Skip to main content
    • Aa
    • Aa

Genetic co-morbidity between neuroticism, anxiety/depression and somatic distress in a population sample of adolescent and young adult twins

  • N. K. Hansell (a1), M. J. Wright (a1), S. E. Medland (a1), T. A. Davenport (a2), N. R. Wray (a1), N. G. Martin (a1) and I. B. Hickie (a2)...

Genetic studies in adults indicate that genes influencing the personality trait of neuroticism account for substantial genetic variance in anxiety and depression and in somatic health. Here, we examine for the first time the factors underlying the relationship between neuroticism and anxiety/depressive and somatic symptoms during adolescence.


The Somatic and Psychological Health Report (SPHERE) assessed symptoms of anxiety/depression (PSYCH-14) and somatic distress (SOMA-10) in 2459 adolescent and young adult twins [1168 complete pairs (35.4% monozygotic, 53% female)] aged 12–25 years (mean=15.5±2.9). Differences between boys and girls across adolescence were explored for neuroticism, SPHERE-34, and the subscales PSYCH-14 and SOMA-10. Trivariate analyses partitioned sources of covariance in neuroticism, PSYCH-14 and SOMA-10.


Girls scored higher than boys on both neuroticism and SPHERE, with SPHERE scores for girls increasing slightly over time, whereas scores for boys decreased or were unchanged. Neuroticism and SPHERE scores were strongly influenced by genetic factors [heritability (h2)=40–52%]. A common genetic source influenced neuroticism, PSYCH-14 and SOMA-10 (impacting PSYCH-14 more than SOMA-10). A further genetic source, independent of neuroticism, accounted for covariation specific to PSYCH-14 and SOMA-10. Environmental influences were largely specific to each measure.


In adolescence, genetic risk factors indexed by neuroticism contribute substantially to anxiety/depression and, to a lesser extent, perceived somatic health. Additional genetic covariation between anxiety/depressive and somatic symptoms, independent of neuroticism, had greatest influence on somatic distress, where it was equal in influence to the factor shared with neuroticism.

