-
Journal of Child and Adolescent... May 2024Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus...
The Impact of Development on Antidepressant and Placebo Response in Anxiety Disorders: A Bayesian Hierarchical Meta-Analytic Examination of Randomized Controlled Trials in Children, Adolescents, and Adults.
Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, = 5367; SSRI = 5,459) and 6232 in SNRI trials (placebo, = 3,128; SNRI = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, < 0.001). SSRIs produced similar improvements for youth and adults ( = 0.129), but SNRIs produced slower improvement in youth than adults ( = 0.018). Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.
PubMed: 38800869
DOI: 10.1089/cap.2024.0016 -
Glia Aug 2024In the central nervous system, the formation of myelin by oligodendrocytes (OLs) relies on the switch from the polymerization of the actin cytoskeleton to its...
In the central nervous system, the formation of myelin by oligodendrocytes (OLs) relies on the switch from the polymerization of the actin cytoskeleton to its depolymerization. The molecular mechanisms that trigger this switch have yet to be elucidated. Here, we identified P21-activated kinase 1 (PAK1) as a major regulator of actin depolymerization in OLs. Our results demonstrate that PAK1 accumulates in OLs in a kinase-inhibited form, triggering actin disassembly and, consequently, myelin membrane expansion. Remarkably, proteomic analysis of PAK1 binding partners enabled the identification of NF2/Merlin as its endogenous inhibitor. Our findings indicate that Nf2 knockdown in OLs results in PAK1 activation, actin polymerization, and a reduction in OL myelin membrane expansion. This effect is rescued by treatment with a PAK1 inhibitor. We also provide evidence that the specific Pak1 loss-of-function in oligodendroglia stimulates the thickening of myelin sheaths in vivo. Overall, our data indicate that the antagonistic actions of PAK1 and NF2/Merlin on the actin cytoskeleton of the OLs are critical for proper myelin formation. These findings have broad mechanistic and therapeutic implications in demyelinating diseases and neurodevelopmental disorders.
Topics: p21-Activated Kinases; Oligodendroglia; Animals; Myelin Sheath; Neurofibromin 2; Rats; Actins; Cells, Cultured; Mice; Mice, Inbred C57BL; Actin Cytoskeleton
PubMed: 38794866
DOI: 10.1002/glia.24570 -
Brain Sciences May 2024Despite the availability of pharmacotherapy and psychotherapy for treating obsessive-compulsive disorder (OCD), alternative approaches need to be explored due to the...
Neuronavigated Right Orbitofrontal 20 Hz Theta Burst Transcranial Magnetic Stimulation Augmentation for Obsessive-Compulsive Disorder with Comorbid Depression and Anxiety Disorders: An Open-Label Study.
BACKGROUND
Despite the availability of pharmacotherapy and psychotherapy for treating obsessive-compulsive disorder (OCD), alternative approaches need to be explored due to the high likelihood of treatment resistance. Neuronavigated 20 Hz theta burst stimulation (TBS-20 Hz), targeting the bilateral dorsolateral prefrontal cortex (DLPFC) augmented with the right orbitofrontal cortex (ROFC), was tested for treating OCD comorbid with depression and anxiety disorders.
METHODS
A retrospective chart review was performed on fourteen patients treated for moderate-to-severe OCD in a private outpatient clinic. Twelve patients had comorbid major depressive disorder (MDD), and thirteen patients had either generalized anxiety disorder (GAD) or panic disorder (PD). Patients completed the Y-BOCS-SR, BDI-II, and BAI rating scales weekly, which were used to measure the changes in OCD, depression, and anxiety symptoms, respectively.
RESULTS
Neuronavigated TBS-20 Hz was sequentially applied to the right DLPFC (RDLPFC), left DLPFC (LDLPFC), and ROFC. A total of 64% (9/14) of patients achieved remission from OCD (Y-BOCS-SR ≤ 14) in an average of 6.1 weeks of treatment (SD = 4.0). A total of 58% (7/12) of patients remitted from MDD (BDI < 13) in an average of 4.1 weeks (SD = 2.8), and 62% (8/13) of patients remitted from GAD/PD (BAI < 8) in an average of 4.3 weeks (SD = 2.5).
CONCLUSIONS
The neuronavigated TBS-20 Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC, significantly reduced OCD, MDD, and GAD/PD symptoms. Randomized sham controls are warranted to validate these results.
