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Continuity and Discontinuity of Affective Disorders and Schizophrenia: Results of a Controlled Family Study

Continuity and Discontinuity of Affective Disorders and Schizophrenia: Results of a Controlled... Abstract Background: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. Methods: Index probands met Research Diagnostic Criteria for SCZ (n=146), schizoaffective (SA [n=115]), bipolar (BP [n=80]), or unipolar major depressive (UP [n=184])disorder. Comparison probands met Research Diagnostic Criteria for alcoholism (n=64) or were sampled from the general population (n=109). A total of 2845 first-degree relatives were blindly diagnosed from interview, informant, and/or record data, with direct interviews completed in 2070 (82% of living first-degree relatives). Results: By Cox's proportional hazards analysis, SCZ, SA, BP, and UP disorders were familial, in that each group of relatives had an increased lifetime morbid risk (vs those with alcoholism and those from the general population) for the proband's diagnosis. The SCZ and BP disorders were transmitted independently: only probands with manic disorders (BP or SA-BP subtype) showed increased familial risks of BP disorder, and only probands with prominent SCZ features (SCZ or SA) showed increased familial risks of SCZ disorder. However, SCZ probands had an increased familial risk for UP disorder (as did SA, BP, and UP probands) and for the SA-UP subtype. Aggregation of depression in families of SCZ probands could not be explained by the subtype of depression, broad or narrow definition of SCZ disorder, presence or absence of history of depression in SCZ probands, whether onset of depression in a relative occurred before or after onset of a proband's SCZ disorder, or assortative mating. Conclusions: These data suggest that there could be a familial relationship between the predispositions to schizophrenia and to major depression. We discuss a number of alternative hypotheses about the nature of this possible relationship. References 1. Griesinger W. Die Pathologie und Therapie der Psychischen Krankheiten . Stuttgart, Germany: Krabbe; 1861. 2. Crow TJ. The continuum of psychosis and its implication for the structure of the gene . Br J Psychiatry . 1986;149:419-429.Crossref 3. Kraepelin E. Psychiatrie . 6th ed. Leipzig, Germany: Barth; 1899. 4. Kendell RE, Brockington IF. The identification of disease entities and the relationship between schizophrenia and affective psychoses . Br JPsychiatry . 1980;137:324-331.Crossref 5. Taylor MA. Are schizophrenia and affective disorder related? a selective literature review . Am J Psychiatry . 1992;149:22-32. 6. Kendler KS. Toward a scientific psychiatric nosology: strengths and limitations . Arch Gen Psychiatry . 1990;47:969-973. 7. Gershon ES, DeLisi LE, Hamovit J, Nurnberger JI, Maxwell ME, Schreiber J, Dauphinais D, Dingman CW II, Guroff JJ. A controlled family study of chronic psychoses . Arch Gen Psychiatry . 1988;45:328-336.Crossref 8. Weissman MM, Merikangas KR, John K, Wickramaratne P, Prusoff BA, Kidd KK. Family-genetic studies of psychiatric disorders: developing technologies . Arch Gen Psychiatry . 1986;43:1104-1116.Crossref 9. Tsuang MT, Winokur G, Crowe RR. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions . Br J Psychiatry . 1980;137:497-504.Crossref 10. Kendler KS, Gruenberg AM, Tsuang MT. Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients: a family study using DSMIII criteria . Arch Gen Psychiatry . 1985;42:770-779.Crossref 11. Coryell W, Zimmerman M. The heritability of schizophrenia and schizoaffective disorder . Arch Gen Psychiatry . 1988;45:323-327.Crossref 12. Baron M, Gruen R, Asnis L, Kane J. Schizoaffective illness, schizophrenia and affective disorders: morbidity risk and genetic transmission . Acta Psychiatr Scand . 1982;65:253-262.Crossref 13. Frangos E, Althanassenas G, Tsitourides S, Katsanou N, Alexandrakou P. Prevalence of DSM-III schizophrenia among the first-degree relatives of schizophrenic probands . Acta Psychiatr Scand . 1985;72:382-386.Crossref 14. Maj M. A family study of two subgroups of schizoaffective patients . Br J Psychiatry . 1989;154:640-643. 15. Kendler KS, Gruenberg AM, Tsuang MT. A DSM-III family study of nonschizophrenic psychotic disorders . Am J Psychiatry . 1985;143:1098-1105. 16. Coryell W, Tsuang MT, McDaniel J. Psychotic features in major depressions: is mood congruence important? J Affect Disord . 1984;7:227-236. 17. Coryell W, Endicott J, Keller M, Andreasen NC. Phenomenology and family history in DSM-III psychotic depression . J Affect Disord . 