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Original Investigation |

A Comprehensive Assessment of Parental Age and Psychiatric Disorders

John J. McGrath, MD1,2; Liselotte Petersen, PhD3,4; Esben Agerbo, DrMedSc3,4,5; Ole Mors, MD4,6; Preben Bo Mortensen, DrMedSc3,4,5; Carsten Bøcker Pedersen, DrMedSc3,4,5
[+] Author Affiliations
1Queensland Brain Institute, University of Queensland, St Lucia, Australia
2Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, Australia
3National Centre for Register-Based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark
4Initiative for Integrative Psychiatric Research, Lundbeck Foundation, Valby, Denmark
5Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
6Aarhus University Hospital, Risskov, Denmark
JAMA Psychiatry. 2014;71(3):301-309. doi:10.1001/jamapsychiatry.2013.4081.
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Importance  There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes.

Objective  To determine the association between maternal and paternal age and a comprehensive range of mental health disorders.

Design, Setting, and Participants  A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period.

Exposures  Maternal and paternal age at the time of offspring’s birth.

Main Outcomes and Measures  We examined a broad range of International Classification of Diseases–defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent.

Results  The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation.

Conclusions and Relevance  The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.

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Figure 1.
Incidence Rate Ratios (IRRs) for Any Psychiatric Disorder by Parental Age

Psychiatric disorders were identified by codes F00 to F99 from the International Statistical Classification of Diseases, 10th Revision, Diagnostic Criteria for Research, by parental age. Persons identified were born from January 1, 1955, through December 31, 2006, and followed up from January 1, 1995, through December 31, 2011. All IRRs are adjusted for age, sex, and calendar year. Tick marks indicate 95% confidence intervals.

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Figure 2.
Incidence Rate Ratios (IRRs) for Diagnoses Due to Psychoactive Substance Abuse, Schizophrenia, Mood Disorders, and Neurotic Disorders by Parental Age

Persons identified were born from January 1, 1955, to December 31, 2006, and followed up from January 1, 1995, to December 31, 2011. All IRRs are adjusted for age, sex, and calendar year. Tick marks indicate 95% confidence intervals. A, Mental and behavioral disorders due to psychoactive substance abuse (International Statistical Classification of Diseases, 10th Revision, Diagnostic Criteria for Research codes F10-F19). B, Schizophrenia and related disorders (F20-F29). C, Mood disorders (codes F30-F39). D, Neurotic, stress-related, and somatoform disorders (codes F40-F48).

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Figure 3.
Incidence Rate Ratios (IRRs) for Personality Disorders, Developmental Disorders, Childhood-Onset Behavioral and Emotional Disorders, and Mental Retardation by Parental Age

Persons identified were born from January 1, 1955, to December 31, 2006, and followed up from January 1, 1995, to December 31, 2011. All IRRs are adjusted for age, sex, and calendar year. Tick marks indicate 95% confidence intervals. A, Specific personality disorders (code F60). B, Pervasive developmental disorders (code F84). C, Behavioral and emotional disorders with onset usually occurring in childhood and adolescence (codes F90-F98). D, Mental retardation (codes F70-F79).

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