Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v) ethanol between gestational days 0.5–8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (A^vy), in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at A^vy. This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the A^vy mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than A^vy, a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v) ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the A^vy allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level. In humans it has been known for some time that exposure to environmental insults during pregnancy can harm a developing fetus and have life-long effects on the individual's health. A well known example is fetal alcohol syndrome, where the children of mothers that consume large amounts of alcohol during pregnancy exhibit growth retardation, changes to the shape and size of the skull, and central nervous system defects. At present the molecular events underlying fetal alcohol syndrome are unknown. We have developed a model of alcohol exposure in the mouse, in which the genetics and the environment can be strictly controlled. We find that chronic exposure of the fetus to a physiologically relevant amount of alcohol during the first half of pregnancy results in epigenetic changes at a sensitive reporter gene and produces fetal alcohol syndrome-like features in some mice. Our model is a useful tool to study the underlying causes of fetal alcohol syndrome, and our work raises the interesting possibility that the long-term physical effects of alcohol exposure during pregnancy are mediated by epigenetic changes established in the fetus and then faithfully remembered for a lifetime. In the future, such epigenetic changes could be used as markers for the preclinical diagnosis and treatment of fetal alcohol spectrum disorders.

Objective: The collaborative care model is recommended for depression in adults with a chronic physical health problem like diabetes. We sought to systematically assess the effect of collaborative care on depression and glycaemia in adults with comorbid depression and diabetes to inform guidelines and practice.Design: Systematic review and meta-analysis.Data sources: We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing, MEDLINE, PsychINFO and reference lists of retrieved articles published before August 2013.Inclusion criteria: Randomised controlled trials (RCTs) on collaborative care (ie, coordinated multidisciplinary model of care) for depression that reported the effects on depression and glycaemic outcomes in adults with comorbid clinically relevant depression and diabetes were eligible.Data extraction and analysis: Data on the mean difference in depression and glycaemic outcomes were extracted and pooled using random effects meta-analysis.Results: Seven RCTs included for review reported effects on depression outcomes in 1895 participants, and glycated haemoglobin (HbA1c) level in 1556 participants. Collaborative care significantly improved the depression score (standardised mean difference was −0.32 (95% CI −0.53 to −0.11); I²=79%) and HbA1c level (weighted mean difference was −0.33% (95% CI −0.66% to −0.00%); I²=72.9%) compared with control conditions. Depression remission did not predict better glycaemic control across studies.Conclusions: Limited evidence from short-to-medium term RCTs predominantly conducted in the USA suggests that collaborative care for depression significantly improves both depression and glycaemia outcomes, independently, in people with comorbid depression and diabetes.