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A longitudinal etiologic model for symptoms of anxiety and depression in women

  • K. S. Kendler (a1) (a2) and C. O. Gardner (a1)

Designed as state measures to monitor treatment response, symptoms of anxiety and depression (SxAnxDep) also have trait-like characteristics. No comprehensive etiologic model for SxAnxDep has illuminated the inter-relationship between their state- and trait-like characteristics, while including key predictor variables.


In a prospective three-wave study of 2395 female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD), we examined, using structural equation modeling, how genes, childhood and past-year environmental stressors, personality and episodes of major depression (MD) and generalized anxiety disorder (GAD) influence SxAnxDep.


The best-fit model, which explained 68–74% of the variance in SxAnxDep, revealed two etiologic pathways. Stable levels of SxAnxDep resulted largely from neuroticism, which in turn was influenced by genetic and early environment risk factors. Occasion-specific influences resulted from stressful events mediated through episodes of MD or GAD. These two pathways, which had approximately equal influences on levels of SxAnxDep, were substantially correlated because the genetic, early environmental and personality factors that impacted on stable symptom levels also predisposed to event exposure and disorder onset. No significant interaction was seen between the two pathways.


SxAnxDep in women in the general population arise from two inter-related causal pathways. The first, the ‘trait-like’ pathway, reflects genetic and early environmental risk factors, and is mediated largely through personality. The second pathway is mediated through episodes of MD and GAD, and is the result of both recent environmental adversities and trait-like factors that influence event exposure and the probability of disorder onset.

