No CrossRef data available.
Article contents
Comorbilidad del trastorno de ansiedad generalizada y el trastorno depresivo mayor: ¿un ejemplo de peliotropía genética?
Published online by Cambridge University Press: 12 May 2020
Resumen
El trastorno de ansiedad generalizada (TAG) y el trastorno depresivo mayor (TDM) son el tipo más común de comorbilidad de ansiedad-estado de ánimo. Hasta el 80% de los sujetos con TAG vital tienen también un trastorno del estado de ánimo comórbido durante suvida. Se han propuesto muchas hipótesis para explicar esta elevada comorbilidad. La pleiotropía, es decir, una mutación genética individual explica (aparentemente) trastornos diferentes, es una de ellas y se revisa aquí. La importancia y fiabilidad de la comorbilidad del TAG y el TDM (1); los datos a favor de la coagregación del TAG y el TDM dentro de las familias (el riesgo de un trastorno en un probando aumenta el riesgo para el otro en los familiares) (2); la herencia sustancial para ambos trastornos según estudios de gemelos con datos para una correlación genética de la unidad entre los dos trastornos (3), y la existencia de numerosos mecanismos (4) que vinculan potencialmente los dos trastornos a genes de vulnerabilidad comunes están de acuerdo con esta hipótesis. Se dan algunos ejemplos de mecanismos potencialmente compartidos (como la disrregulación del CRF o los factores de transcripción anormales) y posibles genes de vulnerabilidad común (por ejemplo, el gen transportador de la serotonina) para destacar la hipótesis de la pleiotropía.
- Type
- Artículo original
- Information
- Copyright
- Copyright © European Psychiatric Association 2004
References
Bibliografía
Alanen, Y.The family in the pathogenesis of schizophrenic and neurotic disorders. Acta Psychiatr Stand 1966 (Suppl 190): 1–654.Google ScholarPubMed
Andrews, G., Stewart, G., Alien, R., Henderson, A.S.The genetics of six neurotic disorders: a twin study. J Affect Disord 1990;19:23–9.CrossRefGoogle ScholarPubMed
Angst, J., Vollrath, M.The natural history of anxiety disorders. Acta Psychiatr Scand 1991;84:446–52.CrossRefGoogle ScholarPubMed
Angold, A., Costello, E.J., Erkanli, A.Comorbidity. J Child Psychol Psychiatry 1999;40:57–87.CrossRefGoogle ScholarPubMed
Avenevoli, S., Stolar, M., Li, J., Dierker, L., Ries Merikangas, K.Comor- bidity of depression in children and adolescents: models and evidence from a prospective high-risk family study. Biol Psychiatry 2001;49:1071–81.CrossRefGoogle Scholar
Ballenger, J.C.Clinical guidelines for establishing remission in patients with depression and anxiety. J Clin Psychiatry 1999;60(Suppl 22):29–34.Google ScholarPubMed
Bennett, A.J., Lesch, K.P., Heils, A., Long, J.C., Lorenz, J.G., Shoaf, S.E., et al. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 2002;7:118–22.CrossRefGoogle ScholarPubMed
Biederman, J., Faraone, S.V., Hirshfeld-Becker, D.R., Friedman, D., Robin, J.A., Rosenbaum, J.E.Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depres- sion. Am J Psychiatry 2001;158:49–57.CrossRefGoogle Scholar
Bijl, R.V., Ravelli, A., van Zessen, G.Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psyctiatry Psychiatr Epidemiol 1998;33:587–95.CrossRefGoogle Scholar
