Central European Journal of Medicine

, Volume 1, Issue 4, pp 392–398 | Cite as

Season of birth interacts with measures of inbreeding in multiplex schizophrenia pedigrees: evidence from genetic isolates in Daghestan

  • Kazima B. Bulayeva
  • John J. McGrath
Research Article


While the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this study include some with more than 200 and some with less than 100 generations of demographical history since their founding. Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore, compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia.


Schizophrenia inbreeding seasonality Daghestan genetic isolates 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    E.F. Torrey, J. Miller, R. Rawlings and R.H. Yolken: “Seasonality of births in schizophrenia and bipolar disorder: a review of the literature”, Schizophr. Res., Vol. 28, (1997), pp. 1–38.PubMedCrossRefGoogle Scholar
  2. [2]
    G. Davies, J. Welham, D. Chant, E.F. Torrey and J. McGrath: “Season of birth effect and latitude: a systematic review and meta-analysis of Northern Hemisphere studies”, Schizophr. Bull., Vol. 29(3), (2003), pp. 587–593.PubMedGoogle Scholar
  3. [3]
    J.J. McGrath and J.L. Welham: “Season of birth and schizophrenia: a systematic review and meta-analysis of data from the Southern Hemisphere”, Schizophr. Res., Vol. 35, (1999), Vol. 237-242.Google Scholar
  4. [4]
    A.S. Brown and E.S. Susser: In utero infection and adult schizophrenia. Ment. Retard. Dev. Disabil. Res. Rev., Vol. 8(1), (2002), pp. 51–57.PubMedCrossRefGoogle Scholar
  5. [5]
    J. McGrath: “Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?”, Schizophr. Res. , Vol. 40(3), (1999), pp. 173–177.PubMedCrossRefGoogle Scholar
  6. [6]
    E. Shur: “Season of birth in high and low genetic risk schizophrenics”, Br. J. Psychiatry, Vol. 140, (1982), pp. 410–415.PubMedCrossRefGoogle Scholar
  7. [7]
    P.B. Mortensen, C.B. Pedersen, T. Westergaard, J. Wohlfahrt, H. Ewald, O. Mors, P.K. Andersen and M. Melbye: “Effects of family history and place and season of birth on the risk of schizophrenia”, N. Engl. J. Med., Vol. 340, (1999), pp. 603–608.PubMedCrossRefGoogle Scholar
  8. [8]
    J.M. Suvisaari, J.K. Haukka and J.K. Lonnqvist: “No association between season of birth of patients with schizophrenia and risk of schizophrenia among their siblings”, Schizophr. Res., Vol. 66(1), (2004), pp. 1–6.PubMedCrossRefGoogle Scholar
  9. [9]
    J.M. Hettema, D. Walsh and K.S. Kendler: “Testing the effect of season of birth on familial risk for schizophrenia and related disorders”, Br. J. Psychiatry, Vol. 168(2), (1996), pp. 205–209.PubMedCrossRefGoogle Scholar
  10. [10]
    A.E. Pulver, K.Y. Liang, P.S. Wolyniec, J. McGrath, B.A. Melton, L. Adler and B. Childs: “Season of birth of siblings of schizophrenic patients”, Br. J. Psychiatry, Vol. 160, (1992), pp. 71–75.PubMedGoogle Scholar
  11. [11]
    E. O’Callaghan, K. Colgan, D. Cotter, C. Larkin, D. Walsh and J.L. Waddington: “Evidence for confinement of winter birth excess in schizophrenia to those born in cities”, Schizophr. Res., Vol. 6, (1992), p. 102.CrossRefGoogle Scholar
  12. [12]
    J. Chotai, A. Serretti, E. Lattuada, C. Lorenzi and R. Lilli: “Gene-environment interaction in psychiatric disorders as indicated by season of birth variations in tryptophan hydroxylase (TPH), serotonin transporter (5-HTTLPR) and dopamine receptor (DRD4) gene polymorphisms”, Psychiatry Res., Vol. 119(1-2), (2003), pp. 99–111.PubMedCrossRefGoogle Scholar
  13. [13]
    G. Seeger, P. Schloss, M.H. Schmidt, A. Ruter-Jungfleisch and F.A. Henn: “Gene environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism”, Neurosci. Lett., Vol. 366(3), (2004), pp. 282–286.PubMedCrossRefGoogle Scholar
  14. [14]
    T.A. Markow: “Genetics and developmental stability: an integrative conjecture on aetiology and neurobiology of schizophrenia”, Psychol. Med., Vol. 22, (1992), pp. 295–305.PubMedCrossRefGoogle Scholar
  15. [15]
    K.B. Bulayeva, S.M. Leal, T.A. Pavlova, R.M. Kurbanov, S.J. Glatt, O.A. Bulayev and M.T. Tsuang: “Mapping genes of complex psychiatric diseases in Daghestan genetic isolates”, Am. J. Med. Genet., B. Neuropsychiatr. Genet., Vol. 132(1), (2005), pp. 76–84.Google Scholar
  16. [16]
    K. Bulayeva et al.: “Genome-Wide Linkage Scan of Schizophrenia: a Cross-Isolates Study”, Genomics, (2006), in press.Google Scholar
  17. [17]
    M. Gadjiev, O. Davudov and S. Shihsaidov: History of Daghestan, Moscow, Nauka, 1996.Google Scholar
  18. [18]
    K. Bulayeva: Genetic basis of human psychophysiology, Moscow, Nauka, 1991.Google Scholar
  19. [19]
    K. Bulayeva, L.B. Jorde, C. Ostler, S. Watkins, O. Bulayev and H. Harpending: “Genetics and population history of Caucasus populations”, Hum. Biol., Vol. 75(6), (2003), pp. 837–853.PubMedGoogle Scholar
  20. [20]
    K. Bulayeva, L. Jorde, S. Watkins, C. Ostler, T.A. Pavlova, O.A. Bulayev, S. Tofanelli, G. Paoli and H. Harpending: “Ethnogenomic diversity of Caucasus, Daghestan”, Am. J. Hum. Biol., Vol. 18(5), (2006), pp. 610–620.PubMedCrossRefGoogle Scholar
  21. [21]
    J.I. Nurnberger, M.C. Blehar, C.A. Kaufmann, C. York-Cooler, S.G. Simpson, J. Harkavy-Friedman, J.B. Severe, D. Malaspina and T. Reich: “Diagnostic interview for genetic studies: rationale, unique features and training”, Arch. Gen. Psychiatry, Vol. 51, (1994), pp. 849–862.PubMedGoogle Scholar
  22. [22]
    K. Bulayeva: “Overview of genetic-epidemiological studies in ethnically and demographically diverse isolates of Dagestan, Northern Caucasus, Russia”, Croat. Med. J., Vol. 47(4), (2006), pp. 641–649.PubMedGoogle Scholar
  23. [23]
    R.A. Yeo, S.W. Gangestad, C. Edgar and R. Thoma: “The evolutionary genetic un derpinnings of schizophrenia: the developmental instability model”, Schizophr.Res., Vol. 39(3), (1999), pp. 197–206.PubMedCrossRefGoogle Scholar
  24. [24]
    C.H. Waddington: “Canalization of development and genetic assimilation of acquired characters”, Nature, Vol. 183(4676), (1959), pp. 1654–1655.PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Kazima B. Bulayeva
    • 1
  • John J. McGrath
    • 2
  1. 1.N.I. Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  2. 2.Queensland Centre for Mental Health Research, Department of PsychiatryUniversity of Queensland, The Park Centre for Mental HealthWacolAustralia

Personalised recommendations