The onset of psychosis is the consequence of complex interactions between genetic vulnerability to psychosis and response to environmental and/or maturational changes. Epigenetics is hypothesized to mediate the interplay between genes and environment leading to the onset of psychosis. We believe we performed the first longitudinal prospective study of genomic DNA methylation during psychotic transition in help-seeking young individuals referred to a specialized outpatient unit for early detection of psychosis and enrolled in a 1-year follow-up. We used Infinium HumanMethylation450 BeadChip array after bisulfite conversion and analyzed longitudinal variations in methylation at 411 947 cytosine–phosphate–guanine (CpG) sites. Conversion to psychosis was associated with specific methylation changes. Changes in DNA methylation were significantly different between converters and non-converters in two regions: one located in 1q21.1 and a cluster of six CpG located in GSTM5 gene promoter. Methylation data were confirmed by pyrosequencing in the same population. The 100 top CpGs associated with conversion to psychosis were subjected to exploratory analyses regarding the related gene networks and their capacity to distinguish between converters and non-converters. Cluster analysis showed that the top CpG sites correctly distinguished between converters and non-converters. In this first study of methylation during conversion to psychosis, we found that alterations preferentially occurred in gene promoters and pathways relevant for psychosis, including oxidative stress regulation, axon guidance and inflammatory pathways. Although independent replications are warranted to reach definitive conclusions, these results already support that longitudinal variations in DNA methylation may reflect the biological mechanisms that precipitate some prodromal individuals into full-blown psychosis, under the influence of environmental factors and maturational processes at adolescence.

Agitation is a heterogeneous concept without a uniformly accepted definition, however, it is generally considered as a state of cognitive and motor hyperactivity characterized by excessive or inappropriate motor or verbal activity with marked emotional arousal. Not only the definition but also other aspects of agitated patients’ care are still unsolved and need consensus and improvement. To help the discussion about agitation among experts and improve the identification, management, and treatment of agitation, the 1st International Experts’ Meeting on Agitation was held in October 2016 in Madrid. It was attended by 20 experts from Europe and Latin America with broad experience in the clinical management of agitated patients. The present document summarizes the key conclusions of this meeting and highlights the need for an updated protocol of agitation management and treatment, the promotion of education and training among healthcare professionals to improve the care of these patients and the necessity to generate clinical data of agitated episodes.

Background: Exposure to endocrine disruptors is on the rise, with new compounds regularly incriminated. In animals and humans, this exposure during critical developmental windows has been associated with various developmental abnormalities, including the emergence of psychiatric disorders. We aimed to review the association between perinatal endocrine disruptor exposure and neurodevelopmental disorders in humans, focusing on cognitive and psychiatric disorders. Methods: We performed a systematic review with key words referring to the fields of neurodevelopment and endocrine disruptors. We reviewed 896 titles, choosing studies on the basis of titles and abstracts. We searched through the methodology sections to find perinatal exposure and neurodevelopmental disorders, following the categories indicated in the Diagnostic and Statistic Manual of Mental Disorders (5th edition). References in some studies brought us to a total of 47 studies included here. Results: Convergent studies report an association between exposure to endocrine disruptors and autism spectrum disorder, attention-deficit hyperactivity disorder, global developmental delay, intellectual disability, communication disorders and unspecified neurodevelopmental disorders. Conclusion: Sufficient data exist to report that exposure to some endocrine disruptors is a risk factor for the emergence of neurodevelopmental disorders. Studying endocrine disruptor exposure in humans is still associated with some limits that are difficult to overcome.