Differences in maternal and paternal age between Schizophrenia and other psychiatric disorders

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Abstract

Advanced parental age has been shown to increase offspring risk for a number of neuropsychiatric disorders including schizophrenia and Down's syndrome. Other psychiatric disorders have been less studied with respect to the effect of parental age on offspring risk. In this study we examine if advanced parental age increased risk for ICD-10 diagnoses. We hypothesized that advanced parental age would increase risk for offspring psychotic disorders and mental retardation but not other ICD-10 diagnoses. We examined follow-up data for 30,965 subjects treated in outpatient psychiatric facilities between 1980 and 2007. Subjects were younger than 18 years of age at their first outpatient visit. A comparison group was obtained from data on registered births in Spain from 1975.

We compared parental age (maternal, paternal, combined) across diagnostic categories using ANOVA and logistic regression was used to estimate the risk of psychopathology in the offspring with advanced parental age (maternal, paternal, combined). Maternal and paternal ages were higher for subjects diagnosed with mental retardation. Risk for psychotic disorders showed a significant linear increase only with advancing maternal age, and not paternal age as is more often reported.

Introduction

Demographic changes in the age of childbearing in past decades have led to investigation of advanced parental age as a putative risk factor for neuropsychiatric disorders in offspring (Cannon, 2009, Heffner, 2004). Advanced paternal age has been associated with increased offspring risk for autism (Larsson et al., 2005), schizophrenia (Zammit et al., 2003), and bipolar disorder (Frans et al., 2008), and has also been associated with neurocognitive (Saha et al., 2009), developmental (Mannerkoski et al., 2007) and social (Weiser et al., 2008) impairment. Advanced maternal age is an important risk factor for chromosomal abnormalities, including Down's syndrome (Roizen and Patterson, 2003), however, its association with other neuropsychiatric disorders, such as autism (Durkin et al., 2008, Reichenberg et al., 2006) and schizophrenia (Ekeus et al., 2006), remains controversial. A number of mechanisms have been proposed for the differential effects of maternal and paternal age including disparities in the ratio and type of mutations during gametogenesis (Arnheim and Calabrese, 2009, Malaspina et al., 2005). Accumulated mutations and chromosomal anomalies in reproductive germ cells might account for the largest part of the risk for mental disorders associated with advanced parental age (Heffner, 2004, Malaspina et al., 2002). Other factors might be personality traits (Zammit et al., 2003), physical disease in elderly parents (Malaspina et al., 2005) and social characteristics (Saha et al., 2009).

Research in this area has been focused on a specific subset of disorders and genetic causality. We found only two studies that compared parental age and psychopathology across multiple diagnostic categories. Gillberg (1982) reported that advanced parental age was associated with psychotic disorders and mental retardation but not emotional disorders, and Ekeus et al (2006) found an increased risk of schizophrenia, but not drug abuse or suicide, in offspring with elderly parents. Neither study systematically assessed the effect of parental age across ICD-10 diagnostic categories as one used a non-systematic diagnostic classification (Gillberg et al) and the other examined only a small subset of ICD-10 diagnoses (Ekeus et al 2006).

This study examines the association of offspring disorder and advanced parental age across all ICD-10 psychiatric diagnoses. We hypothesized that subjects with psychotic disorders and mental retardation would have a greater likelihood of having advanced parental age (maternal, paternal, mean parental) than subjects with other ICD-10 diagnoses and population based controls.

Section snippets

Sample

Data was available for 30,965 psychiatric outpatients attending community Mental Health Centers in the province of Madrid, Spain. Approximately 85% of Mental Health Centers in Madrid province are included. All subjects were younger than 18 years at the time of their first outpatient visit, and follow-up data was collected from January 1st 1980 to December 31st 2007. Subjects were followed for a mean of 2.56 ± 3.7 years. On a subject's initial outpatient visit the date of birth of their parents and

Results

Subjects were on average 8.9 ± 3.8 years of age at the time of their first diagnosis, and 11.7 ± 5.1 years at their last diagnosis. 59.6% were male (n = 18,451) and 40.4% female (n = 12,505). At the time of their first appointment most of the subjects (70.25%) where attending school in accordance with their chronological age, and 12.79% were delayed, 7.69% of subjects were not attending school. 65.93% and 15.43% of subjects had parents who had completed primary and secondary education respectively. The

Discussion

The present study explores the association between all ICD-10 categories of mental disorder and parental age at the time of birth in a large clinical sample. Subjects with mental retardation had the highest mean parental ages compared to all other ICD-10 diagnostic categories and a general population comparison group. Parental age among subjects with psychotic disorders approached a level comparable to the mental retardation group as older subjects (> 25 years) were considered. Consistent with

Role of funding source

Dr. Lopez-Castroman was supported by funds of the “Fundacion Española de Psiquiatria y Salud Mental” for the present study. The study was supported by CAM/UAM (CCG07-UAM/BIO-1925), ETES (PI07/90207) and Koplowitz Foundation research grants, and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. The Spanish Ministry of Health and the organizations cited above had no further role in study design; in the collection, analysis and interpretation of

Contributors

Jorge Lopez-Castroman, David Delgado and Enrique Baca-Garcia conceived and designed the study and drafted the manuscript. Jorge Lopez-Castroman managed the literature searches and analyses. David Delgado and Jorge Lopez-Castroman performed the statistical analysis and analyzed and interpreted the data. Juan José Carballo Belloso, Dianne Currier, Marta Reyes-Torres, Mercedes Navio-Acosta, Pablo Fernandez-Navarro, M. Mercedes Perez-Rodriguez, Ignacio Basurte Villamor, Francisco Ferre Navarrete,

Conflicts of interest

No conflicts declared.

Acknowledgements

Dr. Lopez-Castroman was supported by funds of the “Fundacion Española de Psiquiatria y Salud Mental” and Koplowitz Foundation for the present study. The study was supported by CAM/UAM (CCG07-UAM/BIO-1925), ETES (PI07/90207) and Koplowitz Foundation research grants, and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM.

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