A scalable spiking amygdala model that explains fear conditioning, extinction, renewal and generalization.

The amygdala (AMY) is widely implicated in fear learning and fear behaviour, but it remains unclear how the many biological components present within AMY interact to achieve these abilities. Building on previous work, we hypothesize that individual AMY nuclei represent different quantities and that fear conditioning arises from error-driven learning on the synapses between AMY nuclei. We present a computational model of AMY that (a) recreates the divisions and connections between AMY nuclei and their constituent pyramidal and inhibitory neurons; (b) accommodates scalable high-dimensional representations of external stimuli; (c) learns to associate complex stimuli with the presence (or absence) of an aversive stimulus; (d) preserves feature information when mapping inputs to salience estimates, such that these estimates generalize to similar stimuli; and (e) induces a diverse profile of neural responses within each nucleus. Our model predicts (1) defensive responses and neural activities in several experimental conditions, (2) the consequence of artificially ablating particular nuclei and (3) the tendency to generalize defensive responses to novel stimuli. We test these predictions by comparing model outputs to neural and behavioural data from animals and humans. Despite the relative simplicity of our model, we find significant overlap between simulated and empirical data, which supports our claim that the model captures many of the neural mechanisms that support fear conditioning. We conclude by comparing our model to other computational models and by characterizing the theoretical relationship between pattern separation and fear generalization in healthy versus anxious individuals.

Abstract task sequence initiation deficit dissociates anxiety disorders from obsessive-compulsive disorder and healthy controls.

In everyday life, humans perform sequences of tasks. These tasks may be disrupted in people with obsessive-compulsive disorder (OCD). Symptoms, such as compulsions, can be considered sequential and often cause repetitions of tasks that disrupt daily living (e.g., checking the stove while cooking). Motor sequences have been used to study behavioral deficits in OCD. However, not all sequences are motor sequences. Some are more "abstract" in that they are composed of a series of tasks (e.g., chopping and stirring) rather than being dependent on individual actions or stimuli. These abstract task sequences require cognitive control mechanisms for their execution. Although theory has proposed deficits in these sequences in OCD as well, they have not been directly investigated. We tested the hypotheses that OCD participants exhibit deficits in the control mechanisms specific to abstract task sequences and more general flexible behavior (measured with task switching within the sequences), relative to health controls (HCs) and clinical controls (participants with anxiety disorders [ANX]). A total of 112 participants completed abstract task sequences consisting of simple categorization tasks. Surprisingly, participants with OCD did not perform worse than HCs or ANX. However, ANX participants showed impairments specific to sequential control that did not extend to more general flexible control. Thus, we showed a novel behavioral dissociation between OCD and ANX specific to abstract task sequential control. These results also implicate deficits in specific frontal sequential control neural circuitry in ANX and not in OCD, where implicit sequential deficits may more closely align with striatal circuits.

Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.

BACKGROUND: There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event. METHODS: During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses. RESULTS: Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions. CONCLUSIONS: Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Correspondence to Antici et al. Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

The study by Antici et al. (2024) investigates the effects of virtual reality exposure therapy on social anxiety disorder (SAD), focusing on the relationship between C-reactive protein (CRP) levels in saliva and therapy outcomes. Findings indicate that this therapy not only reduces SAD symptoms and discomfort but also correlates with decreased systemic inflammation, as evidenced by lowered CRP levels. Remarkably, higher baseline CRP levels predicted a greater reduction in anxiety symptoms, suggesting a unique response pattern in SAD compared to other psychological disorders. This study highlights systemic inflammation's significance in SAD and the promise of non-invasive biomarkers like salivary CRP for managing psychological disorders. It calls for more research to understand the underlying mechanisms and validate these initial findings.

Social fear extinction susceptibility is associated with Microbiota-Gut-Brain axis alterations.

Social anxiety disorder is a common psychiatric condition that severely affects quality of life of individuals and is a significant societal burden. Although many risk factors for social anxiety exist, it is currently unknown how social fear sensitivity manifests biologically. Furthermore, since some individuals are resilient and others are susceptible to social fear, it is important to interrogate the mechanisms underpinning individual response to social fear situations. The microbiota-gut-brain axis has been associated with social behaviour, has recently been linked with social anxiety disorder, and may serve as a therapeutic target for modulation. Here, we assess the potential of this axis to be linked with social fear extinction processes in a murine model of social anxiety disorder. To this end, we correlated differential social fear responses with microbiota composition, central gene expression, and immune responses. Our data provide evidence that microbiota variability is strongly correlated with alterations in social fear behaviour. Moreover, we identified altered gene candidates by amygdalar transcriptomics that are linked with social fear sensitivity. These include genes associated with social behaviour (Armcx1, Fam69b, Kcnj9, Maoa, Serinc5, Slc6a17, Spata2, and Syngr1), inflammation and immunity (Cars, Ckmt1, Klf5, Maoa, Map3k12, Pex5, Serinc5, Sidt1, Spata2), and microbe-host interaction (Klf5, Map3k12, Serinc5, Sidt1). Together, these data provide further evidence for a role of the microbiota-gut-brain axis in social fear responses.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Associations between soluble urokinase plasminogen activator receptor (suPAR) concentration and psychiatric disorders - A systematic review and meta-analysis.

BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. METHOD: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). DISCUSSION: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population.

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two-fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

Emotional Changes during Imagery Rescripting of Aversive Social Memories in Social Anxiety Disorder: A Randomized Controlled Trial.

INTRODUCTION: Imagery rescripting (ImRs) is a psychotherapeutic intervention targeting aversive memories. During the three-phase intervention, patients reexperience their aversive memory (phase 1), observe the scene from their adult perspective, and intervene to help their former selves (phase 2), and reexperience it again with the positive changes (phase 3). Previous studies have rarely investigated emotional and regulatory processes taking place during the intervention. OBJECTIVE: This randomized controlled trial investigated self-reported affective and physiological responses during ImRs. METHODS: Seventy-seven patients with social anxiety disorder (SAD) were randomly assigned to a single session of ImRs or a control intervention (recall and discussion of the memory) targeting an aversive social memory. Heart rate (HR) and heart rate variability (HRV) were assessed during and post hoc ratings of positive and negative feelings after baseline and the intervention phases. RESULTS: Relative to the control intervention, ImRs resulted in an initial increase in negative feelings from baseline to phase 1 and a following larger (phase 1 to phase 2) and more stable (phase 2 to phase 3) decrease in negative feelings/increase in positive feelings. On the physiological level, during ImRs compared to the control intervention, mean HR was significantly higher during phase 1 and HRV during phase 3, each compared to baseline. CONCLUSIONS: These results provide further information about the specific sequence of emotional responses on different response levels during ImRs, being consistent with known theories of emotional processing and supposed mechanisms of ImRs.

Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Illness Anxiety Disorder: A Review of the Current Research and Future Directions.

PURPOSE OF REVIEW: We review recent evidence on Illness Anxiety Disorder (IAD), including risk factors and precipitants, diagnostic classification, clinical characteristics of the disorder, and assessment and treatment in both children and adults. RECENT FINDINGS: IAD places a substantial burden on both individuals and society. Despite its impact, understanding of the disorder is lacking and debates remain about whether IAD should be classified as an anxiety disorder and whether it is distinct from Somatic Symptom Disorder. Cognitive behavioural therapy (CBT) is an effective treatment for IAD and there are multiple validated measures of health anxiety available. However, research on health anxiety in children and youth is limited. IAD is chronic, and debilitating, but when identified, it can be effectively treated with CBT. Research using DSM-5 IAD criteria is lacking, and more research is needed to better understand the disorder, particularly in children and youth.

Anxiety and depression symptoms among patients with long COVID: a retrospective cohort study.

Patients suffering from post-acute sequelae of COVID-19 (PASC) have a higher prevalence of anxiety and depression than the general population. The long-term trajectory of these sequelae is still unfolding. To assess the burden of anxiety and depression among patients presenting to the University of Iowa Hospitals and Clinics (UIHC) post-COVID-19 clinic, we analyzed how patient factors influenced Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scores. In this retrospective cohort study, the GAD-7 and PHQ-9 questionnaire scores of patients presenting to the UIHC post-COVID clinic between March 2021-February 2022 (N = 455) were compared to the scores of a sample of patients presenting to the general internal medicine (GIM) clinic during the same period (N = 94). Our analysis showed that patients with an absent history of depression on their electronic medical record (EMR) problem list scored significantly higher on the GAD-7 (mean difference -1.62, 95% CI -3.12 to -0.12, p = 0.034) and PHQ-9 (mean difference -4.45, 95% CI -5.53 to -3.37, p < 0.001) questionnaires compared to their similar counterparts in the GIM clinic. On the other hand, patients with an absent history of anxiety on their EMR problem list scored significantly higher on the GAD-7 (mean difference -2.90, 95% CI -4.0 to -1.80, p < 0.001) but not on the PHQ-9 questionnaire (p = 0.196). Overall, patients with PASC may have experienced a heavier burden of newly manifest anxiety and depression symptoms compared to patients seen in the GIM clinic. This suggests that the mental health impacts of PASC may be more pronounced in patients with no prior history of anxiety or depression.

