Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-05T07:00:04.422Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of fear and anxiety in the familial risk for major depression: a three-generation study

Published online by Cambridge University Press:  14 February 2008

V. Warner ,
P. Wickramaratne  and
M. M. Weissman
V. Warner*
Affiliation:
Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA Department of Psychiatry, Columbia University College of Physicians and Surgeons and the Mailman School of Public Health, New York, NY, USA
P. Wickramaratne
Affiliation:
Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA Department of Psychiatry, Columbia University College of Physicians and Surgeons and the Mailman School of Public Health, New York, NY, USA
M. M. Weissman
Affiliation:
Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA Department of Psychiatry, Columbia University College of Physicians and Surgeons and the Mailman School of Public Health, New York, NY, USA
*
*Address for correspondence: V. Warner, M.P.H., New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032, USA.(Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression.

Method

Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD.

Results

In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns.

Conclusions

These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.

Keywords

Anxietydepressionfearmediatormulti-generation
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 11 , November 2008 , pp. 1543 - 1556
Copyright
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baron, RM, Kenny, DA (1986). The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical consideration. Journal of Personality and Social Psychology 6, 1173–1182.CrossRefGoogle Scholar
Beardslee, WR, Versage, EM, Gladstone, TRG (1998). Children of affectively ill parents: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry 37, 1134–1141.CrossRefGoogle ScholarPubMed
Bechara, A, Tranel, D, Damasio, H, Adolphs, R, Rockland, C, Damasio, AR (1995). Double dissociation of conditioning and declarative knowledge relative to the hippocampus in humans. Science 269, 1115–1118.CrossRefGoogle Scholar
Biederman, J, Petty, C, Hirshfeld-Becker, AH, Faraone, SV, Dang, D, Jackubowski, A, Rosenbaum, JF (2006). A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression. Psychological Medicine 36, 1141–1152.CrossRefGoogle ScholarPubMed
Biederman, J, Petty, CR, Hirshfeld-Becker, DR, Henin, A, Faraone, SV, Fraire, M, Henry, B, McQuade, J, Roesenbaum, JF (2007). Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression. Psychiatry Research 153, 245–252.CrossRefGoogle ScholarPubMed
Brady, EU, Kendall, PC (1992). Comorbidity of anxiety and depression in children and adolescents. Psychological Bulletin 111, 244–255.CrossRefGoogle ScholarPubMed
Breiter, HC, Etcoff, NL, Whalen, P (1996). Response and habituation of the human amygdala during the processing of facial expression. Neuron 17, 875–887.CrossRefGoogle ScholarPubMed
Breslau, N, Schultz, L, Peterson, E (1995). Sex differences in depression: a role for preexisting anxiety. Psychiatry Research 58, 1–12.CrossRefGoogle ScholarPubMed
Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, H, McClay, J, Mill, J, Martin, J, Braithwaite, A, Poulton, R (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389.CrossRefGoogle ScholarPubMed
Cohen, P, Cohen, J, Kasen, S, Noemi Velez, C, Hartmark, C, Johnson, J, Rojas, M, Brook, J, Streuning, EL (1993). An epidemiological study of disorders in late childhood and adolescence. 1. Age- and gender-specific prevalence. Journal of Child Psychology and Psychiatry and Allied Disciplines 34, 851–867.CrossRefGoogle Scholar
Cole, DA, Peeke, LG, Martin, JM, Truglio, R, Seroczynski, AD (1998). A longitudinal look at the relation between depression and anxiety in children and adolescents. Journal of Consulting and Clinical Psychology 66, 451–460.CrossRefGoogle Scholar
