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Table of Contents
Vol. 58, No. 3-4, 2004
Issue release date: March 2005
Section title: Paper
Hum Hered 2004;58:122–130
(DOI:10.1159/000083538)

Computer-Assisted Phenotype Characterization for Genetic Research in Psychiatry

Fangerau H.a,b · Ohlraun S.a,c · Granath R.O.a · Nöthen M.M.d,e · Rietschel M.a,c · Schulze T.G.a,c
aDepartment of Psychiatry, University of Bonn, Bonn, bInstitute for the History of Medicine, University of Düsseldorf, Düsseldorf, cDivision of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, dDepartment of Genomics, Life and Brain Center, University of Bonn, Bonn, and eInstitute of Human Genetics, University of Bonn, Bonn, Germany
email Corresponding Author

Abstract

Psychiatric disorders differ from other complex phenotypes in their lack of objectively assessable biological markers that contribute to the establishment of a research diagnosis for genetic studies. To nevertheless allow for the delineation of genetically meaningful diagnostic entities for psychiatric genetic research, comprehensive phenotype characterization procedures are required. It is widely agreed that these should include the standardized assessment of life-time clinical symptomatology, sociodemographic, and environmental factors. Data should be based on several sources, i.e. diagnostic interviews with probands and their relatives as well as a thorough review of medical records, and final assignment of diagnosis should follow robust algorithms (i.e. best-estimate procedures, consensus diagnosis). Here, we outline a practical implementation of such a phenotype characterization strategy, including patient recruitment, study enrolment procedures, comprehensive diagnostic assessment, and data management. We argue that successful psychiatric phenotype characterization requires flexible tools. For this purpose, we have developed a computer-assisted phenotype characterization inventory, built around the backbone of a relational database. It allows for the straightforward assessment of symptoms, automated error checks and diagnostic assignment, easily manageable data storage and handling, and flexible data transfer between various research centers even across language barriers, while at the same time keeping up with the highest standards for the protection of sensitive patient data.

© 2004 S. Karger AG, Basel


  

Key Words

  • Patient recruitment
  • Best estimate diagnosis
  • Consensus diagnosis
  • Complex disorder
  • Relational database
  • Standardized interview
  • Research diagnosis