1985;9:13-18.Crossref 18. Kendler KS. Familial aggregation of schizophrenia and schizophrenia spectrum disorders . Arch Gen Psychiatry . 1988;45:377-383. 19. Tsuang MT, Fleming JA, Kendler KS, Gruenberg AS. Selection of controls for family studies: biases and implications . Arch Gen Psychiatry . 1988;45:1006-1008.Crossref 20. Winokur G. Unipolar depression: is it divisible into autonomous subtypes? Arch Gen Psychiatry . 1979;36:47-52. 21. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands . Arch Gen Psychiatry . 1982;39:1157-1167.Crossref 22. Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria for a Selected Group of Functional Disorders . 2nd ed. New York, NY: Biometrics Research Division, New York State Psychiatric Institute; 1975. 23. Slater E, Cowie V. The Genetics of Mental Disorder . New York, NY: Oxford University Press Inc; 1971. 24. Mannuzza S, Fyer AJ, Klein DF, Endicott J. Schedule for Affective Disorders and Schizophrenia—Lifetimeversion (modified for the study of anxiety disorders): rationale and conceptual development . J Psychiatr Res . 1986;20:317-325.Crossref 25. Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke JD, Farmer A, Jablenski A, Pickens R, Regier DA, Sartorius N, Towle LH. The Composite International Diagnostic Interview (CIDI): an epidemiologic instrument suitable for use in conjunction with different diagnostic systems in different cultures . Arch Gen Psychiatry . 1988;45:1069-1077.Crossref 26. Spitzer RL, Williams JB, Gibbon M. Structured Clinical Interview for DSM-III-R (SCID) . New York, NY: Biometric Research Department, New York State Psychiatric Institute; 1987. 27. Mannuzza S, Fyer AJ, Endicott J, Klein DF, Robins LN. Family Informant Schedule and Criteria (FISC). New York, NY: Anxiety Disorder Clinic, New York State Psychiatric Institute; 1985. 28. Leboyer M, Maier W, Teherani- M, Lichtermann D, D'Amato T, Franke P, Lépine JP, Minges J, McGuffin P. The reliability of the SADS-LA in a family study setting . Eur Arch Psychiatry Clin Neurosci . 1991;241:165-169.Crossref 29. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodological study . Arch Gen Psychiatry . 1982;39:879-883.Crossref 30. Lee E. Statistical Methods for Survival Data Analysis . Belmont, Calif: Wadsworth Publishing Co; 1980. 31. Dixon WJ (chief ed), Brown MB, Engelman L, Jennrich RI (assistant eds). BMDP Statistical Software Manual . Berkeley, Calif: University of California Press; 1990. 32. Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R, Benkert O. Schizoaffective disorders and mood disorders with incongruent psychotic features: keep separate or combine? evidence from a family study . Am J Psychiatry . 1992;149:1666-1673. 33. 33. Heun R, Maier W. Morbid risks for major disorders and frequencies of personality disorders among spouses of psychiatric inpatients and controls . Compr Psychiatry . 1993;34:137-143.Crossref 34. Baron M, Gruen R, Rainer JD, Kane J, Asnis L, Lord S. A family study of schizophrenic and normal control probands: implications for the spectrum concept of schizophrenia . Am J Psychiatry . 1985;142:447-455. 35. Scharfetter C, NûsperliM. The group of schizophrenias, schizoaffective psychoses, and the affective disorders . Schizophr Bull . 1980;6:586-591.Crossref 36. Angst J, Felder W, Lohmeyer B. Are schizoaffective psychoses heterogenous? II: results of a genetic investigation . J Affect Disord . 1979;1:155-165.Crossref 37. Andreasen NC, Rice J. Endicott J, Coryell W, Grove WM, Reich T. Familial rates of affective disorder: a report from the National Institute of Mental Health Collaborative Study . Arch Gen Psychiatry . 1987;44:461-469.Crossref 38. Weissman MM, Merikangas KR, Wickramaratne P, Kidd KK, Prusoff BA, Leckman JF, Pauls DL. Understanding the clinical heterogeneity of major depression using family data . Arch Gen Psychiatry . 1986;43:430-434.Crossref 39. 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.Crossref 40. Cross-National Collaborative Group. The changing rate of major depression: cross-national comparisons . JAMA . 1992;268:3098-3105.Crossref 41. Kendler KS. The genetics of schizophrenia and related disorders: a review . In: Dunner DL, Gershon ES, Barrett JE, eds. Relatives at Risk for Mental Disorder . New York, NY: Raven Press; 1988:247-266. 42. Kidd KK, Kennedy JL. The genetics of affective disorders . In: Wetterberg L, ed. Genetics of Neuropsychiatric Diseases . New York, NY: Macmillan Publishing Co Inc; 1989:191-198. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Continuity and Discontinuity of Affective Disorders and Schizophrenia: Results of a Controlled Family Study