Cole, SR, Hernan, MA (2002). Fallibility in estimating direct effects. International Journal of Epidemiology 31, 163–165.CrossRefGoogle ScholarPubMed
Costello, EJ, Mustillo, S, Erkanli, A, Keeler, G, Angold, A (2003). Prevalence and development of psychiatric disorders in childhood and adolescence. Archives of General Psychiatry 60, 837–844.CrossRefGoogle ScholarPubMed
Cox, DR (1972). Regression models and life tables. Journal of the Royal Statistical Society of Britain 34, 187–220.Google Scholar
Cox, DR, Oakes, D (1984). Analysis of Survival Data. Chapman & Hall: London.Google Scholar
Davis, M (1998). Are different parts of the extended amygdala involved in fear versus anxiety? Biological Psychiatry 44, 1239–1247.CrossRefGoogle ScholarPubMed
Downey, G, Coyne, JC (1990). Children of depressed parents: an integrative review. Psychological Bulletin 108, 50–76.CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, RL (1978). A diagnostic interview: the schedule for affective disorders and schizophrenia. Archives of General Psychiatry 35, 837–844.CrossRefGoogle ScholarPubMed
Fava, M, Uebelacker, LA, Alpert, JE, Nierenberg, AA, Pava, JA, Rosenbaum, JF (1997). Major depressive subtypes and treatment response. Biological Psychiatry 42, 568–576.CrossRefGoogle ScholarPubMed
File, SE (2000). The amygdala: anxiety and benzodiazepines. In The Amygdala (ed. Aggleton, J.pp. 195–212. Oxford University Press: Oxford.CrossRefGoogle Scholar
Frodl, T, Meisenzahl, E, Zetzsche, T, Born, C, Groll, C, Jager, M, Leinsinger, G, Bottlender, R, Hahn, K, Möller, H-J (2002 a). Hippocampal changes in patients with a first episode of major depression. American Journal of Psychiatry 159, 1112–1118.CrossRefGoogle ScholarPubMed
Frodl, T, Meisenzahl, EM, Zetzsche, T, Born, C, Jäger, M, Groll, C, Bottlender, R, Leinsinger, G, Möller, H-J (2003). Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Biological Psychiatry 53, 338–344.CrossRefGoogle ScholarPubMed
Frodl, T, Meisenzahl, E, Zetzsche, T, Bottlender, R, Born, C, Groll, C, Jager, M, Leinsinger, G, Hahn, K, Möller, H-J (2002 b). Enlargement of the amygdala in patients with a first episode of major depression. Biological Psychiatry 51, 708–714.CrossRefGoogle ScholarPubMed
Funayama, ES, Grillon, C, Davis, M, Phelps, EA (2001). A double dissociation in the affective modulation of startle in humans: effects of unilateral temporal lobectomy. Journal of Cognitive Neuroscience 13, 721–729.CrossRefGoogle ScholarPubMed
Gorman, JM, Kent, JM, Sullivan, GM, Coplan, JD (2000). Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry 157, 493–505.CrossRefGoogle ScholarPubMed
Gray, JA, McNaughton, N (2003). The Neuropsychology of Anxiety. An Enquiry into the Functions of the Septo-Hippocampal System, 2nd edn. Oxford University Press: Oxford.Google Scholar
Grillon, C (2002). Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology. Biological Psychiatry 52, 958–975.CrossRefGoogle ScholarPubMed
Hasler, G, Drevets, WC, Manji, HK, Charney, DS (2004). Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 1765–1781.CrossRefGoogle ScholarPubMed
Heim, C, Nemeroff, CB (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biological Psychiatry 49, 1023–1039.CrossRefGoogle ScholarPubMed
Herdade, KCP, De Andrade Strauss, CV, Junior, HZ, De Barros Viana, M (2006). Effects of medial amygdala inactivation on a panic-related behavior. Behavioural Brain Research 172, 316–323.CrossRefGoogle ScholarPubMed
Jaffee, SR, Moffitt, TE, Caspi, A, Fombonne, E, Poulton, R, Martin, J (2002). Differences in early childhood risk factors for juvenile onset and adult onset depression. Archives of General Psychiatry 58, 215–222.CrossRefGoogle Scholar
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Mureci, P, Williamson, D (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.CrossRefGoogle ScholarPubMed