Birmaher, B., Dahl, R.E., Williamson, D.E., Perel, J.M., Brent, D.A., Axclson, D.A., et al. Growth hormone secretion in children and adolescents at high risk for major depressive disorder. Arch Gen Psychiatry 2000; 57:867–72.CrossRefGoogle ScholarPubMed
Boncinelli, E.Homeobox genes in development. In: Delgado-Escueta, A.V., Wilson, W.A., Olsen, R.W., Porter, R.J., editors. Jasper’s basic mecha- nism of the epilepsies: advances in neurology, vol. 79. Philadelphia: Lippincott; 1999. p. 81–94.Google Scholar
Boyer, R.Do anxiety and depression have a common pathophysiologi- cal mechamsm? Acta Psychiatr Scand 2000;406(Suppl):24–9.CrossRefGoogle Scholar
Braconi, L.Le psiconovrosi e le psicosi nei gemelli. Acta Geneticae Medicae et Gemellologiae 1961;10:100–36.CrossRefGoogle Scholar
Brady, E.U., Kendall, P.C.Comorbidity of anxiety and depression in children and adolescents. Psychol Bull 1992;111:244–55.CrossRefGoogle ScholarPubMed
Breslau, N., Davis, G.C.Further evidence on the doubtfull validity of generaüzed anxiety disorder. Psychiatry Res 1985;16:177–9.CrossRefGoogle Scholar
Breslau, N., Davis, G.C., Prabucki, K.Searching for evidence on the validity of generalizad anxiety disorder: psychopathology in children of anxious mothers. Psychiatry Res 1987;20:285–97.CrossRefGoogle Scholar
Brown, E.Heredity in the psychoneuroses. Proceedings of the Royal Society of Medicine 1942;35:785–90.CrossRefGoogle ScholarPubMed
Bruijn, J.A., Moleman, P., van den Broek, W.W., Mulder, P.G.Trait anxiety and the effect of a single high dose of diazepam in unipolar depression. J Psychiatr Res 2001;35:331–7.CrossRefGoogle ScholarPubMed
Cao, B.J., Li, Y.Reduced anxiety- and depression-like behaviors in Emxl homozygous mutant mice. Brain Res 2002;937:32–40.CrossRefGoogle Scholar
Carón, C., Rutter, M.Comorbidity in child psychopathology: concepts, issues and research strategies. J Child Psychol Psychiatry 1991;32:1063–80.CrossRefGoogle ScholarPubMed
Carter, R.M., Wittchen, H.U., Pfister, H., Kessler, R.C.One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety 2001;13:78–88.CrossRefGoogle Scholar
Cecchi, C., Boncinelli, E.Emx homeogenes and mouse brain development. Trends Neurosci 2000;23:347–52.CrossRefGoogle ScholarPubMed
Church, A.J., Cardoso, F., Dale, R.C., Lees, A.J., Thompson, E.J., Giovannoni, G.Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology 2002;59:227–31.CrossRefGoogle ScholarPubMed
Clayton, P.J., Grove, W.M., Coryell, W., Keller, M., Hirschfeld, R., Fawcett, J.Follow-up and family study of anxious depression. Am J Psychiatry 1991;148:1512–7.Google ScholarPubMed
Cloninger, C.R., Martin, R.L., Clayton, R.A blind follow-up and family study of anxiety neurosis: preliminary analysis of the St. Louis 5000. In: Klein, D.F., Rabkin, J., editors. Anxiety: new research and changing concepts. New York: Raven Press; 1981. p. 137–48.Google Scholar
Cohén, M.The high familial prevalence of neurocirculatory asthenia (anxiety neurosis, effort syndrome). Am J Hum Genet 1951;3:126–58.Google Scholar
Contarino, A., Heinrichs, S.C., Gold, L.H.Understanding corticotropin releasing factor neurobiology: contributions from mutant mice. Neuropeptides 1999;33:1–12.CrossRefGoogle ScholarPubMed
Cyphers, L.H., Phillips, K., Fulker, D.W., Mrazek, D.A.Twin temperament during the transition from infancy to early childhood. J Am Acad Child Adolesc Psychiatry 1990;29:392–7.CrossRefGoogle Scholar
