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Molecular Psychiatry Aug 2023Anxiety Disorders (ANX) such as panic disorder, generalized anxiety disorder, and phobias, are highly prevalent conditions that are moderately heritable. Evidence...
Anxiety Disorders (ANX) such as panic disorder, generalized anxiety disorder, and phobias, are highly prevalent conditions that are moderately heritable. Evidence suggests that DNA methylation may play a role, as it is involved in critical adaptations to changing environments. Applying an enrichment-based sequencing approach covering nearly 28 million autosomal CpG sites, we conducted a methylome-wide association study (MWAS) of lifetime ANX in 1132 participants (618 cases/514 controls) from the Netherlands Study of Depression and Anxiety. Using epigenomic deconvolution, we performed MWAS for the main cell types in blood: granulocytes, T-cells, B-cells and monocytes. Cell-type specific analyses identified 280 and 82 methylome-wide significant associations (q-value < 0.1) in monocytes and granulocytes, respectively. Our top finding in monocytes was located in ZNF823 on chromosome 19 (p = 1.38 × 10) previously associated with schizophrenia. We observed significant overlap (p < 1 × 10) with the same direction of effect in monocytes (210 sites), T-cells (135 sites), and B-cells (727 sites) between this Discovery MWAS signal and a comparable replication dataset from the Great Smoky Mountains Study (N = 433). Overlapping Discovery-Replication MWAS signal was enriched for findings from published GWAS of ANX, major depression, and post-traumatic stress disorder. In monocytes, two specific sites in the FZR1 gene showed significant replication after Bonferroni correction with an additional 15 nominally replicated sites in monocytes and 4 in T-cells. FZR1 regulates neurogenesis in the hippocampus, and its knockout leads to impairments in associative fear memory and long-term potentiation in mice. In the largest and most extensive methylome-wide study of ANX, we identified replicable methylation sites located in genes of potential relevance for brain mechanisms of psychiatric conditions.
Topics: Humans; Animals; Mice; Epigenome; Genome-Wide Association Study; Schizophrenia; DNA Methylation; Anxiety Disorders; CpG Islands
PubMed: 37542162
DOI: 10.1038/s41380-023-02205-w -
Pharmaceutics Nov 2023Messenger RNA (mRNA) vaccines against infectious diseases and for anticancer immunotherapy have garnered considerable attention. Currently, mRNA vaccines encapsulated in... (Review)
Review
Messenger RNA (mRNA) vaccines against infectious diseases and for anticancer immunotherapy have garnered considerable attention. Currently, mRNA vaccines encapsulated in lipid nanoparticles are administrated via intramuscular injection using a needle. However, such administration is associated with pain, needle phobia, and lack of patient compliance. Furthermore, side effects such as fever and anaphylaxis associated with the lipid nanoparticle components are also serious problems. Therefore, noninvasive, painless administration of mRNA vaccines that do not contain other problematic components is highly desirable. Antigen-presenting cells reside in the epidermis and dermis, making the skin an attractive vaccination site. Iontophoresis (ItP) uses weak electric current applied to the skin surface and offers a noninvasive permeation technology that enables intradermal delivery of hydrophilic and ionic substances. ItP-mediated intradermal delivery of biological macromolecules has also been studied. Herein, we review the literature on the use of ItP technology for intradermal delivery of naked mRNA vaccines which is expected to overcome the challenges associated with mRNA vaccination. In addition to the physical mechanism, we discuss novel biological mechanisms of iontophoresis, particularly ItP-mediated opening of the skin barriers and the intracellular uptake pathway, and how the combined mechanisms can allow for effective intradermal delivery of mRNA vaccines.
