Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution.

Background: The role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear. Aims: To investigate the contribution of HLMs to human evolution through post-transcriptional modification. Methods: We applied a deep learning model Seqweaver to predict how HLMs impact RNA-binding protein affinity. Results: We found that only 0.27% of HLMs had significant impacts on RNA-binding proteins at the threshold of the top 1% of human common variations. These HLMs enriched in a set of conserved genes highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and were involved in synapse organisation and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia and schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, suggesting their essential roles in cognition and bipedalism. Conclusions: Our findings suggest that a small subset of human-specific mutations have contributed to human speciation through impacts on post-transcriptional modification of critical brain-related genes.

The use of personal therapy by psychiatrists and psychiatry trainees: a systematic review.

BACKGROUND: It is widely acknowledged that personal therapy positively contributes to the continued personal well-being and ongoing professional development of mental health professionals, including psychiatrists. As a result, most training bodies continue to recommend personal therapy to their trainees. Given its reported value and benefits, one might hypothesize that a high proportion of psychiatrists avail of personal therapy. This systematic review seeks to investigate whether this is the case. AIM: To identify and evaluate the findings derived from all available survey-based studies reporting quantitative data regarding psychiatrists' and psychiatry trainees' engagement in personal therapy. METHOD: A systematic search for survey-based studies about the use of personal therapy by psychiatric practitioners was conducted in four databases and platforms (PubMed, Scopus, Embase and EbscoHost) from inception to May 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for quality using the quality assessment checklist for survey studies in psychology (Q-SSP) and findings summarized using narrative synthesis. RESULTS: The proportion of trainees who engaged in personal therapy ranged from a low of 13.4% in a recent UK based study to a high of 65.3% among Israeli residents. The proportion of fully qualified psychiatrists who engaged in personal therapy varied from 32.1% in South Korea to 89% in New Zealand. CONCLUSION: This review represents the first known attempt to collect and synthesize data aimed at providing insights into the past and current trends in psychiatrists' use of personal therapy across different geographic regions and career stages.

Age-dependent association of cannabis use with risk of psychotic disorder.

BACKGROUND: Epidemiologic research suggests that youth cannabis use is associated with psychotic disorders. However, current evidence is based heavily on 20th-century data when cannabis was substantially less potent than today. METHODS: We linked population-based survey data from 2009 to 2012 with records of health services covered under universal healthcare in Ontario, Canada, up to 2018. The cohort included respondents aged 12-24 years at baseline with no prior psychotic disorder (N = 11 363). The primary outcome was days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder according to validated diagnostic codes. Due to non-proportional hazards, we estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years). Sensitivity analyses explored alternative model conditions including restricting the outcome to hospitalizations and ED visits to increase specificity. RESULTS: Compared to no cannabis use, cannabis use was significantly associated with psychotic disorders during adolescence (aHR = 11.2; 95% CI 4.6-27.3), but not during young adulthood (aHR = 1.3; 95% CI 0.6-2.6). When we restricted the outcome to hospitalizations and ED visits only, the strength of association increased markedly during adolescence (aHR = 26.7; 95% CI 7.7-92.8) but did not change meaningfully during young adulthood (aHR = 1.8; 95% CI 0.6-5.4). CONCLUSIONS: This study provides new evidence of a strong but age-dependent association between cannabis use and risk of psychotic disorder, consistent with the neurodevelopmental theory that adolescence is a vulnerable time to use cannabis. The strength of association during adolescence was notably greater than in previous studies, possibly reflecting the recent rise in cannabis potency.

Oxidative stress parameters in women and men with suicidal thoughts and following a suicide attempt.

Background: This study aimed to evaluate oxidative stress parameters in individuals with depression and schizophrenia, considering gender differences, and manifesting suicidal behavior, encompassing thoughts without a tendency to be realized, thoughts with a tendency to be realized, and suicide attempts. Methods: From among the patients from Department of Psychiatry 120 individuals were selected who met the inclusion criteria and did not meet the exclusion criteria for the study. In the initial phase of the project, patients eligible for the study underwent the M.I.N.I 7.0.2 questionnaire (Mini International Neuropsychiatric Interview). Subsequently, in the second phase of the research, venous blood samples were collected from the patients for the purpose of conducting biochemical assessments, focusing on oxidative stress parameters. Results: The obtained results suggest that redox biomarkers, namely TOS (total oxidation state) and OSI (TOS/TAC ratio), in the blood plasma of women increase in tandem with the severity of suicidal behavior. No notable alterations in SOD (Cu-Zn-superoxide dismutase), GPx (glutathione peroxidase), and GSH (reduced glutathione) concentrations and activity were noted between groups exhibiting suicidal behavior. The observed variations in the concentrations and activity of antioxidant parameters were significant solely in comparison to the control group. Conclusions: Redox biomarkers TOS and OSI could prove valuable in diagnosing women at a genuine risk of committing suicide. On the other hand, antioxidant parameters - SOD, GPx, and GSH may be instrumental in identifying patients with suicidal behaviors, without specifying their intensity.

Linkage of routinely collected NHS data to evaluate liaison mental health services: challenges and lessons learned.

Background: Liaison mental health services provide mental health care to patients in acute hospital settings. Evaluation of liaison services is challenging due to their heterogeneous organisation and delivery, high case throughput and varied patient case mix. We aimed to link routinely collected National Health Service data from secondary care settings, chosen for their service characteristics, to data from primary care to evaluate hospital-based liaison mental health services in England. Methods: We planned to compare patients referred to hospital-based liaison services with comparable patients in the same hospital not referred to liaison services and comparable patients in hospitals without any liaison services. We designed and enacted a methodology to link data from: (1) Hospital Episode Statistics, a database controlled by the National Health Service Digital and (2) ResearchOne, a primary care database controlled by The Phoenix Partnership. Results: Obtaining approvals for the steps prespecified in the methodological protocol took 907 days. Enactment following approvals took 385 days. Data supplied from Hospital Episode Statistics contained 181,063 patients from 6 hospitals (mean = 30,177, standard deviation = 28,875.86) who matched the inclusion and exclusion criteria. Data supplied from ResearchOne contained 33,666 (18.6%) of these patients from the 6 hospitals (mean = 5611, standard deviation = 5206.59). Discussion: Time required for approvals and enactment was attributable to slowness of data handling processes within each data holder and to resolution of technical and organisational queries between them. Variation in number of patients for which data was supplied between databases and between hospitals was attributable to coding inconsistencies and to the limited intersection of patient populations between databases and variation in recording practices between hospitals. Conclusion: Although it is technically feasible to link primary and secondary care data, the current system is challenging, complicated, unnecessarily bureaucratic, time consuming and costly. This limits the number of studies that could be conducted with these rich data sources. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number 13/58/08.

Liaison mental health services are based in acute general hospitals and provide assessment and treatment for people who have both physical and mental health problems. Our aim was to use routinely collected National Health Service data to find out whether general hospital patients referred to liaison mental health services have improved outcomes, compared with patients not referred to liaison services, and comparable patients in hospitals where there are no liaison services. The main outcomes were less time spent in hospital and fewer re-admissions to hospital following discharge. We tried to link data from routine National Health Service sources for hospital and primary care, to compare patients referred to liaison mental health services with similar people in each hospital who had not been referred, and similar people in hospitals without any liaison services at all. We planned to find out how long these people stayed in hospital, whether they were re-admitted and how much was their healthcare cost was. We experienced significant difficulties in being able to link the National Health Service data from the different organisations we approached. The whole process was extremely complex, and a delay in one part of the process resulted delays in other parts. We eventually had to abandon the research without obtaining any meaningful data, although the lessons we learnt will be useful for other researchers, so they can avoid experiencing similar problems. Routinely collected National Health Service data from primary care and secondary care can be linked using the approaches we tried, but we were unable to complete the process within the time frame of the research programme, even with time extensions. Current processes need to be streamlined and standardised with designated clear response times for the different organisations.

Top Ten Tips Palliative Care Clinicians Should Know About the Physical Manifestations of Psychiatric Illness and Treatment.

Addressing the psychiatric aspects of serious illness in palliative care (PC) is crucial to both care delivery and outcomes. Psychiatric comorbidities are common among patients with PC needs and can significantly impact their total burden of symptomatic distress, overall quality of life, functional independence, and healthcare utilization. Yet, these aspects of care are often deferred to mental health consultant teams in the context of busy PC services and often limited human resources. To provide comprehensive and person-centered care, PC clinicians must understand the interplay between medical conditions and psychiatric presentations within a biopsychosocial framework to respond empathically, efficiently, and effectively. This article is the first of a two-part series developed in collaboration with a group of psychiatric-palliative care specialists. This article explores ten common physical manifestations of psychiatric illness and treatment among patients facing serious illnesses. The second article will provide pragmatic tips PC clinicians should know about the psychiatric manifestations of nonpsychiatric serious illness and treatment. Combined, these two articles support a holistic approach that PC clinicians can use to prioritize and integrate both mental and emotional well-being throughout the continuum of serious illness.

Learning to observe art to better understand the patients: A pilot study.

OBJECTIVES: We describe an artwork observation training program proposed to the first-year psychiatry residents in the school of medicine of Montpellier-Nîmes (Université de Montpellier). This course aimed at improving the ability to observe, tolerate ambiguity in healthcare, work as a team, communicate, and develop empathy. We also evaluated the impact of this program on the enhancement of emotional and communication skills in a pilot study. MATERIALS AND METHODS: The artwork observation program based on Visual Thinking Strategies consisted of three sessions of ninety minutes involving two groups of eight medical students. First-year volunteer psychiatry residents were recruited. Before the sessions participants completed the Groningen Reflection ability Scale to evaluate reflection skills. Then, all the participants examined paintings and drawings of the Atger collection, were encouraged to observe carefully, and to engage in active group discussion by means of a structured questioning. Following the session, participants responded to a short survey to assess potential improvement of socio-emotional and communication skills. RESULTS: Fifteen psychiatry residents participated in the pilot study, eight were males. The median age was twenty-five years. The artwork observation program was well accepted by the participants. All the respondents reported improvement of emotional and communication skills, except regarding three empathy items, including the ability to feel the suffering of others which was increased only for 62% of respondents. DISCUSSION: Our program relying on Visual Thinking Strategies may improve the ability to observe carefully, to perceive the mental states of others, and to tolerate uncertainty. Training of such skills may encourage the adoption of self-reflective attitudes. CONCLUSIONS: Such an artistic innovative program should be extended to undergraduate students in medical curriculum.

Qatar's National Mental Health Study-The World Mental Health Qatar.

BACKGROUND: We provide an overview of Qatar's first epidemiological study on prevalence, predictors, and treatment contact for mood and anxiety disorders. AIMS: We highlight the importance of the three-pronged study, its aims, and its key components. MATERIALS & METHODS: The first component comprised a probability-based representative survey of Qatari and non-Qatari (Arab) adult males and females recruited from the general population and interviewed using the International Diagnostic Interview (CIDI version 3.3). The second component, a clinical reappraisal study, assessed concordance between diagnoses based on the CIDI and independent clinical assessments conducted by trained clinical interviewers. The third component comprised a resting-state functional magnetic resonance imaging study of healthy survey respondents who were matched to patients with psychosis. RESULTS: 5000 survey interviews provided data on prevalence and treatment of common mental disorders. Clinical re-interviews (N = 485) provided important diagnostic validity data. Finally, state-of-the art structural and functional brain markers for psychosis were also collected (N = 100). DISCUSSION: Descriptive epidemiological data were collected to inform future mental health priorities in Qatar and situates these within a global context. CONCLUSION: The study fills important gaps in regional and global estimates and establish necessary baseline to develop comprehensive risk estimates for mental health in Qatar's young population.

Top Ten Tips Palliative Care Clinicians Should Know About the Psychiatric Manifestations of Nonpsychiatric Serious Illness and Treatments.