Curtis, A.L., Valentino, R.J.Corticotropin-releasing factor neurotransmission in locus coeruleus: a possible site of antidepressant action. Brain Res Bull 1994;35:581–7.CrossRefGoogle ScholarPubMed
Dahl, R.E., Birmaher, B., Williamson, D.E., Dorn, L., Perel, J., Kaufman, J., et al. Low growth hormone response to growth hormone-releasing hormone in child depression. Biol Psychiatry 2000;48:981–8.CrossRefGoogle ScholarPubMed
Deary, I.J., Battersby, S., Whiteman, M.C., Counor, J.M., Fowkes, F.G., Harmar, A.Neuroticism and polymorphisms in the serotonin transporter gene. Psychol Med 1999;29(3):735–9.CrossRefGoogle ScholarPubMed
Donadi, E.A., Smith, A.G., Louzada-Junior, P., Voltarelli, J.C., Nepom, G.T.HLA class I and class II profiles of patients presenting with Sydenham’s chorea. J Neurol 2000;247:122–8.Google Scholar
Eckart, K., Radulovic, J., Radulovic, M., Jahn, O., Blank, T., Stiedl, O., et al. Actions of CRF and its analogs. Curr Med Chem 1999;6:1035–53.Google ScholarPubMed
Fanous, A., Gardner, C.O., Prescott, C.A., Cancro, R., Kendler, K.S.Neuroticism, major depression and gender: a population-based twin study. Psychol Med 2002;32:719–28.CrossRefGoogle ScholarPubMed
Goldsmith, H.H., Lemery, K.S.Linking temperamental fearfulness and anxiety symptoms: a behavior-genetic perspective. Biol Psychiatry 2000;48(12):1199–209.CrossRefGoogle ScholarPubMed
Goldstein, R.B., Wickramaratne, P.J., Horwath, E., Weissman, M.M.Familial aggregation and phenomenology of ’early’-onset (at or before age 20 years) panic disorder. Arch Gen Psychiatry 1997;54:271–8.CrossRefGoogle ScholarPubMed
Gorwood, R.Genetic association studies in behavioral neuroscience. In: Cruzio, W., Gerlai, R., editors. Molecular genetic techniques for behavioural neuroscience. Amsterdam: Elsevier; 1999. p. 113–21.Google Scholar
Graziani, G., Aroldi, A., Surjan, M., Colussi, G., Petrillo, M., Bianchi Porro, G.Gastric acid secretion in absorptive hyperaclcluria. Lancet 1981;1:442–3.CrossRefGoogle Scholar
Greenberg, B.D., Li, Q., Lucas, F.R., Hu, S., Sirota, L.A., Benjamin, J., et al. Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. Am J Med Genet 2000;96:202–16.3.0.CO;2-J>CrossRefGoogle Scholar
Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400–3.CrossRefGoogle ScholarPubMed
Hettema, J.M., Prescott, C.A., Kendler, K.S.A population-based twin study of generalized anxiety disorder in men and women. J Nerv MentDis 2001;189:413–20.CrossRefGoogle ScholarPubMed
Hirano, T.Molecular basis underlying functional pleiotropy of cytokines and growth factors. Biochem Biophys Res Commun 1999;260:303–8.CrossRefGoogle ScholarPubMed
Hoehe, M.R., Wendel, B., Grunewald, I., Chiaroni, P., Levy, N., Morris Rosendahl, D., et al. Serotonin transponer [5-HTT] gene polymorp- hisms are not associated with susceptibility to mood disorders. Am J MedGenet 1998;81:1–3.3.0.CO;2-2>CrossRefGoogle Scholar
Hudson, J.I., Mangweth, B., Pope, H.G. Jr, De Col, C., Hausmann, A., Gutweniger, S., et at. Family study of affecdve spectrum disorder. Arch Gen Psychiatry 2003;60:170–7.CrossRefGoogle ScholarPubMed
Ihda, S.A study of neurosis by twin method. Psychiatrica Neurologi- ca Japenica 1960;63:861–92.[in Japanese].Google Scholar
