Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control

Background Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD). Method A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON. Results A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD. Conclusions This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology

Time to endoscopic intervention in patients with upper gastrointestinal patients can be improved with pathway provision

BACKGROUND:Patients with upper gastrointestinal malignancy often require admission to hospital with dysphagia or jaundice requiring therapeutic endoscopy. Endoscopic intervention is often effective permitting rapid discharge. An efficient service would permit rapid discharge for patients who are often at the end of life. We noted that a majority of patients in hospital under the gastroenterological oncology were admitted with symptoms requiring therapeutic endoscopy. METHODS: We conducted an audit cycle of the inpatient days before and after pathway implementation. A wait of 1 day was set as acceptable for patients with bleeding as defined by NICE guidance and we set an arbitrary standard of 2 days for patients without bleeding but requiring therapeutic endoscopy. Between the audit cycles, a pathway was built to accommodate these patients. RESULTS: Inpatient waits improved from a median of 3 days to 1 day. There was no difference in outcome between those presenting with bleeding and other symptoms or any difference in patients requiring different procedures. CONCLUSIONS: Waiting times for endoscopy can be improved with the introduction of a targeted pathway of cancer patients. Further issues including cost, quality of life and nutrition require further intervention

Cannabis and depression: A twin model approach to co-morbidity

Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high

Analysis of saccharification in Brachypodium distachyon stems under mild conditions of hydrolysis

Analysis of saccharification in Brachypodium distachyon stems unde

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Scan-Negative Cauda Equina Syndrome A Prospective Cohort Study

Objective: To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with “scan-negative” cauda equina syndrome (CES). Methods: We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability. Results: A total of 198 patients presented consecutively over 28 months. A total of 47 were diagnosed with scan-positive CES (mean age 48 years, 43% female). A total of 76 mixed category patients had nerve root compression/displacement without CES compression (mean age 46 years, 71% female) and 61 patients had scan-negative CES (mean age 40 years, 77% female). An alternative neurologic cause of CES emerged in 14/198 patients during admission and 4/151 patients with mean duration 25 months follow-up. Patients with scan-negative CES had more positive clinical signs of a functional neurologic disorder (11% scan-positive CES vs 34% mixed and 68% scan-negative, p < 0.0001), were more likely to describe their current back pain as worst ever (41% vs 46% and 70%, p = 0.005), and were more likely to have symptoms of a panic attack at onset (37% vs 57% and 70%, p = 0.001). Patients with scan-positive CES were more likely to have reduced/absent bilateral ankle jerks (78% vs 30% and 12%, p < 0.0001). There was no significant difference between groups in the frequency of reduced anal tone and urinary retention. Conclusion: The first well-phenotyped, prospective study of scan-negative CES supports a model in which acute pain, medication, and mechanisms overlapping with functional neurologic disorders may be relevant

Political mobilisation by minorities in Britain: negative feedback of ‘race relations'?

This article uses a political opportunity approach to study the relationship of minority groups to the political community in Britain. The main argument is that the British race relations approach established in the 1960s had an important effect that still shapes the patterns of political contention by different minority groups today. Original data on political claims-making by minorities demonstrate that British 'racialised' cultural pluralism has structured an inequality of opportunities for the two main groups, African-Caribbeans and Indian subcontinent minorities. African-Caribbeans mobilise along racial lines, use a strongly assimilative 'black' identity, conventional action forms, and target state institutions with demands for justice that are framed within the recognised framework of race relations. Conversely, a high proportion of the Indian subcontinent minority mobilisation is by Muslim groups, a non-assimilative religious identity. These are autonomously organised, but largely make public demands for extending the principle of racial equality to their non-racial group. Within the Indian subcontinent minorities, the relative absence of mobilisation by Indian, Sikh and Hindu minorities, who have achieved much better levels of socio-economic success than Pakistani and Bangladeshi Muslims, suggests that there is also a strong socioeconomic basis for shared experiences and grievances as Muslims in Britain. This relativises the notion that Muslim mobilisation is Britain is purely an expression of the right for cultural difference per se, and sees it as a product of the paradoxes of British race relations

Parental depression and offspring psychopathology: A Children of Twins study

Background Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. Method A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. Results In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. Conclusions The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD

Acetylation of H2A.Z is a key epigenetic modification associated with gene deregulation and epigenetic remodeling in cancer

Histone H2A.Z (H2A.Z) is an evolutionarily conserved H2A variant implicated in the regulation of gene expression; however, its role in transcriptional deregulation in cancer remains poorly understood. Using genome-wide studies, we investigated the role of promoter-associated H2A.Z and acetylated H2A.Z (acH2A.Z) in gene deregulation and its relationship with DNA methylation and H3K27me3 in prostate cancer. Our results reconcile the conflicting reports of positive and negative roles for histone H2A.Z and gene expression states. We find that H2A.Z is enriched in a bimodal distribution at nucleosomes, surrounding the transcription start sites (TSSs) of both active and poised gene promoters. In addition, H2A.Z spreads across the entire promoter of inactive genes in a deacetylated state. In contrast, acH2A.Z is only localized at the TSSs of active genes. Gene deregulation in cancer is also associated with a reorganization of acH2A.Z and H2A.Z nucleosome occupancy across the promoter region and TSS of genes. Notably, in cancer cells we find that a gain of acH2A.Z at the TSS occurs with an overall decrease of H2A.Z levels, in concert with oncogene activation. Furthermore, deacetylation of H2A.Z at TSSs is increased with silencing of tumor suppressor genes. We also demonstrate that acH2A.Z anti-correlates with promoter H3K27me3 and DNA methylation. We show for the first time, that acetylation of H2A.Z is a key modification associated with gene activity in normal cells and epigenetic gene deregulation in tumorigenesis