Genetic Factors in Psychopathology

Implications for Prevention
  • Susan E. Nicol
  • L. Erlenmeyer-Kimling


Genetic factors have been implicated in the etiology of many forms of psychopathology, including schizophrenia and the affective disorders, alcoholism and antisocial disorders, anxiety disorders, attention deficit disorder and certain of the specific developmental disorders, and a number of neurological disorders that may have behavioral components. In this chapter, we will focus on schizophrenia and the affective disorders, the psychiatric illnesses that have attracted the largest effort in genetic research thus far, and will review briefly some of the evidence linking genes to these disorders. We will discuss some genetic concepts important to understanding how genes may affect behavior, explore what is known about biological/genetic markers for mental illness, and consider the implications of finding markers in relation to treatment and prevention. We will borrow examples from medical illnesses to illustrate how increasing knowledge of genetic mechanisms sharpens our ability to predict environmental influences on disease incidence and course.


Affective Disorder Genetic Liability Computerize Tomography Enlarge Ventricle Schizophrenia Bulletin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abrams, R., & Taylor, M. A. (1983). The genetics of schizophrenia: A reassessment using modern criteria. American Journal of Psychiatry, 140, 171–175.PubMedGoogle Scholar
  2. Asarnow, R. F., MacCrimmon, D. J., Cleghorn, J., & Steffy, R. A. (1978). The McMaster Waterloo Project: An attentional and clinical assessment of foster children at risk for schizophrenia. In L. Wynne, R. Cromwell, J. Strauss, & S. Matthysee (Eds.), The nature of schizophrenia: New approaches to research and treatment (pp. 339–358 ). New York: Wiley.Google Scholar
  3. Bateson, G., Jackson, D. D., Haley, J., & Weakland, J. (1956). Toward a theory of schizophrenia. Behavioral Science, 7, 215–264.Google Scholar
  4. Berg, K. (1979). Inherited lipoprotein variation and atherosclerotic disease. In A. M. Scann, R. W. Wissler, & G. S. Getz (Eds.), The biochemistry of atherosclerosis (pp. 419–490 ). New York: Marcel Dekker.Google Scholar
  5. Bertelsen, A., Harvald, B., & Hauge, M. (1977). A Danish twin study of manic-depressive disorders. British Journal of Psychiatry, 130, 331–351.CrossRefGoogle Scholar
  6. Bleuler, M. The schizophrenia disorders: Long-term patient andfamily studies. New Haven, CT: Yale University Press.Google Scholar
  7. Botstein, D., White, R. L., Skolnick, M., & Davis, R. W. (1980). Constriction of a genetic linkage map in man using restriction fragment length polymorphisms. American Journal of Human Genetics, 32, 314–331.PubMedGoogle Scholar
  8. Bowers, M. B., Jr. (1977). Psychoses precipitated by psychomimetic drugs. Archives of General Psychiatry, 34, 832–835.PubMedCrossRefGoogle Scholar
  9. Breakey, W. R., Goodell, H., Lorenz, P. C., & McHugh, P. (1974). Hallucinogenic drugs as précipitants of schizophrenia. Psychological Medicine, 4, 255–261.PubMedCrossRefGoogle Scholar
  10. Brown, G. W. (1979). The social etiology of depression—London studies. In R. A. Depue (Ed.), The psychobiology of the depressive disorders: Implications for the effects of stress (pp. 263–289 ). New York: Academic Press.Google Scholar
  11. Brown, G. W., Harris, T., & Copeland, J. R. (1977). Depression and loss. British Journal of Psychiatry, 130, 1–18.PubMedCrossRefGoogle Scholar