Jang, K.L., Livesley, W.J., Vernon, P.A.Heritability of the big five personality dimensions and their facets: a twin study. J Pers 1996;64:577–91.CrossRefGoogle ScholarPubMed
Jang, K.L., Hu, S., Livesley, W.J., Angleitner, A., Riemann, R., Ando, J., et al. Covariance structure of neuroticism and agreeableness: a twin and molecular genetic analysis of the role of the serotonin transporter gene. J Pers Soc Psychol 2001;81:295–304.CrossRefGoogle ScholarPubMed
Johnson, W., McGue, M., Gaist, D., Vaupel, J.W., Christensen, K.Fre- quency and heritability of depression symptomatology in the second half o f life: evidence from Danish twins over 45. Psychol Med 2002;32:1175–85.CrossRefGoogle Scholar
Judd, L.L., Kessler, R.C., Paulas, M.P., Zeller, P.V., Wittchen, H.U., Kunovac, J.L.Comorbidity as a fundamental feature of generalized anxiety disorders: results from the National Comorbidity Study (NCS). Acta Psychiatr Scand 1998;393(Suppl):ó–11.Google Scholar
Kagan, J., Snidman, N.Early childhood predictors of adult anxiety disorders. Biol Psychiatry 1999;46:1536–41.CrossRefGoogle ScholarPubMed
Kendler, K.S., Heath, A.C., Martin, N.G., Eaves, L.J.Symptoms of anxiety and symptoms of depression. Same genes, different environments? Arch Gen Psychiatry 1987;44:451–7.CrossRefGoogle ScholarPubMed
Kendler, K.S., Neale, M.C., Kessler, R.C., Heath, A.C., Eaves, L.J.Generali- zed anxiety disorder in women. A population-based twin study. Arch Gen Psychiatry 1992;49:267–72.CrossRefGoogle Scholar
Kendler, K.S., Neale, M.C., Kessler, R.C., Heath, A.C., Eaves, L.J.Major depression and generalizad anxiety disorder. Same genes, (partly) different environments? Arch Gen Psychiatry 1992;49:716–22.CrossRefGoogle Scholar
Kendler, K.S.Is seeking treatment for depression predicted by a history of depression in relatives? Implications for family studies of affective disorder. Psychol Med 1995;25:807–14.CrossRefGoogle ScholarPubMed
Kendler, K.S.Major depression and generalised anxiety disorder. Same genes, (partly) different enviroments—revisited. Br J Psychiatry 1996;30(Suppl):68–75.CrossRefGoogle Scholar
Kendler, K.S.The diagnostic validity of melancholic major depression in a population-based sample of female twins. Arch Gen Psychiatry 1997;54:299–304.CrossRefGoogle Scholar
Kendler, K.S., Davis, C.G., Kessler, R.C.The familial aggregation of com- mon psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. Br J Psychiatry 1997;170:541–8.CrossRefGoogle Scholar
Kendler, K.S., Gardner, C.O., Prescott, C.A.Toward a comprehensive developmental modal for major depression in women. Am J Psychiatry 2002;159:1133–45.CrossRefGoogle Scholar
Kessler, R.C., McGonagle, K.A., Zhao, S., Nelson, C.B., Hughes, M., Eshleman, S., et al. Lifetime and 12-month prevalence of DSMTII-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19.CrossRefGoogle ScholarPubMed
Kessler, R.The epidemiology of psychiatric comorbidity. In: Tsuang, M., Tohen, M., Zahner, G., editors. Textbook of psychiatric epidemiology. New York: John Wiley & Sons; 1995. p. 179–97.Google Scholar
Kessler, R.C.The prevalence of psychiatric comorbidity. In: Wetzler, S., et al., editors. Treatment strategies for patients with psychiatric comorbidity. New York: John Wiley & Sons; 1997. p. 23–48.Google Scholar
