Hasil untuk "Psychiatry"

J. Hamilton

A. Kleinman

J. Bowlby

E. Kandel

The American Journal of Psychiatry has received a number of letters in response to my earlier "Framework" article (1). Some of these are reprinted elsewhere in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanalysis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be addressed with a brief comment. I therefore have written this article in an attempt to outline the importance of biology for the future of psychoanalysis.

Z. Kronfol, D. Remick

B. Bandelow, J. Zohar, E. Hollander et al.

Ashley R. Tetens, Tyler R. Findlay, Jordyn Craig-Schwartz et al.

Abstract Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive but genetically simple pediatric central nervous system tumor, defined by biallelic inactivation of the chromatin regulator SMARCB1 with remarkably few other cooperating mutations. Despite its genetic homogeneity, ATRT exhibits profound clinical and epigenetic heterogeneity, with three major subgroups (ATRT-TYR, ATRT-MYC, and ATRT-SHH) defined by DNA methylation and transcriptional signatures. Beyond these subgroup-defining features, we aimed to investigate epigenetic variability within tumors by applying whole-genome bisulfite sequencing and probabilistic modeling to quantify stochastic DNA methylation in primary ATRT samples encompassing all three subgroups. We show that ATRT exhibits a destabilized and increasingly stochastic methylome. While ATRT global methylation patterns diverge according to subgroup, some methylation perturbations, such as hypermethylation and increased methylation entropy over bivalent promoters, are consistent across subgroups. We find that methylation stochasticity alterations map onto potential drivers of ATRT, such as LIN28a, the HOXD cluster for ATRT-MYC, and OTX2 for ATRT-TYR, and identify actionable targets, such as hypermethylation of the tumor suppressor CDKN2a across all subgroups. We investigate the sensitivity of the aberrant DNA methylation landscape of ATRT to pharmacologic DNA methyltransferase inhibition (DNMTi) and histone deacetylase inhibition (HDACi). We show that decitabine leads to profound demethylation of patient-derived ATRT cell lines, including reversal of hypermethylation at bivalent promoters and the CDKN2a locus. The addition of HDACi leads to dramatic gene expression changes, including upregulation of innate immune signaling pathways, such as STING/interferon signaling, genes under the regulation of bivalent promoters, and reactivation of the tumor suppressor CDKN2A. The combination of DNMTi and HDACi synergistically reduces cell viability. Taken together, we show that ATRT has a highly stochastic methylome sensitive to epigenetic manipulation.

Saara H. Huoponen, Katrin Sisa, Tom Saari et al.

ABSTRACT Aim The aim of the study was to survey the observed incidence of adverse effects (AEs) related to electroconvulsive therapy (ECT) in Finnish neuromodulation units, as well as to explore what medical interventions are used to prevent and treat them in those units. Methods An electronic survey was conducted among Finnish neuromodulation units at the end of 2022. The survey included 35 questions related to AEs and their prevention and/or treatment in the responding units’ ECT patient populations. Results Our survey reached 19 out of 26 units in Finland, with 17 units completing the full questionnaire. Headache, myalgia and postictal confusion (PIC) emerged as the most frequently reported AEs. Nausea and high blood pressure were reported less often. Only a few units reported AEs known to be rare, such as accidental awareness during general anesthesia and the aspiration of gastric contents. However, there was considerable variation in the recognition and treatment of those ECT‐related AEs the diagnosis of which depends more on patients’ self‐reporting, including headache, myalgia or nausea. Five units (29%) reported frequent or occasional headache or myalgia and four units (24%) reported occasional nausea experienced by their patients, but these AEs were addressed pharmacologically in those units neither by prophylaxis nor by treatment. This raises concern about whether these AEs are perceived as an insignificant issue in delivering ECT treatment, thus requiring no intervention, or if those AEs should be better recognized and and managed more actively. Conclusions AEs related to ECT treatment are common, but some still appear poorly recognized and treated. Regarding treatment adherence, minimizing potential AEs whenever feasible can be considered important. A thorough preoperative assessment of patients is required to identify possible risk factors for AEs. An objective and structured evaluation tool for recognizing adverse effects in patients undergoing ECT treatment would be useful.

