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Catatonia has many potential underlying causes, but in some patients, no clear etiology is identified, sparking growing interest in its genetic basis. We aimed to provide the first comprehensive synthesis of genetic abnormalities in catatonia.
Methods
In this systematic review (PROSPERO CRD42023455118) we searched MEDLINE All, Embase Classic + Embase, PsycINFO, and AMED up to August 15, 2023, for studies on genetic testing and catatonia phenotyping in all age groups. Catatonia was diagnosed using specified diagnostic criteria or description of clinical features. Risk of bias was assessed using the Joanna Briggs Institute quality assessment tools. Results were summarized with a narrative synthesis.
Results
We included 99 studies involving 8600 individuals. Sex was reported for 6080 individuals, of whom 3208 (52.8%) were male. Mean age at onset of catatonia was 28.8 years (SD 16.3). The median duration of the index catatonic episode was 180 days (IQR 38 to 668). Stupor and mutism were the most frequently reported symptoms. Forty-seven genetic conditions were reported in catatonia, including Phelan-McDermid syndrome (n = 80), 22q11.2 deletion syndrome (n = 23), and Down’s syndrome (n = 19). Study quality was good in 29 studies, moderate in 53, and poor in 17. The major focus of association studies has centered on periodic catatonia; despite identifying candidate genes at both 22q13 and 15q15, none have been replicated.
Conclusions
Catatonia can manifest in a wide range of genetic syndromes, suggesting a shared vulnerability across diverse genetic and developmental disorders. We did not identify a unique phenomenology or treatment response profile in genetic associations of catatonia.
Neuropsychiatry training in the UK currently lacks a formal scheme or qualification, and its demand and availability have not been systematically explored. We conducted the largest UK-wide survey of psychiatry trainees to examine their experiences in neuropsychiatry training.
Results
In total, 185 trainees from all UK training regions completed the survey. Although 43.6% expressed interest in a neuropsychiatry career, only 10% felt they would gain sufficient experience by the end of training. Insufficient access to clinical rotations was the most common barrier, with significantly better access in London compared with other regions. Most respondents were in favour of additional neurology training (83%) and a formal accreditation in neuropsychiatry (90%).
Clinical implications
Strong trainee interest in neuropsychiatry contrasts with the limited training opportunities currently available nationally. Our survey highlights the need for increased neuropsychiatry training opportunities, development of a formalised training programme and a clinical accreditation pathway for neuropsychiatry in the UK.
Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination.
Aims
To assess the factors that predict an adverse outcome within 24 h of seclusion termination.
Method
In a cohort study of individuals secluded in psychiatric intensive care units, we investigated factors associated with any of the following outcomes: actual violence, attempted violence, or reinitiation of seclusion within 24 h of seclusion termination. Among the seclusion episodes that were initiated between 29 March 2018 and 4 March 2019, we investigated the exposures of medication cooperation, seclusion duration, termination out of working hours, involvement of medical staff in the final seclusion review, lack of insight, and agitation or irritability. In a mixed-effects logistic regression model, associations between each exposure and the outcome were calculated. Odds ratios were calculated unadjusted and adjusted for demographic and clinical variables.
Results
We identified 254 seclusion episodes from 122 individuals (40 female, 82 male), of which 106 (41.7%) had an adverse outcome within 24 h of seclusion termination. Agitation or irritability was associated with an adverse outcome, odds ratio 1.92 (95% CI 1.03 to 3.56, P = 0.04), but there was no statistically significant association with any of the other exposures, although confidence intervals were broad.
Conclusions
Agitation or irritability in the hours preceding termination of seclusion may predict an adverse outcome. The study was not powered to detect other potentially clinically significant factors.
We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.
Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia.
Methods
Electronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case–control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality.
Results
We identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 μmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45–0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29–1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment.
Conclusions
In the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.
Mixtures of herbicides have been proposed as strategies to prevent or delay the evolution of resistance to the resistance-prone sulfonylurea and imidazolinone herbicides that inhibit acetolactate synthase. These herbicides have become or are becoming widely used in soybean, wheat, rice, and other major crops. For a mixture to be efficacious in preventing resistance, the less resistance-prone component(s) should have the following traits compared to the vulnerable herbicide: a) control the same spectra of weeds; b) have the same persistence; c) have a different target site; d) be degraded in a different manner; and e) preferably exert negative cross-resistance. We compared the proposed mixing partners for use with several widely used acetolactate synthase inhibiting herbicides to these criteria and found that: a) all have somewhat different weed spectra; e.g. none control common cocklebur as well as imazaquin or imazethapyr in soybean, or kochia as well as chlorsulfuron in winter wheat; b) all are far less persistent than these vulnerable herbicides. Less persistent sulfonylureas are now on the market but are in limited use. Late in the season, the mixing partner is not present while the vulnerable herbicide remains active; c) most have different target sites; d) in soybean most mixing partners are degraded differently than vulnerable herbicides. In wheat virtually all herbicides used without safeners are degraded by monooxygenases, thus it is impossible to meet this criterion in this crop; e) none of the mixing partners exert negative cross-resistance. The present mixtures may have superior or more cost-effective weed control properties than the acetolactate synthase inhibitors used alone, but they do not meet all the criteria for resistance management. Not meeting the key criteria of identical control spectra and equal persistence aggravates future resistance problems, as has happened with insecticides.
There are several novels that pique our common interest, but Zola's ambition to put a ‘scientific aim above all others' in his 19th-century novel Thérèse Raquin provides a particularly interesting topic for collective reflection. After being criticised for vulgarity, in the preface to the second edition of his work Zola justified his portrayal of a gruesome ménage àtrois as being analogous to the ‘analytical work that surgeons conduct on cadavers'. Criticism of Zola's work often focuses on whether he achieves the degree of reductionism and determinism that he allegedly strove for or whether, in fact, his predilections for the gothic and fantastic overshadow the novel's scientific, ‘surgical’ veneer. Similarly, psychiatric case notes often begin with a highly formulaic scientific account, yet on closer inspection digress to read more like a tragic novel.
Combinatory logic and lambda-calculus, originally devised in the 1920s, have since developed into linguistic tools, especially useful in programming languages. The authors' previous book served as the main reference for introductory courses on lambda-calculus for over 20 years: this version is thoroughly revised and offers an account of the subject with the same authoritative exposition. The grammar and basic properties of both combinatory logic and lambda-calculus are discussed, followed by an introduction to type-theory. Typed and untyped versions of the systems, and their differences, are covered. Lambda-calculus models, which lie behind much of the semantics of programming languages, are also explained in depth. The treatment is as non-technical as possible, with the main ideas emphasized and illustrated by examples. Many exercises are included, from routine to advanced, with solutions to most at the end of the book.
Edited by
Alex S. Evers, Washington University School of Medicine, St Louis,Mervyn Maze, University of California, San Francisco,Evan D. Kharasch, Washington University School of Medicine, St Louis
Makienko’s conjecture, a proposed addition to Sullivan’s dictionary, can be stated as follows: the Julia set of a rational function R:ℂ∞→ℂ∞ has buried points if and only if no component of the Fatou set is completely invariant under the second iterate of R. We prove Makienko’s conjecture for rational functions with Julia sets that are decomposable continua. This is a very broad collection of Julia sets; it is not known if there exists a rational function whose Julia set is an indecomposable continuum.