Genetic epidemiologic studies of affective disorders in childhood and adolescence

  • Kathleen Ries Merikangas


The application of the methods of genetic epidemiology appears to be one of the most promising avenues to unravel the complex mechanisms through which genes may exert their influence. The approaches of genetic epidemiology are particularly important for those diseases which are characterized by moderate degrees of heritability and lack of direct correspondence between the underlying vulnerability factors and the ultimate expression of the disease, as is the case for affective disorders. The application of the methods of genetic epidemiology to children of affected parents may also elucidate environmental risk factors and early signs of the disorder. Perhaps the most important implication of the identification of genetic markers for affective disorders is the opportunity for prevention of the disorders. Early identification of youngsters who do manifest early signs of the disorders would facilitate secondary and tertiary prevention of the consequences of those conditions.


Public Health Epidemiologic Study Important Implication Genetic Marker Environmental Risk 
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  1. Angold A (1988) Childhood and adolescent depression: I. Epidemiological and aetiological aspects. Br J Psychiatry 152:601–617Google Scholar
  2. Angst J, Merikangas KR Scheidegger P, Wicki W (1990) Recurrent brief depression: a new subtype of affective disorder. J Affect Disord 19:37–38Google Scholar
  3. Baron M, Freimer NF, Risch N, Lerer B, Alexander JR, Straub RE, Asokan S, Das K, Peterson A, Amos J, Endicott J, Ott J, Gilliam C (1993) Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. Nature Genetics 3:49–55Google Scholar
  4. Beardslee WR, Bemporad J, Keller MB, Klerman GL (1983) Children of parents with major affective disorder: A review. Am J Psychiatry 140:825–832Google Scholar
  5. Beaudet A, Bowcock A, Buchwald M, et al. (1986) Linkage of cystic fibrosis to two tightly linked DNA markers: Joint report from a collaborative study. Am J Hum Genet 39:681–693Google Scholar
  6. Bernstein GA (1991) Comorbidity and severity of anxiety and depressive disorders in a clinic sample. J Am Acad Child Adolesc Psychiatry 30:43–50Google Scholar
  7. Bernstein GA, Garfinkel BD (1986) School phobia: The overlap of affective and anxiety disorders. J Am Acad Child Psychiatry 25:235–241Google Scholar
  8. Bertelsen A, Harvald B, Hauge M (1977) A Danish Twin Study of Manic-depressive disorders. Br J Psychiatry 130:330Google Scholar
  9. Boyd JH, Burke JD, Gruenberg E, et al. (1984). Exclusion criteria of DSM-III: A study of co-occurrence of hierarchy-free syndromes. Arch Gen Psychiatry 41:983–989Google Scholar
  10. Brunshaw JM, Szatmari P (1988) The agreement between behaviour checklists and structured psychiatric interviews for children. Can J Psychiatry, 33:474–480Google Scholar
  11. Cadoret RJ, O'Gorman TW, Heywood E, Troughton E (1985) Genetic and environmental factors in major depression. J Affect Disord 9:155–164Google Scholar
  12. Clifford CA, Hopper JL, Fulker DW (1984) A genetic and environmental analysis of a twin family study of alcohol use, anxiety, and depression. Genet Epidemiol 1:63–79Google Scholar
  13. Cohen P, Brook JS, Cohen J, Velez N, Garcia M (1990) Common and uncommon pathways to adolescent psychopathology and problem behavior. In: Straight and Devious Pathways from Childhood to Adulthood. Robins L, Rutter M (eds). Cambridge University Press, London, pp 242–258Google Scholar
  14. Conners CK, Himmelhoch H, Goyette CH, Ulrich RF, Neil JF (1979) Children of parents with affective illness. J Am Acad Child Adolesc Psychiatry 18:600–607Google Scholar
  15. Cytryn L, McKnew DH Jr, Bartko JJ, Lamour M, Hamovitt JH (1982) Offspring of patients with affective disorders: II. J Am Acad Child Adolesc Psychiatry 21:389–391Google Scholar
  16. Decina P, Kestenbaum CJ, Farber S, Kron L, Gargan M, Sackeim HA, Fieve RR (1983) Clinical and psychological assessment of children of bipolar probands. Am J Psychiatry, 140:548–553Google Scholar
  17. Downey G, Coyne JC (1990) Children of depressed parents: An integrative review. Psychol Bull 108:50–76Google Scholar
  18. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE (1987) Bipolar affective disorders linked to the DNA markers on chromosome II. Nature 325:783–787Google Scholar