PubMed: 38790461
DOI: 10.3390/brainsci14050483 -
Comprehensive Psychiatry Aug 2024The diversity of patients' symptomatology among people seeking treatment on community-based mental health services poses significant challenges to traditional models of...
BACKGROUND
The diversity of patients' symptomatology among people seeking treatment on community-based mental health services poses significant challenges to traditional models of care. Recent approaches favor identifying transdiagnostic factors that allow a better understanding of patient heterogeneity and designing more effective and quality interventions. This study examines the heterogeneity of patients with internalizing symptoms based on profiles identified with cognitive and motivational control variables. Differences between these profiles on dimensional measures of psychopathology and quality of life are examined.
METHODS
263 patients were selected by non-probabilistic sampling procedures on mental health services in the province of Huelva (Spain). A latent class analysis on the standardized scale scores of The Behavioral Inhibition/Behavioral Activation System Scales and the Effortful Control Scale of the Adult Temperament Questionnaire Short-Form was conducted. Profiles were compared on the scores of the Inventory of Depression and Anxiety Symptoms-II, the WHO Disability Assessment Schedule II, and the Health Assessment Questionnaire SF-36.
RESULTS
The four latent profile solution is the one that showed the best fit indicators and substantive interpretability, with a kappa of 0.94 in the cross-validation procedure with 75% of the sample. No sex differences were found between the profiles (χ 5.17, p = .160). Profiles #1 and #3, both characterized by an imbalance between low activation and high inhibition, had lower well-being, lower functionality, and quality of life. When comparing profile #2 (featuring the highest inhibitory control) lower scores on most internalizing scales are observed, specially claustrophobia, social anxiety, panic mania. Profile #4 (low control, high activation, and high inhibition) showed greater scores on both mania and euphoria and lower scores on emotional role.
CONCLUSIONS
We identified four distinctive profiles that had overly increased behavioral inhibition (as expected in internalizing disorders) and differed in the degree of imbalance between inhibition and activation systems, and between motivational systems and top-down cognitive control. The profile characterized by high activation and reduced cognitive (inhibitory) control was the one showing greater mood-related symptoms and lower levels of quality of life. These profiles could be generated by treatment providers to guide clinical management in an evidence-based manner.
Topics: Humans; Quality of Life; Male; Female; Adult; Middle Aged; Motivation; Spain; Anxiety; Cognition; Depression; Surveys and Questionnaires
PubMed: 38788615
DOI: 10.1016/j.comppsych.2024.152498 -
Qualitative Research in Medicine &... Mar 2024The coronavirus pandemic provoked worldwide changes to the workplace, leading to rapid changes in lifestyles and working conditions. While organizations and governments...
The coronavirus pandemic provoked worldwide changes to the workplace, leading to rapid changes in lifestyles and working conditions. While organizations and governments struggled to develop regulations and policies, individuals were forced to find ways to manage work and life. During the pandemic and quarantine, a group of knowledge workers from around the world convened virtually and agreed to use qualitative autoethnographic methods to study how the quarantine disrupted their conventional patterns of work and care. In this article, we apply two communication perspectives-uncertainty reduction theory and re-silience-to participant diaries to understand how participants represent internal and external stressors, the efforts diarists employed to overcome those stressors, and their varying success in doing so. Post-hoc application of these communication concepts suggests that the diarists, though privileged in some ways, were not exempt from the social, professional, and emotional consequences of the pandemic and that their efforts to enact resilience were unevenly successful, especially in relation to their use of communications technology. Diarists reported struggling with uncertainty at numerous levels and that uncertainty contributed to individual emotional and cultural distress. Disruptions to work, home, and communities significantly affected wellbeing and ability to cope with challenges. Added to this were the complex and competing roles that diarists felt as they struggled to work from home, parent, and remain engaged.