References

  1. Andreasen NC: From molecule to mind: genetics, genomics, and psychiatry. Am J Psychiatry 2003;160:613.

    External Resources

  2. Merikangas KR, Risch N: Will the genomics revolution revolutionize psychiatry? Am J Psychiatry 2003;160:625–635.
  3. Insel TR, Collins FS: Psychiatry in the genomics era. Am J Psychiatry 2003;160:616–620.
  4. Merikangas KR, Chakravarti A, Moldin SO, Araj H, Blangero JC, Burmeister M, Crabbe J Jr, Depaulo JR Jr, Foulks E, Freimer NB, Koretz DS, Lichtenstein W, Mignot E, Reiss AL, Risch NJ, Takahashi JS: Future of genetics of mood disorders research. Biol Psychiatry 2002;52:457–477.
  5. Skuse DH: Endophenotypes and child psychiatry. Br J Psychiatry 2001;178:395–396.
  6. Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.
  7. Tilley L, Morgan K, Kalsheker N: Genetic risk factors in Alzheimer’s disease. Mol Pathol 1998;51:293–304.
  8. Brant SR, Panhuysen CI, Bailey-Wilson JE, Rohal PM, Lee S, Mann J, Ravenhill G, Kirschner BS, Hanauer SB, Cho JH, Bayless TM: Linkage heterogeneity for the IBD1 locus in Crohn’s disease pedigrees by disease onset and severity. Gastroenterology 2000;119:1483–1490.
  9. Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P: Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 1993;328:697–702.
  10. McMahon FJ, Thomas CJ, Koskela RJ, Breschel TS, Hightower TC, Rohrer N, Savino C, McInnis MG, Simpson SG, DePaulo JR: Integrating clinical and laboratory data in genetic studies of complex phenotypes: a network-based data management system. Am J Med Genet 1998;81:248–256.
  11. Altman RB., Klein TE: Challenges for biomedical informatics and pharmacogenomics. Annu Rev Pharmacol Toxicol 2002;42:113–133.
  12. Bonvicini KA: The art of recruitment: the foundation of family and linkage studies of psychiatric illness. Fam Process 1998;37:153–165.
  13. Schulze TG, Muller DJ, Krauss H, Gross M, Bauer I, Fangerau-Lefevre H, Illes F, Ohlraun S, Fimmers R, Cichon S, Held T, Propping P, Nothen MM, Maier W, Rietschel M: Caught in the trio trap? Potential selection bias inherent to association studies using parent-offspring trios. Am J Med Genet 2001;105:351–353.
  14. 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.
  15. Merikangas KR, Spence MA, Kupfer DJ: Linkage studies of bipolar disorder: methodologic and analytic issues. Report of MacArthur Foundation Workshop on Linkage and Clinical Features in Affective Disorders. Arch Gen Psychiatry 1989;46:1137–1141.
  16. Leboyer M, McGuffin P: Collaborative strategies in the molecular genetics of the major psychoses. Br J Psychiatry 1991;158:605–610.
  17. Spitzer RL, Williams JB, Gibbon M, First MB: The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry 1992;49:624–629.
  18. Mannuzza S, Fyer AJ, Endicott J, et al: Family Informant Schedule and Criteria (FISC). New York, Anxiety Disorder Clinic, New York State Psychiatric Institute, 1985.
  19. Geddes JR, Lawrie SM: Obstetric complications and schizophrenia: a meta-analysis. Br J Psychiatry 1995;167:786–793.
  20. McNeil TF, Sjöström K: The McNeil-Sjöström OC scale: a comprehensive scale for measuring obstetric complications. Malmö, Lund University Press, 1994.
  21. Brown GW, Harris TO: Social origins of depression: a study of psychiatric disorder in women. London, Tavistock, 1978.
  22. Dohrenwend BS, Krasnoff L, Askenasy AR, Dohrenwend BP: Exemplification of a method for scaling life events: the Peri Life Events Scale. J Health Soc Behav 1978;19:205–229.
  23. Paykel ES: The Interview for Recent Life Events. Psychol Med 1997;27:301–310.
  24. Cannon-Spoor HE, Potkin SG, Wyatt RJ: Measurement of premorbid adjustment in chronic schizophrenia. Schizophr Bull 1982;8:470–484.
