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Gene–environment interplay in depressive symptoms: moderation by age, sex, and physical illness

  • A. J. Petkus (a1), C. R. Beam (a2), W. Johnson (a3), J. Kaprio (a4) (a5), T. Korhonen (a4) (a5) (a6), M. McGue (a7) (a8), J. M. Neiderhiser (a9), N. L. Pedersen (a10) (a11), C. A. Reynolds (a12), M. Gatz (a10) (a11) and for the IGEMS Consortium...

Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness.


The analysis sample included 24 436 twins aged 40–90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms.


Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness.


Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.

Corresponding author
*Address for correspondence: M. Gatz, Ph.D., Department of Psychology, University of Southern California, Los Angeles, CA 90089-1061, USA. (Email:
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Members of the IGEMS Consortium are given in the Appendix.

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LF Berkman , CS Berkman , S Kasl , DH Freeman Jr., L Leo , AD Ostfeld , J Cornoni-Huntley , J Brody (1986). Depressive symptoms in relation to physical health and functioning in the elderly. American Journal of Epidemiology 124, 372388.

LJ Bierut , AC Heath , KK Bucholz , SH Dinwiddie , PA Madden , DJ Statham , MP Dunne , NG Martin (1999). Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women? Archives of General Psychiatry 56, 557563.

D Carmelli , GE Swan , M Kelly-Hayes , PA Wolf , T Reed , B Miller (2000). Longitudinal changes in the contribution of genetic and environmental influences to symptoms of depression in older male twins. Psychology and Aging 15, 505510.

K Christensen , NV Holm , M McGue , L Corder , JW Vaupel (1999). A Danish population-based twin study on general health in the elderly. Journal of Aging and Health 11, 4964.

JK Djernes (2006). Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatrica Scandinavia 113, 372387.

D Finkel , M McGue (1993). The origins of individual differences in memory among the elderly: a behavior genetic analysis. Psychology and Aging 8, 527537.

D Finkel , NL Pedersen (2004). Processing speed and longitudinal trajectories of change for cognitive abilities: The Swedish Adoption/Twin Study of Aging. Aging, Neuropsychology, and Cognition. Special Issue: Longitudinal Studies of Cognitive Aging 11, 325345.

A Fiske , JL Wetherell , M Gatz (2009). Depression in older adults. Annual Review of Clinical Psychology 5, 363389.

C Forlani , M Morri , B Ferrari , E Dalmonte , M Menchetti , D De Ronchi , AR Atti (2014). Prevalence and gender differences in late-life depression: a population-based study. American Journal of Geriatric Psychiatry 22, 370380.

CE Franz , MJ Lyons , R O'Brien , MS Panizzon , K Kim , R Bhat , MD Grant , R Toomey , S Eisen , H Xian , WS Kremen (2011). A 35-year longitudinal assessment of cognition and midlife depression symptoms: the Vietnam Era Twin study of aging. The American Journal of Geriatric Psychiatry 19, 559570.

M Gatz , NL Pedersen , R Plomin , JR Nesselroade , GE McClearn (1992). The importance of shared genes and shared environments for symptoms of depression in older adults. Journal of Abnormal Psychology 101, 701708.

M Gatz , CR Reynolds , D Finkel , CJ Hahn , Y Zhou , C Zavala (2015b). Data harmonization in aging research: not so fast. Journal of Experimental Aging Research 41, 475495.

NA Gillespie , KM Kirk , DM Evans , AC Heath , IB Hickie , NG Martin (2004). Do the genetic or environmental determinants of anxiety and depression change with age? A longitudinal study of Australian twins. Twin Research 7, 3953.

AC Heath , RC Kessler , MC Neale , JK Hewitt , LJ Eaves , KS Kendler (1993). Testing hypotheses about direction of causation using cross sectional family data. Behavior Genetics 23, 2950.

W Johnson (2007). Genetic and environmental influences on behavior: capturing all the interplay. Psychological Review 114, 423440.

W Johnson , M McGue , D Gaist , JW Vaupel , K Christensen (2002). Frequency and heritability of depression symptomatology in the second half of life: evidence from Danish twins over 45. Psychological Medicine 32, 11751185.

LL Judd , PJ Schettler , HS Akiskal (2002). The prevalence, clinical relevance, and public health significance of subthreshold depressions. Psychiatric Clinics of North America 25, 685698.

J Kaprio (2013). The Finnish Twin Cohort Study: an update. Twin Research and Human Genetics 16, 157162.

J Kaprio , M Koskenvuo (2002). Genetic and environmental factors in complex diseases: the older Finnish Twin Cohort. Twin Research and Human Genetics 5, 358365.

KS Kendler , CO Gardner (2014). Sex differences in the pathways to Major Depression: a study of opposite-sex twin pairs. The American Journal of Psychiatry 171, 426435.

KS Kendler , M Gatz , CO Gardner , NL Pedersen (2006). A Swedish national twin study of lifetime major depression. American Journal of Psychiatry 163, 109114.