Kendler, KS, Gardner, CO, Gatz, M, Pedersen, NL (2007). The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychological Medicine 37, 453–462.CrossRefGoogle Scholar
Kendler, KS, Gardner, CO, Prescott, CA (2002). Toward a comprehensive developmental model for major depression in women. American Journal of Psychiatry 159, 1133–1145.CrossRefGoogle Scholar
Kendler, KS, Gardner, CO, Prescott, CA (2006). Toward a comprehensive developmental model for major depression in men. American Journal of Psychiatry 163, 115–124.CrossRefGoogle Scholar
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ (1992). Major depression and generalized anxiety disorder. Same genes, (partly) different environments? Archives of General Psychiatry 49, 716–722.CrossRefGoogle ScholarPubMed
Kleinbaum, DG (1996). Survival Analysis. Springer-Verlag: New York.CrossRefGoogle Scholar
Kovacs, M, Akiskal, HS, Gatsonis, C, Parrone, PL (1994). Childhood onset dysthymia disorder clinical features and prospective naturalistic outcome. Archives of General Psychiatry 51, 365–374.CrossRefGoogle ScholarPubMed
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. Archives of General Psychiatry 46, 776–782.Google Scholar
Leckman, JF, Sholomskas, D, Thompson, D, Belanger, A, Weissman, MM (1982). Best estimate of lifetime diagnosis: a methodological study. Archives of General Psychiatry 39, 879–883.CrossRefGoogle ScholarPubMed
LeDoux, JE (1996). The Emotional Brain. Simon & Schuster: New York.Google Scholar
LeDoux, JE (2002). Synaptic Self. Viking Penguin: Middlesex.Google Scholar
Lewinsohn, PM, Gotlib, IH, Seeley, JR (1995). Adolescent psychopathology: IV. Specificity of psychosocial risk factors for depression and substance abuse in older adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 34, 1221–1229.CrossRefGoogle ScholarPubMed
Lin, DY, Wei, LJ (1989). The robust inference for the proportional hazards model. Journal of the American Statistical Association 84, 1074–1078.CrossRefGoogle Scholar
MacMillan, S, Szeszko, PR, Moore, GJ, Madden, R, Lorch, E, Banerjee, P, Rosenberg, DR (2003). Increased amygdala:hippocampal volume ratios associated with severity of anxiety in pediatric major depression. Journal of Child and Adolescent Psychopharmacology 13, 65–73.CrossRefGoogle ScholarPubMed
Mannuzza, S, Fyer, AJ, Klein, DF, Endicott, J (1986). Schedule for Affective Disorder and Schizophrenia – Lifetime Version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual development. Journal of Psychiatric Research 20, 317–325.CrossRefGoogle Scholar
Merikangas, KR, Zhang, H, Avenevoli, S, Acharyya, S, Neuenschwander, M, Angst, J (2003). Longitudinal trajectories of depression and anxiety in a prospective community study. Archives of General Psychiatry 60, 993–1000.CrossRefGoogle Scholar
Middeldorp, CM, Cath, DC, Van Dyck, R, Boomsma, DI (2005). The comorbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychological Medicine 35, 611–624.CrossRefGoogle ScholarPubMed
Muthen, LK, Muthen, B (1998–2004). Mplus User's Guide. Third Edition. Muthen & Muthen: Los Angeles, CA.Google Scholar
Niehoff, DL, Kuhar, MJ (1983). Benzodiazepine receptors: localization in rat amygdala. Journal of Neuroscience 3, 2091–2097.CrossRefGoogle ScholarPubMed
Onoe, H, Tsukada, H, Nishiyama, S, Nakanishi, S, Inoue, O, Langstrom, B, Watanabe, YA (1996). Subclass of GABAA/benzodiazepine receptor exclusively localized in the limbic system. Neuroreport 8, 117–122.CrossRefGoogle ScholarPubMed
Orvaschel, H (2006). Structured and semistructured interviews. In Clinician's Handbook of Child Behavioral Assessment (ed. Hersen, M.), pp. 159–179. Elsevier Academic Press: San Diego.CrossRefGoogle Scholar
Parker, G, Hadzi-Pavlovic, D (2004). Is the female preponderance in major depression secondary to a gender difference in specific anxiety disorders? Psychological Medicine 34, 461–470.CrossRefGoogle ScholarPubMed
Phelps, EA, O'Connor, KJ, Gatenby, JC, Gore, JC, Grillon, C, Davis, M (2001). Activation of the left amygdala to a cognitive representation of fear. Nature Neuroscience 4, 437–441.CrossRefGoogle ScholarPubMed
