CENTER ON BEHAVIORAL MEDICINE

BODY-MIND CONNECTION

BEHAVIORAL GENETICS

Behavioral Genetics:  Research Article

Behavioral Genetics Menu

Lifetime Major Depression

CITATION:  Kendler, K.S., et al. (2006)  A Swedish National Twin Study of Lifetime Major Depression.  Am J Psychiatry 2006; 163:109–114.

ABSTRACT: 

Objective: Substantial evidence supports the heritability of lifetime major depression.  Less clear is whether genetic influences in major depression are more important in women than in men and whether genetic risk factors are the same in the two sexes. It is not known whether genetic effects on major depression are constant across historical cohorts. 

Method: Lifetime major depression was assessed at personal interview by modified DSM-IV criteria in 42,161 twins, including 15,493 complete pairs, from the national Swedish Twin Registry. Twin models were evaluated by using the program Mx. Results: Model fitting indicated that the heritability of liability to major depression was significantly higher in women (42%) than men (29%) and the genetic risk factors for major depression were moderately correlated in men and women. No significant differences were seen in the etiologic roles of genetic and environmental factors in major depression in three cohorts spanning birth years 1900–1958. 

Conclusions: In the largest sample to date, lifetime major depression was moderately heritable, with estimates similar to those in prior studies. In accord with some but not other previous investigations,
this study suggests both that the heritability of major depression is higher in women than in men and that some genetic risk factors for major depression are sex-specific in their effect. No evidence was found for differences in the roles of genetic and environmental risk factors in major depression in birth cohorts spanning nearly six decades.

References

1. Murray CJL, Lopez AD: Evidence-based health policy: lessons
from the Global Burden of Disease study. Science 1996; 274:
740–743

2. Tsuang MT, Faraone SV: The Genetics of Mood Disorders. Baltimore,
Johns Hopkins University Press, 1990

3. Sullivan PF, Neale MC, Kendler KS: Genetic epidemiology of
major depression: review and meta-analysis. Am J Psychiatry
2000; 157:1552–1562

4. Lyons MJ, Eisen SA, Goldberg J, True W, Lin N, Meyer JM,
Toomey R, Faraone SV, Merren J, Merla-Ramos M, Tsuang MT:
A registry-based twin study of depression in men. Arch Gen
Psychiatry 1998; 55:468–472

5. Bierut LJ, Heath AC, Phil D, Bucholz KK, Dinwiddie SH, Madden
PAF, Statham DJ, Dunne MP, Martin NG: Major depressive disorder
in a community-based twin sample. Arch Gen Psychiatry
1999; 56:557–563

6. Kendler KS, Gardner CO, Neale MC, Prescott CA: Genetic risk
factors for major depression in men and women: similar or different
heritabilities and same or partly distinct genes? Psychol
Med 2001; 31:605–616

7. McGuffin P, Katz R, Watkins S, Rutherford J: A hospital-based
twin register of the heritability of DSM-IV unipolar depression.
Arch Gen Psychiatry 1996; 53:129–136

8. Kendler KS, Pedersen NL, Johnson L, Neale MC, Mathe AA: A pilot
Swedish twin study of affective illness, including hospitaland
population-ascertained subsamples. Arch Gen Psychiatry
1993; 50:699–706

9. Kendler KS, Pedersen NL, Neale MC, Mathe AA: A pilot Swedish
twin study of affective illness including hospital- and population-
ascertained subsamples: results of model fitting. Behav
Genet 1995; 25:217–232

10. Kendler KS, Prescott CA, Neale MC, Pedersen NL: Temperance
board registration for alcohol abuse in a national sample of
Swedish male twins born 1902–1949. Arch Gen Psychiatry
1997; 54:178–184

11. Kendler KS, Karkowski LM, Pedersen NL: Tobacco consumption
in Swedish twins reared apart and reared together. Arch Gen
Psychiatry 2000; 57:886–892

12. Lichtenstein P, De Faire U, Floderus B, Svartengren M, Svedberg
P, Pedersen NL: The Swedish Twin Registry: a unique resource
for clinical, epidemiological and genetic studies. J Intern Med
2002; 252:184–205

13. Kessler RC, Andrews G, Mroczek D, Ustun B, Wittchen H-U: The
World Health Organization Composite International Diagnostic
Interview Short Form (CIDI-SF). Int J Methods Psychiatr Res
1998; 7:171–185

14. Spitzer RL, Williams JBW: Structured Clinical Interview for DSMIII-
R (SCID). New York, New York State Psychiatric Institute, Biometrics
Research, 1985

15. Neale MC, Boker SM, Xie G, Maes HH: Mx: Statistical Modeling,
5th ed. Richmond, Virginia Commonwealth University, Medical
College of Virginia, 1999

16. Little RJA, Rubin DB: Statistical Analysis With Missing Data. New
York, John Wiley & Sons, 1987

17. Akaike H: Factor analysis and AIC. Psychometrika 1987; 52:
317–332

18. Williams LJ, Holahan PJ: Parsimony-based fit indices for multiple-
indicator models: do they work? Structural Equation Modeling
1994; 1:161–189

