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Seasonality of births in horizontal strabismus: comparison with birth seasonality in schizophrenia and other disease conditions

  • A. B. Agarwal (a1), K. Cassinelli (a2), L. A. Johnson (a1) (a2), K. Matsuda (a3), B. Kirkpatrick (a4), W. Yang (a5) and C. S. von Bartheld (a1)...


Recent work has implicated one type of horizontal strabismus (exotropia) as a risk factor for schizophrenia. This new insight raises questions about a potential common developmental origin of the two diseases. Seasonality of births is well established for schizophrenia. Seasonal factors such as light exposure affect eye growth and can cause vision abnormalities, but little is known about seasonality of births in strabismus. We examined birth seasonality in people with horizontal strabismus in a retrospective study in Washoe County, Nevada, and re-examined similar previously obtained data from Osaka, Japan. We then compared seasonal patterns of births between strabismus, refractive error, schizophrenia and congenital toxoplasmosis. Patients with esotropia had a significant seasonality of births, with a deficit in March, then increasing to an excess in September, while patients with exotropia had a distinctly different pattern, with an excess of births in July, gradually decreasing to a deficit in November. These seasonalities were statistically significant with either χ2 or Kolmogorov–Smirnov-type statistics. The birth seasonality of esotropia resembled that for hyperopia, with an increase in amplitude, while the seasonality for myopia involved a phase-shift. There was no correlation between seasonality of births between strabismus and congenital toxoplasmosis. The pattern of an excess of summer births for people with exotropia was remarkably similar to the well-established birth seasonality of one schizophrenia subtype, the deficit syndrome, but not schizophrenia as a whole. This suggests a testable hypothesis: that exotropia may be a risk factor primarily for the deficit type of schizophrenia.


Corresponding author

Address for correspondence: C. S. von Bartheld, Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. E-mail:


