Gender Dysphoria in Young People: A Model of Chronic Stress.

BACKGROUND: Gender dysphoria (GD) refers to the distress that may accompany gender incongruence, often heightened at the onset of puberty, with the development of secondary sex characteristics. Children and adolescents may be especially vulnerable to severe stressors, including GD, with potentially irreversible effects if these exposures occur during critical periods of development and brain maturation. SUMMARY: We describe the evidence for GD as a chronic stressor, drawing parallels to other established models of stress, activating both innate psychological and biological stress responses. As well as being an inherently distressing experience, a person who experiences GD may also experience minority stress. Minority stress has been demonstrated in young people who experience GD with higher rates of social rejection and internalized stigma and shame. The biological stress response in young people with GD is illustrated through the activation of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and pro-inflammatory response. The number of young people who report experiencing GD has increased exponentially worldwide in the past decade, demanding a change in the clinic infrastructure. Paediatric endocrinologists and specialists in mental health work together to both support psychosocial well-being and offer individualized treatment to align the phenotype with gender identity with the aim of alleviating the distress of GD. Medical interventions may include puberty suppression and gender-affirming hormones. Ongoing monitoring is required prior to initiation and during treatment to ensure that the goals of treatment are being achieved.

Associations between significant head injury and persisting disability and violent crime in women in prison in Scotland, UK: a cross-sectional study.

BACKGROUND: The prevalence of head injury is estimated to be as high as 55% in women in prison and might be a risk factor for violent offending, but evidence is equivocal. The extent of persisting disability is unknown, making decisions about service needs difficult. The UN recognises vulnerabilities in women in prison, but does not include head injury. This study aimed to investigate relationships among head injury, comorbidities, disability, and offending in women in prison. METHODS: In this cross-sectional study, women were recruited between Feb 2, 2018, and Sept 30, 2019, from four prisons across Scotland, UK: Her Majesty's Prison (HMP) Cornton Vale, Her Majesty's Young Offenders Institute Polmont, HMP Edinburgh, and HMP Greenock (detaining approximately 355 individuals at the time of recruitment). Women were included if they were aged older than 16 years, fluent in English, able to participate in face-to-face assessment and provide informed consent, and did not have a severe acute disorder of cognition or communication. Head injury, cognition, disability, mental health, and history of abuse and problematic substance use were assessed by interview. History of head injury was assessed with the Ohio State University Traumatic Brain Injury Identification method and disability was assessed with the Glasgow Outcome at Discharge Scale. Comparisons were made between women with and without a history of significant head injury. FINDINGS: We recruited 109 (31%) of the 355 women in these prisons. The sample was demographically representative of the approximately 400 individuals in women's prisons in Scotland. Significant head injury (SHI) was found in 85 (78%) of 109 women, of whom 34 (40%) had associated disability. Repeat head injury was reported in 71 (84%) of the 85 women with SHI and, in most cases, this resulted from domestic abuse that had occurred over many years. Women with a history of SHI were significantly more likely to have a history of violent offences than those without a history of SHI (66 [79%] of 85 women in the SHI group vs 13 [54%] of 24 women in the no-SHI group had committed a violent offence; odds ratio [OR] 3·1, 95% CI 1·2-8·1). This effect remained significant after adjusting for current factors (3·1, 1·1-9·0), including comorbidities associated with post-traumatic stress disorder, and was no longer statistically significant after adjusting for historical factors (3·3, 1·0-10·9), such as abuse as a child or adult. Women with SHI had spent longer in prison than women without SHI after adjustment for current (rate ratio 3·4, 1·3-8·4) or historical (3·5, 1·3-9·2) risk factors. INTERPRETATION: It is recognised that women in prison are vulnerable because of histories of abuse and problematic substance use; however, history of SHI needs to be included when developing criminal justice policy, interventions to reduce mental health morbidity, and assessment and management of risk of violent offending. FUNDING: The Scottish Government.

The intra-day dynamics of affect, self-esteem, tiredness, and suicidality in Major Depression.

Despite growing interest in the temporal dynamics of Major Depressive Disorder (MDD), we know little about the intra-day fluctuations of key symptom constructs. In a study of momentary experience, the Experience Sampling Method captured the within-day dynamics of negative affect, positive affect, self-esteem, passive suicidality, and tiredness across clinical MDD (N= 31) and healthy control groups (N= 33). Ten symptom measures were taken per day over 6 days (N= 2231 observations). Daily dynamics were modeled via intra-day time-trends, variability, and instability in symptoms. MDD participants showed significantly increased variability and instability in negative affect, positive affect, self-esteem, and suicidality. Significantly different time-trends were found in positive affect (increased diurnal variation and an inverted U-shaped pattern in MDD, compared to a positive linear trend in controls) and tiredness (decreased diurnal variation in MDD). In the MDD group only, passive suicidality displayed a negative linear trend and self-esteem displayed a quadratic inverted U trend. MDD and control participants thus showed distinct dynamic profiles in all symptoms measured. As well as the overall severity of symptoms, intra-day dynamics appear to define the experience of MDD symptoms.

DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by genetic variation, indicating a potential role for differential epigenetic regulation in disease aetiology. The aim of this study was to assess genome-wide DNA methylation changes specifically associated with ulcerative colitis (UC), Crohn's disease (CD) and IBD activity. METHODS: DNA methylation was quantified in peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and 39 controls using the Infinium HumanMethylation450 BeadChip. Technical and functional validation was performed using pyrosequencing and the real-time polymerase chain reaction. Cross-tissue replication of the top differentially methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained from paediatric IBD cases and controls. RESULTS: A total of 3196 probes were differentially methylated between CD cases and controls, while 1481 probes were differentially methylated between UC cases and controls. There was considerable (45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC differentially methylated region (promoter region of TRIM39-RPP2) was also significantly hypomethylated in colonic mucosa from paediatric UC patients. In addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found reduced TRAF6 gene expression in PBMCs of IBD patients. CONCLUSIONS: Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.