Explaining variability in ciclosporin exposure in adult kidney transplant recipients

International audienc

Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size, and have limited clinical relevance. These concerns have prompted a paradigm shift towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Hence, we uniquely built/validated supervised neuroanatomical machine learning (ML) models for individual-level inferences, using the largest up to date neuroimaging database on youth anxiety disorders: ENIGMA Anxiety Consortium (N=3,343; Age: 10-25 years; Global Sites: 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (Panic Disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status, and symptom severity (AUC’s 0.59-0.63). Classifications were driven by neuroanatomical features (cortical thickness/surface area, subcortical volumes) in fronto-striato-limbic and temporo-parietal regions. This benchmark study provides estimates on individual-level classification performances that can be realistically achieved with ML using neuroanatomical data, within a large, heterogenous, and multi-site sample of youth with anxiety disorders

Extraversion is linked to volume of the orbitofrontal cortex and amygdala

Contains fulltext : 103145.pdf (publisher's version ) (Open Access)Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel Based Morphometry (VBM) approach. Multiple regression analyses were performed to test for associations of neuroticism and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive) and females (negative). Neuroticism scores did not significantly correlate with these brain regions. As extraversion is regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.6 p

Melioidosis in travelers: An analysis of Dutch melioidosis registry data 1985–2018

Background: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an opportunistic infection across the tropics. Here, we provide a systematic overview of imported human cases in a non-endemic country over a 25-year period. Methods: All 5

The Relationship Between Reductionism and Prediction in Psychiatry: A Survey

Introduction. Biological psychiatry has yet to find clinically useful biomarkers despite much effort. Is this because the field needs better methods and more data, or are current conceptualizations of mental disorders too reductionistic? Although this is an important question, there seems to be no consensus on what it means to be a “reductionist”. Aims. This paper aims to; a) to clarify the views of researchers on different types of reductionism; b) to examine the relationship between these views and the degree to which researchers believe mental disorders can be predicted from biomarkers; c) to compare these predictability estimates with the performance of machine learning models that have used biomarkers to distinguish cases from controls. Methods. We created a survey on reductionism and the predictability of mental disorders from biomarkers, and shared it with researchers in biological psychiatry. Furthermore, a literature review was conducted on the performance of machine learning models in predicting mental disorders from biomarkers. Results. The survey results showed that 9% of the sample were dualists and 57% were explanatory reductionists. There was no relationship between reductionism and perceived predictability. The estimated predictability of 11 mental disorders using currently available methods ranged between 65-80%, which was comparable to the results from the literature review. However, the participants were highly optimistic about the ability of future methods in distinguishing cases from controls. Moreover, although behavioral data were rated as the most effective data type in predicting mental disorders, the participants expected biomarkers to play a significant role in not just predicting, but also defining mental disorders in the future

The development of an fMRI protocol to investigate vmPFC network topology underlying the generalization of behavioral control

Experiencing behavioral control over stress can have long lasting and generalizing effects. The controllability of a physical threat, for example, affects the processing of subsequent social stress. Animal research has shown that the vmPFC plays a critical role in behavioral control and orchestrating subcortical responses. However, translational research on these neural systems in humans is sparse and we therefore aimed to develop a paradigm to test the generalization effect of behavioral control on vmPFC functioning. A pilot study was performed in which subjects (n=18) were first randomly assigned to one of two versions of a signal detection task, where feedback was either paired with a controllable or an uncontrollable mild shock. Subsequently, subjects underwent a social evaluative threat fMRI paradigm to measure their response to the anticipation of speaking in public. The analyses tested whether the controllability manipulation influenced behavioral and physiological responses and vmPFC network topology. Results showed that overall subjects were faster to respond to potential shock trials in the signal detection task, and there was a trend significant difference between the controllable or uncontrollable group. No significant differences between the two groups were observed on other behavioral or physiological responses. fMRI results showed higher vmPFC efficiency in the controllable threat group at baseline and recovery but similar to the uncontrollable group during speech anticipation. The current report establishes the feasibility of the protocol and adequately-powered follow-up research is needed to further evaluate the generalization effect on the behavioral, physiological and neural level

Mental imagery affects subsequent automatic defense responses

Automatic defense responses promote survival and appropriate action under threat. They have also been associated with the development of threat-related psychiatric syndromes. Targeting such automatic responses during threat may be useful in populations with frequent threat exposure. Here, two experiments explored whether mental imagery as a pre-trauma manipulation could influence fear bradycardia (a core characteristic of freezing) during subsequent analogue trauma (affective picture viewing). Image-based interventions have proven successful in the treatment of threat-related disorders, and are easily applicable. In Experiment 1 43 healthy participants were randomly assigned to an imagery script condition. Participants executed a passive viewing task with blocks of neutral, pleasant and unpleasant pictures after listening to an auditory script that was either related (with a positive or a negative outcome) or unrelated to the unpleasant pictures from the passive viewing task. Heart rate was assessed during script listening and during passive viewing. Imagining negative related scripts resulted in greater bradycardia (neutral-unpleasant contrast) than imagining positive scripts, especially unrelated. This effect was replicated in Experiment 2 (N = 51), again in the neutral-unpleasant contrast. An extra no-script condition showed that bradycardia was not induced by the negative related script, but rather that a positive script attenuated bradycardia. These preliminary results might indicate reduced vigilance after unrelated positive events. Future research should replicate these findings using a larger sample. Either way, the findings show that highly automatic defense behavior can be influenced by relatively simple mental imagery manipulations

The generalization of behavioral control over physical threats to social stressors in humans: A pilot fMRI study.

Behavioral control, the ability to manage one’s exposure to a given stressor, influences the impacts of both the present and future stressors. Behavioral control over a stressor may decrease stress caused by the stressor, and promote resilience towards future stressors. A lack of behavioral control may exacerbate the stress response and lead to learned helplessness, a generalized view that one cannot control other, unrelated stressors in their environment. The ventromedial prefrontal cortex (vmPFC) may detect the presence of behavioral control over a stressor and communicate this to subcortical regions involved in stress responses, such as the nucleus accumbens (NAc). Building on previous research in animals and humans, piloted a paradigm to investigate how behavioral control over a physical threat (electric shocks), generalizes to responses for a subsequent social stressor (anticipation of public speaking). Our manipulation of behavioral control over a physical threat effected perceived control but not stress, and no effects generalized to the subsequent social stressor in behavioral, physiological, or neural responses. We discuss refinements to the paradigm to strengthen the effect of the manipulation, the potential impacts of statistical power on the present results, and metrics to measure the generalization of behavioral control in addition to vmPFC-subcortical connectivity