The Lancet Psychiatry

Mila Redzic, Stefan Szymkowiak, Barry McColl

Cerebrovascular dysfunction, leading to inadequate brain perfusion and oxygenation, is a major contributor to cognitive decline and dementia. Chronic hypoxia is a putative mechanism of vascular-mediated brain damage, particularly in relation to white matter lesions, as demonstrated by human neuroimaging and histopathology studies. Moreover, increasing evidence suggests that microglia, the primary immune cells of the brain parenchyma, may play a key role in modulating cerebrovascular disease outcomes. Indeed, unpublished work from our lab using a model of chronic cerebral hypoperfusion found greater vascular and white matter abnormalities concomitant with reduced microglial-vascular interactions in mice lacking the microglial immunoreceptor triggering receptor expressed on myeloid cells 2 (TREM2). However, the underlying mechanisms remain incompletely understood. Therefore, this project aims to further investigate whether microglial TREM2 signalling contributes to cerebrovascular resilience, and specifically vasculoprotection, focusing on the context of hypoxia. To address this, we are housing mice at 8%O2 to achieve chronic mild hypoxia (CMH). As corroborated by our studies, CMH induces cerebral microbleeds associated with parenchymal fibrinogen leakage in both grey and white matter regions (Figure 1), and is thus a reductionist approach well-suited for examining microglial mechanisms conferring vasculoprotection. Ongoing studies in young (5-6 months) and aged (15-18 months) cohorts are utilising histology and immunostaining to determine the impact of TREM2 deficiency and ageing on CMH-induced phenotypes, with particular focus on profiling microbleed burden, BBB integrity and interactions between microglia and other cell types within the neurovascular unit. Given that TREM2 is a key regulator of microglial metabolism and lipid processing, future work will utilise flow cytometry and spatial lipidomics to characterise microglia and brain lipid metabolism during CMH, thus providing insight into immunometabolic changes that may underpin microglial vasculoprotection in hypoxia. Findings from these studies will increase our understanding of microglia-vascular interactions, which can ultimately be exploited to promote resilience to cerebrovascular and other hypoxia- related pathologies.

Vincenzo Marcelli, Vincenzo Marcelli, Beatrice Giannoni et al.

Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist.

Rajiv Tandon

Shaheen E. Lakhan

Sara Calderoni

M. Turki, J. Firas, H. E. Mhiri et al.

Introduction Poor sleep quality is a major health problem worldwide. University students tend to suffer from problems of sleep regularity, quantity and quality, which can affect their academic performance, and have a serious impact on their psychological and physical well-being. Objectives The aim of this study was to assess the prevalence of insomnia among Tunisian university students, and to identify its associated factors. Methods We conducted a cross-sectional web-based study among university students from several Tunisian faculties. Data were collected using a questionnaire spread throughout social media (Facebook), using the Google Forms® platform, during September and October 2022. We used the “Insomnia Severity Index” (ISI) to assess the severity of insomnia. Results A total of 144 students completed the questionnaire. Their mean age was 23.38±3.27 years, with a sex-ration (F/M) of 2.8. Among them, 70.1% were single and 68.8% lived with family. Among our participants, 10.4% were followed for chronic somatic disease, 11.1% for chronic mental disease, while 29.2% have already been diagnosed and treated for sleep disturbances. ISI showed that 72.2% of students suffered from insomnia: 45.1% Subthreshold insomnia, 19.4% moderate clinical insomnia and 7.6% severe clinical insomnia. Insomnia was significantly more frequent among psychoactive substances users (75.7% vs 57.6%; p=0.043). ISI scores were significantly higher among cannabis users (17.4 vs 11.06; p=0.025). Conclusions Our study highlighted that insomnia is prevalent within the university student population, and psychoactive substances consumption seems to worsen it. Thus, when designing interventions to improve sleep quality among students, the main determinants need to be taken into consideration. Disclosure of Interest None Declared