19. Kendler KS: Overview: a current perspective on twin studies of
schizophrenia. Am J Psychiatry 1983; 140:1413–1425

20. McGue M, Christensen K: Genetic and environmental contributions
to depression symptomatology: evidence from Danish
twins 75 years of age and older. J Abnorm Psychol 1997; 106:
439–448

21. Jansson M, Gatz M, Berg S, Johansson B, Malmberg B, McClearn
GE, Schalling M, Pedersen NL: Gender differences in heritability
of depressive symptoms in the elderly. Psychol Med 2004; 34:
471–479

22. Aneshensel CS, Estrada AL, Hansell MJ, Clark VA: Social psychological
aspects of reporting behavior: lifetime depressive episode
reports. J Health Soc Behav 1987; 28:232–246

23. Wells JE, Horwood LJ: How accurate is recall of key symptoms
of depression? a comparison of recall and longitudinal reports.
Psychol Med 2004; 34:1001–1011

24. Fennig S, Schwartz JE, Bromet EJ: Are diagnostic criteria, time
of episode and occupational impairment important determinants
of the female:male ratio for major depression? J Affect
Disord 1994; 30:147–154

25. Kendler KS, Gardner CO, Prescott CA: Are there sex differences
in the reliability of a lifetime history of major depression and
its predictors? Psychol Med 2001; 31:617–625

26. Faraone SV, Lyons MJ, Tsuang MT: Sex differences in affective
disorder: genetic transmission. Genet Epidemiol 1987; 4:331–
343

27. Kendler KS, Silberg JL, Neale MC, Kessler RC, Heath AC, Eaves LJ:
Genetic and environmental factors in the aetiology of menstrual,
premenstrual and neurotic symptoms: a populationbased
twin study. Psychol Med 1992; 22:85–100

28. Seeman MV: Psychopathology in women and men: focus on
female hormones. Am J Psychiatry 1997; 154:1641–1647

29. Nash MW, Huezo-Diaz P, Williamson RJ, Sterne A, Purcell S,
Hoda F, Cherny SS, Abecasis GR, Prince M, Gray JA, Ball D, Asherson
P, Mann A, Goldberg D, McGuffin P, Farmer A, Plomin R,
Craig IW, Sham PC: Genome-wide linkage analysis of a composite
index of neuroticism and mood-related scales in extreme
selected sibships. Hum Mol Genet 2004; 13:2173–2182

30. Holmans P, Zubenko GS, Crowe RR, DePaulo JR Jr, Scheftner
WA, Weissman MM, Zubenko WN, Boutelle S, Murphy-Eberenz
K, MacKinnon D, McInnis MG, Marta DH, Adams P, Knowles JA,
Gladis M, Thomas J, Chellis J, Miller E, Levinson DF: Genomewide
significant linkage to recurrent, early-onset major depressive
disorder on chromosome 15q. Am J Hum Genet 2004; 74:
1154–1167

31. Abkevich V, Camp NJ, Hensel CH, Neff CD, Russell DL, Hughes
DC, Plenk AM, Lowry MR, Richards RL, Carter C, Frech GC, Stone
S, Rowe K, Chau CA, Cortado K, Hunt A, Luce K, O’Neil G, Poarch
J, Potter J, Poulsen GH, Saxton H, Bernat-Sestak M, Thompson V,
Gutin A, Skolnick MH, Shattuck D, Cannon-Albright L: Predisposition
locus for major depression at chromosome 12q22-
12q23.2. Am J Hum Genet 2003; 73:1271–1281

32. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ: A longitudinal
twin study of personality and major depression in
women. Arch Gen Psychiatry 1993; 50:853–862

33. Fanous A, Gardner CO, Prescott CA, Cancro R, Kendler KS: Neuroticism,
major depression and gender: a population-based
twin study. Psychol Med 2002; 32:719–728

34. Fullerton J, Cubin M, Tiwari H, Wang C, Bomhra A, Davidson S,
Miller S, Fairburn C, Goodwin G, Neale MC, Fiddy S, Mott R, Allison
DB, Flint J: Linkage analysis of extremely discordant and
concordant sibling pairs identifies quantitative-trait loci that
influence variation in the human personality trait neuroticism.
Am J Hum Genet 2003; 72:879–890

35. Prusoff BA, Merikangas KR, Weissman MM: Lifetime prevalence
and age of onset of psychiatric disorders: recall 4 years later. J
Psychiatr Res 1988; 22:107–117

36. Rice JP, Rochberg M, Endicott J, Lavori PW, Miller C: Stability of
psychiatric diagnoses: an application to the affective disorders.
Arch Gen Psychiatry 1992; 49:824–830

37. Williams JBW, Gibbon M, First MB, Spitzer RL, Davies M, Borus J,
Howes MJ, Kane J, Pope HG, Rounsaville B, Wittchen H-U: The
Structured Clinical Interview for DSM-III-R (SCID), II: multisite
test-retest reliability. Arch Gen Psychiatry 1992; 49:630–636

38. Foley DL, Neale MC, Kendler KS: Reliability of a lifetime history
of major depression: implications for heritability and co-morbidity.
Psychol Med 1998; 28:857–870

39. Soldani F, Sullivan PF, Pedersen NL: Mania in the Swedish Twin
Registry: criterion validity and prevalence. Aust NZ J Psychiatry
2005; 39:235–243