Mental health issues are widespread and significant among individuals with serious illness. Among patients receiving palliative care (PC), psychiatric comorbidities are common and impact patient quality of life. Despite their prevalence, PC clinicians face challenges in effectively addressing the intricate relationship between medical and psychiatric disorders due to their complex, intertwined and bidirectionally influential nature. This article, created collaboratively with a team of psychiatric-palliative care experts, is the second in a two-part series examining the bidirectional relationship between medical and psychiatric illness in PC. This article explores 10 prevalent psychiatric manifestations associated with severe illness and its treatment. Building upon the first article, which focused on 10 common physical manifestations of psychiatric illness among patients receiving PC, these two articles advocate for an integrated approach to PC that prioritizes mental and emotional wellbeing across the continuum of serious illness.

Personalized medicine in old age psychiatry and Alzheimer's disease.

Elderly patients show us unfolded lives with unique individual characteristics. An increasing life span is associated with increasing physical and mental disease burden. Alzheimer's disease (AD) is an increasing challenge in old age. AD cannot be cured but it can be treated. The complexity of old age and AD offer targets for personalized medicine (PM). Targets for stratification of patients, detection of patients at risk for AD or for future targeted therapy are plentiful and can be found in several omic-levels.

Psychometric Assessment of an Item Bank for Adaptive Testing on Patient-Reported Experience of Care Environment for Severe Mental Illness: Validation Study.

BACKGROUND: The care environment significantly influences the experiences of patients with severe mental illness and the quality of their care. While a welcoming and stimulating environment enhances patient satisfaction and health outcomes, psychiatric facilities often prioritize staff workflow over patient needs. Addressing these challenges is crucial to improving patient experiences and outcomes in mental health care. OBJECTIVE: This study is part of the Patient-Reported Experience Measure for Improving Quality of Care in Mental Health (PREMIUM) project and aims to establish an item bank (PREMIUM-CE) and to develop computerized adaptive tests (CATs) to measure the experience of the care environment of adult patients with schizophrenia, bipolar disorder, or major depressive disorder. METHODS: We performed psychometric analyses including assessments of item response theory (IRT) model assumptions, IRT model fit, differential item functioning (DIF), item bank validity, and CAT simulations. RESULTS: In this multicenter cross-sectional study, 498 patients were recruited from outpatient and inpatient settings. The final PREMIUM-CE 13-item bank was sufficiently unidimensional (root mean square error of approximation=0.082, 95% CI 0.067-0.097; comparative fit index=0.974; Tucker-Lewis index=0.968) and showed an adequate fit to the IRT model (infit mean square statistic ranging between 0.7 and 1.0). DIF analysis revealed no item biases according to gender, health care settings, diagnosis, or mode of study participation. PREMIUM-CE scores correlated strongly with satisfaction measures (r=0.69-0.78; P<.001) and weakly with quality-of-life measures (r=0.11-0.21; P<.001). CAT simulations showed a strong correlation (r=0.98) between CAT scores and those of the full item bank, and around 79.5% (396/498) of the participants obtained a reliable score with the administration of an average of 7 items. CONCLUSIONS: The PREMIUM-CE item bank and its CAT version have shown excellent psychometric properties, making them reliable measures for evaluating the patient experience of the care environment among adults with severe mental illness in both outpatient and inpatient settings. These measures are a valuable addition to the existing landscape of patient experience assessment, capturing what truly matters to patients and enhancing the understanding of their care experiences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02491866; https://clinicaltrials.gov/study/NCT02491866.

Unraveling the Inferno: An Arson Case Series.

Firesetting behaviors present multifaceted challenges that intersect the realms of mental health, law, and societal welfare. While distinct in nature, firesetting, arson, and pyromania collectively embody a spectrum of behaviors that cause harm with profound implications for mental health and legal system. Firesetting is a behavior, arson is a criminal offense, and pyromania is a classified psychiatric diagnosis. Nevertheless, the underlying motivations for these behaviors in the context of psychiatric symptomatoloty remain poorly understood. Arson alone exacts a staggering financial toll in the United States, emphasizing the urgent need to understand the reason behind these acts. Within legal contexts, mental health professionals frequently encounter individuals exhibiting firesetting behaviors while consulting on legal cases. The strong correlation between firesetting behavior and mental disorders shows a dire need for extensive and detailed collaboration between psychiatric experts, legal practitioners, and fire services. Here, we describe a series of firesetting cases and their ties to the mental health and legal systems underscoring the imperative for integrated, multifaceted approaches to address this pressing societal concern.