  25. Krauss H, Marwinski K, Schulze T, Müller DJ, Held T, Rietschel M, Maier W, Freyberger HJ: Reliability and validity of the German version of the Premorbid Adjustment Scale (PAS). Nervenarzt 2000;71:188–194.
  26. Barnes TR, Braude WM: Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 1985;42:874–878.
  27. Simpson GM, Angus JW: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 1970;suppl 212:11–19.
  28. Guy W: ECDEU Assessment Manual for Psychopharmacology, revised edition. Rockville, U.S. Department of Health and Human Service, Alcohol Drug Abuse and Mental Health Administration, NIMH Psychopharmacology Research Branch, 1976.
  29. Simpson GM, Lee JH, Zoubok B, Gardos G: A rating scale for tardive dyskinesia. Psychopharmacology (Berl) 1979;64:171–179.
  30. Kay SR, Opler LA, Fishbein A: Positive and Negative Syndrome Scale rating manual. Social and Behavioral Sciences Documents, 1987.
  31. Endicott J, Spitzer RL, Fleiss JL, Cohen J: The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976;33:766–771.
  32. McGuffin P, Farmer A, Harvey I: A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 1991;48:764–770.
  33. Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  34. Reitan R: Trail Making Test: Manual for Administration, Scoring, and Interpretation. Bloomington, Indiana University Press, 1975.
  35. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF: Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Res 1979;1:131–139.
  36. Coccaro EF, Berman ME, Kavoussi RJ: Assessment of life history of aggression: development and psychometric characteristics. Psychiatry Res 1997;73:147–157.
  37. Patton JH, Stanford MS, Barratt ES: Factor structure of the Barratt impulsiveness scale. J Clin Psychol 1995;51:768–774.
  38. Parker G: Parental characteristics in relation to depressive disorders. Br J Psychiatry 1979;134:138–147.
  39. Kendler KS, Neale MC, Prescott CA, Kessler RC, Heath AC, Corey LA, Eaves LJ: Childhood parental loss and alcoholism in women: a causal analysis using a twin-family design. Psychol Med 1996;26:79–95.
  40. Cox BJ, Enns MW, Clara IP: The parental bonding instrument: confirmatory evidence for a three-factor model in a psychiatric clinical sample and in the National Comorbidity Survey. Soc Psychiatry Psychiatr Epidemiol 2000;35:353–357.
  41. Martin J, Anderson J, Romans S, Mullen P, O’Shea M: Asking about child sexual abuse: methodological implications of a two stage survey. Child Abuse Negl 1993;17:383–392.
  42. Mullen PE, Martin JL, Anderson JC, Romans SE, Herbison GP: Childhood sexual abuse and mental health in adult life. Br J Psychiatry 1993;163:721–732.
  43. Nelson EC, Heath AC, Madden PA, Cooper ML, Dinwiddie SH, Bucholz KK, Glowinski A, McLaughlin T, Dunne MP, Statham DJ, Martin NG: Association between self-reported childhood sexual abuse and adverse psychosocial outcomes: results from a twin study. Arch Gen Psychiatry 2002;59:139–145.
  44. Kendler KS, Bulik CM, Silberg J, Hettema JM, MyersJ, Prescott CA: Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry 2000;57:953–959.
  45. Bifulco A, Brown GW: Cognitive coping response to crises and onset of depression. Soc Psychiatry Psychiatr Epidemiol 1996;31:163–172.
  46. Roche PA, Annas GJ: Protecting genetic privacy. Nat Rev Genet 2001;2:392–396.
  47. Austin MA: Ethical issues in human genome epidemiology: a case study based on the Japanese American Family Study in Seattle, Washington. Am J Epidemiol 2002;155:585–592.
  48. Schulze TG, McMahon FJ: Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. Hum Hered 2004;58:127–134.

