Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice () that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells - disrupting this gradient reroutes axons away from their target.
View Article and Find Full Text PDFMajor depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via "trial and error". Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining data across trials poses numerous challenges.
View Article and Find Full Text PDF[This corrects the article DOI: 10.2196/31862.].
View Article and Find Full Text PDFBackground: Major depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological and behavioral substrates are associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning (ML) shows promise in predicting treatment response in MDD, but its application is limited by challenges to the clinical interpretability of ML models, and clinicians often lack confidence in model results.
View Article and Find Full Text PDFInitiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence.
View Article and Find Full Text PDFDopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice ( ) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells - disrupting this gradient reroutes axons away from their target.
View Article and Find Full Text PDFAifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty physicians who were either staff or residents in psychiatry or family medicine completed a study in which they had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD.
View Article and Find Full Text PDFBackground: Approximately two-thirds of patients with major depressive disorder do not achieve remission during their first treatment. There has been increasing interest in the use of digital, artificial intelligence-powered clinical decision support systems (CDSSs) to assist physicians in their treatment selection and management, improving the personalization and use of best practices such as measurement-based care. Previous literature shows that for digital mental health tools to be successful, the tool must be easy for patients and physicians to use and feasible within existing clinical workflows.
View Article and Find Full Text PDFBackground: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.
Aims: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression.
The conditioned place preference (CPP) paradigm is widely used in rodent research to test the rewarding and aversive properties of different stimuli. Despite its relative simplicity, commercially available CPP systems are often costly. Here we describe the construction of a CPP setup and a behavioral data analysis pipeline incorporating: • a CPP box which can be built in a single day by using widely available and affordable materials.
View Article and Find Full Text PDFThe guidance cue receptor DCC controls mesocortical dopamine development in adolescence. Repeated exposure to an amphetamine regimen of 4 mg/kg during early adolescence induces, in male mice, downregulation of DCC expression in dopamine neurons by recruiting the Dcc microRNA repressor, microRNA-218 (miR-218). This adolescent amphetamine regimen also disrupts mesocortical dopamine connectivity and behavioral control in adulthood.
View Article and Find Full Text PDFThe molting during Drosophila development is tightly regulated by the ecdysone hormone. Several steps of the ecdysone biosynthesis have been already identified but the regulation of the entire process has not been clarified yet. We have previously reported that dATAC histone acetyltransferase complex is necessary for the steroid hormone biosynthesis process.
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