Pharmacologic Treatment of Malignant Catatonia Without Electroconvulsive Therapy: A Case Report.

Malignant catatonia is a rare, life-threatening variant of catatonia requiring prompt treatment. Malignant catatonia is characterized by typical catatonia symptoms of psychomotor, neurologic, and behavioral changes complicated by autonomic instability, with an estimated mortality rate of 50% or more when untreated. Electroconvulsive therapy (ECT) is considered the definitive and most effective treatment for malignant catatonia, with minimal literature on the efficacy of pharmacological interventions alone. Timely access to life-saving ECT may be limited in some hospitals due to restrictive laws on the use of ECT when the patient is incapacitated or due to lack of treatment availability. This case report describes the successful pharmacologic treatment of a patient with malignant catatonia where ECT was unobtainable due to legal restrictions and lack of access to treatment. The patient was initially commenced on lorazepam but continued to deteriorate, subsequently developing complications of aspiration pneumonia and Clostridium difficile colitis. The patient's malignant catatonia resolved with a combination of lorazepam, memantine, and a one-time dose of dantrolene. This complex case highlights the challenges of treating malignant catatonia in under-resourced systems or jurisdictions with restrictive ECT laws and adds additional data on the successful use of pharmacologic interventions for malignant catatonia where ECT is impractical or delayed.

Improvement in Selective Serotonin Reuptake Inhibitor-Associated Sexual Dysfunction With Buspirone: Examining the Evidence.

Sexual dysfunction is a common problem for patients taking antidepressants, with the highest prevalence rates observed with selective serotonin reuptake inhibitors (SSRIs). Sexual dysfunction can be distressing for patients and may lead to medication non-adherence; thus, it is important for the prescribers to be aware of the available treatment strategies, as well as of the strength of the evidence that supports their use. We present the case of a patient who developed delayed ejaculation after the initiation of sertraline for the treatment of depression. The patient's sexual dysfunction resolved after the addition of buspirone. A discussion of this case is followed by a review of the existing literature examining the possible role of buspirone in the treatment of SSRI-induced sexual dysfunction.

Discovery of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Individuals With Common Psychiatric Comorbidities: A Retrospective Case Review.

INTRODUCTION: A retrospective analysis was conducted of a data set collected in an outpatient behavioral health clinic to assess medication metabolism and methylenetetrahydrofolate reductase (MTHFR) and to see if there was a correlation with certain diagnoses and/or gender. METHOD: The outpatient routine completed genetic testing on their patients and the test results were later collected through a third-party company, which completed the pharmacogenomic test analyzing genetic variations in DNA, medication metabolism, and an MTHFR deficiency. RESULTS: This study reviewed 186 patients seen in an outpatient setting who were tested for an MTHFR deficiency and compared their psychiatric diagnoses and the number of failed medication attempts. Of those 186 patients, 77 had normal MTHFR enzyme function, 85 were found to have a moderate MTHFR deficiency, and 24 had a severe MTHFR deficiency. Those with a severe MTHFR deficiency had a higher number of medication trials as compared to those without the deficiency and there were overall more patients with a moderate MTHFR deficiency in this data set. CONCLUSION: Currently, MTHFR deficiency is not commonly tested due to lack of insurance coverage and provider knowledge, and due to the cost of the test itself. Thus, the diagnosis can often be missed.

A Curriculum on Digital Psychiatry for a US-Based Psychiatry Residency Training Program: Pilot Implementation Study.

