2. Introduction  Schizophrenia ↓ Neuro-developmental Disorder ↕ Pathogenesis in gestation and early childhood ↕ Further research is needed

3.  Advanced paternal age ↓ New mutations ↓ Adverse effect on fetal brain development ↓ Risk of Schizophrenia ↕ Attention to the ? role for new mutations

4.  During development of male germ cells ↓ More cell divisions than in Female cells ↓ Copy error mutations as age advances ↕ ↑ Vulnerability of sperm from older fathers to de novo mutations Crow, 2000

5. Advancing paternal age ↓ ↑ Sporadic de novo mutations ↓  Cancer & Achondroplasia Crow, 2003  Miscarriages  Birth deformities  Autism  Schizophrenia Sukanta et al, 2009

6. Literature Review  A large Israeli birth cohort  658 patients with Schizophrenia and related Non- affective psychoses  Paternal age was found to be a strong and significant predictor of Schizophrenia (Malaspina et al, 2001)

7.  A large Swedish record linkage database (7,54330 of cohort born from 1973-1980)  The overall hazard ratio for each 10 year increase in paternal age was calculated  1.47 for schizophrenia and 1.12 for Non- schizophrenic Non-affective psychosis (Attila et al, 2004)

8.  The Medical Birth Register, Military Service Conscription Register & Inpatient Hospital Discharge Register  The risk of schizophrenia was 4.62 times higher in subjects with paternal age > 50 years than those of 21–24 years (Rasmussen et al, 2006)

9.  Reanalysis of data on 33,437 children from the US Collaborative Perinatal Project (CPP)  The offspring of older fathers show subtle impairments on tests of neuro-cognitive ability during infancy and childhood (Sukanta et al, 2009)

10. Recent western studies ↓ Data from large birth cohort ↓ Risk of advanced paternal age on Schizophrenia ↕ Necessity of such Study in our set-up also

11. Indian Research  Fathers of the Affected Sib Pairs were significantly older at the time of the birth of the ill offspring(N=203) compared to those of Sporadic Cases ( Thara et al, Personal communication, 2009)

12. Aim  To study the association between “Paternal age at conception & Development of Schizophrenia” among the patients diagnosed with Schizophrenia

13. Methodology  Retrospective file review  June 2004 - June 2009  Sequential sampling  Cases (290) – Schizophrenia (ICD-10 criteria)  Controls (290) - Non-Schizophrenia subjects  Study was approved by the hospital ethics committee

14. Sample Total sample (N=580) Schizophrenia (N=290) Non- Schizophrenia (N =290)

15. Variables Age of both parents at birth of subject Duration of marriage of parents at birth Age of onset of disorder Birth order Socioeconomic status

16. Statistical Analysis  Odd’s Ratio for predicting the effect of paternal age on development of illness among both the cases & controls  Chi square & t-test for comparison of variables among the two variants of Schizophrenia (SPSS 13.0)

17. Results

19. Table -1 Variables Non-Schizophrenia N 1 =290 (%) Schizophrenia N 2 =250 (% ) Odd’s Ratio (95% CI) p-value Paternal Age (yrs) <=30 31-40 >40 118 (40.7) 138 (47.6) 34 (11.7) 101 (40.6) 108 (43.4) 40 (16.1) 1 0.91 (0.63, 1.32) 1.37 (0.81, 2.33) 0.63 0.24 Maternal Age (yrs) <=20 21-30 31-40 >40 57 (19.7) 182 (62.8) 43 (14.8) 8 (2.8) 56 (22.4) 138 (55.2) 46 (18.4) 10 (4.0) 1 0.77 (0.5, 1.2) 1.09 (0.62, 1.9) 1.3 (0.47, 3.5) 0.24 0.76 0.64 Duration of marriage of parents (yrs) <=1 2-4 5-9 10-14 >=15 79 (27.2) 81 (27.9) 71 (24.5) 35 (12.1) 24 (8.3) 65 (25.9) 58 (23.1) 53 (21.1) 34 (13.5) 41 (16.3) 1 0.87 (0.54, 1.34) 0.9 (0.56, 1.47) 1.18(0.66, 2.09) 2.08 (1.14, 3.79) 0.56 0.69 0.57 0.017*

20. Logistic regression analysis Maternal age taken as co-variant Hosmer and Lemeshow test, p value = 0.753 Not significant in predicting the risk of Schizophrenia

21. Table-2 Variant of Schizophrenia → Variables ↓ Paranoid (N=151) Mean ± SD Non-paranoid (N=98) Mean (±Mean ± SD SD) p-value Paternal Age (yrs)33.19 ±7.0233.05 ±7.920.205 Maternal Age (yrs)26.22 ±6.4626.51 ±7.580.07 Duration of marriage of parents (yrs) 6.29 ±5.587.08 ±6.30 0.344

22. Table-3 VariablesParanoid (N=177) Mean ± SD Non-paranoid (N=113) Mean ± SD Total (N=283) p-value Age of onset (yrs)28.25 ±10.4424.38 ±7.93 0.04* Birth order  Order 1 & Single child  Midle order (2 & 3)  >3 50 (28.9) 72 (41.6) 51 (29.5) 23 (20.9) 50 (45.4) 37 (33.6) 73 (25.8) 122 (43.1) 88 (31.1) 0.322 Socio-economic Status  Lower  Middle 79 (44.6) 98 (55.4) 72 (64.3) 40 (35.7) 151 (52.2) 138 (47.8) 0.001**

23. Discussion Most of the earlier studies had taken large pool of sample from Birth cohorts, Population Registries and Hospital Records Our sample was smaller in comparison to those studies

24. The western studies utilized data from the population registries and cohorts The study by Thara et al (2009) was based on the data derived from structured interview This study basically depended on the ages documented in the case records ? rough estimate→?reliability

25.  Earlier studies had shown significant association of paternal age on Schizophrenia  Our study also showed trend of increased risk of Schizophrenia in the patients with paternal age above 40 yrs Incidentally, it also revealed significant association between duration of marriage of parents at birth & Schizophrenia in the child

26. Conclusion  This study tried to explore the association between paternal age and Schizophrenia in a hospital based sample  Subjects born to fathers over 40 yrs were at higher risk of developing Schizophrenia  The findings cannot be generalized because of methodological limitations

27.  Using Birth cohorts or Population based prospective studies may bring out possible associations in the future

28. Acknowledgements : Dr Suma, Junior Resident Dr Praveen A., Senior Resident Dr Sreejayan K., Asst. Professor THANK YOU!