Abraham Reichenberg

Advanced paternal age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the paternal age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced paternal age.

Autism is a neurodevelopmental disorder characterized by social deficiencies, language impairments, and repetitive behavior patterns.¹ The disorder begins early in life, has a high heritability, and is associated with a marked reduction in birth rates.²

Responses to public health need require information on the distribution of mental and physical ill health by demographic and socioeconomic factors at the local community level. The South East London Community Health (SELCoH) study is a community psychiatric and physical morbidity survey. Trained interviewers conducted face-to-face computer assisted interviews with 1698 adults aged 16 years and over, from 1076 randomly selected private households in two south London boroughs. We compared the prevalence of common mental disorders, hazardous alcohol use, long standing illness and general physical health by demographic and socioeconomic indicators. Unadjusted and models adjusted for demographic and socioeconomic indicators are presented for all logistic regression models. Of those in the sample, 24.2% reported common mental disorder and 44.9% reported having a long standing illness, with 15.7% reporting hazardous alcohol consumption and 19.2% rating their health as fair or poor. The pattern of indicators identifying health inequalities for common mental disorder, poor general health and having a long term illness is similar; individuals who are socioeconomically disadvantaged have poorer health and physical health worsens as age increases for all groups. The prevalence of poor health outcomes by ethnic group suggests that there are important differences between groups, particularly for common mental disorder and poor general health. Higher socioeconomic status was protective for common mental disorder, fair or poor health and long standing illness, but those with higher socioeconomic status reported higher levels of hazardous alcohol use. The proportion of participants who met the criteria for common mental disorder with co-occurring functional limitations was similar or greater to those with poor physical health. Health service providers and policy makers should prioritise high risk, socially defined groups in combating inequalities in individual and co-occurring poor mental and physical problems. In population terms, poor mental health has a similar or greater burden on functional impairment than long term conditions and perceived health.

Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged 50 years were 2.2 times (95% confidence interval: 1.26–3.88: P=0.006) more likely to have autism than offspring of men aged 29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (Pde novo aberration and mutations or epigenetic alterations associated with aging.

Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. The neuropsychological profile is typically characterized by prominent specific deficits in memory and learning, working memory, executive functions, attention, and processing speed, …