BACKGROUND: Digital psychiatry, defined as the application of health technologies to the prevention, assessment, and treatment of mental health illnesses, is a growing field. Interest in the clinical use of these technologies continues to grow. However, psychiatric trainees receive limited or no formal education on the topic. OBJECTIVE: This study aims to pilot a curriculum on digital psychiatry for a US-based psychiatry residency training program and examine the change in learner confidence regarding appraisal and clinical recommendation of digital mental health apps. METHODS: Two 60-minute sessions were presented through a web-based platform to postgraduate year 2-4 residents training in psychiatry at a US-based adult psychiatry residency program. Learner confidence was assessed using pre- and postsession surveys. RESULTS: Matched pre- and postsession quizzes showed improved confidence in multiple domains aligning with the course objectives. This included the structured appraisal of digital mental health apps (P=.03), assessment of a patient's digital health literacy (P=.01), formal recommendation of digital health tools (P=.03), and prescription of digital therapeutics to patients (P=.03). Though an improvement from baseline, mean ratings for confidence did not exceed "somewhat comfortable" on any of the above measures. CONCLUSIONS: Our study shows the feasibility of implementing a digital psychiatry curriculum for residents in multiple levels of training. We also identified an opportunity to increase learner confidence in the appraisal and clinical use of digital mental health apps through the use of a formal curriculum.

A level playing field? Evaluation of the virtual Objective Structured Clinical Examination in Psychiatry and Addiction Medicine: A mixed methods study.

OBJECTIVE: The Objective Structured Clinical Examination (OSCE) has been used for clinical assessment of a broad range of medical student competencies in Psychiatry and Addiction Medicine. However, there has been little research into online assessments. We investigated the virtual OSCE (v-OSCE) from the user perspective to better understand its acceptability, usefulness, benefits, challenges and potential improvements. METHODS: At the conclusion of the v-OSCE, all participants (medical students, examiners and simulated patients) were invited to participate in a brief online survey, based on the Technology and Acceptance Model. Freeform qualitative feedback was also obtained to explore participants' experiences and attitudes. RESULTS: Participants reported the v-OSCE was acceptable, efficient, convenient and easy to use. It was perceived as useful for demonstrating students' interviewing skills and interacting with the simulated patient. Benefits included greater convenience, reduced stress and travel time. Challenges were similar to those experienced in 'real world' telepsychiatry, primarily related to assessment of non-verbal cues and emotional prosody. CONCLUSIONS: Our findings inform recommendations for improving online examinations. These include increased preparation, practice and professionalism, to better simulate the in-person experience. Study credibility was strengthened by the triangulation of qualitative, quantitative and psychometric data.

Model-Based Approaches to Investigating Mismatch Responses in Schizophrenia.

Alterations of mismatch responses (ie, neural activity evoked by unexpected stimuli) are often considered a potential biomarker of schizophrenia. Going beyond establishing the type of observed alterations found in diagnosed patients and related cohorts, computational methods can yield valuable insights into the underlying disruptions of neural mechanisms and cognitive function. Here, we adopt a typology of model-based approaches from computational cognitive neuroscience, providing an overview of the study of mismatch responses and their alterations in schizophrenia from four complementary perspectives: (a) connectivity models, (b) decoding models, (c) neural network models, and (d) cognitive models. Connectivity models aim at inferring the effective connectivity patterns between brain regions that may underlie mismatch responses measured at the sensor level. Decoding models use multivariate spatiotemporal mismatch response patterns to infer the type of sensory violations or to classify participants based on their diagnosis. Neural network models such as deep convolutional neural networks can be used for improved classification performance as well as for a systematic study of various aspects of empirical data. Finally, cognitive models quantify mismatch responses in terms of signaling and updating perceptual predictions over time. In addition to describing the available methodology and reviewing the results of recent computational psychiatry studies, we offer suggestions for future work applying model-based techniques to advance the study of mismatch responses in schizophrenia.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

[Changes in the perception of benefits and risks of antidepressive pharmacotherapy]. / Wandel von Nutzen und Risiko antidepressiver Pharmakotherapie.

Antidepressive pharmacotherapy has undergone various phases in its history. The euphoria of the early years on the relief of depressive symptoms was followed by a long period of clinical experience and intensive scientific work resulting in a more balanced perspective. Current debates circle around the actual effectiveness, especially with respect to long-term treatment, the prevention of suicide and the sequelae of discontinuation of an antidepressant. The evaluation of antidepressants as a group and often also the risk-benefit ratio of an individual treatment change over time. Antidepressants are typical for many forms of psychiatric treatment which, in a term from Hanfried Helmchen, are just as Janus-faced as psychiatry in a general sense is as a science and as a clinical discipline.