Corresponding author
*Address for correspondence: Dr N. K. Hansell, Genetic Epidemiology, Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Queensland, Australia 4029. (Email:
Hide All
APA (2000). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC.
Angold A, Erkanli A, Silberg J, Eaves L, Costello EJ (2002). Depression scale scores in 8–17-year-olds: effects of age and gender. Journal of Child Psychology and Psychiatry 43, 10521063.
Bartels M, van de Aa N, van Beijsterveldt CE, Middeldorp CM, Boomsma DI (2011). Adolescent self-report of emotional and behavioral problems: interactions of genetic factors with sex and age. Journal of the Canadian Academy of Child and Adolescent Psychiatry 20, 3552.
Birley AJ, Gillespie NA, Heath AC, Sullivan PF, Boomsma DI, Martin NG (2006). Heritability and nineteen-year stability of long and short EPQ-R Neuroticism scales. Personality and Individual Differences 40, 737747.
Boomsma DI, Beem AL, van den Berg M, Dolan CV, Koopmans JR, Vink JM, de Geus EJ, Slagboom PE (2000). Netherlands twin family study of anxious depression (NETSAD). Twin Research 3, 323334.
Costa PT, McCrae RR (1992). Revised NEO Personality Inventory (NEO PI-R) and NEO Five-Factor Inventory (NEO-FFI): Professional Manual. PAR: Lutz.
Dimsdale JE, Dantzer R (2011). A biological substrate for somatoform disorders: importance of pathophysiology. Psychosomatic Medicine 69, 850854.
Eysenck HJ, Eysenck SBG (1975). Manual for the Eysenck Personality Questionnaire (Adult and Junior). Digits: San Diego, CA.
Eysenck SBG (1972). Junior Eysenck Personality Inventory. EdITS/Educational and Industrial Testing Service: San Diego, CA.
Fanous A, Gardner CO, Prescott CA, Cancro R, Kendler KS (2002). Neuroticism, major depression and gender: a population-based twin study. Psychological Medicine 32, 719728.
Feigon SA, Waldman ID, Levy F, Hay DA (2001). Genetic and environmental influences on separation anxiety disorder symptoms and their moderation by age and sex. Behavior Genetics 31, 403411.
Franic S, Middeldorp CM, Dolan CV, Ligthart L, Boomsma DI (2010). Childhood and adolescent anxiety and depression: beyond heritability. Journal of the American Academy of Child & Adolescent Psychiatry 49, 820829.
Freeman MF, Tukey JW (1950). Transformations related to the angular scale and the square root. Annals of Mathematical Statistics 21, 607611.
Frokjaer VG, Vinberg M, Erritzoe D, Baare W, Holst KK, Mortensen EL, Arfan H, Madsen J, Jernigan TL, Kessing LV, Knudsen GM (2010). Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding. Neuropsychopharmacology 35, 11291137.
Gillespie N, Kirk KM, Heath AC, Martin NG, Hickie I (1999). Somatic distress as a distinct psychological dimension. Social Psychiatry and Psychiatric Epidemiology 34, 451458.
Gillespie NA, Evans DE, Wright MM, Martin NG (2004). Genetic simplex modeling of Eysenck's dimensions of personality in a sample of young Australian twins. Twin Research 7, 637648.
Gillespie NA, Zhu G, Heath AC, Hickie IB, Martin NG (2000). The genetic aetiology of somatic distress. Psychological Medicine 30, 10511061.
Goldberg DA (1996). A dimensional model for common mental disorders. British Journal of Psychiatry 168, 4449.
Hamilton BA, Naismith SL, Scott EM, Purcell S, Hickie IB (2011). Disability is already pronounced in young people with early stages of affective disorders: data from an early intervention service. Journal of Affective Disorders 131, 8491.
Happonen M, Pulkkinen L, Kaprio J, van der Meere J, Viken RJ, Rose RJ (2002). The heritability of depressive symptoms: multiple informants and multiple measures. Journal of Child Psychology and Psychiatry 43, 471479.
Hetrick SE, Parker AG, Hickie IB, Purcell R, Yung AR, McGorry PD (2008). Early identification and intervention in depressive disorders: towards a clinical staging model. Psychotherapy and Psychosomatics 77, 263270.
Hettema JM, Neale MC, Myers JM, Prescott CA, Kendler KS (2006). A population-based twin study of the relationship between neuroticism and internalizing disorders. American Journal of Psychiatry 163, 857864.
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.
Hickie I, Bennett B, Lloyd A, Heath A, Martin N (1999 a). Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study. Psychological Medicine 29, 269277.
Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A (2006). Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. British Medical Journal 333, 575.
Hickie I, Hadzi-Pavlovic D, Ricci C (1997). Reviving the diagnosis of neurasthenia. Psychological Medicine 27, 989994.
Hickie I, Kirk K, Martin N (1999 b). Unique genetic and environmental determinants of prolonged fatigue: a twin study. Psychological Medicine 29, 259268.