  12. Cloninger, C. R., Reich, T., & Yokoyama, S. (1983). Genetic diversity, genome organization, and investigation of the etiology of psychiatric diseases. Psychiatric Developments, 3, 225–246.Google Scholar
  13. Cornbatt, B. A., & Erlenmeyer-Kimling, L. (1984). Early attentional predictors of adolescent behavioral disturbances in children at risk for schizophrenia: Specificity and predictive validity. In N. F. Watt, E. J. Anthony, L. C. Wynne, & J. Rolf (Eds.), Children at risk for schizophrenia: A longitudinal perspective (pp. 198–211 ). New York: Cambridge University Press.Google Scholar
  14. Cornblatt, B. A., & Erlenmeyer-Kimling, L. (1985). Global attentional deviance as a marker of risk for schizophrenia: Specificity and predictive validity of abnormal psychology. Journal of Abnormal Psychology, 94 (4), 470–486.PubMedCrossRefGoogle Scholar
  15. Coyne, J. C., & Gotlib, I. H. (1983). The role of cognition in depression: A critical appraisal. Psychological Bulletin, 94, 472–505.PubMedCrossRefGoogle Scholar
  16. DeAmicis, L., & Cromwell, R. L. (1979). Reaction time crossover in process schizophrenic patients, their relatives, and control subjects. Journal of Nervous and Mental Disease, 167, 593–600.PubMedCrossRefGoogle Scholar
  17. DeAmicis, L. A., Huntzinger, R. S., & Cromwell, R. L. (1981). Magnitude of reaction time crossover in process schizophrenic patients in relation to the first-degree relatives. Journal of Nervous and Mental Disease, 169, 64–65.PubMedCrossRefGoogle Scholar
  18. DiMascio, A., Weissman, M. M., Prosoff, B. A., Neu, C., Zwilling, M., & Klerman, G. L. (1979). Differential symptom reduction by drugs and psychotherapy in acute depression. Archives of General Psychiatry, 36, 1450–1456.PubMedCrossRefGoogle Scholar
  19. Egeland, J. A., & Hostetter, A. M. (1983). Amish study, I: Affective disorders among the Amish, 1976–1980. American Journal of Psychiatry, 140, 56–61.PubMedGoogle Scholar
  20. Erlenmeyer-Kimling, L. (1976). Schizophrenia: A bag of dilemmas. Social Biology 23: 123–134.PubMedGoogle Scholar
  21. Erlenmeyer-Kimling, L. (1977). Issues pertaining to prevention and intervention in genetic disorders affecting human behavior. In G. W. Albee & J. M. Joffee (Eds.), Primary prevention in psychopathology (pp. 68–91 ). Hanover, NH: University Press of New England.Google Scholar
  22. Erlenmeyer-Kimling, L., & Cornblatt, B. (1978). Attentional measures in a study of children at high risk for schizophrenia. In L. Wynne, R. L. Cromwell, & S. Matthysse (Eds.), The nature of schizophrenia: New approaches to research and treatment (pp. 359–365 ). New York: Wiley.Google Scholar
  23. Erlenmeyer-Kimling, L., & Cornblatt, B. (1984). Biobehavioral risk factors in children of schizophrenic parents. Journal of Autism and Childhood Schizophrenia, 14 (4), 357–374.CrossRefGoogle Scholar
  24. Erlenmeyer-Kimling, L., Cornblatt, B., Friedman, D., Marcuse, Y., Rutschmann, J., Simmens, S., & Devi, S. (1982). Neurological electrophysiological and attentional deviations in children at risk for schizophrenia. In H. A. Nasrallah & F. Henn (Eds.), Schizophrenia as a brain disease (pp. 61–98 ). New York: Oxford University Press.Google Scholar
  25. Erlenmeyer-Kimling, L., Cornblatt, B., & Golden, R. (1983). Early indicators of vulnerability to schizophrenia in children at high genetic risk. In S. B. Guze, F. J. Earls, & J. E. Barrett (Eds.), Childhood psychopathology and development (pp. 247–261 ). New York: Raven Press.Google Scholar