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1. Wadhwa, PD, Buss, C, Entringer, S, Swanson, JM. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med. 2009; 27, 358368.
2. Gluckman, PD, Hanson, MA, Buklijas, T. A conceptual framework for the developmental origins of health and disease. J Dev Orig Health Dis. 2010; 1, 618.
3. Almond, D, Currie, J. Killing me softly: the fetal origins hypothesis. J Econ Perspect. 2011; 25, 153172.
4. Torrey, EF, Miller, J, Rawlings, R, Yolken, RH. Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr Res. 1997; 28, 138.
5. Davies, G, Welham, J, Chant, D, Torrey, EF, McGrath, J. A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull. 2003; 29, 587593.
6. Bembenek, A. Seasonality of birth in schizophrenia patients. Literature review. Psychiatr Pol. 2005; 39, 259270.
7. Schiffman, J, Maeda, JA, Hayashi, K, et al. Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder. Schizophr Res. 2006; 81, 253260.
8. Mohney, BG, McKenzie, JA, Capo, JA, et al. Mental illness in young adults who had strabismus as children. Pediatrics. 2008; 122, 10331038.
9. Korn, H. Schizophrenia and eye movement – a new diagnostic and therapeutic concept. Med Hypotheses. 2004; 62, 2934.
10. Toyota, T, Yoshitsugu, K, Ebihara, M, et al. Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B. Hum Mol Genet. 2004; 13, 551561.
11. Yoshitsugu, K, Yamada, K, Toyota, T, et al. A novel scale including strabismus and ‘cuspidal ear’ for distinguishing schizophrenia patients from controls using minor physical anomalies. Psychiatry Res. 2006; 145, 249258.
12. Ndlovu, D, Nhleko, S, Pillay, Y, et al. The prevalence of strabismus in schizophrenic patients in Durban, KwaZulu Natal. S Afr Optom. 2011; 70, 101108.
13. Agarwal, AB, Christensen, AJ, Feng, CY, et al. Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? PeerJ. 2017; 5, e4214.
14. von Noorden, GK, Campos, EC. Binocular Vision and Ocular Motility, 6th edn, 2002. Mosby: St. Louis.
15. Matsuda, K, Yokoyama, T, Nakagawa, M, et al. Statistical analysis of the incidence of hyperopia by month of birth. Nippon Ganka Kiyo (Folia Ophthalmol Jpn). 1986; 37, 440443.
16. Mandel, Y, Grotto, I, El-Yaniv, R, et al. Season of birth, natural light, and myopia. Ophthalmology. 2008; 115, 686692.
17. Matsuda, K, Yokoyama, T, Fukui, M, Morita, T, Kozaki, M. Inverse analysis of the relationship between ocular refraction and birth month using matrix equations. Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc). 2016; 120, 533539.
18. Matsuda, K, Nakagawa, M, Yokoyama, T, et al. Incidence of strabismus by season of birth. Ganka Rinsho Iho (Jpn Rev Clin Ophthalmol). 1985; 79, 21152118.
19. Chew, E, Remaley, NA, Tamboli, A, et al. Risk factors for esotropia and exotropia. Arch Ophthalmol. 1994; 112, 13491355.
20. Saha, S, Chant, D, Welham, J, McGrath, J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005; 2, e141.
21. Messias, E, Kirkpatrick, B, Bromet, E, et al. Summer birth and deficit schizophrenia: a pooled analysis from 6 countries. Arch Gen Psychiatry. 2004; 61, 985989.
22. Meenken, C, Rothova, A, Kijlstra, A, Oosting, J. Seasonal variation in congenital toxoplasmosis. Br J Ophthalmol. 1991; 75, 639.
23. The Stanley Medical Research Institute. Epidemiological similarities and differences between toxoplasmosis and schizophrenia. Updated July, 2017. Retrieved from
24. Torrey, EF, Bartko, JJ, Yolken, RH. Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull. 2012; 38, 642647.
25. Carpenter, WT Jr, Heinrichs, DW, Wagman, AM. Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatr. 1988; 145, 578583.
26. Kirkpatrick, B, Buchanan, RW, Ross, DE, Carpenter, WT Jr. A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry. 2001; 58, 165171.
27. Kirkpatrick, B, Galderisi, S. Deficit schizophrenia: an update. World Psychiatry. 2008; 7, 143147.
28. Ross, DE, Thaker, GK, Buchanan, RW, et al. Eye tracking disorder in schizophrenia is characterized by specific ocular motor defects and is associated with the deficit syndrome. Biol Psychiatry. 1997; 42, 781796.
29. Ross, DE. The deficit syndrome and eye tracking disorder may reflect a distinct subtype within the syndrome of schizophrenia. Schizophr Bull. 2000; 26, 855866.
30. Nkam, I, Thibaut, F, Denise, P, et al. Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia. Schizophr Res. 2001; 48, 145153.
31. von Bartheld CS, Agarwal AB, Feng CY, et al. Why is exotropia (one specific type of strabismus) a significant risk factor for schizophrenia? 5th Biennial Schizophrenia International Research Society Conference, Florence, Italy, April 2–6, 2016. npj Schizophrenia. 2016; 2, 78, Abstract T212.
32. Choi, TB, Lee, DA, Oelrich, FO, et al. A retrospective study of eye disease among first grade children in Los Angeles. J Am Optom Assoc. 1995; 66, 484488.
33. Martinez-Bakker, M, Bakker, KM, King, AA, Rohani, P. Human birth seasonality: latitudinal gradient and interplay with childhood disease dynamics. Proc Biol Sci. 2014; 281, 20132438.
34. Maruo, T, Kubota, N, Arimoto, H. The results of examinations for strabismus and amblyopia in elementary and secondary school pupils (in Japanese). Ganka Rinsho Iho (Jpn Rev Clin Ophthalmol). 1977; 71, 712714.
35. Matsuda, S, Kahyo, H. Geographical differences and time trends in the seasonality of birth in Japan. Int J Epidemiol. 1994; 23, 107118.