R. Keikha, S.M. Hashemi-Shahri, A. Jebali

Introduction: The expression of specific miRNAs and their mRNA targets are changed in infectious disease. The aim of this study was to analyze the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their mRNA targets in the serum of COVID-19 patients with different grades. Methods: COVID-19 patients with different grades were enrolled in this study and the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their target mRNAs was analyzed by q-PCR. Results: The relative expression of anti- neuroinflammatory miRNAs (mir-21, mir-124, and mir-146a) was decreased and the relative expression of their target mRNAs (IL-12p53, Stat3, and TRAF6) was increased. Also, the relative expression of pro-neuroinflammatory miRNAs (mir-326, mir-155, and mir-27b) was increased and the relative expression of their target mRNA (PPARS, SOCS1, and CEBPA) was decreased in COVID-19 patients with increase of disease grade. A negative significant correlation was seen between mir-21 and IL-12p53 mRNA, mir-124 and Stat3 mRNA, mir-146a and TRAF6 mRNA, mir-27b and PPARS mRNA, mir-155 and SOCS1 mRNA, and between mir-326 and CEBPA mRNA in COVID-19 patients (P < 0.05). Conclusions: This study showed that the relative expression of anti- neuroinflammatory miRNAs was decreased and the relative expression of their targeted mRNAs was increased in COVID-19 patients from asymptomatic to critical illness. Also, this study showed that the relative expression of pro-neuroinflammatory miRNAs was increased and the relative expression of their targeted mRNA was decreased in COVID-19 patients from asymptomatic to critical illness. Resumen: Introducción: La expresión de miARN específicos y sus dianas de ARNm se modifican en las enfermedades infecciosas. El objetivo de este estudio fue analizar la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm dianas en el suero de pacientes con COVID-19 de diferentes grados. Métodos: Se incluyeron en este estudio pacientes con COVID-19 de diferentes grados y se analizó la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm diana mediante q-PCR. Resultados: La expresión relativa de miARN anti-neuroinflamatorios (mir-21, mir-124 y mir-146a) disminuyó y la expresión relativa de sus ARNm diana (IL-12p53, Stat3 y TRAF6) aumentó. Además, la expresión relativa de miARN pro-neuroinflamatorios (mir-326, mir-155 y mir-27b) aumentó y la expresión relativa de su ARNm diana (PPARS, SOCS1 y CEBPA) disminuyó en pacientes con COVID-19 con aumento del grado de enfermedad. Se observó una correlación negativa significativa entre ARNm de mir-21 e IL-12p53, ARNm de mir-124 y Stat3, ARNm de mir-146a y TRAF6, ARNm de mir-27b y PPARS, ARNm de mir-155 y SOCS1, y entre mir-326 y ARNm de CEBPA en pacientes con COVID-19 (p < 0,05). Conclusiones: Este estudio mostró que la expresión relativa de miARN anti-neuroinflamatorios disminuyó y la expresión relativa de sus ARNm diana se incrementó en pacientes con COVID-19 de enfermedad asintomática a crítica. Además, este estudio mostró que la expresión relativa de miARN pro-neuroinflamatorios aumentó y la expresión relativa de su ARNm diana disminuyó en pacientes con COVID-19 de enfermedad asintomática a crítica.

A. Hwong, Y. Li, R. Morin et al.

Introduction Older adults with schizophrenia often have multiple chronic conditions, or multimorbidity, yet most prior research has focused on single medical conditions. Objectives To characterize multimorbidity patterns and utilization among older adults with schizophrenia to understand how multimorbidity affects this population and their clinical service needs. Methods This retrospective cohort study included veterans aged 50 years and older with schizophrenia and followed their comorbid diagnoses and utilization (outpatient, inpatient, and emergency) from 2012 to 2019. Comorbid diagnoses included myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease (COPD), cancer, dementia, traumatic brain injury, hepatitis C, osteoarthritis, renal disease, chronic pain, sleep disorder, depression, dysthymia, posttraumatic stress disorder (PTSD), general anxiety disorder, alcohol use disorder, other substance use disorder, and tobacco use disorder. Latent class analysis was used to identify latent profiles of psychiatric and medical comorbidity. Chi-square and F-tests were used to assess differences in demographics, comorbidities, and utilization across the latent classes. Results The cohort included 82,495 adults with schizophrenia. Three distinct multimorbidity classes were identified: Minimal Comorbidity (67.0% of the cohort), High Comorbidity (17.6%) and Substance Use Disorders and Related Conditions (SUDRC) (15.4%). The Minimal Comorbidity class had <10% prevalence of all comorbid diagnoses. The High Comorbidity class had >20% prevalence of congestive heart failure, COPD, dementia, renal disease, sleep disorder, and depression. The SUDRC class had >70% prevalence of alcohol and drug use disorders and >20% prevalence of COPD, hepatitis C, depression, and PTSD. Although the High Comorbidity class had the highest rates of chronic medical conditions, the SUDRC class had the highest rates of emergency and inpatient medical care and emergency, inpatient, and outpatient mental health care utilization. Comparing across classes, all p-values were <.001 for utilization. Conclusions Older adults with schizophrenia are a heterogeneous group with distinct multimorbidity classes and different patterns of utilization. Those with high prevalence of substance use disorders had the highest rates of emergency and inpatient medical and overall mental health care utilization. Tailoring integrated care services to target specific clinical needs could improve outcomes for this population. Disclosure of Interest None Declared

Alessandra Martinelli, Chiara Bonetto, Federica Bonora et al.