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References (50)

Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1993.01820230041004
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. Methods: Index probands met Research Diagnostic Criteria for SCZ (n=146), schizoaffective (SA [n=115]), bipolar (BP [n=80]), or unipolar major depressive (UP [n=184])disorder. Comparison probands met Research Diagnostic Criteria for alcoholism (n=64) or were sampled from the general population (n=109). A total of 2845 first-degree relatives were blindly diagnosed from interview, informant, and/or record data, with direct interviews completed in 2070 (82% of living first-degree relatives). Results: By Cox's proportional hazards analysis, SCZ, SA, BP, and UP disorders were familial, in that each group of relatives had an increased lifetime morbid risk (vs those with alcoholism and those from the general population) for the proband's diagnosis. The SCZ and BP disorders were transmitted independently: only probands with manic disorders (BP or SA-BP subtype) showed increased familial risks of BP disorder, and only probands with prominent SCZ features (SCZ or SA) showed increased familial risks of SCZ disorder. However, SCZ probands had an increased familial risk for UP disorder (as did SA, BP, and UP probands) and for the SA-UP subtype. Aggregation of depression in families of SCZ probands could not be explained by the subtype of depression, broad or narrow definition of SCZ disorder, presence or absence of history of depression in SCZ probands, whether onset of depression in a relative occurred before or after onset of a proband's SCZ disorder, or assortative mating. Conclusions: These data suggest that there could be a familial relationship between the predispositions to schizophrenia and to major depression. We discuss a number of alternative hypotheses about the nature of this possible relationship. References 1. Griesinger W. Die Pathologie und Therapie der Psychischen Krankheiten . Stuttgart, Germany: Krabbe; 1861. 2. Crow TJ. The continuum of psychosis and its implication for the structure of the gene . Br J Psychiatry . 1986;149:419-429.Crossref 3. Kraepelin E. Psychiatrie . 6th ed. Leipzig, Germany: Barth; 1899. 4. Kendell RE, Brockington IF. The identification of disease entities and the relationship between schizophrenia and affective psychoses . Br JPsychiatry . 1980;137:324-331.Crossref 5. Taylor MA. Are schizophrenia and affective disorder related? a selective literature review . Am J Psychiatry . 1992;149:22-32. 6. Kendler KS. Toward a scientific psychiatric nosology: strengths and limitations . Arch Gen Psychiatry . 1990;47:969-973. 7. Gershon ES, DeLisi LE, Hamovit J, Nurnberger JI, Maxwell ME, Schreiber J, Dauphinais D, Dingman CW II, Guroff JJ. A controlled family study of chronic psychoses . Arch Gen Psychiatry . 1988;45:328-336.Crossref 8. Weissman MM, Merikangas KR, John K, Wickramaratne P, Prusoff BA, Kidd KK. Family-genetic studies of psychiatric disorders: developing technologies . Arch Gen Psychiatry . 1986;43:1104-1116.Crossref 9. Tsuang MT, Winokur G, Crowe RR. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions . Br J Psychiatry . 1980;137:497-504.Crossref 10. Kendler KS, Gruenberg AM, Tsuang MT. Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients: a family study using DSMIII criteria . Arch Gen Psychiatry . 1985;42:770-779.Crossref 11. Coryell W, Zimmerman M. The heritability of schizophrenia and schizoaffective disorder . Arch Gen Psychiatry . 1988;45:323-327.Crossref 12. Baron M, Gruen R, Asnis L, Kane J. Schizoaffective illness, schizophrenia and affective disorders: morbidity risk and genetic transmission . Acta Psychiatr Scand . 1982;65:253-262.Crossref 13. Frangos E, Althanassenas G, Tsitourides S, Katsanou N, Alexandrakou P. Prevalence of DSM-III schizophrenia among the first-degree relatives of schizophrenic probands . Acta Psychiatr Scand . 1985;72:382-386.Crossref 14. Maj M. A family study of two subgroups of schizoaffective patients . Br J Psychiatry . 1989;154:640-643. 15. Kendler KS, Gruenberg AM, Tsuang MT. A DSM-III family study of nonschizophrenic psychotic disorders . Am J Psychiatry . 1985;143:1098-1105. 16. Coryell W, Tsuang MT, McDaniel J. Psychotic features in major depressions: is mood congruence important? J Affect Disord . 1984;7:227-236. 17. Coryell W, Endicott J, Keller M, Andreasen NC. Phenomenology and family history in DSM-III psychotic depression . J Affect Disord . 