Hickie I, Koschera A, Hadzi-Pavlovic D, Bennett B, Lloyd A (1999 c). The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care. Psychological Medicine 29, 855861.
Hickie I, Lloyd A, Wakefield D, Parker G (1990). The psychiatric status of patients with the chronic fatigue syndrome. British Journal of Psychiatry 156, 534540.
Hickie IB, Davenport TA, Hadzi-Pavlovic D, Koschera A, Naismith SL, Scott EM, Wilhelm KA (2001 a). Development of a simple screening tool for common mental disorders in general practice. Medical Journal of Australia 175, S10S24.
Hickie IB, Davenport TA, Scott EM, Hadzi-Pavlovic D, Naismith SL, Koschera A (2001 b). Unmet need for recognition of common mental disorders in Australian general practice. Medical Journal of Australia 175 (Suppl.) S18S24.
Hickie IB, Rogers NL (2011). Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet 378, 621631.
Kato K, Sullivan PF, Evengard B, Pedersen NL (2009). A population-based twin study of functional somatic syndromes. Psychological Medicine 39, 497505.
Kendler KS, Gardner CO, Gatz M, Pederson NL (2007). The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychological Medicine 37, 453462.
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.
Kirk KM, Hickie IB, Martin NG (1999). Fatigue as related to anxiety and depression in a community-based sample of twins aged over 50. Social Psychiatry and Psychiatric Epidemiology 34, 8590.
Kirmayer LJ, Robbins JM, Paris J (1994). Somatoform disorders: personality and the social matrix of somatic distress. Journal of Abnormal Psychology 103, 125136.
Kotov R, Gamez W, Schmidt F, Watson D (2010). Linking ‘big’ personality traits to anxiety, depressive, and substance use disorders: a meta-analysis. Psychological Bulletin 136, 768821.
Kraemer HC (2007). DSM categories and dimensions in clinical and research contexts. International Journal of Methods in Psychiatric Research 16, S8–S15.
Krueger RF, Chentsova-Dutton YE, Markon KE, Goldberg D, Ormel J (2003). A cross-cultural study of the structure of comorbidity among common psychopathological syndromes in the general health care setting. Journal of Abnormal Psychology 112, 437447.
Lamb DJ, Middeldorp CM, van Beijsterveldt CEM, Bartels M, van der Aa N, Polderman TJC, Boomsma DI (2010). Heritability of anxious-depressive and withdrawn behavior: age-related changes during adolescence. Journal of American Academy of Child & Adolescent Psychiatry 49, 248255.
McCrae RR, Costa PT (2004). A contemplated revision of the NEO Five-Factor Inventory. Personality and Individual Differences 36, 587596.
McCrae RR, Costa PT (2010). NEO Inventories for the NEO Personality Inventory-3 (NEO-PI-3), NEO Five-Factor Inventory-3 (NEO-FFI-3), NEO Personality Inventory-Revised (NEO PI-R): Professional Manual. PAR: Lutz, FL.
McCrae RR, Costa PT Jr., Terracciano A, Parker WD, Mills CJ, de Fruyt F, Mervielde I (2002). Personality trait development from age 12 to age 18: longitudinal, cross-sectional, and cross-cultural analyses. Journal of Personality and Social Psychology 83, 14561468.
McGorry P (2011). Transition to adulthood: the critical period for pre-emptive, disease-modifying care for schizophrenia and related disorders. Schizophrenia Bulletin 37, 524530.
McGorry PD, Purcell R, Goldstone S, Amminger GP (2011). Age of onset and timing of treatment for mental and substance use disorders: implications for preventive intervention strategies and models of care. Current Opinion in Psychiatry 24, 301306.
McGregor B, Pfitzner J, Zhu G, Grace M, Eldridge A, Pearson J, Mayne C, Aitken JF, Green AC, Martin NG (1999). Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins. Genetic Epidemiology 16, 4053.
Martin NG, Jardine R, Andrews G, Heath AC (1988). Anxiety disorders and neuroticism: are there genetic factors specific to panic. Acta Psychiatrica Scandinavica 77, 698706.
Medland SE, Nyholt DR, Painter JN, McEvoy BP, McRae AF, Zhu G, Gordon SD, Ferreira MA, Wright MJ, Henders AK, Campbell MJ, Duffy DL, Hansell NK, Macgregor S, Slutske WS, Heath AC, Montgomery GW, Martin NG (2009). Common variants in the trichohyalin gene are associated with straight hair in Europeans. American Journal of Human Genetics 85, 750755.
Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J (2010). Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication – Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry 49, 980989.
Neale MC, Boker SM, Xie G, Maes HH (2003). Mx: Statistical Modeling. Department of Psychiatry: Richmond, VA.
Neale MC, Cardon LR (1992). Methodology for Genetic Studies of Twins and Families. Kluwer Academic Publishers: Dordrecht.
Neale MC, Eaves LJ, Kendler KS (1994). The power of the classical twin study to resolve variation in threshold traits. Behavior Genetics 24, 239258.
