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Background In the Western world, more than 2 million people were exposed in utero to diethylstilbestrol. In exposed individuals and in their descendants, several adverse outcomes have been linked to such exposure, like cancers, genital malformations and, less consistently, psychiatric disorders. Disruption of epigenetic homeostasis was proposed as the molecular substratum of this environmental factor but was not fully proven. Methods We selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to diethylstilbestrol. We analyzed DNA methylation using Human Methylation 450 DNA Analysis BeadChip ® . We performed a methylome-wide association analysis searching for specific methylation changes in exposed versus unexposed individuals. Secondary, we compared exposed individuals with and without genital malformation, and with and without psychosis. Results No differentially methylated regions were identified between exposed and unexposed individuals. Yet, our analyses showed that exposed individuals with genital or psychotic abnormalities have several specific differentially methylated regions compared with exposed individuals without complication. These CpGs were located in genes relevant for cancer (ADAMTS9), genital abnormalities (HOOK2) and psychiatric diseases (ZFP57). Conclusions In utero exposure to diethylstilbestrol is not associated with changes in methylation profiles. In exposed individuals though, specific traits are associated with methylomic modifications encompassing genomic regions, mostly involved in cancer and neurodevelopment, leading to heterogeneous consequences. [ABSTRACT FROM AUTHOR]

Introduction: Folates, the main actors in one-carbon (C1) metabolism, are involved in synthesising monoamines and maintaining genomic stability. Previous studies support the association between C1 metabolism and schizophrenia. The main purpose of this study was to assess the prevalence of plasma folate, and/or vitamin B12 deficiencies and hyperhomocysteinemia in young patients with psychotic disorders., Methods: We included young inpatients (15-30 years old) with psychosis between 2014 and 2017 from Sainte-Anne Hospital in Paris. Plasma folate, vitamin B12 deficiency and homocysteinemia dosages were done at admission. Clinical data were extracted retrospectively, and patients diagnosed with a first-episode psychosis (FEP), schizophrenia, schizoaffective disorder, or persistent delusional disorder were retained for the analysis., Results: Among the 334 inpatients, 188 (56%) had C1 dosages available (135 males; 53 females). From the 188 patients, 32% had a C1 abnormality. This abnormality reached 38% of FEP patients. The most frequent abnormality was folate deficiency: 21% of all patients and 27% of FEP. Lower levels of folates were found in males compared to females ( p = 0.02) and were correlated with more severe disorder, as assessed by Clinical Global Impression - Severity (CGI-S; p = 0.009). Antipsychotic dosage was positively associated with B12 levels ( p = 0.013) and negatively with homocysteinemia ( p = 0.034)., Conclusion: One-carbon metabolism anomalies in young patients with psychotic disorders are highly prevalent, reaching almost half of the patients with FEP. Potential protective effects from females and antipsychotics have emerged. These results spotlight the need for new therapeutic prospects, such as folate supplementation, to achieve personalised medical approaches to the early stages of psychotic disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frajerman, Urban, Rivollier, Plaze, Chaumette, Krebs and Scoriels.)

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 (5 th 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.

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: In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis., Methods: From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip® in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We also compared exposed individuals with (n = 7) and without psychosis (n = 30)., Results: There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9). Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 (ZFP57)., Conclusions: In utero exposure to DES was not associated with methylation changes at specific CpG or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.

Background: Little is known about differences in mental health comorbidity and quality of life in individuals with social anxiety disorder (SAD) according to the number and the types of feared situations., Methods: Using a US nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions, we performed latent class analysis to compare the prevalence rates of mental disorders and quality of life measures across classes defined by the number and the types of feared social situations among individuals with SAD., Results: Among the 2,448 participants with a lifetime diagnosis of SAD, we identified three classes of individuals who feared most social situations but differed in the number of feared social situations (generalized severe [N = 378], generalized moderate [N = 1,049] and generalized low [N = 443]) and a class of subjects who feared only performance situations [N = 578]. The magnitude of associations between each class and a wide range of mental disorders and quality of life measures were consistent with a continuum model, supporting that the deleterious effects of SAD on mental health may increase with the number of social situations feared. However, we found that individuals with the "performance only" specifier may constitute an exception to this model because these participants had significantly better mental health than other participants with SAD., Conclusions: Our findings give additional support to the recent changes made in the DSM-5, including the introduction of the "performance only" specifier and the removal of the "generalized" specifier to promote the dimensional approach of the number of social fears., (© 2016 Wiley Periodicals, Inc.)

Background: Whether there are systematic sex differences in posttraumatic stress disorder (PTSD) symptom expression remains debated. Using methods based on item response theory (IRT), we aimed at examining differences in the likelihood of reporting DSM-IV symptoms of PTSD between women and men, while stratifying for major trauma type and equating for PTSD severity., Method: We compared data from women and men in a large nationally representative adult sample, the National Epidemiologic Survey on Alcohol and Related Conditions. Analyses were conducted in the full population sample of individuals who met the DSM-IV criterion A (n=23,860) and in subsamples according to trauma types., Results: The clinical presentation of the 17 DSM-IV PTSD symptoms in the general population did not substantially differ in women and men in the full population and by trauma type after equating for levels of PTSD severity. The only exception was the symptom "foreshortened future", which was more likely endorsed by men at equivalent levels of PTSD severity., Limitations: The retrospective nature of the assessment of PTSD symptoms could have led to recall bias. Our sample size was too small to draw conclusions among individuals who experienced war-related traumas., Conclusions: Our findings suggest that the clinical presentation of PTSD does not differ substantially between women and men. We also provide additional psychometric support to the exclusion of the symptom "foreshortened future" from the diagnostic criteria for PTSD in the DSM-5., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Schizophrenia is a frequent and disabling disease associated with heterogeneous psychiatric phenotypes. It emerges during childhood, adolescence or young adulthood and has dramatic consequences for the affected individuals, causing considerable familial and social burden, as well as increasing health expenses. Although some progress has been made in the understanding of their physiopathology, many questions remain unsolved, and the disease is still poorly understood. The prevailing hypothesis regarding psychotic disorders proposes that a combination of genetic and/or environmental factors, during critical periods of brain development increases the risk for these illnesses. Epigenetic regulations, such as DNA methylation, can mediate gene x environment interactions at the level of the genome and may provide a potential substrate to explain the variability in symptom severity and family heritability. Initially, epigenetics was used to design mitotic and meiotic changes in gene transcription that could not be attributed to genetic mutations. It referred later to changes in the epigenome not transmitted through the germline. Thus, epigenetics refers to a wide range of molecular mechanisms including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. These mechanisms alter the way the transcriptional factors bind the DNA, modulating its expression. Prenatal and postnatal environmental factors may affect these epigenetics factors, having responsability in long-term DNA transcription, and influencing the development of psychiatric disorders., Object: The object of this review is to present the state of knowledge in epigenetics of schizophrenia, outlining the most recent findings in the matter., Methods: We did so using Pubmed, researching words such as 'epigenetics', 'epigenetic', 'schizophrenia', 'psychosis', 'psychiatric'. This review summarizes evidences mostly for two epigenetic mechanisms: DNA methylation and post-translational histone modifications., Results: First, in terms of epidemiology and transmission, the theoretical model of epigenetics applies to schizophrenia. Then, most environmental factors that have proved a link with this disease, may generate epigenetic mechanisms. Next, mutations have been found in regions implied in epigenetic mechanism among populations with schizophrenia. Some epigenetic alterations in DNA regions have been previously linked with neurodevelopmental abnormalities. In psychosis, some authors have found methylation differences in COMT gene, in reelin gene and in some genes implicated in dopaminergic, serotoninergic, GABAergic and glutamatergic pathways. Histone modifications have been described, in particular the H3L4 histone methylation. Finally, we tried to underline the difficulties in epigenetic research, notably in psychiatry, and the limits in this matter., Conclusion: The epigenetic field may explain a lot of questions around the physiopathology of the complex psychiatric disease that is schizophrenia. It may be a substratum to the prevailing hypothesis of gene x environment interaction. The research in the matter is definitely expanding. It justifies easily the need to improve the effort in the domain to overpass some limits inherent to the matter., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)