Urbanicity, biological stress system functioning and mental health in adolescents

Growing up in an urban area has been associated with an increased chance of mental health problems in adults, but less is known about this association in adolescents. We examined whether current urbanicity was associated with mental health problems directly and indirectly via biological stress system functioning. Participants (n = 323) were adolescents from the Dutch general population. Measures included home and laboratory assessments of autonomic nervous system and hypothalamic-pituitary-adrenal axis functioning, neighborhood-level urbanicity and socioeconomic status, and mother- and adolescent self-reported mental health problems. Structural equation models showed that urbanicity was not associated with mental health problems directly. Urbanicity was associated with acute autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity such that adolescents who lived in more urban areas showed blunted biological stress reactivity. Furthermore, there was some evidence for an indirect effect of urbanicity on mother-reported behavioral problems via acute autonomic nervous system reactivity. Urbanicity was not associated with overall autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity or basal hypothalamic-pituitary-adrenal axis functioning. Although we observed some evidence for associations between urbanicity, biological stress reactivity and mental health problems, most of the tested associations were not statistically significant. Measures of long-term biological stress system functioning may be more relevant to the study of broader environmental factors such as urbanicity

Walk to me when I smile, step back when I’m angry: emotional faces modulate whole-body approach–avoidance behaviors

Facial expressions are potent social cues that can induce behavioral dispositions, such as approach–avoidance tendencies. We studied these tendencies by asking participants to make whole-body forward (approach) or backward (avoidance) steps on a force plate in response to the valence of social cues (happy or angry faces) under affect-congruent and incongruent mappings. Posturographic parameters of the steps related to automatic stimulus evaluation, step initiation (reaction time), and step execution were determined and analyzed as a function of stimulus valence and stimulus–response mapping. The main result was that participants needed more time to initiate a forward step towards an angry face than towards a smiling face (which is evidence of a congruency effect), but with backward steps, this difference failed to reach significance. We also found a reduction in spontaneous body sway prior to the step with the incongruent mapping. The results provide a crucial empirical link between theories of socially induced action tendencies and theories of postural control and suggest a motoric basis for socially guided motivated behavior

Information extraction from free text for aiding transdiagnostic psychiatry: constructing NLP pipelines tailored to clinicians’ needs

Background: Developing predictive models for precision psychiatry is challenging because of unavailability of the necessary data: extracting useful information from existing electronic health record (EHR) data is not straightforward, and available clinical trial datasets are often not representative for heterogeneous patient groups. The aim of this study was constructing a natural language processing (NLP) pipeline that extracts variables for building predictive models from EHRs. We specifically tailor the pipeline for extracting information on outcomes of psychiatry treatment trajectories, applicable throughout the entire spectrum of mental health disorders (“transdiagnostic”). Methods: A qualitative study into beliefs of clinical staff on measuring treatment outcomes was conducted to construct a candidate list of variables to extract from the EHR. To investigate if the proposed variables are suitable for measuring treatment effects, resulting themes were compared to transdiagnostic outcome measures currently used in psychiatry research and compared to the HDRS (as a gold standard) through systematic review, resulting in an ideal set of variables. To extract these from EHR data, a semi-rule based NLP pipeline was constructed and tailored to the candidate variables using Prodigy. Classification accuracy and F1-scores were calculated and pipeline output was compared to HDRS scores using clinical notes from patients admitted in 2019 and 2020. Results: Analysis of 34 questionnaires answered by clinical staff resulted in four themes defining treatment outcomes: symptom reduction, general well-being, social functioning and personalization. Systematic review revealed 242 different transdiagnostic outcome measures, with the 36-item Short-Form Survey for quality of life (SF36) being used most consistently, showing substantial overlap with the themes from the qualitative study. Comparing SF36 to HDRS scores in 26 studies revealed moderate to good correlations (0.62—0.79) and good positive predictive values (0.75—0.88). The NLP pipeline developed with notes from 22,170 patients reached an accuracy of 95 to 99 percent (F1 scores: 0.38 – 0.86) on detecting these themes, evaluated on data from 361 patients. Conclusions: The NLP pipeline developed in this study extracts outcome measures from the EHR that cater specifically to the needs of clinical staff and align with outcome measures used to detect treatment effects in clinical trials

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

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Motor and sensory dissociative phenomena with induced catalepsy

Contains fulltext : 55645.pdf (publisher's version ) (Closed access)The purpose of this study was to investigate dissociative symptoms that may occur as an epiphenomenon of tactile-induced catalepsy. In 15 participants, catalepsy was induced in the right arm, and dissociative symptoms were evaluated using a self-report questionnaire. In comparison with the left, noncataleptic arm, the right cataleptic arm was perceived differently. In addition to increased rigidity, the cataleptic arm was characterized by the presence of paresthesias, a decreased perception of sense and a decreased awareness of the arm. Moreover, the self-reported changes in perception were significantly correlated to the hypnotically induced arm-immobilization part of the Stanford Hypnotic Susceptibility Scale. In conclusion, catalepsy induction elicits a variety of dissociative symptoms and provides a useful research paradigm for the study of motor-perceptual dissociative phenomena