  26. Erlenmeyer-Kimling, L., Marcuse, Y., Cornblatt, B., Friedman, D., Rainer, J. D., & Rutschmann, J. (1984). The New York high-risk project. In N. F. Watt, E. J. Anthony, L. C. Wynne, & J. Rolf (Eds.), Children at risk for schizophrenia: A longitudinal perspective (pp. 169–189 ). New York: Cambridge University Press.Google Scholar
  27. Erlenmeyer-Kimling, L., Friedman, D., Cornblatt, B., and Jacobsen, R. (1985). Electrodermal recovery data on children of schizophrenic parents. Journal of Psychiatry Research, 14, 149–161.CrossRefGoogle Scholar
  28. Fischer, M. (1971). Psychoses in the offspring of schizophrenic monozygotic twins and their normal co-twins. British Journal of Psychiatry, 118, 43–52.PubMedCrossRefGoogle Scholar
  29. Friedman, D., Cornblatt, B., Vaughan, H. G., Jr., & Erlenmeyer-Kimling, L. (In press). Event-related potentials in children at risk for schizophrenia during two versions of the continuous performance test. Psychiatry Research.Google Scholar
  30. Gershon, E. S., Bunney, W. E., Jr., Leckman, J. F., VanEerdewegh, M., & DeBauche, B. A. (1976). The inheritance of affective disorders: A review of data and of hypotheses. Behavior Genetics, 6, 227–261.PubMedCrossRefGoogle Scholar
  31. Gershon, E. S., Targum, S. D., Matthysse, S., & Bunney, W. E., Jr. (1979). Color blindness not closely linked to bipolar illness. Archives of General Psychiatry, 36, 1423–1430.PubMedCrossRefGoogle Scholar
  32. Glueck, C. J. (1982). Colestipol and probucol: Treatment of primary and familial hypercholesterolemia and amelioration of atherosclerosis. Annals of Internal Medicine, 96, 475–482.PubMedGoogle Scholar
  33. Goldin, L. R., & Gershon, E. S. (1983). Association and linkage studies of genetic marker loci in major psychiatric disorders. Psychiatric Developments, 4, 387–418.Google Scholar
  34. Goldstein, J. L., & Brown, M. S. (1982). The LDL receptor defect in familial hypercholesterolemia: Implications for pathogenesis and therapy. Medical Clinics of North America, 66, 335–362.PubMedGoogle Scholar
  35. Goldstein, M. J. (1981). New developments in interventions with families of schizophrenics. San Francisco: Jossey-Bass.Google Scholar
  36. Gottesman, I. I. (1965). Personality and natural selection. In S. G. Vandenberg (Ed.), Methods and goals in human behavior genetics (pp. 63–74 ). New York: Academic Press.Google Scholar
  37. Gottesman, I. I. (1968). Severity/concordance and diagnostic refinement in the Maudsley-Bethlehem schizo-phrenic twin study. In D. Rosenthal & S. S. Kety (Eds.), The transmission of schizophrenia (pp. 37–48 ). New York: Pergamon Press.Google Scholar
  38. Gottesman, I. I., & Shields, J. (1972). Schizophrenia and genetics: A twin study vantage point. New York: Academic Press.Google Scholar
  39. Gottesman, I. I., & Shields, J. (1982). Schizophrenia: The epigeneticpuzzle. New York: Cambridge University Press.Google Scholar
  40. Gusella, J. F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E., Watkins, P. C., O’Hira, K., Wallace, M. R., Sakaguchi, A. Y., Young, A. B., Shoulson, I., Bonitta, E., & Martin, J. B. (1983). A polymorphic DNA marker genetically linked to Huntington’s disease. Nature, 306, 234–238.PubMedCrossRefGoogle Scholar
  41. Heston, L. L. (1966). Psychiatric disorders in foster home reared children of schizophrenic mothers. British Journal of Psychiatry, 112, 819–825.PubMedCrossRefGoogle Scholar
  42. Holzman, P. S., Levy, D. L., & Proctor, L. R. (1978). The several qualities of attention in schizophrenia. In L. C. Wynne, R. L. Cromwell, & S. Matthysse (Eds.), The nature of schizophrenia: New approaches to research and treatment. New York: Wiley.Google Scholar