36. Bradbury, TN, Miller, GA. Season of birth in schizophrenia: a review of evidence, methodology, and etiology. Psychol Bull. 1985; 98, 569594.
37. Verdoux, H, Takei, N, Cassou de Saint-Mathurin, R, Bourgeois, M. Analysis of the seasonal variation of schizophrenic births using a Kolmogorov-Smirnov type statistic. Eur Psychiatry. 1997; 12, 111116.
38. Nwogu, EC, Iwueze, IS, Nlebedim, VU. Some tests for seasonality in time series data. J Mod Appl Stat Meth. 2016; 15, 382399.
39. Freedman, LS. The use of a Kolmogorov–Smirnov type statistic in testing hypotheses about seasonal variation. J Epidemiol Community Health. 1979; 33, 223228.
40. Walter, SD. The power of a test for seasonality. Br J Prev Soc Med. 1977; 31, 137140.
41. Logar, J, Soba, B, Premru-Srsen, T, Novak-Antolic, Z. Seasonal variations in acute toxoplasmosis in pregnant women in Slovenia. Clin Microbiol Infect. 2005; 11, 852855.
42. Sagel, U, Mikolajczyk, RT, Krämer, A. Seasonal trends in acute toxoplasmosis in pregnancy in the federal state of Upper Austria. Clin Microbiol Infect. 2010; 16, 515517.
43. Dollfus, S, Brazo, P, Langlois, S, et al. Month of birth in deficit and non-deficit schizophrenic patients. Eur Psychiatry. 1999; 14, 349351.
44. Lam, DA, Miron, JA. Global patterns of seasonal variation in human fertility. Ann N Y Acad Sci. 1994; 709, 928.
45. Friger, M, Shoham-Vardi, I, Abu-Saad, K. Trends and seasonality in birth frequency: a comparison of Muslim and Jewish populations in southern Israel: daily time series analysis of 200 009 births, 1988-2005. Hum Reprod. 2009; 24, 14921500.
46. Kallel, L, Brunelin, J, Zghal, A, et al. Summer birth and deficit schizophrenia in Tunisia. Psychiatry Res. 2007; 152, 273275.
47. Kirkpatrick, B, Ram, R, Amador, XF, et al. Summer birth and the deficit syndrome of schizophrenia. Am J Psychiatry. 1998; 155, 12211226.
48. Kirkpatrick, B, Castle, D, Murray, RM, Carpenter, WT Jr. Risk factors for the deficit syndrome of schizophrenia. Schizophr Bull. 2000; 26, 233242.
49. Messias, E, Kirkpatrick, B. Summer birth and deficit schizophrenia in the epidemiological catchment area study. J Nerv Ment Dis. 2001; 189, 608612.
50. Tek, C, Kirkpatrick, B, Kelly, C, McCreadie, RG. Summer birth and deficit schizophrenia in Nithsdale, Scotland. J Nerv Ment Dis. 2001; 189, 613617.
51. Kirkpatrick, B, Tek, C, Allardyce, J, Morrison, G, McCreadie, RG. Summer birth and deficit schizophrenia in Dumfries and Galloway, southwestern Scotland. Am J Psychiatry. 2002; 159, 13821387.
52. Kirkpatrick, B, Herrera Castanedo, S, Vazquez-Barquero, JL. Summer birth and deficit schizophrenia: Cantabria, Spain. J Nerv Ment Dis. 2002; 190, 526532.
53. Mete, L, Sarıkaya, Ö, Erol, A. The relationship of deficit syndrome with clinical symptoms, summer births and heritability in patients with schizophrenia. Turk Psikiyatri Derg. 2015; 26, 229235.
54. Brown, AS, Patterson, PH. Maternal infection and schizophrenia: implications for prevention. Schizophr Bull. 2011; 37, 284290.
55. McGrath, J, Selten, JP, Chant, D. Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration—data from Australia and the Netherlands. Schizophr Res. 2002; 54, 199212.
56. Messias, E, Mourao, C, Maia, J, et al. Season of birth and schizophrenia in Northeast Brazil: relationship to rainfall. J Nerv Ment Dis. 2006; 194, 870873.
57. Häfner, H, Haas, S, Pfeifer-Kurda, M, Eichhorn, S, Michitsuji, S. Abnormal seasonality of schizophrenic births. A specific finding? Eur Arch Psychiatry Neurol Sci. 1987; 236, 333342.
58. Tochigi, M, Okazaki, Y, Kato, N, Sasaki, T. What causes seasonality of birth in schizophrenia? Neurosci Res. 2004; 48, 111.
59. Odegård, O. Season of birth in the population of Norway, with particular reference to the September birth maximum. Br J Psychiatry. 1977; 131, 339344.
60. McMahon, G, Zayats, T, Chen, YP, et al. Season of birth, daylight hours at birth, and high myopia. Ophthalmology. 2009; 116, 468473.
61. Nickla, DL. Ocular diurnal rhythms and eye growth regulation: where we are 50 years after Lauber. Exp Eye Res. 2013; 114, 2534.
62. Welham, J, Chant, D, Saha, S, et al. No association between the deficit syndrome in psychosis and summer birth in a Southern hemisphere country. Aust N Z J Psychiatry. 2006; 40, 935936.
63. Franzek, E, Beckmann, H. Gene-environment interaction in schizophrenia: season-of-birth effect reveals etiologically different subgroups. Psychopathology. 1996; 29, 1426.
64. Silverstein, SM, Wang, Y, Keane, BP. Cognitive and neuroplasticity mechanisms by which congenital or early blindness may confer a protective effect against schizophrenia. Frontiers Psychol. 2013; 3, Article 624.
65. Landgraf, S, Osterheider, M. “To see or not to see: that is the question.” The “Protection-Against-Schizophrenia” (PaSZ) model: evidence from congenital blindness and visuo-cognitive aberrations. Frontiers Psychol. 2013; 4, Article 352.
66. Kilgore, KP, Barraza, RA, Hodge, DO, McKenzie, JA, Mohney, BG. Surgical correction of childhood intermittent exotropia and the risk of developing mental illness. Am J Ophthalmol. 2014; 158, 788792.
67. Ochoa, S, Usall, J, Cobo, J, Labad, X, Kulkarni, J. Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review. Schizophr Res Treatment. 2012; 916198.



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