1985;9:13-18.Crossref 18. Kendler KS. Familial aggregation of schizophrenia and schizophrenia spectrum disorders . Arch Gen Psychiatry . 1988;45:377-383. 19. Tsuang MT, Fleming JA, Kendler KS, Gruenberg AS. Selection of controls for family studies: biases and implications . Arch Gen Psychiatry . 1988;45:1006-1008.Crossref 20. Winokur G. Unipolar depression: is it divisible into autonomous subtypes? Arch Gen Psychiatry . 1979;36:47-52. 21. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands . Arch Gen Psychiatry . 1982;39:1157-1167.Crossref 22. Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria for a Selected Group of Functional Disorders . 2nd ed. New York, NY: Biometrics Research Division, New York State Psychiatric Institute; 1975. 23. Slater E, Cowie V. The Genetics of Mental Disorder . New York, NY: Oxford University Press Inc; 1971. 24. Mannuzza S, Fyer AJ, Klein DF, Endicott J. Schedule for Affective Disorders and Schizophrenia—Lifetimeversion (modified for the study of anxiety disorders): rationale and conceptual development . J Psychiatr Res . 1986;20:317-325.Crossref 25. Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke JD, Farmer A, Jablenski A, Pickens R, Regier DA, Sartorius N, Towle LH. The Composite International Diagnostic Interview (CIDI): an epidemiologic instrument suitable for use in conjunction with different diagnostic systems in different cultures . Arch Gen Psychiatry . 1988;45:1069-1077.Crossref 26. Spitzer RL, Williams JB, Gibbon M. Structured Clinical Interview for DSM-III-R (SCID) . New York, NY: Biometric Research Department, New York State Psychiatric Institute; 1987. 27. Mannuzza S, Fyer AJ, Endicott J, Klein DF, Robins LN. Family Informant Schedule and Criteria (FISC). New York, NY: Anxiety Disorder Clinic, New York State Psychiatric Institute; 1985. 28. Leboyer M, Maier W, Teherani- M, Lichtermann D, D'Amato T, Franke P, Lépine JP, Minges J, McGuffin P. The reliability of the SADS-LA in a family study setting . Eur Arch Psychiatry Clin Neurosci . 1991;241:165-169.Crossref 29. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodological study . Arch Gen Psychiatry . 1982;39:879-883.Crossref 30. Lee E. Statistical Methods for Survival Data Analysis . Belmont, Calif: Wadsworth Publishing Co; 1980. 31. Dixon WJ (chief ed), Brown MB, Engelman L, Jennrich RI (assistant eds). BMDP Statistical Software Manual . Berkeley, Calif: University of California Press; 1990. 32. Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R, Benkert O. Schizoaffective disorders and mood disorders with incongruent psychotic features: keep separate or combine? evidence from a family study . Am J Psychiatry . 1992;149:1666-1673. 33. 33. Heun R, Maier W. Morbid risks for major disorders and frequencies of personality disorders among spouses of psychiatric inpatients and controls . Compr Psychiatry . 1993;34:137-143.Crossref 34. Baron M, Gruen R, Rainer JD, Kane J, Asnis L, Lord S. A family study of schizophrenic and normal control probands: implications for the spectrum concept of schizophrenia . Am J Psychiatry . 1985;142:447-455. 35. Scharfetter C, NûsperliM. The group of schizophrenias, schizoaffective psychoses, and the affective disorders . Schizophr Bull . 1980;6:586-591.Crossref 36. Angst J, Felder W, Lohmeyer B. Are schizoaffective psychoses heterogenous? II: results of a genetic investigation . J Affect Disord . 1979;1:155-165.Crossref 37. Andreasen NC, Rice J. Endicott J, Coryell W, Grove WM, Reich T. Familial rates of affective disorder: a report from the National Institute of Mental Health Collaborative Study . Arch Gen Psychiatry . 1987;44:461-469.Crossref 38. Weissman MM, Merikangas KR, Wickramaratne P, Kidd KK, Prusoff BA, Leckman JF, Pauls DL. Understanding the clinical heterogeneity of major depression using family data . Arch Gen Psychiatry . 1986;43:430-434.Crossref 39. 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.Crossref 40. Cross-National Collaborative Group. The changing rate of major depression: cross-national comparisons . JAMA . 1992;268:3098-3105.Crossref 41. Kendler KS. The genetics of schizophrenia and related disorders: a review . In: Dunner DL, Gershon ES, Barrett JE, eds. Relatives at Risk for Mental Disorder . New York, NY: Raven Press; 1988:247-266. 42. Kidd KK, Kennedy JL. The genetics of affective disorders . In: Wetterberg L, ed. Genetics of Neuropsychiatric Diseases . New York, NY: Macmillan Publishing Co Inc; 1989:191-198.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Nov 1, 1993

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