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Background Early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1). Aims To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon 1F NR3C1 promoter in bipolar disorder. Method A sample of people with bipolar disorder (n=99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant. Results The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (β = 0.52, 95% CI 0.46-0.59, P ≪ 0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status. Conclusions Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder, [ABSTRACT FROM AUTHOR]

Background: Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. Methods: We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. Results: We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. Limitations: The modest sample size and the absence of women in our series could limit the impact of our results. Conclusion: Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis. [ABSTRACT FROM AUTHOR]

The National Center of Competence in Research project "SYNAPSY" aims at identifying certain mechanisms of psychiatric and cognitive disorders, in order to improve the understanding and the genesis of such pathologies, and to promote the development of better diagnostic tools and of new therapeutic approaches. It provides an excellent opportunity for clinical psychiatrists and neuroscientists to develop a synergic mode of collaboration. On the basis of questions stemming from clinical practice and in the frame of patients cohorts, various research projects in neuroscience should lead to progresses that may have a considerable impact on clinical practice.

The authors assessed whether collection by mail of saliva and buccal cells for genetic analysis was feasible in participants recruited through the Internet. In 2003, 14,773 visitors of a smoking cessation website were invited by e-mail to take part in the study. Salivettes (plastic vials containing a cotton roll) were mailed to participants, for collection of saliva and buccal cells. Because of limited resources, the authors stopped recruitment when 392 participants (3% of 14,733) were registered. They received 315 saliva samples back (80% of 392). Salivary cotinine was analyzed in 145 daily smokers. Cotinine concentration could be assessed in 141 samples (97%) (range 0.7-899 ng/ml, median 260 ng/ml). DNA extraction was achieved in all the 285 samples in which it was attempted. Quality of DNA was assessed by optical density measurements and by polymerase chain reaction amplification of a gene coding for the alpha-4 nicotinic receptor, with the detection of a known polymorphism. Successful results were obtained in 235 samples (82% of 285). Thus collecting saliva by mail for cotinine and DNA analysis in participants recruited through the internet produced samples of good quality at a reasonable cost. This approach should be valuable for genetic epidemiology and pharmacogenetic research.