PubMed: 38140019
DOI: 10.3390/pharmaceutics15122678 -
The Psychiatric Quarterly Dec 2023Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for... (Review)
Review
Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for treating BPD. This study aimed to investigate the efficacy and safety of aripiprazole in patients with BPD. On July 2, 2021, the protocol (CRD42021256647) was registered in PROSPERO. PubMed, Scopus, Web of Science, Ovid-Medline, Embase, PsycINFO, and Cochrane (CENTRAL) were searched without regard for language or publication date. We also searched trial registries on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomized clinical trials with adult patients diagnosed with BPD met the inclusion criteria. The Cochrane risk of bias for randomized trials (RoB-2) method was used to assess the quality of the included studies. We included two previously published randomized clinical trials. There were 76 patients with BPD, with 38, 12, and 26 assigned to the aripiprazole, olanzapine, and placebo groups, respectively. Most patients (88.16%) were females, with ages ranging from 22.1 to 28.14 yr. Aripiprazole has been proven to reduce anxiety, depression, anger, hostility, clinical severity, and obsessive-compulsive behavior, insecurity, melancholy, anxiety, aggressiveness/hostility, phobic anxiety, paranoid thinking, psychoticism, and somatization. The adverse effects were headache, insomnia, restlessness, tremor, and akathisia. The risk of bias was considerable in both trials, which is somewhat problematic considering that prejudice can lead to incorrect outcomes and conclusions. Aripiprazole has demonstrated encouraging outcomes in the treatment of patients with BPD. More randomized controlled studies are needed.
Topics: Adult; Female; Humans; Male; Aripiprazole; Borderline Personality Disorder; Antipsychotic Agents; Olanzapine; Anxiety Disorders
PubMed: 37566261
DOI: 10.1007/s11126-023-10045-8 -
Current Psychiatry Reports Sep 2023This examines significant trends and developments in the utilization of virtual reality (VR) and augmented reality (AR) simulations in the field of mental health and... (Review)
Review
PURPOSE OF REVIEW
This examines significant trends and developments in the utilization of virtual reality (VR) and augmented reality (AR) simulations in the field of mental health and education. The objective is to gain insights into the emerging applications of VR/AR in mental health interventions and their potential impact on patient outcomes. The review also includes personal observations on the effectiveness and challenges associated with VR/AR simulations and the rise of exciting, disruptive artificial intelligence large language models. The findings of this review contribute to the understanding of the current state of VR/AR technology in mental health and highlight potential future directions in this rapidly evolving field.
RECENT FINDINGS
Recent studies have shown that VR/AR simulation is an effective and promising approach for treating various anxiety disorders, including specific phobias, social anxiety disorder, and post-traumatic stress disorder (PTSD). Simulated environments can be tailored to induce provoking situations, allowing individuals to learn from and gradually confront and grow in controlled and safe environments. Recent findings in the field of virtual reality simulations in mental health indicate that VR/AR exposure therapy is effective for treating anxiety disorders, while interventions show promise in improving social skills in individuals working with patients. In a broader sense, the use of VR/AR as an educational tool shows enormous potential now that functional generative artificial intelligence (AI) is recently available.
Topics: Humans; Artificial Intelligence; Mental Health; Anxiety Disorders; Language; Phobia, Social
PubMed: 37624512
DOI: 10.1007/s11920-023-01438-4 -
The American Journal of Psychiatry Jun 2024Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group...
OBJECTIVE
Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).
METHODS
Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.
RESULTS
Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.
CONCLUSIONS
Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
PubMed: 38859702
DOI: 10.1176/appi.ajp.20230032 -
Archives of Women's Mental Health Oct 2023Fear of childbirth exists on a continuum of severity, and the most severe form is commonly referred to as tocophobia. Although a rare entity, tocophobia is a common...
Fear of childbirth exists on a continuum of severity, and the most severe form is commonly referred to as tocophobia. Although a rare entity, tocophobia is a common reason for requesting an elective cesarean section. It is generally considered a specific phobia but is not recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a diagnostic entity. To improve the assessment and treatment of tocophobia, research is warranted to clarify its relationship with commonly occurring psychiatric disorders in pregnancy.
Topics: Pregnancy; Female; Humans; Cesarean Section; Phobic Disorders; Parturition; Fear; Delivery, Obstetric
PubMed: 37548800
DOI: 10.1007/s00737-023-01362-9 -
Cognitive Neuropsychiatry Nov 2023Patients with functional disorders (FD) often experience cognitive problems such as forgetfulness and distractibility alongside physical symptoms that cannot be...
INTRODUCTION
Patients with functional disorders (FD) often experience cognitive problems such as forgetfulness and distractibility alongside physical symptoms that cannot be attributed to a known somatic disease.
METHOD
Test scores of cognitive tests and psychiatric rating scales of 100 outpatients diagnosed with a functional disorder were compared to a control group (n = 300) of patients with other diagnoses and to test norms for the general population.
