Dialogues in Clinical Neuroscience最新文献

In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a β-catenin ( Ctnnb1 )-driven, transcriptional nephrogenic program. In conjunction, induced mesenchymal NPCs transition through a pre-tubular aggregate to an epithelial renal vesicle, the precursor for each nephron. How this critical mesenchymal-to-epithelial transition (MET) is regulated is unclear. In an in vitro mouse NPC culture model, activation of the Wnt pathway results in the aggregation of induced NPCs into closely-packed, cell clusters. Genetic removal of β-catenin resulted in a failure of both Wnt pathway-directed transcriptional activation and the formation of aggregated cell clusters. Modulating extracellular Ca ²⁺ levels showed cell-cell contacts were Ca ²⁺ -dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identified Cdh2 , Cdh4 and Cdh11 in uninduced NPCs and the up-regulation of Cdh3 and Cdh4 accompanying the Wnt pathway-induced MET. Genetic removal of all four cadherins, and independent removal of α-catenin, which couples Cdh-β-catenin membrane complexes to the actin cytoskeleton, abolished cell aggregation in response to Wnt pathway activation. However, the β-catenin driven inductive transcriptional program was unaltered. Together with the accompanying paper (Bugacov et al ., submitted), these data demonstrate that distinct cellular activities of β-catenin - transcriptional regulation and cell adhesion - combine in the mammalian kidney programs generating differentiated epithelial nephron precursors from mesenchymal nephron progenitors.

Summary statement: Our study highlights the role of Wnt-β-catenin pathway regulation of cadherin-mediated cell adhesion in the mesenchymal to epithelial transition of induced nephron progenitor cells.

Introduction: There is a growing interest in the study of the neurobiological correlates of internet gaming disorder (IGD), and new techniques are beginning to be implemented for this purpose, such as independent component analysis (ICA). Aims: The present narrative review aimed to explore the studies that had used ICA for the study of the different brain networks possibly associated with IGD. Methods: We specifically focussed on three of the main networks: default-mode network, executive-control and salience networks. Results: Most studies have identified alterations in these three brain networks in individuals with IGD, which may be involved in the development and maintenance of this disorder. Conclusion: More studies are needed to deepen an understanding of the specific role of each in the symptomatology and treatment of IGD.

This narrative overview summarises the work on exercise addiction (EA) over the past 12 years and exposes critical conceptual and methodological issues. More than 1000 articles exist on EA, conceptualised as uncontrolled training harming the individual. Still, EA has no clinical diagnosis criteria at this time. Research is increasing continuously, but it is stale in advancing knowledge. Scalar measurement and lack of differentiation between addictive and instrumental exercise could be reasons for insufficient progress. Exercise addiction fits in the framework of behavioural addictions, but excessive exercise patterns also co-occur with other morbidities, including eating or body-image disorders. In these cases, exercise is instrumental; it functions to achieve a non-exercise-related goal. Therefore, it is essential to separate primary from secondary EA. Based on the interactional model, significant stress and capacity-exceeding ambitions fuel primary EA, while chief motives behind secondary EA embed body image dissatisfaction and eating disorders. Few reports exist on EA's brain mechanisms, which could delay its classification as a distinct psychiatric dysfunction. Treatment of EA involves cognitive-behavioural approaches, but we know little about their effectiveness. Conceptually focussed psychophysiological research and in-depth interviews, complementing scalar data, could answer several open questions in this widely studied but relatively stagnant scholastic field.

Objectives: The current guidelines aim to evaluate the role of pharmacological agents in the treatment of patients with compulsive sexual behaviour disorder (CSBD). They are intended for use in clinical practice by clinicians who treat patients with CSBD.

Methods: An extensive literature search was conducted using the English-language-literature indexed on PubMed and Google Scholar without time limit, supplemented by other sources, including published reviews.

Results: Each treatment recommendation was evaluated with respect to the strength of evidence for its efficacy, safety, tolerability, and feasibility. Psychoeducation and psychotherapy are first-choice treatments and should always be conducted. The type of medication recommended depended mainly on the intensity of CSBD and comorbid sexual and psychiatric disorders. There are few randomised controlled trials. Although no medications carry formal indications for CSBD, selective-serotonin-reuptake-inhibitors and naltrexone currently constitute the most relevant pharmacological treatments for the treatment of CSBD. In cases of CSBD with comorbid paraphilic disorders, hormonal agents may be indicated, and one should refer to previously published guidelines on the treatment of adults with paraphilic disorders. Specific recommendations are also proposed in case of chemsex behaviour associated with CSBD.

Conclusions: An algorithm is proposed with different levels of treatment for different categories of patients with CSBD.

