and adolescents with ADHD.
J Am Acad Child Adolesc Psychiatry.
2000;
39
1432-1437
40
Faraone S V, Doyle A E.
The nature and heritability of attention-deficit/hyperactivity disorder.
Child Adolesc Psychiatr Clin N Am.
2001;
10
299-316
41
Biederman J, Faraone S V, Monuteaux M C.
Impact of exposure to parental attention-deficit hyperactivity disorder on clinical features and dysfunction in the offspring.
Psychol Med.
2002;
32
817-827
42
Zametkin A J, Nordahl T E, Gross M, King A C, Semple W E, Rumsey J, Hamburger S, Cohen R M.
Cerebral glucose metabolism in adults with hyperactivity of childhood onset.
N Engl J Med.
1990;
323
1361-1366
43
Smalley S L, McCracken J, McGough J.
Refining the ADHD phenotype using affected sibling pair families.
Am J Med Genet.
2001;
105
31-33
44
Hudziak J J, Heath A C, Madden P F, Reich W, Bucholz K K, Slutske W, Bierut L J, Neuman R J, Todd R D.
Latent class and factor analysis of DSM-IV ADHD: a twin study of female adolescents.
J Am Acad Child Adolesc Psychiatry.
1998;
37
848-857
45
Faraone S V, Biederman J, Mick E, Williamson S, Wilens T, Spencer T, Weber W, Jetton J, Kraus I, Pert J, Zallen B.
Family study of girls with attention deficit hyperactivity disorder.
Am J Psychiatry.
2000;
157
1077-1083
46
Schachar R, Wachsmuth R.
Hyperactivity and parental psychopathology.
J Child Psychol Psychiatry.
1990;
31
381-392
47
Faraone S V, Biederman J, Chen W J, Milberger S, Warburton R, Tsuang M T.
Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD.
J Abnorm Psychol.
1995;
104
334-345
48
Faraone S V, Biederman J, Mennin D, Russell R, Tsuang M T.
Familial Subtypes of Attention Deficit Hyperactivity Disorder: A 4-year Follow-up Study of Children from Antisocial-ADHD Families. J.
Child Psychol Psychiat.
1998;
39
1045-1053
49
Frick P J, Kamphaus R W, Lahey B B, Loeber R, Christ M A, Hart E L, Tannenbaum L E.
Academic underachievement and the disruptive behavior disorders.
J Consult Clin Psychol.
1991;
59
289-294
50
Deutsch C K, Swanson J M, Bruell J H, Cantwell D P, Weinberg F, Baren M.
Overrepresentation of adoptees in children with the attention deficit disorder.
Behav Genet.
1982;
12
231-238
51
Alberts-Corush J, Firestone P, Goodman J T.
Attention and impulsivity characteristics of the biological and adoptive parents of hyperactive and normal control children.
Am J Orthopsychiatry.
1986;
56
413-423
52
Cadoret R J, Stewart M A.
An adoption study of attention deficit/ hyperactivity/ aggression and their relationship to adult antisocial personality.
Compr Psychiatry.
1991;
32
73-82
53
Doyle A E, Faraone S V.
Familial links between Attention Deficit Hyperactivity Disorder, Conduct Disorder and Bipolar Disorder.
Curr Psychiatry Rep.
2002;
4
146-152
54
Quist J F, Barr C L, Schachar R, Roberts W, Malone M, Tannock R, Basile V, Beitchman J, Kennedy J L.
Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD).
Mol Psychiatry.
2000;
5
537-541
55 Hässler F, Irmisch G. Biochemische Störungen bei Kindern mit hyperkinetischen Störungen. In: Steinhausen HC. Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen. Stuttgart; 2000: 87-101
56
Biederman J, Spencer T J.
Genetics of childhood disorders: XIX. ADHD, Part 3: Is ADHD a noradrenergic disorder?.
J Am Acad Child Adolesc Psychiatry.
2000;
39
1330-1333
57
Fisher S E, Francks C, McCracken J T, McGough J J, Marlow A J, MacPhie I L, Newbury D F, Crawford L R, Palmer C G, Woodward J A, Del'Homme M, Cantwell D P, Nelson S F, Monaco A P, Smalley S L.
A genomewide scan for loci involved in attention-deficit/hyperactivity disorder.
Am J Hum Genet.
2002;
70
1183-1196
Dr. P. Heiser
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters · Philipps-Universität Marburg
Schützenstraße 49
35039 Marburg
eMail: heiser@mailer.uni-marburg.de