  43. Holzman, P. S., Kringlen, E., Levy, D. L., & Haberman, S. J. (1980). Deviant eye tracking in twins discordant for psychosis—A replication. Archives of General Psychiatry, 37, 627–631.PubMedCrossRefGoogle Scholar
  44. Holzman, P. S., Solomon, C. M., Levin, S., & Waternaux, C. S. (1984). Pursuit eye movement dysfunctions in schizophrenia: Family evidence for specificity. Archives of General Psychiatry, 41, 136–139.PubMedCrossRefGoogle Scholar
  45. Janes, C. L., Hesselbrock, V., & Stern, J. A. (1978). Parental psychopathology, age and race as related to electrodermal activity in children. Psychophysiology, 15, 24–34.PubMedCrossRefGoogle Scholar
  46. Kallmann, F. J. (1938). The genetics of schizophrenia. New York: J. J. Augustin.Google Scholar
  47. Kaufman, I. C., & Rosenblum, L. A. (1967). Depression in infant monkeys separated from their mothers. Science, 155, 1030–1031.PubMedCrossRefGoogle Scholar
  48. Kendler, K. S. (1983). Heritability of schizophrenia [Letter to the editor]. American Journal of Psychiatry, 140, 131.Google Scholar
  49. Kety, S. S., Rosenthal, D., Wender, P. H., & Schulsinger, F. (1976). Studies based on a total sample of adopted individuals and their relatives: Why they were necessary, what they demonstrated and failed to demonstrate. Schizophrenic Bulletin, 2, 413–428.Google Scholar
  50. Kringlen, E. (1967). Heredity and environment in the functional psychoses. London: Heinemann.Google Scholar
  51. Kupfer, D. J. (1976). REM latency: A psychobiologic marker for primary depressive disease. Biological Psychiatry, 11, 159–174.PubMedGoogle Scholar
  52. Larson, C. A., & Nyman, G. E. (1974). Schizophrenia: Outcome in a birth cohort. Psychiatria Clinica, 7, 50–55.PubMedGoogle Scholar
  53. Leckman, J. F., Gershon, E. S., McGinniss, M. H., Targum, S. D., & Dibble, E. D. (1979). New data do not suggest linkage between the Xg blood group and bipolar illness. Archives of General Psychiatry, 36, 1435–1441.PubMedCrossRefGoogle Scholar
  54. Lidz, T. (1973). The origin and treatment of schizophrenic disorders. New York: Basic Books.Google Scholar
  55. Maser, J. D., & Keith, S. J. (1983). CT scans and schizophrenia: Report on workshop. Schizophrenia Bulletin, 9, 265–283.PubMedGoogle Scholar
  56. McGuffin, P., Farmer, A. E., Gottesman, I. I., Murray, R. M., & Reveley, A. M. (1984). Twin concordance for operationally defined schizophrenia: Confirmation of familiality and heritability. Archives of General Psychiatry, 41, 541–545.PubMedCrossRefGoogle Scholar
  57. Mednick, S. A., & Schulsinger, F. (1968). Some pre-morbid characteristics related to breakdown in children with schizophrenic mothers. In D. Rosenthal & S. S. Kety (Eds.), The transmission of schizophrenia (pp. 267–291 ). Oxford: Pergamon Press.Google Scholar
  58. Meehl, P. E. (1972). Specific genetic etiology, psychodynamics and therapeutic nihilism. International Journal of Mental Health, 1, 10–27.Google Scholar
  59. Mendlewicz, J., & Rainer, J. D. (1977). Adoption study supporting genetic transmission in manic-depressive illness. Nature, 268, 327–329.PubMedCrossRefGoogle Scholar
  60. Mendlewicz, J., Fleiss, J. L., & Fieve, R. R. (1972). Evidence for X-linkage in the transmission of manic-depressive illness. Journal of the American Medical Association, 222, 1624–1627.PubMedCrossRefGoogle Scholar
  61. Motulsky, A. G., & Boman, H. (1975). Screening for the hyperlipidemias. In A. Milunsky (Eds.), The prevention of mental retardation and genetic disease (pp. 306–316 ). Philadelphia, PA: Saunders.Google Scholar
  62. Nicol, S. E., & Gottesman, I. I. (1983). Clues to the genetics and neurobiology of schizophrenia. American Scientist, 71, 398–404.Google Scholar