  19. Endicott J, Spitzer RL (1978) A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia — lifetime version (modified for the study of anxiety disorders). Arch Gen Psychiatry 35:837–844Google Scholar
  20. Falconer DS (1965) The inheritance of liability to certain diseases, estimated from the incidence among relatives. Ann Hum Genet 29:51–76Google Scholar
  21. Feinstein AR (1970) The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis 23:455–468Google Scholar
  22. Friend SH, Bernard R, Rogelj S, et al. (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:643–646Google Scholar
  23. Gershon ES, et al. (1985) Diagnoses in school-age children of bipolar affective disorder patients and normal controls. J Affect Disord 8(3):283–291Google Scholar
  24. Goodwin DW, Schulsinger F, Knop J (1977) Psychopathology in adopted and non-adopted daughters of alcoholics. Arch Gen Psychiatry 34:1005–1009Google Scholar
  25. Grigoroiu-Serbanescu M, Christodorescu D, Jipescu I, Totoescu A, Marinescu E, Ardelean V (1989) Psychopathology in children aged 10–17 of bipolar parents: Rates and correlates of the severity of the psychopathology. J Affect Disord 16:167–179Google Scholar
  26. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Sitoulson I, Bonilla E, Martin JB (1982) A polymorphic DNA marker genetically linked to Huntington's Disease. Nature 306:234–238Google Scholar
  27. Hall JF, Ming KL, Newman B, Marrow JE, Anderson LA, Huey B, King MC (1990) Linkage of early onset familial breast cancer to chromosome 17q21. Science 250:1684–1689Google Scholar
  28. Hammen C, Gordon D, Burge D, Adrian C, Jaenicke C, Hiroto D (1987) Maternal affective disorders, illness and stress: Risk for children's psychopathology. Am J Psychiatry 144:6Google Scholar
  29. Hodges K, McKnew D, Cytryn L, Stern L, Kline J (1982) The Child Assessment Schedule (CAS) diagnostic interview: A report on reliability and validity. J Am Acad Child Adolesc Psychiatry 21:468–473Google Scholar
  30. Holmes SJ, Robins LN (1988) The role of parental disciplinary practices in the development of depression and alcoholism. Psychiatry 51:24–36Google Scholar
  31. Keller MB, Beardslee WR, Dorer DJ, Lavori PW, Samuelson H, Klerman GL (1986) Impact of severity and chronicity of parental affective illness on adaptive functioning and psychopathology in children. Arch Gen Psychiatry 43:930–937Google Scholar
  32. Kelsoe JR, Ginns EE, Egeland JA, Gerhard DS, Goldstein AM, Bale SJ Pauls DL, Long RT, Kidd KK, Conte G, Housman DE, Paul S (1989) Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature 16:238Google Scholar
  33. Kendler KS, Heath A, Martin NG (1986) Symptoms of anxiety and depression in a volunteer twin population. Arch Gen Psychiatry 43:213–221Google Scholar
  34. Kestenbaum CJ, Bird HR (1978) A reliability study of the mental health assessment form for school age children. J Am Acad Child Psychiatry 17:338–347Google Scholar
  35. Klein DN, Depue RA (1985) Obsessional personality traits and risk for bipolar affective disorder: An offspring study. J Abnorm Psychol 94:291–297Google Scholar
  36. Kovacs M, Gatsonis C, Paulauskas SL, Richards C (1989) Depressive disorders in childhood. IV. A longitudinal study of comorbidity with and risk for anxiety disorders. Arch Gen Psychiatry. 46:776–782Google Scholar
  37. Kunkel LM, et al (1986) Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 322:73Google Scholar
  38. LaRoche C, Sheiner R, Lester E, Benierakis C, Marrache M, Engelsmann F, Chiefetz P (1987) Children of parents with manic-depressive illness: A follow-up study. Can J Psychiatry 32:563–569Google Scholar
  39. MacMahon B (1968) Gene-environment interaction in human disease. J Psych Res 6 [Suppl 1]: 393–402Google Scholar
  40. McClellan JM, Rubert MP, Reichler RJ, Sylvester CE (1990) Attention deficit disorder in children at risk for anxiety and depression. J Am Acad Child Adolesc Psychiatry 29:534–539Google Scholar
  41. McGuffin P, Katz R, Rutherford J (1991) Nature, nuture and depression: A twin study. Psychol Med 21:329Google Scholar
  42. Mendlewicz J, Rainer JD (1977) Adoption study supporting genetic transmission on manic-depressive illness. Nature 268:327Google Scholar
  43. Merikangas KR, Angst J, Isler H (1990) Migraine and psychopathology: Results of the Zurich cohort study of young adults. Arch Gen Psychiatry 47:849–853Google Scholar
  44. Merikangas KR, Prusoff BA, Weissman MM (1988) Parental concordance for affective disorders: Psychopathology in offspring. J Affect Disord 15:279–290Google Scholar
