Comorbidity and Quality of Life in Adults with Hair Pulling Disorder

Hair pulling disorder (HPD; trichotillomania) is thought to be associated with significant psychiatric comorbidity and functional impairment. However, few methodologically rigorous studies of HPD have been conducted, rendering such conclusions tenuous. The following study examined comorbidity and psychosocial functioning in a well-characterized sample of adults with HPD (N=85) who met DSM-IV criteria, had at least moderate hair pulling severity, and participated in a clinical trial. Results revealed that 38.8% of individuals with HPD had another current psychiatric diagnosis and 78.8% had another lifetime (present and/or past) psychiatric diagnosis. Specifically, HPD showed substantial overlap with depressive, anxiety, addictive, and other body-focused repetitive behavior disorders. The relationships between certain comorbidity patterns, hair pulling severity, current mood and anxiety symptoms, and quality of life were also examined. Results showed that current depressive symptoms were the only predictor of quality of life deficits. Implications of these findings for the conceptualization and treatment of HPD are discussed

Autonomy–connectedness, self-construal, and acculturation:Associations with mental health in a multicultural society

The present study investigated the associations between self-construal, acculturation, and autonomy?connectedness, as well as the relations between autonomy?connectedness and psychopathological symptoms, controlling for self-construal and acculturation. Participants were 1,209 Dutch individuals, of whom 693 (57.3%) were immigrants with a non-Western background. Results showed that an independent self-construal was positively associated with self-awareness and capacity for managing new situations, and was negatively associated with sensitivity to others (which are the three components of autonomy?connectedness). Moreover, an interdependent self-construal was negatively associated with self-awareness and capacity for managing new situations, and was positively associated with sensitivity to others. Importantly, the latter associations were similar for both Dutch natives and immigrants, and the associations between acculturation and autonomy?connectedness were small and nonsignificant. Autonomy?connectedness, after controlling for self-construal and acculturation, explained a large amount of additional variance in anxiety (12.7%) and depression (14.1), and a medium amount of additional variance in drive for thinness (3.7%) and bulimia (4.8%). Autonomy?connectedness, thus, seems to be an important construct for people with a Western background, as well as for immigrants with a non-Western background

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis

Aims: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor-α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures. Methods: Patients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2-year follow-up BMD measurements were included. BMD of lumbar spine (L1–L4) and hip (total proximal femur) were measured using dual-energy X-ray absorptiometry. Spinal radiographs (Th4–L4) were scored for vertebral fractures according to the Genant method. Results: In the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z-scores increased significantly; median from −1.5 (interquartile range [IQR] −2.2 to 0.4) to 0.1 (IQR −1.5 to 1.0); P <.001 and median from −1.0 (IQR −1.6 to −0.7) to −0.8 (IQR −1.2 to 0.0); P =.006 over 2 years, respectively. In patients also treated with tumour necrosis factor-α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2-year change +8.6% [IQR 2.4 to 19.6; P =.009] and +3.6% [IQR 0.7–9.0; P =.007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2-year change +3.6%; IQR 0.7 to 9.0; P =.011) and no improvement was seen in hip BMD (median −0.6%; IQR −3.1 to 5.1; P =.61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle-aged men. Conclusion: This explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred

Group autonomy enhancing treatment versus cognitive behavioral therapy for anxiety disorders:A cluster‐randomized clinical trial

Background Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects. Methods A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements). Results Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d = .16 or smaller at post-test). Anxiety reduction was similar across conditions (d = .059 at post-test) and neither therapy was superior on long term. Conclusion This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders. The study was preregistered at the Netherlands Clinical Trial Registry (https://www.trialregister.nl/trial/6250

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells. These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-type-specific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer

Group autonomy enhancing treatment versus cognitive behavioral therapy for anxiety disorders: A cluster-randomized clinical trial

Background: Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects. Methods: A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements). Results: Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d =.16 or smaller at post-test). Anxiety reduction was similar across conditions (d =.059 at post-test) and neither therapy was superior on long term. Conclusion: This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders

Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits

Background: Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits. Results We selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA;CLDND1), and BMI with six CpGs and two genes (PID1;LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression. Conclusions: Our study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD

Multi-Omics Analysis Reveals MicroRNAs Associated With Cardiometabolic Traits

MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and

Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation.

The immune-specialized environment of the healthy brain is tightly regulated to prevent excessive neuroinflammation. However, after cancer development, a tissue-specific conflict between brain-preserving immune suppression and tumor-directed immune activation may ensue. To interrogate potential roles of T cells in this process, we profiled these cells from individuals with primary or metastatic brain cancers via integrated analyses on the single-cell and bulk population levels. Our analysis revealed similarities and differences in T cell biology between individuals, with the most pronounced differences observed in a subgroup of individuals with brain metastasis, characterized by accumulation of CXCL13-expressing CD39 &lt;sup&gt;+&lt;/sup&gt; potentially tumor-reactive T (pTRT) cells. In this subgroup, high pTRT cell abundance was comparable to that in primary lung cancer, whereas all other brain tumors had low levels, similar to primary breast cancer. These findings indicate that T cell-mediated tumor reactivity can occur in certain brain metastases and may inform stratification for treatment with immunotherapy

Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease

Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease