NIGHTMARES AND SUICIDE: PREDICTING RISK IN DEPRESSION

Background: There is growing evidence of an association of a number of subjective and objective sleep parameters (especially nightmares) and elevated suicidal risk in different clinical populations as well as in the general populations. Subjects and methods: This is a cross-sectional naturalistic study of 52 inpatients (28 females and 24 males, aged from 24 to 75 years) meeting criteria for a current depressive episode within Recurrent Depressive Disorder (RDD) or Bipolar Disorder (BD) according to ICD-10. All patients were evaluated with the Hamilton Depression Rating Scale (HDRS), followed by a direct interview about their dreams’ content and emotional charge, as well as about suicidal thoughts and plans or previous attempts. Results: Patients with RDD suffered significantly more frequently from nightmares than those with BD, p<0.05. Within the RDD group, experiencing nightmares was associated with significantly higher scores on the HDRS suicide risk item (2.36 vs 1.00), higher frequency of suicide attempts (35% vs 6%), and lower likelihood for lack of detectable suicide risk (21% vs 81%), p<0.05. These differences were not explained by significant difference in the severity of depressive symptoms (28.00 vs 24.75, p=0.16). We were unable to detect such differences in the bipolar subgroup. No gender influences on the association of nightmares and suicidal risk were observed. Conclusions: Depressed patients suffering from nightmares showed significantly higher suicide risk. Depression appeared to be a stronger risk factor for suicidal behavior when accompanied with nightmares. This was only valid for unipolar depression, while the results concerning bipolar depression were inconclusive

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms.

Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis

Genetic causes of familial pituitary adenomas

peer reviewe

GENETICS IN ENDOCRINOLOGY: Somatic and germline mutations in the pathogenesis of pituitary adenomas.

Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors has been a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes had been shown to predispose to pituitary tumor formation. In the last decade several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor- interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggest that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview on the genetic pathophysiology of pituitary adenomas and their clinical relevance