  63. Nuechterlein, K. H. (1983). Signal detection in vigilance tasks and behavioral attributes among offspring of schizophrenic mothers and among hyperactive children. Journal of Abnormal Psychiatry, 92, 4–28.CrossRefGoogle Scholar
  64. Nyman, A. K. (1978). Non-regressive schizophrenia: Clinical course and outcome. Acta Psychiatrica Scandinavica. (Suppl. 272 ), 1–143.Google Scholar
  65. Pope, H. G., Jonas, J. M., Cohen, B. M., & Lipinski, J. F. (1982). Failure to find evidence of schizophrenia in first-degree relatives of schizophrenic probands. American Journal of Psychiatry, 139, 826–828.PubMedGoogle Scholar
  66. Prentky, R. A., Salzman, L. F., & Klein, R. H. (1981). Habituation and conditioning of skin conductance responses in children at risk. Schizophrenia Bulletin, 7, 281–291.PubMedGoogle Scholar
  67. Rao, D. C., Morton, N. E., Gottesman, I. I., & Lew, R. (1981). Path analysis of qualitative data on pairs of relatives: Application to schizophrenia. Human Heredity, 31, 325–333.PubMedCrossRefGoogle Scholar
  68. Reich, T., Clayton, P., & Winokur, G. (1969). Family history studies: V. The genetics of mania. American Journal of Psychiatry, 125, 1358–1369.PubMedGoogle Scholar
  69. Reich, T., James, J. W., & Morris, C. A. (1972). The use of multiple thresholds in determining the mode of transmission of semi-continuous traits. Annals of Human Genetics, 36, 163–184.PubMedCrossRefGoogle Scholar
  70. Rosenthal, D., Wender, P. H., Kety, S. S., Schulsinger, F., Welner, J., & Ostergaard, L. (1968). Schizophrenics’ offspring reared in adoptive homes. In D. Rosenthal & S. S. Kety (Eds.), The transmission of schizophrenia (pp. 377–391 ). Oxford: Pergamon Press.Google Scholar
  71. Rush, A. J. (1982). Short-term psychotherapies for depression: Behavioral, interpersonal, cognitive, and psychodynamic approaches. New York: Guilford Press.Google Scholar
  72. Rush, A. J., Beck, A. T., Kovacs, M., & Hollon, S. (1977). Comparative efficacy of cognitive therapy and imipramine in the treatment of depressed outpatients. Cognitive Therapy and Research, 1, 17–37.CrossRefGoogle Scholar
  73. Sasazuki, T., McDevitt, H. O., & Grumet, F. C. (1977). The association between genes in the major histocompatability complex and disease susceptibility. Annual Review of Medicine, 28, 425–452.PubMedCrossRefGoogle Scholar
  74. Sitaram, N., Nürnberger, J. I., Jr., Gershon, E. S., & Gillin, J. C. (1980). Faster cholinergic REM sleep induction in euthymic patients with primary affective illness. Science, 208, 200–201.PubMedCrossRefGoogle Scholar
  75. Spitz, R. A. (1947). Anaclitic depression: An inquiry into the genesis of psychiatric conditions in early childhood. II. The Psychoanalytic Study of the Child, 2, 313–343.Google Scholar
  76. Spring, B.J. (1980). Shift of attention in schizophrenics, siblings of schizophrenics, and depressed patients. Journal of Nervous and Mental Disease, 168, 133–140.PubMedCrossRefGoogle Scholar
  77. Sutton, H. E. (1965). An introduction to human genetics. New York: Holt, Rinehardt & Winston.Google Scholar
  78. Tatetsu, S. (1968). Langdauernde psychische strörungen infolge chronischen intravenösen pervitin-missbranches. In J. J. Lopez Ibor (Ed.), Proceedings of the Fourth World Congress of Psychiatry (pp. 891–894). International Congress Series No. 150. Amsterdam: Excerpta Medica Foundation.Google Scholar
  79. Taylor, M. A., Abrams, R., & Gaztanaga, P. (1975). Manic depressive illness and schizophrenia: A partial validation of research diagnostic criteria utilizing neuropsychological testing. Comprehensive Psychiatry, 16, 91.PubMedCrossRefGoogle Scholar
