Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.

The methylation of cytosine to 5-methylcytosine (5-meC) is an important epigenetic DNA modification in many bacteria, plants, and mammals, but its relevance for important model organisms, including Caenorhabditis elegans and Drosophila melanogaster, is still equivocal. By reporting the presence of 5-meC in a broad variety of wild, laboratory, and industrial yeasts, a recent study also challenged the dogma about the absence of DNA methylation in yeast species. We would like to bring to attention that the protocol used for gas chromatography/mass spectrometry involved hydrolysis of the DNA preparations. As this process separates cytosine and 5-meC from the sugar phosphate backbone, this method is unable to distinguish DNA- from RNA-derived 5-meC. We employed an alternative LC–MS/MS protocol where by targeting 5-methyldeoxycytidine moieties after enzymatic digestion, only 5-meC specifically derived from DNA is quantified. This technique unambiguously identified cytosine DNA methylation in Arabidopsis thaliana (14.0% of cytosines methylated), Mus musculus (7.6%), and Escherichia coli (2.3%). Despite achieving a detection limit at 250 attomoles (corresponding to <0.00002 methylated cytosines per nonmethylated cytosine), we could not confirm any cytosine DNA methylation in laboratory and industrial strains of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Saccharomyces boulardii, Saccharomyces paradoxus, or Pichia pastoris. The protocol however unequivocally confirmed DNA methylation in adult Drosophila melanogaster at a value (0.034%) that is up to 2 orders of magnitude below the detection limit of bisulphite sequencing. Thus, 5-meC is a rare DNA modification in drosophila but absent in yeast.

The phenomenology of late-life depression differs only in part from that of early-life depression. Major depression in older people may have a more somatic presentation, whereas feelings of guilt and loss of sexual function may be more prevalent in younger people.

BackgroundTo study late-life depression and its unfavourable course and co morbidities in The Netherlands.MethodsWe designed the Netherlands Study of Depression in Older Persons (NESDO), a multi-site naturalistic prospective cohort study which makes it possible to examine the determinants, the course and the consequences of depressive disorders in older persons over a period of six years, and to compare these with those of depression earlier in adulthood.ResultsFrom 2007 until 2010, the NESDO consortium has recruited 510 depressed and non depressed older persons (≥ 60 years) at 5 locations throughout the Netherlands. Depressed persons were recruited from both mental health care institutes and general practices in order to include persons with late-life depression in various developmental and severity stages. Non-depressed persons were recruited from general practices. The baseline assessment included written questionnaires, interviews, a medical examination, cognitive tests and collection of blood and saliva samples. Information was gathered about mental health outcomes and demographic, psychosocial, biological, cognitive and genetic determinants. The baseline NESDO sample consists of 378 depressed (according to DSM-IV criteria) and 132 non-depressed persons aged 60 through 93 years. 95% had a major depression and 26.5% had dysthymia. Mean age of onset of the depressive disorder was around 49 year. For 33.1% of the depressed persons it was their first episode. 41.0% of the depressed persons had a co morbid anxiety disorder. Follow up assessments are currently going on with 6 monthly written questionnaires and face-to-face interviews after 2 and 6 years.ConclusionsThe NESDO sample offers the opportunity to study the neurobiological, psychosocial and physical determinants of depression and its long-term course in older persons. Since largely similar measures were used as in the Netherlands Study of Depression and Anxiety (NESDA; age range 18-65 years), data can be pooled thus creating a large longitudinal database of clinically depressed persons with adequate power and a large set of neurobiological, psychosocial and physical variables from both younger and older depressed persons.

Risk of neural tube defects (NTDs) is determined by genetic and environmental factors, among which folate status appears to play a key role. However, the precise nature of the link between low folate status and NTDs is poorly understood, and it remains unclear how folic acid prevents NTDs. We investigated the effect of folate level on risk of NTDs in splotch (Sp(2)(H)) mice, which carry a mutation in Pax3. Dietary folate restriction results in reduced maternal blood folate, elevated plasma homocysteine and reduced embryonic folate content. Folate deficiency does not cause NTDs in wild-type mice, but causes a significant increase in cranial NTDs among Sp(2)(H) embryos, demonstrating a gene-environment interaction. Control treatments, in which intermediate levels of folate are supplied, suggest that NTD risk is related to embryonic folate concentration, not maternal blood folate concentration. Notably, the effect of folate deficiency appears more deleterious in female embryos than males, since defects are not prevented by exogenous folic acid. Folate-deficient embryos exhibit developmental delay and growth retardation. However, folate content normalized to protein content is appropriate for developmental stage, suggesting that folate availability places a tight limit on growth and development. Folate-deficient embryos also exhibit a reduced ratio of s-adenosylmethionine (SAM) to s-adenosylhomocysteine (SAH). This could indicate inhibition of the methylation cycle, but we did not detect any diminution in global DNA methylation, in contrast to embryos in which the methylation cycle was specifically inhibited. Hence, folate deficiency increases the risk of NTDs in genetically predisposed splotch embryos, probably via embryonic growth retardation.

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BackgroundWe aimed to examine the course of depression during 2-year follow-up in a group clinically depressed older persons. Subsequently, we studied which socio-demographic and clinical characteristics predict a depression diagnoses at 2-year follow-up.MethodsData were used from the Netherlands Study of Depression in Older persons (NESDO; N = 510). Diagnoses of depression DSM-IV-TR criteria were available from 285 patients at baseline and at 2-year follow-up. Severity of the depressive symptoms, as assessed with the Inventory of Depressive Symptoms (IDS), was obtained from 6-monthly postal questionnaires. Information about socio-demographic and clinical variables was obtained from the baseline measurement.ResultFrom the 285 older persons who were clinically depressed at baseline almost half (48.4%) also suffered from a depressive disorder two years later. Patients with more severe depressive symptoms, comorbid dysthymia, younger age of onset and more chronic diseases were more likely to be depressed at 2-year follow-up. 61% of the persons that were depressed at baseline had a chronic course of depressive symptoms during these two years.ConclusionsLate-life depression often has a chronic course, even when treated conform current guidelines for older persons. Our results suggest that physical comorbidity may be candidate for adjusted and intensified treatment strategies of older depressed patients with chronic and complex pathology.

This LC-ESI-MS/MS method is easy to perform and offers reproducibility, selectivity and sensitivity for studying DNA methylation. The method allows a sample throughput of approximately 200 samples/week. The MTHFR C677T genotype influences age-related changes in DNA methylation.