The impact of badmouthing of medical specialties to medical students.

OBJECTIVES: This study aimed to evaluate the proportion of Irish medical students exposed to 'badmouthing' of different specialities and to ascertain: the degree of criticism of specialities based on the seniority of clinical or academic members of staff; if 'badmouthing' influenced student career choice in psychiatry; and attitudes of medical students towards psychiatry as a speciality and career choice. METHODS: Medical students in three Irish universities were invited to complete an online survey to determine the frequency and effect of non-constructive criticism on choice of medical specialty. The online questionnaire was distributed to Royal College of Surgeons in Ireland (RCSI), University of Galway (UoG) and University College Dublin (UCD) in the academic year 2020-2021. RESULTS: General practice (69%), surgery (65%) and psychiatry (50%) were the most criticised specialties. Criticism was most likely to be heard from medical students. 46% of students reported reconsidering a career in psychiatry due to criticism from junior doctors. There was a positive perception of psychiatry with 27% of respondents considering psychiatry as a first-choice specialty. CONCLUSIONS: Criticism of psychiatry by doctors, academics and student peers negatively influences students' career choice, which could be contributing to recruitment difficulties in psychiatry.

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects.

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.

Autoantibodies and Psychosis.

Research into antibody-mediated disease, in response to immune dysfunction or to tumour development, has rapidly expanded in recent years. Antibodies binding to neuroreceptors can cause psychiatric features, including psychosis, in a minority of patients as well as neurological features. The responsiveness of some of these cases to immunotherapy supports the hypothesis that antibody-associated mechanisms play a role in the pathogenesis of psychotic diseases. The purpose of this chapter is to review autoantibodies that are most likely to be relevant for patients with psychotic symptoms. Herein, we describe receptor structure and mechanism of action, clinical and psychiatric features for the growing number of neuronal surface antibodies, including those to the N-methyl-D-aspartate (NMDA) receptor. The identification of a subgroup of patients with psychiatric features having antibody-mediated disease highlights the importance of considering the diagnosis, particularly in those patients presenting with a first episode of psychosis.

Serum Prolactin and Bone Mineral Density in Schizophrenia: A Systematic Review.

The relationship between serum prolactin and bone mineral density (BMD) in schizophrenia is unclear. We conducted a literature review of databases from inception until December 2018 for cross-sectional, case-control, prospective and retrospective studies analyzing correlations between serum prolactin and BMD measured using dual energy X-ray absorptiometry or quantitative ultrasound at any skeletal site in people with schizophrenia. Data was summarized with a best evidence synthesis. This review identified 15 studies (1 longitudinal study, 10 cross-sectional and 4 case-control studies; 1,360 individuals with a psychotic disorder; mean age 45.1 ± 9.4 [standard deviation] years, female 742 [54.6%], mean illness duration 17.7 ± 11.3 years) assessing the relationship between serum prolactin and BMD in schizophrenia. There was a statistically significant inverse correlation between serum prolactin and BMD identified in eight of the studies (53% of all studies), suggesting mixed evidence for an association between serum prolactin and BMD. Of those studies which identified a significant inverse correlation between serum prolactin and BMD (n = 5), 152 (52.1%) of patients were treated with prolactin raising antipsychotics, compared to 197 (48.1%) of patients in those studies which did not identify a significant correlation between prolactin and BMD. Available studies cannot resolve the link between excess prolactin and reduced BMD in schizophrenia. Future studies should be longitudinal in design and combine measures of serum prolactin along with other risk factors for reduced BMD such as smoking and vitamin D and sex hormone levels in assessing the relationship between prolactin and BMD in schizophrenia.

Tobacco smoking and nicotine dependence in first episode and established psychosis.

AIM: People with psychotic disorders have increased premature mortality in comparison with the general population, with high rates of cigarette use a contributing factor. We aimed to describe the prevalence of cigarette use and nicotine dependence (ND) in first episode psychosis (FEP), and established psychosis; and to investigate associations between clinical symptoms and ND. METHODOLOGY: Smoking and clinical data were collected from two cohorts: 181 people with FEP recruited as part of the Physical Health and Substance Use Measures in First Onset Psychosis (PUMP) study and from 432 people with established psychosis recruited as part of the Improving physical health and reducing substance use in psychosis randomised controlled trial (IMPaCT RCT). RESULTS: The prevalence of cigarette smoking was 78% in FEP and 62% in established psychosis. Forty nine percent (n = 60) of smokers in the FEP cohort and 69% (n = 183) of smokers with established psychosis were highly nicotine dependent. Being a highly nicotine dependent smoker was significantly associated with higher PANSS positive symptom scores (F = 5.480 p = 0.004), and with decreased scores on the Rosenberg self-esteem scale (F = 3.261, p = 0.039) in established psychosis. There was no diagnostic specificity identified in relation to smoking or ND in both groups. CONCLUSION: High rates of cigarette usage and nicotine dependence are problems from the early stages of psychosis. ND is higher in people with established psychosis. Smoking cessation strategies as part of comprehensive management of psychotic disorders at every stage require further development and evaluation.

Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis.

We present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.