Kessler, R.C.The epidemiology of puré and comorbid generalizad anxiety disorder: a review and evaluation of recent research. Acta Psychiatr Scand 2000;406(Suppl):7–13.Google Scholar
Lake, R.I., Eaves, L.J., Maes, H.H.s, Heath, A.C., Martin, N.G.Further evidence against the environmental transmission of individual differences in neuroticism from a collaborative study of 45,850 twins and relatives on two continents. Behav Genet 2000;30:223–33.CrossRefGoogle ScholarPubMed
Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., et al. Association of anxiety-retated traits with a polymorphism in the serotonin transporter gene regulatory región. Science 1996;274:1527–31.CrossRefGoogle ScholarPubMed
Lieb, R., Isensee, B., Hofler, M., Pfister, H., Wittchen, H.U.Parental major depression and the risk of depression and other mental disorders in offspring: a prospective-longitudinal community study. Arch Gen Psychiatry 2002;59:365–74.CrossRefGoogle ScholarPubMed
Malhi, G.S., Moore, J., McGuffin, P.The genetics of major depressive disorder. Curr Psychiatry Rep 2000;2:165–9.CrossRefGoogle ScholarPubMed
Mallamaci, A., Ianuone, R., Briata, P., Pintonello, L., Mercurio, S., Boncinelli, E., et al. EMX2 protein in the developing mouse brain and olfactory area. Mech Dev 1998;77:165–72.CrossRefGoogle ScholarPubMed
Mansbach, R.S., Brooks, E.N., Chen, Y.L.Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist. Eur J Pharmacol 1997;323:21–6.CrossRefGoogle ScholarPubMed
Matheny, A.P. JrChildren’s behavioral inhibition over age and across situations: genetic similarity for a trait during change. J Pers 1989;57:215–35.CrossRefGoogle ScholarPubMed
Mazzanti, C.M., Lappalainen, J., Long, J.C., Bengel, D., Naukkarinen, H., Eggert, M., et al. Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Arch Gen Psychiatry 1998;55:936–40.CrossRefGoogle ScholarPubMed
McElroy, J.F., Ward, K.A., Zeller, K.L., Jones, K.W., Gilligan, P.J., He, L., et al. The CRF[1] receptor antagonist DMP696 produces anxiolytic effects and inhibits the stress-induced hypothalamic-pituitary-adrenal axis activation without sedation or ataxia in rats. Psychopharmacology (Berl 2002;165:86–92.CrossRefGoogle ScholarPubMed
McGuffin, P., Katz, R., Bebbington, P.Hazard, heredity and depression. A family study. J Psychiatr Res 1987;21:365–75.CrossRefGoogle ScholarPubMed
Mclnnes, R.Observations on heridity in neurosis. Proceedings of the Royal Society of Medicine 1937;30:895–904.CrossRefGoogle Scholar
Mendlewicz, J., Papadimitriou, G., Wilmotte, J.Family study of panic disorder: comparison with generalized anxiety disorder, major depression, and normal subjects. Psychiatr Genet 1993;3:73–8.CrossRefGoogle Scholar
Merikangas, K.R., Mehta, R.L., Molnar, B.E., Walters, E.E., Swendsen, J.D., Aguilar-Gaziola, S., et al. Comorbidity of substance use disorders with mood and anxiety disorders: results of the International Consortium in Psychiatric Epidemiology. Addict Behav 1998;23:893–907.CrossRefGoogle ScholarPubMed
Merikangas, K.R., Swendsen, J.D., Preisig, M.A., Chazan, R.Z.Psychopathology and temperament in parents and offspring: results of a family study. J Affect Disord 1998;51:63–74.CrossRefGoogle ScholarPubMed