  45. Merikangas KR, Rounsaville BJ, Prusoff BA (1991) Familial factors in vulnerability to substance abuse. In: Glantz M, Pickens R (eds) Vulnerability to Drug Abuse. American Psychological Association Press, Washington D.C., pp 79–98Google Scholar
  46. Mitchell J, McCauley E, Burke P, Calderon R, Schloredt K (1989) Psychopathology in parents of depressed children and adolescents. J Am Acad Child Adolesc Psychiatry 28(3):352–357Google Scholar
  47. Mitchell J, McCauley E, Burke PM, Moss SJ (1988) Phenomenology of depression in children and adolescents. J Am Acad Child Adolesc Psychiatry 27:12–20Google Scholar
  48. Nurnberger JI, Hamovit J, Hibbs E, Pellegrini D, Guroff JJ, Maxwell ME, Smith A, Gershon ES (1988) A high-risk study of primary affective disorder: Selection of subjects, initial assessment, and 1-to 2-year follow-up. In: Dunner DL, Gershon ES, Barrett JE (eds) Relatives at Risk for Mental Disorder. Raven Press, New York, pp 161–177Google Scholar
  49. Orvaschel H (1985) Psychiatric interviews suitable for use in research with children and adolescents. Psychopharmacol Bull 21:737–745Google Scholar
  50. Orvaschel H, Sholomskas D, Weissman MM (1980) The Assessment of Psychopathology and Behavioral Problems in Children: A Review of Scales Suitable for Epidemiological and Clinical Research (1967–1979). Alcohol, Drug Abuse and Mental Health Administration, Rockville, MDGoogle Scholar
  51. Orvaschel H, Walsh-Allis G, Ye W (1988) Psychopathology in children of parents with recurrent depression. J Abnorm Child Psychol 16:17–28Google Scholar
  52. Parker G (1979) Parental characteristics in relation to depressive disorders. Br J Psychiatry 134:138–147Google Scholar
  53. Reinherz HZ, Stewart-Berghauer G, Pakiz B, Frost AK, Moeykens BA, Holmes WM (1989) The relationship of early risk and current mediators to depressive symptomatology in adolescence. J Am Acad Child Adolesc Psychiatry 28(6):942–947Google Scholar
  54. Rohde P, Lewinsohn PM, Seeley JR (1991) Comorbidity of unipolar depression: II. Comorbidity with other mental disorders in adolescents and adults. J Abnorm Psychol 100(2):214–222Google Scholar
  55. Rutter M (1989) Isle of Wight revisited: Twenty-five years of child psychiatric epidemiology. J Am Acad Child Adolesc Psychiatry 28(5):633–653Google Scholar
  56. Rutter M, Tizard J, Yule W, Graham P, Whitmore K (1976) Research report: Isle of Wight studies, 1964–1974. Psychol Med 6:313–332Google Scholar
  57. Strauss CC, Last CG, Hersen M, Kazdin AE (1988) Association between anxiety and depression in children and adolescents with anxiety disorders. J Abnorm Child Psychol 16(1):57–68Google Scholar
  58. Susser M (1985) Separating heredity and environment. Am J Prev Med 1:5–23Google Scholar
  59. Sylvester CE, Hyde TS, Reichler RJ (1988) Clinical psychopathology among children of adults with panic disorder. In: Dunner DL, Gershon ES, Barrett JE (eds) Relatives at Risk for Mental Disorder. Raven Press, New York, pp 87–99Google Scholar
  60. Torgersen S (1990) A twin-study perspective of the comorbidity of anxiety and depression. Comorbidity of Mood and Anxiety Disorders. In: Maser JD, Cloninger CR (eds) American Psychiatric Press, Washington, DC, pp 367–380Google Scholar
  61. Turner SM, Beidel DC, Costello A (1987) Psychopathology in the offspring of anxiety disorders patients. J Consult Clin Psychol 55:229–235Google Scholar
  62. Weissman MM (1987) Children of Depressed Parents (Abstract for Sixth Annual Science Reporters Conference). Arch Gen PsychiatryGoogle Scholar
  63. Weissman MM (1990) Evidence for comorbidity of anxiety and depression: Family and genetic studies of children. In: Maser JD, Cloninger CR (eds) Comorbidity of Mood and Anxiety Disorders. American Psychiatric Press, Washington DC, pp 349–368Google Scholar
  64. Welner Z, Welner A, McCrary MD, Leonard MA (1977) Psychopathology in children of inpatients with depression: A controlled study. J Nerv Ment Dis 164:408–413Google Scholar
  65. Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I (1986) Psychiatric disorders in the biological and adoptive families and adoptive individuals with affective disorders. Arch Gen Psychiatry 43:923Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Kathleen Ries Merikangas
    • 1
  1. 1.Genetic Epidemiology Research Unit, Department of PsychiatryYale University School of MedicineNew HavenUSA

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