PubMed: 38784526
DOI: 10.4081/qrmh.2024.11797 -
Frontiers in Neuroscience 2024Central 5-hydroxytryptaminergic dorsal raphe nucleus (5-HTDRN)-bed nucleus of stria terminalis (BNST) neural circuit dysfunction is one of the important neurobiological... (Review)
Review
Central 5-hydroxytryptaminergic dorsal raphe nucleus (5-HTDRN)-bed nucleus of stria terminalis (BNST) neural circuit dysfunction is one of the important neurobiological basis of anxiety and fear disorders. Under stress, 5-hydroxytryptamine (5-HT) neurons act on BNST receptors to attenuate anxiety and fear responses or enhance anxiety and fear. In BNST, corticotropin releasing factor neurons play a role in regulating emotions by reversely regulating excitatory or inhibitory 5-HT neurons. The composition of 5-HTDRN-BNST neural circuit, the pathological changes of 5-HTDRN-BNST neural circuit function damage under stress, and the effects of 5-HTDRN-BNST neural circuit on anxiety disorder, panic disorder and post-traumatic stress disorder were analyzed and are summarized in this paper. The characteristics of functional changes of the neural circuit and its effects on brain functional activities provide a basis and ideas for the treatment of anxiety and fear disorders through the regulation of 5-HTDRN-BNST neural circuit, and they also provide a new perspective for understanding the pathological mechanism of such diseases.
PubMed: 38784088
DOI: 10.3389/fnins.2024.1362899 -
PloS One 2024In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the...
AIM
In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the present study, we aimed to investigate the emotional responses to earthquakes using immersive virtual reality (VR), which can provide a more realistic experience.
METHODS
In total, 24 healthy young adults (12 males, 21.4 ± 0.2 years old) participated. Participants were required to watch earthquake and neutral videos while wearing a head-mounted display and near-infrared spectroscopy (NIRS), during which physiological signals, including pulse rate and cerebral blood flow (CBF) in the dorsolateral prefrontal cortex, were measured. We also analyzed changes in sympathetic and parasympathetic indices and obtained seven emotion ratings: valence, arousal, dominance, fear, astonishment, anxiety, and panic.
RESULTS
The VR earthquake videos evoked negative subjective emotions, and the pulse rate significantly decreased. Sympathetic nerve activity tended to decrease, whereas CBF in the left prefrontal cortex showed a slight increase, although this was not significant.
CONCLUSIONS
This study showed that measurements combined with NIRS and immersive VR have the potential to capture emotional responses to different stimuli.
Topics: Humans; Earthquakes; Male; Spectroscopy, Near-Infrared; Emotions; Virtual Reality; Female; Young Adult; Heart Rate; Cerebrovascular Circulation; Adult; Prefrontal Cortex; Arousal
PubMed: 38781193
DOI: 10.1371/journal.pone.0304107 -
Psychological Services May 2024The COVID-19 pandemic led many in-office therapeutic programs to pivot to virtual programming without empirical data supporting the acceptability and efficacy of the...
The COVID-19 pandemic led many in-office therapeutic programs to pivot to virtual programming without empirical data supporting the acceptability and efficacy of the remote-delivered adaptations. These adaptations were essential for continuing care and addressing surging youth psychological problems at the time. To serve adolescents with comorbid psychiatric disorders and associated problems (e.g., emotion dysregulation), we adapted and implemented virtual and hybrid formats of a dialectical behavior therapy for adolescents (DBT-A; Rathus & Miller, 2015) program within a public university training clinic, such as separating the traditional multifamily group into adolescent-only and caregiver-only groups. Building on qualitative reports on virtual DBT-A, we explored preliminary service user and clinical outcomes of the virtual and hybrid DBT-A adolescent skills group component in a longitudinal retrospective cohort study for teenagers treated during the first 2 years of the pandemic ( = 21; 81% Hispanic/Latinx; 100% White). Aim 1 described service user outcomes (e.g., retention, group cohesion, client satisfaction) in the remote-delivered skills groups. Most youth completed treatment. Caregiver satisfaction was high, whereas adolescent satisfaction was mild. Aim 2 explored preliminary clinical outcomes of remote-delivered skills group adaptations. Overall anxiety, panic, and two emotion regulation facets (i.e., emotional awareness; goal pursuit when upset) significantly reduced across treatment. There were no significant reductions in depression. No suicide attempts or suicides occurred during the program. Further work is needed to clarify the efficacy of telehealth formats of DBT-A skills groups in larger, more racially diverse samples and to identify which adolescents are most appropriate for virtual and/or hybrid DBT-A. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38780559
DOI: 10.1037/ser0000863 -
Frontiers in Psychiatry 2024Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals... (Review)
Review
Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.
PubMed: 38779550
DOI: 10.3389/fpsyt.2024.1296569