    External Resources

  

Author Contacts

Thomas G. Schulze, MD
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health
University of Heidelberg, J5
D–68159 Mannheim (Germany)
Tel. +49 621 1703 6056, Fax +49 621 1703 6055, E-Mail schulze@zi-mannheim.de

  

Article Information

Received: June 30, 2004
Accepted: August 27, 2004
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 48

  

Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 58, No. 3-4, Year 2004 (Cover Date: Released March 2005)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.ch/hhe


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Psychiatric disorders differ from other complex phenotypes in their lack of objectively assessable biological markers that contribute to the establishment of a research diagnosis for genetic studies. To nevertheless allow for the delineation of genetically meaningful diagnostic entities for psychiatric genetic research, comprehensive phenotype characterization procedures are required. It is widely agreed that these should include the standardized assessment of life-time clinical symptomatology, sociodemographic, and environmental factors. Data should be based on several sources, i.e. diagnostic interviews with probands and their relatives as well as a thorough review of medical records, and final assignment of diagnosis should follow robust algorithms (i.e. best-estimate procedures, consensus diagnosis). Here, we outline a practical implementation of such a phenotype characterization strategy, including patient recruitment, study enrolment procedures, comprehensive diagnostic assessment, and data management. We argue that successful psychiatric phenotype characterization requires flexible tools. For this purpose, we have developed a computer-assisted phenotype characterization inventory, built around the backbone of a relational database. It allows for the straightforward assessment of symptoms, automated error checks and diagnostic assignment, easily manageable data storage and handling, and flexible data transfer between various research centers even across language barriers, while at the same time keeping up with the highest standards for the protection of sensitive patient data.

© 2004 S. Karger AG, Basel


  

Author Contacts

Thomas G. Schulze, MD
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health
University of Heidelberg, J5
D–68159 Mannheim (Germany)
Tel. +49 621 1703 6056, Fax +49 621 1703 6055, E-Mail schulze@zi-mannheim.de

  

Article Information

Received: June 30, 2004
Accepted: August 27, 2004
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 48

  

Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 58, No. 3-4, Year 2004 (Cover Date: Released March 2005)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.ch/hhe


Article / Publication Details

First-Page Preview
Abstract of Paper

Received: 6/30/2004
Accepted: 8/27/2004
Published online: 3/21/2005
Issue release date: March 2005

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Andreasen NC: From molecule to mind: genetics, genomics, and psychiatry. Am J Psychiatry 2003;160:613.