KS Kendler , LM Thornton , SE Gilman , RC Kessler (2000). Sexual orientation in a U.S. national sample of twin and nontwin sibling pairs. American Journal of Psychiatry 157, 18431846.

RC Kessler , C Foster , PS Webster , JS House (1992). The relationship between age and depressive symptoms in two national surveys. Psychology and Aging 7, 119126.

T Korhonen , U Broms , J Varjonen , K Romanov , M Koskenvuo , T Kinnunen , J Kaprio (2007). Smoking behaviour as a predictor for depression among Finnish men and women – a prospective study of adult twins. Psychological Medicine 37, 705715.

WS Kremen , H Thompson-Brenner , YJ Leung , MD Grant , CE Franz , SA Eisen , KC Jacobson , C Boake , MJ Lyons (2006). Genes, environment, and time: the Vietnam Era Twin Study of Aging (VETSA). Twin Research and Human Genetics 9, 10091022.

JJ McArdle , F Hamagami (2003). Structural equation models for evaluating dynamic concepts within longitudinal twin analyses. Behavioral Genetics 33, 137159.

GE McClearn , B Johansson , S Berg , NL Pedersen , F Ahern , SA Petrill , R Plomin (1997). Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276, 15601563.

M McGue , K Christensen (1997). Genetic and environmental contributions to depression symptomatology: evidence from Danish twins 75 years of age and older. Journal of Abnormal Psychology 106, 439448.

S Meeks , SA Murrell , RC Mehl (2000). Longitudinal relationships between depressive symptoms and health in normal older and middle-aged adults. Psychology and Aging 15, 100109.

M Neale , M Hunter , JN Pritikin , M Zahery , TR Brick , RM Kickpatrick , R Estabrook , TC Bates , H Maes , SM Boker (2016). Open Mx 2.0: extended structural equation and statistical modeling. Psychometrika 81, 535549.

M Neale , E Roysamb , K Jacobson (2006). Multivariate genetic analysis of sex limitation and GxE interaction. Twin Research and Human Genetics 9, 481489.

NL Pedersen , K Christensen , A Dahl , D Finkel , C Franz , M Gatz , BN Horwitz , B Johansson , W Johnson , WS Kremen , MJ Lyons , B Malmberg , M McGue , JM Neiderhiser , I Peterson , CA Reynolds (2013). IGEMS: The Consortium on Interplay of Genes and Environment across Multiple Studies. Twin Research and Human Genetics 16, 481489.

M Roth , E Tym , CQ Mountjoy , FA Huppert , H Hendrie , S Verma , R Goodard (1986). CAMDEX: a standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry 149, 698709.

F Salvi , MD Miller , A Grilli , R Giorgi , AL Towers , V Morichi , L Spazzafumo , L Mancinelli , E Espinosa , A Rappelli , P Dessì-Fulgheri (2008). A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. Journal of the American Geriatrics Society 56, 19261931.

KM Scott , C Lim , A Al-Hamzawi , J Alonso , R Bruffaerts , JM Caldas-de-Almeida , S Florescu , G de Girolamo , C Hu , P de Jonge , N Kawakami , ME Medina-Mora , J Moskalewicz , F Navarro-Mateu , S O'Neill , M Piazza , J Pasada-Villa , Y Torres , RC Kessler (2016). Association of mental disorders with subsequent chronic physical conditions: world mental health surveys from 17 countries. JAMA Psychiatry 73, 150158.

A Skytthe , L Christiansen , KO Kyvik , FL Bødker , L Hvidberg , I Petersen , MMF Nielsen , P Bingley , J Hjelmborg , Q Tan , NV Holm , JW Vaupel , M McGue , K Christensen (2013). The Danish Twin Registry: linking surveys, national registers, and biological information. Twin Research and Human Genetics 16, 104111.

CM Sonnenberg , ATF Beekman , DJH Deeg , W van Tilburg (2000). Sex differences in late life depression. Acta Psychiatrica Scandinavica 101, 286292.

AR Sutin , A Terracciano , Y Milaneschi , Y An , L Ferrucci , AB Zonderman (2013). The trajectory of depressive symptoms across the adult lifespan. JAMA Psychiatry 70, 803811.

S Takkinen , A Tolvanen , J Kaprio , S Berg , M Koskenvuo , T Rantanen (2004). The genetic and environmental effects on depressive symptoms among older female twins. Twin Research 7, 626636.

JM Twenge (2015). Time period and birth cohort differences in depressive symptoms in the U.S., 1982–2013. Social Indicators Research 121, 437454.

S van der Sluis , D Posthuma , CV Dolan (2012). A note on false positives and power in GxE modelling of twin data. Behavior Genetics 42, 170186.

C Van Hulle , B Lahey , P Rathouz (2013). Operating characteristics of alternative statistical methods for detecting gene-by-measured environment interaction in the presence of gene-environment correlation in twin and sibling studies. Behavior Genetics 43, 7184.

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