Merikangas, K.R., Angst, J.Comorbidity and social phobia: evidence from clinical, epidemiologic, and genetic studies. Eur Arch Psychiatry Clin Neurosci 1995;244:297–303.CrossRefGoogle ScholarPubMed
Meyer, B.Personality and mood correlates o f avoidant personality disorder. J Personal Disord 2002;16:174–88.CrossRefGoogle Scholar
Miller, E.M.On the correlation of myopia and intelligence. Genet Soc Gen Psychol Monogr 1992;118:361–83.Google ScholarPubMed
Noyes, R. Jr, Clancy, J., Crowe, R., Hoenk, R.P., Slymen, D.J.The familial prevalence of anxiety neurosis. Arch Gen Psychiatry 1978;35:1057–74.CrossRefGoogle ScholarPubMed
Noyes, R. Jr, Clarkson, C., Crowe, R.R., Yates, W.R., McChesney, C.M.A family study o f generalized anxiety disorder. Am J Psychiatry 1987;144:1019–24.Google Scholar
Noyes, R. Jr, Woodman, C., Garvey, M.J., Cook, B.L., Suelzer, M., Clancy, J., et al. Generalized anxiety disorder vs. panic disorder. Distinguishing characteristics ard patterns of comorbidity. J Nerv Ment Dis 1992;180:369–79.CrossRefGoogle Scholar
Offord, D.R., Boyle, M.H., Campbell, D., Goering, P., Lin, E., Wong, M., et al. One year prevalence of psychiatric disorder in Ontarians 15 to 64 years of age. Can J Psychiatry 1996;41:559–63.CrossRefGoogle ScholarPubMed
Ohara, K., Suzuki, Y., Ochiai, M., Tsukamoto, T., Tani, K., Ohara, K.Avariable- number-tandem-repeat of the serotonin transporter gene and anxiety disorders. Prog Neuropsychopharmacol Biol Psychiatry 1999;23:55–65.CrossRefGoogle Scholar
Olfson, M., Fireman, H., Weissman, M.M., León, A.C., Sheehan, D.V., Kathol, R.G., et al. Mental disorders and disability among patients in a primary cure group practice. Ara J Psychiatry 1997;154:1734–40.CrossRefGoogle Scholar
Ormel, J., VonKorff, M., Ustun, T.B., Pini, S., Korten, A., Oldehinkel, T.Common mental disorders and disability across cultures. Results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA 1994;272:1741–8.CrossRefGoogle Scholar
Parker, G., Wilhelm, K., Mitchell, P., Austin, M.P., Roussos, J., Gladstone, G.The Influence of anxiety as a risk to early onset major depression. J Affect Disord 1999;52:11–7.CrossRefGoogle ScholarPubMed
Price, L.H., Goddard, A.W., Barr, L.C., Goodman, W.K.Pharmacological challenges in anxiety disorders. In: Bloom, F.E., Kupfer, D.J., editors. Psychopharmacology: the fourth generation of progress. New York: Raven press; 1995. p. 1311–23.Google Scholar
Rickels, K., Rynn, M.Pharmacotherapy of generalizad anxiety disorder. J Clin Psychiatry 2002;S14:9–16.Google Scholar
Rijsdijk, F.V., Sham, P.C., Sterne, A., Purcell, S., McGuffm, P., Farmer, A., et al. Life events and depression in a community sample of siblings. Psychol Med 2001;31:401–10.CrossRefGoogle Scholar
Robinson, J.L., Kagan, J., Reznick, J.S., Corley, R.The heritability of inhibited and uninhibited behavior: a twin study. Dev Psychol 1992;28:1030–7.CrossRefGoogle Scholar
Rotter, J., Rimoin, D., Samloff, I.Genetic heterogeneity in peptic ulcer. Lancet 1979;1:1088–9.CrossRefGoogle ScholarPubMed
Rosenbaum, J.F., Biederman, J., Hirshfeld-Becker, D.R., Kagan, J., Snidman, N., Friedman, D., et al. A controlled study of behavioral inhibition in children of parents with panic disorder and depression. Am J Psychiatry 2000;157:2002–10.CrossRefGoogle ScholarPubMed