High stake clinical choices in psychiatry can be impacted by external irrelevant factors. A strong understanding of the cognitive and behavioural mechanisms involved in clinical reasoning and decision-making is fundamental in improving healthcare quality. Indeed, the decision in clinical practice can be influenced by errors or approximations which can affect the diagnosis and, by extension, the prognosis: human factors are responsible for a significant proportion of medical errors, often of cognitive origin. Both patient's and clinician's cognitive biases can affect decision-making procedures at different time points. From the patient's point of view, the quality of explicit symptoms and data reported to the psychiatrist might be affected by cognitive biases affecting attention, perception or memory. From the clinician's point of view, a variety of reasoning and decision-making pitfalls might affect the interpretation of information provided by the patient. As personal technology becomes increasingly embedded in human lives, a new concept called digital phenotyping is based on the idea of collecting real-time markers of human behaviour in order to determine the 'digital signature of a pathology'. Indeed, this strategy relies on the assumption that behaviours are 'quantifiable' from data extracted and analysed through connected tools (smartphone, digital sensors and wearable devices) to deduce an 'e-semiology'. In this article, we postulate that implementing digital phenotyping could improve clinical reasoning and decision-making outcomes by mitigating the influence of patient's and practitioner's individual cognitive biases.

Introduction: Chemsex is defined by the use of psychoactive substances to facilitate or improve sexual relations. Our objectives were to assess the prevalence of the practice of 'chemsex' in a population of French university students and to identify socio-demographic and clinical factors associated with this practice.

Material and methods: We have used an anonymous online questionnaire comprising 15 questions on socio-demographic characteristics, chemsex use, sexual satisfaction, the type of substances used in this sexual context and their route of administration.

Results: A total of 680 people were included in our study. Among them, 22.5% reported chemsex behaviour in the past year. Using a multivariate analysis, factors associated with chemsex were dating application use (p = 0.049) and pornography use [viewing more than once per month (p = 0.002)]. Having a sexual partner involved in chemsex (p < 0.0001), celibacy (p = 0.007), sexual orientations other than heterosexual (p = 0.0013) and especially bisexuality (p = 0.0002) were also significantly associated with chemsex.

Conclusion: This is the first study reporting a high prevalence of chemsex in a university student population. Further larger studies should be conducted to confirm these results showing a high prevalence of this at-risk behaviour.

This article is a historical review of the medical and psychiatric diagnoses associated with transgender people across epochs. Ancient Greek and Roman writings already mention gender change. Before a diagnosis even existed, historical documents described the lives of numerous people whom we would consider transgender today. The development of medical classifications took off in the nineteenth century, driven by the blooming of natural sciences. In the nineteenth century, most authors conflated questions of sexual orientation and gender. For example, the psychiatrist Krafft-Ebing reported cases of transgender people but understood them as paranoia, or as the extreme degree of severity in a dimension of sexual inversion. In the early 1900s, doctors such as Magnus Hirschfeld first distinguished homosexual and transgender behaviour. The usual term for transgender people was transvestite, before Harry Benjamin generalised the term transsexual in the mid-20th century. The term transgender became common in the 1970s. This article details the evolution of diagnoses for transgender people from DSM-III and ICD-10 to DSM-5 and ICD-11.

Background: A severe form of pathological social withdrawal, 'hikikomori,' has been acknowledged in Japan, spreading worldwide, and becoming a global health issue. The pathophysiology of hikikomori has not been clarified, and its biological traits remain unexplored.

Methods: Drug-free patients with hikikomori (n = 42) and healthy controls (n = 41) were recruited. Psychological assessments for the severity of hikikomori and depression were conducted. Blood biochemical tests and plasma metabolome analysis were performed. Based on the integrated information, machine-learning models were created to discriminate cases of hikikomori from healthy controls, predict hikikomori severity, stratify the cases, and identify metabolic signatures that contribute to each model.

Results: Long-chain acylcarnitine levels were remarkably higher in patients with hikikomori; bilirubin, arginine, ornithine, and serum arginase were significantly different in male patients with hikikomori. The discriminative random forest model was highly performant, exhibiting an area under the ROC curve of 0.854 (confidential interval = 0.648-1.000). To predict hikikomori severity, a partial least squares PLS-regression model was successfully created with high linearity and practical accuracy. In addition, blood serum uric acid and plasma cholesterol esters contributed to the stratification of cases.

Conclusions: These findings reveal the blood metabolic signatures of hikikomori, which are key to elucidating the pathophysiology of hikikomori and also useful as an index for monitoring the treatment course for rehabilitation.

Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.