Compressive stresses in cancer: characterization and implications for tumour progression and treatment.

Beyond their many well-established biological aberrations, solid tumours create an abnormal physical microenvironment that fuels cancer progression and confers treatment resistance. Mechanical forces impact tumours across a range of biological sizes and timescales, from rapid events at the molecular level involved in their sensing and transmission, to slower and larger-scale events, including clonal selection, epigenetic changes, cell invasion, metastasis and immune response. Owing to challenges with studying these dynamic stimuli in biological systems, the mechanistic understanding of the effects and pathways triggered by abnormally elevated mechanical forces remains elusive, despite clear correlations with cancer pathophysiology, aggressiveness and therapeutic resistance.

Associations Between Neighborhood Resources and Youths' Response to Reward Omission in a Task Modeling Negatively Biased Environments.

Objective: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards.

Irritability, Negative Life Events and the Course of Anxiety and Depressive Symptoms in a Clinical Sample of Youth: A Longitudinal Study.

Objective: Irritability, the tendency to react with anger, and the experience of negative life events (NLE) have independently been associated with the emergence of anxiety and depression. Here, we investigate how irritability and cumulative effects of NLE interactively predict the course of anxiety and depression in the context of common psychiatric disorders.

Method: 432 youth with no psychiatric diagnosis, or a diagnosis of an anxiety disorder, Attention-Deficit/ Hyperactivity Disorder (ADHD), or Disruptive Mood Dysregulation Disorder (DMDD), participated in this study.

Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations.

Objective: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure.

Multivariate Assessment of Inhibitory Control in Youth: Links With Psychopathology and Brain Function.

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8-18 years old) with varying symptom types and levels.

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

Objective: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT.

Editorial: Large Datasets, Small Effect Sizes: Considerations Regarding Optimized Approaches to Identify Targets for Early Interventions Fostering Brain Health.

The origins of youth psychopathology are best studied by integrating clinical and developmental science, an approach known as developmental psychopathology. This relatively young scientific discipline views youth psychopathology as the result of the dynamic interplay of neurobiological, psychological, and environmental risk and protective factors that transcend traditional diagnostic categories. Etiological questions within this framework include whether clinically relevant phenotypes, such as perturbed emotion regulation cross-sectionally linked to atypical brain morphometry, drive deviations from normative neurodevelopmental trajectories or should be viewed as the consequence of atypical brain maturation.

A meta-analysis on the uncinate fasciculus in depression.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression ( = 5016) to healthy individuals ( = 18 425).

Robust caregiver-youth discrepancies in irritability ratings on the affective reactivity index: An investigation of its origins.

Objective: The Affective Reactivity Index (ARI) is widely used to assess young people's irritability symptoms, but youth and caregivers often diverge in their assessments. Such informant discrepancy might be rooted in poor psychometric properties, the differential conceptualization of irritability across informants, or reflect sociodemographic and clinical characteristics. We use an out-of-sample replication approach and leverage longitudinal data, available for a subset of the participants, to test these hypotheses.

Production of indigo by recombinant bacteria.

Unlabelled: Indigo is an economically important dye, especially for the textile industry and the dyeing of denim fabrics for jeans and garments. Around 80,000 tonnes of indigo are chemically produced each year with the use of non-renewable petrochemicals and the use and generation of toxic compounds. As many microorganisms and their enzymes are able to synthesise indigo after the expression of specific oxygenases and hydroxylases, microbial fermentation could offer a more sustainable and environmentally friendly manufacturing platform.

Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors.

The COVID-19 pandemic is a chronically stressful event, particularly for youth. Here, we examine (i) changes in mood and anxiety symtpoms, (ii) pandemic-related stress as a mediator of change in symptoms, and (ii) threat processing biases as a predictor of increased anxiety during the pandemic. A clinically well-characterized sample of 81 youth ages 8-18 years (M = 13.

Context-dependent amygdala-prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces.

Irritability, defined as proneness to anger, is among the most common reasons youth are seen for psychiatric care. Youth with irritability demonstrate aberrant processing of anger-related stimuli; however, the neural mechanisms remain unknown. We applied a drift-diffusion model (DDM), a computational tool, to derive a latent behavioral metric of attentional bias to angry faces in youth with varying levels of irritability during functional magnetic resonance imaging (fMRI).

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety.

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.

The uncinate fasciculus in individuals with and at risk for bipolar disorder: A meta-analysis.

Background: Bipolar disorder (BD) is a severe mental disorder, characterized by prominent mood swings and emotion regulation (ER) deficits. The uncinate fasciculus (UF), a white matter tract connecting the amygdala and the ventral prefrontal cortex, has been implicated in ER. Aberrancies in UF microstructure may be an endophenotype associated with increased risk for BD.

Aberrant Subnetwork and Hub Dysconnectivity in Adult Bipolar Disorder: A Multicenter Graph Theory Analysis.

Neuroimaging evidence implicates structural network-level abnormalities in bipolar disorder (BD); however, there remain conflicting results in the current literature hampered by sample size limitations and clinical heterogeneity. Here, we set out to perform a multisite graph theory analysis to assess the extent of neuroanatomical dysconnectivity in a large representative study of individuals with BD. This cross-sectional multicenter international study assessed structural and diffusion-weighted magnetic resonance imaging data obtained from 109 subjects with BD type 1 and 103 psychiatrically healthy volunteers.

Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates.

Background: Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis designed to model mutual dependencies between symptom dimensions and neural measures.

White Matter Microstructure in Individuals With and At Risk for Bipolar Disorder: Evidence for an Endophenotype From a Voxel-Based Meta-analysis.

Background: Aberrant white matter (WM) microstructure has been proposed as a mechanism underlying bipolar disorder (BD). Given the strong genetic underpinnings of both WM microstructure and BD, such WM aberrations may be not only a disease marker, but also an endophenotype of BD. If so, they should be observable in individuals at risk for BD (AR) (i.

Exposure-Based Cognitive-Behavioral Therapy for Disruptive Mood Dysregulation Disorder: An Evidence-Based Case Study.

Severe, chronic irritability is one of the most frequently reported problems in youth referred for psychiatric care. Irritability predicts adult depressive and anxiety disorders, and long-term impairment. Reflecting this pressing public health need, severe, chronic, and impairing irritability is now codified by the DSM-5 diagnosis of disruptive mood dysregulation disorder (DMDD).

Aberrant probabilistic reinforcement learning in first-degree relatives of individuals with bipolar disorder.

Background: Motivational dysregulation represents a core vulnerability factor for bipolar disorder. Whether this also comprises aberrant learning of stimulus-reinforcer contingencies is less clear.

Methods: To answer this question, we compared healthy first-degree relatives of individuals with bipolar disorder (n = 42) known to convey an increased risk of developing a bipolar spectrum disorder and healthy individuals (n = 97).

Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study.

Background: Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC).

White matter microstructure in youth with and at risk for bipolar disorder.

Objectives: Bipolar disorder (BD) and familial risk for BD have been associated with aberrant white matter (WM) microstructure in the corpus callosum and fronto-limbic pathways. These abnormalities might constitute trait or state marker and have been suggested to result from aberrant maturation and to relate to difficulties in emotion regulation.

Methods: To determine whether WM alterations represent a trait, disease or resilience marker, we compared youth at risk for BD (n = 36 first-degree relatives, REL) to youth with BD (n = 36) and healthy volunteers (n = 36, HV) using diffusion tensor imaging.

Combining fMRI during resting state and an attention bias task in children.

Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks to a threat-based attention task.