RESULTS
Out of the 100 patients with functional disorders, 59 reported significant subjective cognitive symptoms. A moderate difference (d = 0.5-0.7) was found between the FD group mean and the population mean in processing speed tests, as well as in four psychiatric rating scales (depression, anxiety, phobias, somatisation) but there were no statistically significant differences in verbal and nonverbal reasoning or in logical memory. Somatisation and logical verbal memory scores were higher in the FD group compared to the control group.
CONCLUSION
The findings of the study suggest that a decline in processing speed is a central feature in the cognitive profile of patients with functional disorders.
Topics: Humans; Cognition; Cognition Disorders; Memory; Memory Disorders; Neuropsychological Tests; Psychiatric Status Rating Scales
PubMed: 37889124
DOI: 10.1080/13546805.2023.2275336 -
Annals of Medicine Dec 2023Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its...
BACKGROUND
Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE.
METHOD
This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis.
RESULTS
CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement ( = 25.093, <.001, =.065) and positively predicted behavioural disaffection ( = 22.169, <.001, =.057) to IPE, suggesting between-network validity.
CONCLUSIONS
Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.
Topics: Humans; Male; Female; Phobia, Social; Hong Kong; Interprofessional Education; Interprofessional Relations; Anxiety; Students
PubMed: 37166406
DOI: 10.1080/07853890.2023.2210842 -
Medicine Nov 2023Kinesiophobia is an excessive, irrational, debilitating fear of physical movement and activity caused by a sense of vulnerability to pain or re-injury, which can have a... (Review)
Review
Kinesiophobia is an excessive, irrational, debilitating fear of physical movement and activity caused by a sense of vulnerability to pain or re-injury, which can have a direct impact on physical functioning and mental well-being of patients. This paper aims to provide reliable support for future in-depth research on kinesiophobia through scientometrics and historical review. Studies on kinesiophobia published from 2002 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were used to conduct bibliometric analysis of the included studies and map knowledge domains. Keywords were manually clustered, and the results were analyzed and summarized in combination with a literature review. A total of 4157 original research articles and reviews were included. Research on kinesiophobia is developing steadily and has received more attention from scholars in recent years. There are regional differences in the distribution of research. Chronic pain is the focus of research in this field. A multidisciplinary model of pain neuroscience education combined with physical therapy based on cognitive-behavioral therapy and the introduction and development of virtual reality may be the frontier of research. There is a large space for the study of kinesiophobia. In the future, to improve regional academic exchanges and cooperation, more attention should be given to the clinical applicability and translation of scientific work, which will be conducive to improving the quality of life and physical and mental health outcomes of kinesiophobia patients.
Topics: Humans; Kinesiophobia; Quality of Life; Bibliometrics; Chronic Pain; Cognitive Behavioral Therapy
PubMed: 37932995
DOI: 10.1097/MD.0000000000035872 -
Journal of Affective Disorders Dec 2023Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder,... (Review)
Review
BACKGROUND
Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, and specific phobias. The role of functional abnormalities in the discrimination of these disorders can be tested with machine learning (ML) techniques. Here, we aim to provide a comprehensive overview of ML studies exploring the potential discriminating role of functional brain alterations identified by functional magnetic resonance imaging (fMRI) in anxiety disorders.
METHODS
We conducted a search on PubMed, Web of Science, and Scopus of ML investigations using fMRI as features in patients with anxiety disorders. A total of 12 studies (resting-state fMRI n = 5, task-based fMRI n = 6, resting-state and task-based fMRI n=1) met our inclusion criteria.
RESULTS
Overall, the studies showed that, regardless of the classifiers, alterations in functional connectivity and aberrant neural activation involving the amygdala, anterior cingulate cortex, hippocampus, insula, orbitofrontal cortex, temporal pole, cerebellum, default mode network, dorsal attention network, sensory network, and affective network were able to discriminate patients with anxiety from controls, with accuracies spanning from 36 % to 94 %.
LIMITATIONS
The small sample size, different ML approaches and heterogeneity in the selection of regions included in the multivariate pattern analyses limit the conclusions of the present review.
CONCLUSIONS
ML methods using fMRI as features can distinguish patients with anxiety disorders from healthy controls, indicating that these techniques could be used as a helpful tool for the diagnosis and the development of more targeted treatments for these disorders.
Topics: Humans; Anxiety Disorders; Phobic Disorders; Panic Disorder; Anxiety; Brain; Magnetic Resonance Imaging; Brain Mapping
PubMed: 37683943
DOI: 10.1016/j.jad.2023.09.006