    External Resources

  2. Merikangas KR, Risch N: Will the genomics revolution revolutionize psychiatry? Am J Psychiatry 2003;160:625–635.
  3. Insel TR, Collins FS: Psychiatry in the genomics era. Am J Psychiatry 2003;160:616–620.
  4. Merikangas KR, Chakravarti A, Moldin SO, Araj H, Blangero JC, Burmeister M, Crabbe J Jr, Depaulo JR Jr, Foulks E, Freimer NB, Koretz DS, Lichtenstein W, Mignot E, Reiss AL, Risch NJ, Takahashi JS: Future of genetics of mood disorders research. Biol Psychiatry 2002;52:457–477.
  5. Skuse DH: Endophenotypes and child psychiatry. Br J Psychiatry 2001;178:395–396.
  6. Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.
  7. Tilley L, Morgan K, Kalsheker N: Genetic risk factors in Alzheimer’s disease. Mol Pathol 1998;51:293–304.
  8. Brant SR, Panhuysen CI, Bailey-Wilson JE, Rohal PM, Lee S, Mann J, Ravenhill G, Kirschner BS, Hanauer SB, Cho JH, Bayless TM: Linkage heterogeneity for the IBD1 locus in Crohn’s disease pedigrees by disease onset and severity. Gastroenterology 2000;119:1483–1490.
  9. Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P: Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 1993;328:697–702.
  10. McMahon FJ, Thomas CJ, Koskela RJ, Breschel TS, Hightower TC, Rohrer N, Savino C, McInnis MG, Simpson SG, DePaulo JR: Integrating clinical and laboratory data in genetic studies of complex phenotypes: a network-based data management system. Am J Med Genet 1998;81:248–256.
  11. Altman RB., Klein TE: Challenges for biomedical informatics and pharmacogenomics. Annu Rev Pharmacol Toxicol 2002;42:113–133.
  12. Bonvicini KA: The art of recruitment: the foundation of family and linkage studies of psychiatric illness. Fam Process 1998;37:153–165.
  13. Schulze TG, Muller DJ, Krauss H, Gross M, Bauer I, Fangerau-Lefevre H, Illes F, Ohlraun S, Fimmers R, Cichon S, Held T, Propping P, Nothen MM, Maier W, Rietschel M: Caught in the trio trap? Potential selection bias inherent to association studies using parent-offspring trios. Am J Med Genet 2001;105:351–353.
  14. 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.
  15. Merikangas KR, Spence MA, Kupfer DJ: Linkage studies of bipolar disorder: methodologic and analytic issues. Report of MacArthur Foundation Workshop on Linkage and Clinical Features in Affective Disorders. Arch Gen Psychiatry 1989;46:1137–1141.
  16. Leboyer M, McGuffin P: Collaborative strategies in the molecular genetics of the major psychoses. Br J Psychiatry 1991;158:605–610.
  17. Spitzer RL, Williams JB, Gibbon M, First MB: The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry 1992;49:624–629.
  18. Mannuzza S, Fyer AJ, Endicott J, et al: Family Informant Schedule and Criteria (FISC). New York, Anxiety Disorder Clinic, New York State Psychiatric Institute, 1985.
  19. Geddes JR, Lawrie SM: Obstetric complications and schizophrenia: a meta-analysis. Br J Psychiatry 1995;167:786–793.
  20. McNeil TF, Sjöström K: The McNeil-Sjöström OC scale: a comprehensive scale for measuring obstetric complications. Malmö, Lund University Press, 1994.
  21. Brown GW, Harris TO: Social origins of depression: a study of psychiatric disorder in women. London, Tavistock, 1978.
  22. Dohrenwend BS, Krasnoff L, Askenasy AR, Dohrenwend BP: Exemplification of a method for scaling life events: the Peri Life Events Scale. J Health Soc Behav 1978;19:205–229.
  23. Paykel ES: The Interview for Recent Life Events. Psychol Med 1997;27:301–310.
  24. Cannon-Spoor HE, Potkin SG, Wyatt RJ: Measurement of premorbid adjustment in chronic schizophrenia. Schizophr Bull 1982;8:470–484.
  25. Krauss H, Marwinski K, Schulze T, Müller DJ, Held T, Rietschel M, Maier W, Freyberger HJ: Reliability and validity of the German version of the Premorbid Adjustment Scale (PAS). Nervenarzt 2000;71:188–194.
  26. Barnes TR, Braude WM: Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 1985;42:874–878.
  27. Simpson GM, Angus JW: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 1970;suppl 212:11–19.
  28. Guy W: ECDEU Assessment Manual for Psychopharmacology, revised edition. Rockville, U.S. Department of Health and Human Service, Alcohol Drug Abuse and Mental Health Administration, NIMH Psychopharmacology Research Branch, 1976.
  29. Simpson GM, Lee JH, Zoubok B, Gardos G: A rating scale for tardive dyskinesia. Psychopharmacology (Berl) 1979;64:171–179.
  30. Kay SR, Opler LA, Fishbein A: Positive and Negative Syndrome Scale rating manual. Social and Behavioral Sciences Documents, 1987.
  31. Endicott J, Spitzer RL, Fleiss JL, Cohen J: The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976;33:766–771.
  32. McGuffin P, Farmer A, Harvey I: A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 1991;48:764–770.
  33. Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  34. Reitan R: Trail Making Test: Manual for Administration, Scoring, and Interpretation. Bloomington, Indiana University Press, 1975.
  35. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF: Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Res 1979;1:131–139.
  36. Coccaro EF, Berman ME, Kavoussi RJ: Assessment of life history of aggression: development and psychometric characteristics. Psychiatry Res 1997;73:147–157.
  37. Patton JH, Stanford MS, Barratt ES: Factor structure of the Barratt impulsiveness scale. J Clin Psychol 1995;51:768–774.
  38. Parker G: Parental characteristics in relation to depressive disorders. Br J Psychiatry 1979;134:138–147.
  39. Kendler KS, Neale MC, Prescott CA, Kessler RC, Heath AC, Corey LA, Eaves LJ: Childhood parental loss and alcoholism in women: a causal analysis using a twin-family design. Psychol Med 1996;26:79–95.
  40. Cox BJ, Enns MW, Clara IP: The parental bonding instrument: confirmatory evidence for a three-factor model in a psychiatric clinical sample and in the National Comorbidity Survey. Soc Psychiatry Psychiatr Epidemiol 2000;35:353–357.
  41. Martin J, Anderson J, Romans S, Mullen P, O’Shea M: Asking about child sexual abuse: methodological implications of a two stage survey. Child Abuse Negl 1993;17:383–392.
  42. Mullen PE, Martin JL, Anderson JC, Romans SE, Herbison GP: Childhood sexual abuse and mental health in adult life. Br J Psychiatry 1993;163:721–732.
  43. Nelson EC, Heath AC, Madden PA, Cooper ML, Dinwiddie SH, Bucholz KK, Glowinski A, McLaughlin T, Dunne MP, Statham DJ, Martin NG: Association between self-reported childhood sexual abuse and adverse psychosocial outcomes: results from a twin study. Arch Gen Psychiatry 2002;59:139–145.
  44. Kendler KS, Bulik CM, Silberg J, Hettema JM, MyersJ, Prescott CA: Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry 2000;57:953–959.
  45. Bifulco A, Brown GW: Cognitive coping response to crises and onset of depression. Soc Psychiatry Psychiatr Epidemiol 1996;31:163–172.
  46. Roche PA, Annas GJ: Protecting genetic privacy. Nat Rev Genet 2001;2:392–396.
  47. Austin MA: Ethical issues in human genome epidemiology: a case study based on the Japanese American Family Study in Seattle, Washington. Am J Epidemiol 2002;155:585–592.
  48. Schulze TG, McMahon FJ: Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. Hum Hered 2004;58:127–134.

    External Resources