Parental age and risk of schizophrenia: a case-control study.

Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors. We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history. Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83). Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.

Byrne M ，Agerbo E ，Ewald H ，Eaton WW ，Mortensen PB ... -  《archives of general psychiatry》

Parental socio-economic status and risk of first admission with schizophrenia- a Danish national register based study.

We examined the relationships between measures of parental and personal socio-economic status and risk of first admission with schizophrenia in order to identify whether low socio-economic status in cases is a consequence of the illness process or is a familial risk factor. A national population-based nested case-control study based on Danish longitudinal registers was conducted. The sample included 7704 first admissions with ICD-8 or ICD-10 schizophrenia admitted to a psychiatric facility in Denmark between 1981 and 1998 and 192590 individually time-, age- and gender-matched population controls identified through national registers, and their parents and siblings. Socio-economic indicators measured in the year prior to admission and background factors for cases, controls, and parents were included. Risk of schizophrenia was associated with unemployment, low educational attainment, being single, lower wealth status, low income, and being childless. Increased risk was associated with a family history of psychiatric disorders, birth in urban areas, birth outside of Denmark, and having three of more siblings. Increased risk of schizophrenia was associated with parental unemployment and parental lower income, but was not associated with parental wealth. Risk for schizophrenia was associated with higher education in parents. Increased risk of first admission was associated with socio-economic disadvantage in cases. Although we found some associations between parental unemployment and parental higher education and risk of schizophrenia, there was little evidence that low parental socio-economic status increases the risk of schizophrenia.

Byrne M ，Agerbo E ，Eaton WW ，Mortensen PB ... -  《SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY》

Advancing paternal age and bipolar disorder.

Advancing paternal age has been reported as a risk factor for neurodevelopmental disorders. To determine whether advanced paternal age is associated with an increased risk of BPD in the offspring and to assess if there was any difference in risk when analyzing patients with early-onset BPD separately. A nationwide nested case-control study based on Swedish registers was performed. Risk for BPD in the offspring of older fathers was estimated using conditional logistic regression analysis controlling for potential confounding of parity, maternal age, socioeconomic status, and parental family history of psychotic disorders. Identification of 7,328,100 individuals and their biological parents by linking the nationwide Multigeneration Register and the Hospital Discharge Register. A total of 13,428 patients with a BPD diagnosis on at least 2 separate hospital admissions was identified. Five healthy control subjects matched for sex and year of birth were randomized to each case. Main Outcome Measure Bipolar disorder based on ICD codes at discharge from hospital treatment. An association between paternal age and risk for BPD in the offspring of older men was noted. The risk increased with advancing paternal age. After controlling for parity, maternal age, socioeconomic status, and family history of psychotic disorders, the offspring of men 55 years and older were 1.37 (95% confidence interval [CI], 1.02-1.84) times more likely to be diagnosed as having BPD than the offspring of men aged 20 to 24 years. The maternal age effect was less pronounced. For early-onset (<20 years) cases, the effect of paternal age was much stronger (odds ratio, 2.63; 95% CI, 1.19-5.81), whereas no statistically significant maternal age effect was found. Advanced paternal age is a risk factor for BPD in the offspring. The results are consistent with the hypothesis that advancing paternal age increases the risk for de novo mutations in susceptibility genes for neurodevelopmental disorders.

Frans EM ，Sandin S ，Reichenberg A ，Lichtenstein P ，Långström N ，Hultman CM ... -  《-》

Parental psychiatric hospitalisation and offspring schizophrenia.

The risk of schizophrenia has been linked with a family history of schizophrenia and less strongly with other psychiatric disorders in family members. Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Case Register, we studied the relationship between offspring risk of schizophrenia and a range of psychotic and non-psychotic psychiatric diagnoses in parents. Psychiatric admission data after 1969 were available for 7047 cohort members born between 1959 and 1961, and for 7006 mothers and 6993 fathers. Univariate analysis showed that neurosis, alcohol and substance dependence in both parents were associated with elevated risk of offspring schizophrenia; in addition, maternal schizophrenia, affective disorder and personality disorder were associated with elevated risk. Controlling for parental age, parental social status, and parental psychiatric co-diagnosis, offspring risk of schizophrenia was associated with maternal schizophrenia (OR = 15.41 with 95% CI 5.96-39.81) and, independently, with paternal hospitalisation with neurosis (OR = 5.90 with 95% CI 2.23-15.62). The risk of schizophrenia associated with paternal neurosis remained significant after excluding offspring of parents with non-affective psychosis from the sample. These findings suggest that genetic and family studies should not only focus on parental history of schizophrenia since the simple distinction between positive and negative family history could not accurately describe offspring risk in this sample.

Sørensen HJ ，Mortensen EL ，Reinisch JM ，Mednick SA ... -  《-》

Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status.

Research suggests that heredity and early fetal development play a causal role in autism. This case-control study explored the association between perinatal factors, parental psychiatric history, socioeconomic status, and risk of autism. The study was nested within a cohort of all children born in Denmark after 1972 and at risk of being diagnosed with autism until December 1999. Prospectively recorded data were obtained from nationwide registries in Denmark. Cases totaled 698 children with a diagnosis of autism; each case was individually matched by gender, birth year, and age to 25 controls. Analyses by conditional logistic regression produced risk ratios and 95% confidence intervals. Adjusted analyses showed that the risk of autism was associated with breech presentation (risk ratio (RR) = 1.63, 95% confidence interval (CI): 1.18, 2.26), low Apgar score at 5 minutes (RR = 1.89, 95% CI: 1.10, 3.27), gestational age at birth <35 weeks (RR = 2.45, 95% CI: 1.55, 3.86), and parental psychiatric history (schizophrenia-like psychosis: RR = 3.44, 95% CI: 1.48, 7.95; affective disorder: RR = 2.91, 95% CI: 1.65, 5.14). Analyses showed no statistically significant association between risk of autism and weight for gestational age, parity, number of antenatal visits, parental age, or socioeconomic status. Results suggest that prenatal environmental factors and parental psychopathology are associated with the risk of autism. These factors seem to act independently.

Larsson HJ ，Eaton WW ，Madsen KM ，Vestergaard M ，Olesen AV ，Agerbo E ，Schendel D ，Thorsen P ，Mortensen PB ... -  《AMERICAN JOURNAL OF EPIDEMIOLOGY》