  80. Tsuang, M. T., Kendler, K. S., & Gruenberg, A. M. (1985). A blind family study of DSM-III schizophrenia. In T. Sakai & T. Tsuboi (Eds.), Genetic aspects of human behavior (pp. 57–61 ). Tokyo: Aino Hospital Foundation, Igaku-Shoin.Google Scholar
  81. Turner, W. J. (1979). Genetic markers for schizotaxia. Biological Psychiatry, 14, 177–206.PubMedGoogle Scholar
  82. Vaughn, C., & Leff, J. P. (1976). The influence of family and social factors on the course of psychiatric illness. British Journal of Psychiatry, 129, 125–137.PubMedCrossRefGoogle Scholar
  83. Weinberger, D. R., Bigelow, L. B., Kleinman, J. E., Klein, S. T., Rosenblatt, J. E., & Wyatt, R. J. (1980). Cerebral ventricular enlargement in chronic schizophrenia: Association with poor response to treatment. Archives of General Psychiatry, 37, 11–14.PubMedCrossRefGoogle Scholar
  84. Weinberger, D. R., Cannon-Spoor, H. E., Potkin, S. G., and Wyatt, R. J. (1980). Poor premorbid adjustment and CT scan abnormalities in chronic schizophrenia. American Journal of Psychiatry, 137, 1410–1413.PubMedGoogle Scholar
  85. Weinberger, D. R., Wagner, R. L., & Wyatt, R. J. (1983). Neuropathological studies of schizophrenia: A selective review. Schizophrenia Bulletin, 9, 193–212.PubMedGoogle Scholar
  86. Weissman, M., & Klerman, G. (1977). Sex differences and the epidemiology of depression. Archives of General Psychiatry, 34, 98–111.PubMedCrossRefGoogle Scholar
  87. Weissman, M. M., Merikangas, K. R., Pauls, D. L., Leckman, J. F., & Gammon, G. D. (1983). Heritability of schizophrenia [Letter to the editor]. American Journal of Psychiatry, 140, 131–132.Google Scholar
  88. Weitkamp, L. R., Stancer, H. C., Persad, E., Flood, C., & Guttormsen, S. (1981). Depressive disorders and HLA: A gene on chromosome 6 that can affect behavior. New England Journal of Medicine, 305, 1301–1306.PubMedCrossRefGoogle Scholar
  89. Wender, P. H., Rosenthal, D., Kety, S. S., Schulsinger, F., & Welner, J. (1974). Cross-fostering: A research strategy for clarifying the role of genetic and experiential factors in the etiology of schizophrenia. Archives of General Psychiatry, 30, 121–128.PubMedCrossRefGoogle Scholar
  90. Winokur, G. (1974). The division of depressive illness into depression spectrum disease and pure depressive disease. International Pharmacopsychiatry, 9, 5–13.PubMedGoogle Scholar
  91. Winters, K. C., Stone, A. A., Weintraub, S., & Neale, J. M. (1981). Cognitive and attentional deficits in children vulnerable to psychopathology. Journal of Abnormal Child Psychology, 9, 435–453.PubMedCrossRefGoogle Scholar
  92. Wood, R. L., & Cook, M. (1979). Attentional deficit in siblings of schizophrenics. Psychological Medicine, 9, 465–467.PubMedCrossRefGoogle Scholar
  93. Zerbin-Riidin, E. (1966). “Schizophrenic” head injured persons and their families. Unpublished manuscript (Abstr. # 356). Report of the Third International Congress on Human Genetics, Chicago, IL.Google Scholar
  94. Zerbin-Riidin, E. (1969). Zur Genetik der depressiven Erkrankungen. In H. Hippius, H. Selbach, H. F. Hofmann, & K. C. Mezey (Eds.), Das depressive Syndrom (pp. 37–56 ). Munich: Urban and Schwarzenberg.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Susan E. Nicol
    • 1
  • L. Erlenmeyer-Kimling
    • 2
  1. 1.Department of PsychiatryHennepin County Medical CenterMinneapolisUSA
  2. 2.Division of Developmental Behavioral Studies, Medical GeneticsNew York State Psychiatric InstituteNew YorkUSA

Personalised recommendations