Abstract Background People with mental disorders are far more likely to be unemployed than the general population. Two internationally recognized, evidence-based models of interventions for employment for people with severe mental health problems are Individual Placement Support and the Clubhouse. In Italy, a common model is the ‘social enterprise’ (SE), which is a programme run by non-profit organisations that help individuals with disabilities to be employed. Despite SEs spread and relevance in Italy, there are no studies about Italian samples. This paper reports on a pilot evaluation of psychosocial and work outcomes of a SE based in Verona, Italy. The study aims to investigate if people with SMI involved in SE job placements may achieve personal recovery and better outcomes over time, and in comparison with a comparable group of users. Methods This is a pilot descriptive study with three components. A longitudinal design that comprised a functioning description of 33 SE members with a psychiatric disability in two time-points (when they joined the SE—on average 5 years before the study recruitment, and at the study recruitment—year 2018); and a repeated collection of job details of the 33 members in three time points: 2 years before the recruitment,—year 2016; 1 year before the recruitment – year 2017; and at the recruitment—year 2018. An assessment at the recruitment time—year 2018, of SE users’ satisfaction with the job placement, symptoms, functioning, and quality of life (QoL). A cross-sectional study that compared the 33 SE members at the recruitment time—year 2018, with a matched group of people with the following criteria: living in local supported accommodations, being unemployed and not SE members. The two groups were compared on ratings of psychopathology, functioning, and QoL. Descriptive analyses were done. Results At the recruitment time – year 2018, all SE participants showed a significant better functioning (p < 0.001) than when they joined the SE—when they had been employed for an average of 5 years. In comparison to the matched group, SE members had significantly better functioning (p = 0.001), psychopathology (p = 0.007), and QoL (p = 0.034). According to their SE membership status, participants comprised trainees (21.2%) and employee members (78.8%). Trainees compared to employees had lower autonomies, functioning, QoL and more severe psychopathology. Over the two years prior to study recruitment, trainees showed stable poor autonomies, while employee members showed a variation from average autonomies in the 2 years before the recruitment time – year 2016, to good ones at the recruitment time – year 2018. Over the two years, all SE members set increasing numbers of objectives in all three domains. All SE participants reported high levels of satisfaction with all aspects of the job placement. Conclusions SE that provides tailored support to assist people to gain employment skills may be an effective component in helping recovery from SMI.

Stian Solem, Adrian Wells, Leif Edward Ottesen Kennair et al.

Abstract Objective Metacognitive therapy (MCT) and cognitive–behavior therapy (CBT) are effective treatments for generalized anxiety disorder. In this study, we followed‐up patients who had previously participated in a randomized controlled trial of MCT compared against CBT. Method We collected 9‐year follow‐up data on 39 out of 60 original patients (i.e., 65% response rate). Results At 9 years, the recovery rates were 57% for MCT and 38% for CBT (completer analysis). Following MCT, 43% maintained their recovery status and a further 14% achieved recovery. Following CBT, the sustained recovery rate was 13%, while a further 25% achieved recovery. Patients in the MCT condition showed significantly more improvement with respect to symptoms of worry and anxiety. In the CBT group, 23.1% were re‐diagnosed with generalized anxiety disorder (GAD) compared with 9.5% in the MCT group. Conclusions This follow‐up study showed a continuation of gains in both treatments at long‐term follow‐up, but with outcomes continuing to favor MCT and strengthening its comparative superiority.

Satya Narayana Patro, Khawaja Hassan Haroon, Khansabegum Tamboli et al.

The anterior choroidal artery (AChA) is a small artery commonly arising from the supraclinoid segment of the internal carotid artery (ICA). The significance of the AChA is related to its strategic supply to various important structures of the brain, such as the optic tract, the posterior limb of the internal capsule, the cerebral peduncle, the lateral geniculate body, medial temporal lobe, medial area of pallidum, and the choroid plexus [J Neurol. 1988;235:387–91]. The AChA syndrome in its complete form consists of the triad of hemiplegia, hemisensory loss, and hemianopia. However, incomplete forms are more frequent in clinical practice [Stroke. 1994;25:837–42]. Isolated infarction in the AChA territory is relatively rare. The presumed pathogenic mechanisms of AChA infarction are cardiac emboli, large-vessel atherosclerosis, dissection of the ICA, small-vessel occlusion, or other determined or undetermined causes [Stroke. 1994;25:837–42 and J Neurol Sci. 2009;281:80–4].