Parker JD, Taylor GJ, Bagby RM (1989). The alexithymia construct: relationship with sociodemographic variables and intelligence. Comprehensive Psychiatry 30, 434441.
Pennebaker JW, Watson D (1991). The psychology of somatic symptoms. In Current Concepts of Somatization (ed. Kirmayer L. J. and Robbins J. M.). American Psychiatric Press: Washington DC.
Raison CL, Capuron L, Miller AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 2431.
Rettew DC, Vink JM, Willemsen G, Doyle A, Hudziak JJ, Boomsma DI (2006). The genetic architecture of neuroticism in 3301 Dutch adolescent twins as a function of age and sex: a study from the Dutch Twin Register. Twin Research and Human Genetics 9, 2429.
Rice F, Harold GT, Thapar A (2002). Assessing the effects of age, sex, and shared environment on the genetic aetiology of depression in childhood and adolescence. Journal of Child Psycholgy & Psychiatry 43, 10391051.
Rief W, Hennings A, Riemer S, Euteneuer F (2010). Psychobiological differences between depression and somatization. Journal of Psychosomatic Research 68, 496502.
Rief W, Pilger F, Ihle D, Verlerk R, Scharpe S, Maes M (2004). Psychobiological aspects of somatoform disorders: contributions of monoaminergic transmitter systems. Neuropsychobiology 49, 2429.
Robbins JM, Kirmayer LJ (1991). Cognitive and social factors in somatization. In Current Concepts of Somatization: Research and Clinical Perspectives (ed. Kirmayer L. J. and Robbins J. M.), pp. 107141. American Psychiatric Press: Washington DC.
Ruscio J, Ruscio AM (2000). Informing the continuity controversy: a taxometric analysis of depression. Journal of Abnormal Psychology 109, 473487.
Sakashita C, Slade T, Andrews G (2007). Empirical investigation of two assumptions in the diagnosis of DSM-IV major depressive episode. Australian and New Zealand Journal of Psychiatry 41, 1723.
Slade T, Andrews G (2005). Latent structure of depression in a community sample: a taxometric analysis. Psychological Medicine 35, 489497.
Sund AM, Larsson B, Wichstrom L (2001). Depressive symptoms among young Norwegian adolescents as measured by The Mood and Feelings Questionnaire (MFQ). European Child & Adolescent Psychiatry 10, 222229.
Sutin AR, Terracciano A, Deiana B, Naitza S, Ferrucci L, Uda M, Schlessinger D, Costa PT Jr. (2010). High neuroticism and low conscientiousness are associated with interleukin-6. Psychological Medicine 40, 14851493.
Terracciano A, Costa Jr. PT, McCrae RR (2006). Personality plasticity after age 30. Personality and Social Psychology Bulletin 32, 999–1009.
Ustun TB, Sartorius N (eds.) (1995). Mental Illness in General Health Care: An International Study. John Wiley & Sons: London.
Vaccarino AL, Sills TL, Evans KR, Kalali AH (2009). Multiple pain complaints in patients with major depressive disorder. Psychosomatic Medicine 71, 159162.
Vallejo MA, Jordan CM, Diaz MI, Comeche MI, Ortega J (2007). Psychological assessment via the internet: a reliability and validity study of online (vs paper-and-pencil) versions of the General Health Questionnaire-28 (GHQ-28) and the Symptoms Check-List-90-Revised (SCL-90-R). Journal of Medical Internet Research 9, e2.
van der Linden G, Chalder T, Hickie I, Koschera A, Sham P, Wessely S (1999). Fatigue and psychiatric disorder: different or the same? Psychological Medicine 29, 863868.
Vassend O, Roysamb E, Nielsen CS (2011). Neuroticism and self-reported somatic health: a twin study. Psychology & Health. Published online: 14 June 2011. doi:10.1080/08870446.2010.540665.
Vercoulen JH, Swanink CM, Zitman FG, Vreden SG, Hoofs MP, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G (1996). Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet 347, 858861.
Vollmer-Conna U, Fazou C, Cameron B, Li H, Brennan C, Luck L, Davenport T, Wakefield D, Hickie I, Lloyd A (2004). Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychological Medicine 34, 12891297.
Wijeratne C, Hickie I, Davenport T (2006). Is there an independent somatic symptom dimension in older people? Journal of Psychosomatic Research 61, 197204.
Wray NR, Birley AJ, Sullivan PF, Visscher PM, Martin NG (2007). Genetic and phenotypic stability of measures of neuroticism over 22 years. Twin Research and Human Genetics 10, 695702.
Wright MJ, Martin NG (2004). The Brisbane Adolescent Twin Study: outline of study methods and research projects. Australian Journal of Psychology 56, 6578.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 6
Total number of PDF views: 76 *
Loading metrics...

Abstract views

Total abstract views: 337 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th October 2017. This data will be updated every 24 hours.