Association between maternal depression symptoms and child telomere length.

The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299). Mothers completed structured questionnaires assessing depression during pregnancy (Edinburgh Depression Scale), at 9 months (Edinburgh Depression Scale), and at 54 months postpartum (Patient Health Questionnaire 9). Regression methods were used to investigate the relationship between telomere length (DNA from saliva) and maternal depression score recorded at each stage. Significant covariates included in the final model were: maternal age at pregnancy; child sex; child ethnicity; gestational age group, and rurality group. Child telomere length was found to be longer if their mother had a higher depression score at both postpartum time points tested (9 months of age; coefficient 0.003, SE = 0.001, P = 0.01, 54 months of age; coefficient 0.003, SE = 0.002, P = 0.02). Although these findings seem paradoxical, increased telomere length may be an adaptive response to early life stressors. We propose several testable hypotheses for these results and to determine if the positive association between depression and telomere length is a developmental adaptation or an indirect consequence of environmental factors.

Modelling brain dopamine-serotonin vesicular transport disease in Caenorhabditis elegans.

Brain dopamine-serotonin vesicular transport disease is a rare disease caused by autosomal recessive mutations in the SLC18A2 gene, which encodes the VMAT2 protein. VMAT2 is a membrane protein responsible for vesicular transport of monoamines, and its disruption negatively affects neurotransmission. This results in a severe neurodevelopmental disorder affecting motor skills and development, and causes muscular hypotonia. The condition was initially described in a consanguineous Saudi Arabian family with affected siblings homozygous for a P387L mutation. We subsequently found a second mutation in a New Zealand family (homozygous P237H), which was later also identified in an Iraqi family. Pramipexole has been shown to have some therapeutic benefit. Transgenic Caenorhabditis elegans were developed to model the P237H and P387L mutations. Investigations into dopamine- and serotonin-related C. elegans phenotypes, including pharyngeal pumping and grazing, showed that both mutations cause significant impairment of these processes when compared with a non-transgenic N2 strain and a transgenic containing the wild-type human SLC18A2 gene. Preliminary experiments investigating the therapeutic effects of serotonin and pramipexole demonstrated that serotonin could successfully restore the pharyngeal pumping phenotype. These analyses provide further support for the role of these mutations in this disease.