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Advanced paternal age is a risk factor for schizophrenia in Iranians.

Naserbakht M, Ahmadkhaniha HR, Mokri B, Smith CL - Ann Gen Psychiatry (2011)

Bottom Line: There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk.Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers.However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tehran University of Medical Science, Tehran, Iran. dr_ahmadkhaniha@yahoo.com.

ABSTRACT

Background: Since 1958 many, but not all studies have demonstrated that paternal age is a risk factor for schizophrenia. There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk. The small number of children in Western families makes risk comparisons between siblings born at different paternal ages difficult. In contrast, more Eastern families have children both at early and later periods of life. In the present study, a cross-sectional population study in an Iranian population was performed to compare frequency of schizophrenia in younger offspring (that is, older paternal age) versus older offspring.

Methods: A total of 220 patients with the diagnosis of schizophrenia (cases) from both psychiatric hospitals and private clinics and 220 individuals from other hospital wards (controls), matched for sex and age were recruited for this study. Patients with neurological problem, substance abuse, mental retardation and mood disorder were excluded from both groups.

Results: Birth rank comparisons revealed that 35% vs 24% of the cases vs the controls were in the third or upper birth rank (P = 0.01). Also, the mean age of fathers at birth in case group (30 ± 6.26 years) was significantly more than the control group (26.45 ± 5.64 years; P = 0.0001). The age of 76 fathers at birth in case group was over 32 versus 33 fathers in control group. Individuals whose fathers' age was more than 32 (at birth) were at higher risk (2.77 times) for schizophrenia versus others (P < 0.0001, 95% CI 1.80 to 4.27). The maternal age at parturition of the case versus controls groups was 26.1 ± 5.41 vs 25.07 ± 4.47 (P = 0.02). Logistic regression analysis suggests that maternal age is less likely to be involved in the higher risk of schizophrenia than advanced parental age.

Discussion: This study demonstrates a relationship between paternal age and schizophrenia in large families of an Iranian population. Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers. However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment. Further research on samples such as those collected here are needed to sort out the contributions of de novo mutations versus epigenetic changes to schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Distribution of paternal age in case and control subjects.
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Figure 1: Distribution of paternal age in case and control subjects.

Mentions: Paternal age at parturition of the proband was significantly different between the case and control groups. For instance, the mean paternal age at birth was 30 ± 6.26 versus 26.45 ± 5.64, in case versus control groups, respectively (P = 0.0001) (Tables 1 and 2). A significantly higher number of fathers with an age of ≥32 were in the case group versus the control group (Table 3). Analysis of the paternal age distribution (Figure 1) revealed that the fathers of the case group tended to have children at an earlier age, but that a greater number (76, 35%) of cases' fathers age were ≥32, than those in control group (n = 33, 15%). Individuals with fathers' ages at birth ≥32 were 2.77 times at higher risk for schizophrenia (P < 0.0001), OR = 3.7 (95% CI 1.9 to 7.3). The mean age of mothers at birth was marginally different (P = 0.02) between the case and control groups (26 versus 25.07, respectively). Logistic regression analysis (Table 4), adjusting for the effect of maternal age, birth rank and family history, indicated that paternal age is an independent predisposing factor to schizophrenia; its OR was 3.78 (95% CI 1.9 to 7.3).


Advanced paternal age is a risk factor for schizophrenia in Iranians.

Naserbakht M, Ahmadkhaniha HR, Mokri B, Smith CL - Ann Gen Psychiatry (2011)

Distribution of paternal age in case and control subjects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094249&req=5

Figure 1: Distribution of paternal age in case and control subjects.
Mentions: Paternal age at parturition of the proband was significantly different between the case and control groups. For instance, the mean paternal age at birth was 30 ± 6.26 versus 26.45 ± 5.64, in case versus control groups, respectively (P = 0.0001) (Tables 1 and 2). A significantly higher number of fathers with an age of ≥32 were in the case group versus the control group (Table 3). Analysis of the paternal age distribution (Figure 1) revealed that the fathers of the case group tended to have children at an earlier age, but that a greater number (76, 35%) of cases' fathers age were ≥32, than those in control group (n = 33, 15%). Individuals with fathers' ages at birth ≥32 were 2.77 times at higher risk for schizophrenia (P < 0.0001), OR = 3.7 (95% CI 1.9 to 7.3). The mean age of mothers at birth was marginally different (P = 0.02) between the case and control groups (26 versus 25.07, respectively). Logistic regression analysis (Table 4), adjusting for the effect of maternal age, birth rank and family history, indicated that paternal age is an independent predisposing factor to schizophrenia; its OR was 3.78 (95% CI 1.9 to 7.3).

Bottom Line: There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk.Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers.However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tehran University of Medical Science, Tehran, Iran. dr_ahmadkhaniha@yahoo.com.

ABSTRACT

Background: Since 1958 many, but not all studies have demonstrated that paternal age is a risk factor for schizophrenia. There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk. The small number of children in Western families makes risk comparisons between siblings born at different paternal ages difficult. In contrast, more Eastern families have children both at early and later periods of life. In the present study, a cross-sectional population study in an Iranian population was performed to compare frequency of schizophrenia in younger offspring (that is, older paternal age) versus older offspring.

Methods: A total of 220 patients with the diagnosis of schizophrenia (cases) from both psychiatric hospitals and private clinics and 220 individuals from other hospital wards (controls), matched for sex and age were recruited for this study. Patients with neurological problem, substance abuse, mental retardation and mood disorder were excluded from both groups.

Results: Birth rank comparisons revealed that 35% vs 24% of the cases vs the controls were in the third or upper birth rank (P = 0.01). Also, the mean age of fathers at birth in case group (30 ± 6.26 years) was significantly more than the control group (26.45 ± 5.64 years; P = 0.0001). The age of 76 fathers at birth in case group was over 32 versus 33 fathers in control group. Individuals whose fathers' age was more than 32 (at birth) were at higher risk (2.77 times) for schizophrenia versus others (P < 0.0001, 95% CI 1.80 to 4.27). The maternal age at parturition of the case versus controls groups was 26.1 ± 5.41 vs 25.07 ± 4.47 (P = 0.02). Logistic regression analysis suggests that maternal age is less likely to be involved in the higher risk of schizophrenia than advanced parental age.

Discussion: This study demonstrates a relationship between paternal age and schizophrenia in large families of an Iranian population. Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers. However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment. Further research on samples such as those collected here are needed to sort out the contributions of de novo mutations versus epigenetic changes to schizophrenia.

No MeSH data available.


Related in: MedlinePlus