Corresponding author
*Address for correspondence: K. S. Kendler, M.D., Virginia Institute for Psychiatric and Behavioral Genetics of VCU, Box 980126, Richmond, VA 23298-0126, USA. (Email:
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APA (1980). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn.American Psychiatric Association: Washington, DC.
APA (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised (DSM-III-R). American Psychiatric Association: Washington, DC.
Bentler, PM (1990). Comparative fit indexes in structural models. Psychological Bulletin 107, 238246.
Blom, G (1958). Statistical Estimates and Transformed Beta Variables. John Wiley & Sons, Inc.: New York.
Bolger, N, Schilling, EA (1991). Personality and the problems of everyday life: the role of neuroticism in exposure and reactivity to daily stressors. Journal of Personality 59, 355386.
Boomsma, DI, van Beijsterveldt, CE, Hudziak, JJ (2005). Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register. Genes, Brain, and Behavior 4, 466481.
Breslau, N, Davis, GC (1985). DSM-III generalized anxiety disorder: an empirical investigation of more stringent criteria. Psychiatry Research 15, 231238.
Burke, WJ, Gergel, I, Bose, A (2002). Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. Journal of Clinical Psychiatry 63, 331336.
Clark, LA, Watson, D, Mineka, S (1994). Temperament, personality, and the mood and anxiety disorders. Journal of Abnormal Psychology 103, 103116.
Coppen, A, Metcalfe, M (1965). Effect of a depressive illness on M.P.I. scores. British Journal of Psychiatry 111, 236239.
Derogatis, LR, Lipman, RS, Covi, L (1973). SCL-90: an outpatient psychiatric rating scale – preliminary report. Psychopharmacology Bulletin 9, 1328.
Duncan-Jones, P, Fergusson, DM, Ormel, J, Horwood, LJ (1990). A model of stability and change in minor psychiatric symptoms: results from three longitudinal studies. Psychological Medicine. Monograph Supplement 18, 128.
Eysenck, HJ, Eysenck, SBG (1964). Manual of the Eysenck Personality Inventory. London University Press: London.
Eysenck, SBG, Eysenck, HJ, Barrett, P (1985). A revised version of the psychoticism scale. Personality and Individual Differences 6, 2129.
Fava, M, Alpert, J, Nierenberg, AA, Mischoulon, D, Otto, MW, Zajecka, J, Murck, H, Rosenbaum, JF (2005). A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. Journal of Clinical Psychopharmacology 25, 441447.
Fergusson, DM, Horwood, LJ, Lawton, JM (1989). The relationships between neuroticism and depressive symptoms. Social Psychiatry and Psychiatric Epidemiology 24, 275281.
Gillespie, NA, Kirk, KM, Evans, DM, Heath, AC, Hickie, IB, Martin, NG (2004). Do the genetic or environmental determinants of anxiety and depression change with age? A longitudinal study of Australian twins. Twin Research 7, 3953.
Headey, B (2010). The set point theory of well-being has serious flaws: on the eve of a scientific revolution? Social Indicators Research 97, 721.
Headey, B, Wearing, A (1989). Personality, life events, and subjective well-being: toward a dynamic equilibrium model. Journal of Personality and Social Psychology 57, 731739.
Hettema, JM, Prescott, CA, Kendler, KS (2004). Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism. American Journal of Psychiatry 161, 15811587.
Hirschfeld, RM, Klerman, GL, Clayton, PJ, Keller, MB, McDonald-Scott, P, Larkin, BH (1983). Assessing personality: effects of the depressive state on trait measurement. American Journal of Psychiatry 140, 695699.
Horwood, LJ, Fergusson, DM (1986). Neuroticism, depression and life events: a structural equation model. Social Psychiatry 21, 6371.
Jardine, R, Martin, NG, Henderson, AS (1984). Genetic covariation between neuroticism and the symptoms of anxiety and depression. Genetic Epidemiology 1, 89107.
John, OP, Srivastava, S (1999). The big-five trait taxonomy: history, measurement, and theoretical perspectives. In Handbook of Personality: Theory and Research, 2nd edn (ed. Pervin, L. A. and John, O. P.), pp. 102139. Guilford Press: New York.
Judd, LL, Rapaport, MH, Yonkers, KA, Rush, AJ, Frank, E, Thase, ME, Kupfer, DJ, Plewes, JM, Schettler, PJ, Tollefson, G (2004). Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder. American Journal of Psychiatry 161, 18641871.
Kendler, KS, Baker, JH (2007). Genetic influences on measures of the environment: a systematic review. Psychological Medicine 37, 615626.
Kendler, KS, Bulik, CM, Silberg, J, Hettema, JM, Myers, J, Prescott, CA (2000). Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Archives of General Psychiatry 57, 953959.
Kendler, KS, Gardner, CO, Lichtenstein, P (2008). A developmental twin study of symptoms of anxiety and depression: evidence for genetic innovation and attenuation. Psychological Medicine 38, 15671575.
Kendler, KS, Gatz, M, Gardner, C, Pedersen, NL (2006). Personality and major depression: a Swedish longitudinal, population-based twin study. Archives of General Psychiatry 63, 11131120.
Kendler, KS, Heath, A, Martin, NG, Eaves, LJ (1986). Symptoms of anxiety and depression in a volunteer twin population. The etiologic role of genetic and environmental factors. Archives of General Psychiatry 43, 213221.
Kendler, KS, Karkowski, LM, Prescott, CA (1998). Stressful life events and major depression: risk period, long-term contextual threat, and diagnostic specificity. Journal of Nervous and Mental Disease 186, 661669.
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ (1992). Generalized anxiety disorder in women. A population-based twin study. Archives of General Psychiatry 49, 267272.
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ (1993). A longitudinal twin study of personality and major depression in women. Archives of General Psychiatry 50, 853862.
Kendler, KS, Prescott, CA (1999). A population-based twin study of lifetime major depression in men and women. Archives of General Psychiatry 56, 3944.
Kendler, KS, Prescott, CA (2006). Genes, Environment, and Psychopathology: Understanding the Causes of Psychiatric and Substance Use Disorders. Guilford Press: New York.
Lee, S, Tsang, A, Ruscio, AM, Haro, JM, Stein, DJ, Alonso, J, Angermeyer, MC, Bromet, EJ, Demyttenaere, K, de Girolamo, G, de Graaf, R, Gureje, O, Iwata, N, Karam, EG, Lepine, JP, Levinson, D, Medina-Mora, ME, Browne, MAO, Posada-Villa, J, Kessler, RC (2009). Implications of modifying the duration requirement of generalized anxiety disorder in developed and developing countries. Psychological Medicine 39, 11631176.
Lucas, RE, Clark, AE, Georgellis, Y, Diener, E (2004). Unemployment alters the set point for life satisfaction. Psychological Science 15, 813.
Magnus, K, Diener, E, Fujita, F, Pavot, W (1993). Extraversion and neuroticism as predictors of objective life events: a longitudinal analysis. Journal of Personality and Social Psychology 65, 10461053.
McGue, M, Christensen, K (1997). Genetic and environmental contributions to depression symptomatology: evidence from Danish twins 75 years of age and older. Journal of Abnormal Psychology 106, 439448.
Moos, R, Moos, B (1986). Family Environment Scale Manual. Consulting Psychologists Press: Palo Alto, CA.
Muthen, LK, Muthen, BO (2007). Mplus User's Guide: Fifth Edition. Muthen & Muthen: Los Angeles, CA.
O'Connor, TG, Neiderhiser, JM, Reiss, D, Hetherington, EM, Plomin, R (1998). Genetic contributions to continuity, change, and co-occurrence of antisocial and depressive symptoms in adolescence. Journal of Child Psychology and Psychiatry 39, 323336.
Ormel, J, Schaufeli, WB (1991). Stability and change in psychological distress and their relationship with self-esteem and locus of control: a dynamic equilibrium model. Journal of Personality and Social Psychology 60, 288299.
Ormel, J, Wohlfarth, T (1991). How neuroticism, long-term difficulties, and life situation change influence psychological distress: a longitudinal model. Journal of Personality and Social Psychology 60, 744755.
Parker, G, Tupling, H, Brown, L (1979). A parental bonding instrument. British Journal of Medical Psychology 52, 110.
Post, RM (1992). Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. American Journal of Psychiatry 149, 9991010.
Silberg, JL, Heath, AC, Kessler, R, Neale, MC, Meyer, JM, Eaves, LJ, Kendler, KS (1990). Genetic and environmental effects on self-reported depressive symptoms in a general population twin sample. Journal of Psychiatric Research 24, 197212.
Spitzer, RL, Williams, JBW (1985). Structured Clinical Interview for DSM-III-R (SCID). Biometrics Research Department, New York State Psychiatric Institute: New York.
Steiger, JH (1990). Structural model evaluation and modification: an interval estimation approach. Multivariate Behavioral Research 25, 173180.
Taylor, MJ (2007). Rapid onset of true antidepressant action. Current Psychiatry Reports 9, 475479.
Tucker, LR, Lewis, C (1973). A reliability coefficient for maximum likelihood factor analysis. Psychometrika 38, 110.
van Os, J, Park, SB, Jones, PB (2001). Neuroticism, life events and mental health: evidence for person-environment correlation. British Journal of Psychiatry (Suppl.) 40, s72s77.
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