Phillips, RG, LeDoux, JE (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience 106, 274–285.CrossRefGoogle ScholarPubMed
Pine, D, Cohen, P, Gurley, D, Brook, J, Ma, Y (1998). The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Archives of General Psychiatry 55, 56–64.CrossRefGoogle ScholarPubMed
Pine, DS, Cohen, P, Brook, J (2001). Adolescent fears as predictors of depression. Biological Psychiatry 50, 721–724.CrossRefGoogle ScholarPubMed
Rosenberg, DR, MacMaster, FP, Mirza, Y, Easter, PC (2006). Imaging and neurocircuitry of pediatric major depression. Clinical Neuropsychiatry 3, 219–229.Google Scholar
Roth, WT (2005). Physiological markers for anxiety: panic disorder and phobias. International Journal of Psychophysiology 58, 190–198.CrossRefGoogle ScholarPubMed
Rothman, KJ, Greenland, S (1998). Modern Epidemiology, 2nd edn. Lippincott-Raven: Philadelphia, PA.Google Scholar
Roy, MA, Neale, MC, Pedersen, NL, Mathe, AA, Kendler, KS (1995). A twin study of generalized anxiety disorder and major depression. Psychological Medicine 25, 1037–1049.CrossRefGoogle ScholarPubMed
Shaffer, D, Fisher, P, Dulcan, MK, Davies, M (1996). The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA study. Journal of the American Academy of Child and Adolescent Psychiatry 35, 865–877.CrossRefGoogle ScholarPubMed
Shrout, PE, Bolger, N (2002). Mediation in experimental and nonexperimental studies: new procedures and recommendations. Psychological Methods 7, 422–445.CrossRefGoogle ScholarPubMed
Silberg, JL, Rutter, M, Eaves, L (2001). Genetic and environmental influences on the temporal association between earlier anxiety and later depression in girls. Biological Psychiatry 49, 1040–1049.CrossRefGoogle ScholarPubMed
Walker, DL, Davis, M (1997). Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned and unconditioned fear. Journal of Neuroscience 17, 9375–9383.CrossRefGoogle ScholarPubMed
Weissman, MM, Fendrich, M, Warner, V, Wickramaratne, PJ (1992). Incidence of psychiatric disorder in offspring at high and low risk for depression. Journal of the American Academy of Child and Adolescent Psychiatry 31, 640–648.CrossRefGoogle ScholarPubMed
Weissman, MM, Gammon, GD, John, K, Merikangas, KR, Warner, V, Prusoff, BA, Sholomskas, D (1987). Children of depressed parents: increased psychopathology and early onset of major depression. Archives of General Psychiatry 44, 847–853.CrossRefGoogle ScholarPubMed
Weissman, MM, Gershon, ES, Kidd, KK, Prusoff, BA, Leckman, JF, Dibble, E, Hamovit, J, Thompson, DL, Guroff, JJ (1984). Psychiatric disorders in the relatives of probands with affective disorders. The Yale University–National Institute of Mental Health Collaborative Study. Archives of General Psychiatry 41, 13–21.CrossRefGoogle ScholarPubMed
Weissman, MM, Myers, JK (1978). Affective disorders in a United States community: the use of research diagnostic criteria in an epidemiological survey. Archives of General Psychiatry 35, 1304–1311.CrossRefGoogle Scholar
Weissman, MM, Warner, V, Wickramaratne, P, Moreau, D, Olfson, M (1997). Offspring of depressed parents: ten years later. Archives of General Psychiatry 54, 932–940.CrossRefGoogle Scholar
Weissman, MM, Wickramaratne, P, Nomura, Y, Warner, V, Verdeli, H, Pilowsky, D, Grillon, C, Bruder, G (2005). Offspring at high and low risk for depression: a three generation study. Archives of General Psychiatry 62, 29–36.CrossRefGoogle Scholar
Wickramaratne, PJ, Weissman, MM (1998). Onset of psychopathology in offspring by developmental phase and parental depression. Journal of the American Academy of Child and Adolescent Psychiatry 37, 933–942.CrossRefGoogle ScholarPubMed
Wittchen, H-U, Kessler, RC, Pfister, H, Lieb, M (2000). Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Acta Psychiatric Scandinavica 102 (Suppl. 406), 14–25.CrossRefGoogle Scholar