Roy, M.A., Neale, M.C., Kendler, K.S.Selecting a control group in studies of the familial coaggregation of two disorders: a quantitative genetics perspective. Am J Med Genet 1997;74:296–303.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Sartorius, N., Ustun, T.B., Lecrubier, Y., Wittchen, H.U.Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care. Br J Psychiatry 1996;30(Suppl):38–43.CrossRefGoogle Scholar
Scherrer, J.F., True, W.R., Xían, H., Lyons, M.J., Eisen, S.A., Goldberg, J., et al. Evidence for genetic Influences common and specific to symptoms of generalized anxiety and panic. J Affect Disord 2000;57:25–35.CrossRefGoogle ScholarPubMed
Shields, J., Slater, E.La similarité du diagnosdc chez les jumeaux et le problém de la spécificité biologique daos les névroses et les troubles de la personnalité. Evol Psychiatr (Paris) 1966;31:441–51.Google Scholar
Schonfeld, W.H., Verboncocur, C.J., Fifer, S.K., Lipschutz, R.C., Luteck, D.P., Buesching, D.R.The functioning and well-being of patients with unrecognized anxiety disorders and major depressive disorder. J Affect Disord 1997;43:105–19.CrossRefGoogle ScholarPubMed
Skodol, A.E., Schwartz, S., Dohrenwend, B.P., Levav, I., Shrout, P.E.Minor depression in a cohort of young adults in Israel. Arch Gen Psychiatry 1994;51:542–51.CrossRefGoogle Scholar
Skre, I., Onstad, S., Torgersen, S., Lygren, S., Kringlen, E.A twin study of DSM-III-R anxiety disorders. Acta Psychiatr Scand 1993;88:85–92.CrossRefGoogle ScholarPubMed
Slater, E.Psychotic and neurotic illnesses in twins. London: Her Majesty’s Stationery Office; 1953 Medical Research coflncil special report series No. 278.Google ScholarPubMed
Todd, R.D., Botteron, K.N.Etiology and genetics of early-onset mood disorders. Child Adolesc Psychiatr Clin N Am 2002; 11:499–518.CrossRefGoogle ScholarPubMed
Torgersen, S.Genetics of neurosis. The effects of sampling variation upon the twin concordance ratio. Br J Psychiatry 1983;142:126–32.CrossRefGoogle ScholarPubMed
Tsuang, M.T., Faraone, S.V.The genetics of mood disorders. Baltimore (MD): Johns Hopkins University Press; 1990.Google Scholar
Uhde, T.W., Vittone, B.J., Siever, L.J., Kaye, W.H., Post, R.M.Blunted growth hormone response to clonidine in panic disorder patients. Biol Psychiatry 1986;21:1081–5.CrossRefGoogle ScholarPubMed
Vora, S., Davidson, M., Seaman, C., Miranda, A.F., Noble, N.A., Tanaka, K.R., et al. Heterogeneity of the molecular Iesions in inherited phosphofructokinase deficiency. J Clin Invest 1983;72:1995–2006.CrossRefGoogle Scholar
Williamson, D.E., Coleman, K., Bacanu, S.A., Devlin, B.J., Rogers, J., Ryan, N.D., et al. Heritability of fearful-anxious endophenotypes in infant rhesus macaques: a preliminary report. Biol Psychiatry 2003;53:284–91.CrossRefGoogle ScholarPubMed
Wittchen, H.U.Generalized anxiety disorder: prevalence, barden, and cost to society. Depress Anxiety 2002;16:162–71.CrossRefGoogle Scholar
Wolk, S.I., Horwath, E., Goldstein, R.B., Wickramaratne, P., Weissman, M.M.Comparison of R.D.C., DSM-III, DSM-III-R diagnostic criteria for generalizad anxiety disorder. Anxiety 1996;2:71–9.3.0.CO;2-G>CrossRefGoogle Scholar
Zimmerman, M., Chelminski, I., McDermut, W.Major depressive disorder and axis I diagnostic comorbidity. J Clin Psychiatry 2002;63:187–93.CrossRefGoogle ScholarPubMed