Altered single-subject gray matter structural networks in social anxiety disorder.

Previous fMRI studies have reported more random brain functional graph configurations in social anxiety disorder (SAD). However, it is still unclear whether the same configurations would occur in gray matter (GM) graphs. Structural MRI was performed on 49 patients with SAD and on 51 age- and gender-matched healthy controls (HC). Single-subject GM networks were obtained based on the areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared, and the structure-function coupling was examined. These network measures were further correlated with the clinical characteristics in the SAD group. Compared with controls, the SAD patients demonstrated globally decreased clustering coefficient and characteristic path length. Altered topological properties were found in the fronto-limbic and sensory processing systems. Altered metrics were associated with the illness duration of SAD. Compared with the HC group, the SAD group exhibited significantly decreased structural-functional decoupling. Furthermore, structural-functional decoupling was negatively correlated with the symptom severity in SAD. These findings highlight less-optimized topological configuration of the brain structural networks in SAD, which may provide insights into the neural mechanisms underlying the excessive fear and avoidance of social interactions in SAD.

Disrupted brain gray matter connectome in social anxiety disorder: a novel individualized structural covariance network analysis.

Phenotyping approaches grounded in structural network science can offer insights into the neurobiological substrates of psychiatric diseases, but this remains to be clarified at the individual level in social anxiety disorder (SAD). Using a recently developed approach combining probability density estimation and Kullback-Leibler divergence, we constructed single-subject structural covariance networks (SCNs) based on multivariate morphometry (cortical thickness, surface area, curvature, and volume) and quantified their global/nodal network properties using graph-theoretical analysis. We compared network metrics between SAD patients and healthy controls (HC) and analyzed the relationship to clinical characteristics. We also used support vector machine analysis to explore the ability of graph-theoretical metrics to discriminate SAD patients from HC. Globally, SAD patients showed higher global efficiency, shorter characteristic path length, and stronger small-worldness. Locally, SAD patients showed abnormal nodal centrality mainly involving left superior frontal gyrus, right superior parietal lobe, left amygdala, right paracentral gyrus, right lingual, and right pericalcarine cortex. Altered topological metrics were associated with the symptom severity and duration. Graph-based metrics allowed single-subject classification of SAD versus HC with total accuracy of 78.7%. This finding, that the topological organization of SCNs in SAD patients is altered toward more randomized configurations, adds to our understanding of network-level neuropathology in SAD.

How much do adverse childhood experiences contribute to adolescent anxiety and depression symptoms? Evidence from the longitudinal study of Australian children.

This study aims to: (i) examine the association between adverse childhood experiences (ACEs) and elevated anxiety and depressive symptoms in adolescents; and (ii) estimate the burden of anxiety and depressive symptoms attributable to ACEs.Data were analyzed from 3089 children followed between Waves 1 (age 4-5 years) and 7 (16-17 years) of the Longitudinal Study of Australian Children. Logistic regression was used to estimate the associations between ACEs and child-reported elevated anxiety and depressive symptoms at age 16-17. Anxiety and depressive symptoms were measured using the Children's Anxiety Scale and Short Mood and Feelings Questionnaire, respectively. The punaf command available in STATA 14 was used to calculate the population attributable fraction (PAF).Before the age of 18 years, 68.8% of the children had experienced two or more ACEs. In the analysis adjusted for confounding factors, including co-occurring ACEs, both history and current exposure to bullying victimisation and parental psychological distress were associated with a statistically significant increased likelihood of elevated anxiety and depressive symptoms at age 16-17. Overall, 47% of anxiety symptoms (95% CI for PAF: 35-56) and 21% of depressive symptoms (95% CI: 12-29) were attributable to a history of bullying victimisation. Similarly, 17% (95% CI: 11-25%) of anxiety and 15% (95% CI: 4-25%) of depressive symptoms at age 16-17 years were attributable to parental psychological distress experienced between the ages of 4-15 years.The findings demonstrate that intervention to reduce ACEs, especially parental psychological distress and bullying victimisation, may reduce the substantial burden of mental disorders in the population.

Psychometrics of the Korean Version of the screen for adult anxiety related disorders (SCAARED).

BACKGROUND: For enhanced management of anxiety disorders, early screening and accurate diagnostic differentiation are essential. The Screen for Adult Anxiety Related Disorders (SCAARED) has been developed to identify and categorize anxiety disorders, thereby facilitating timely and appropriate interventions. In line with this, we aimed to translate and validate the Korean version of the SCAARED questionnaire for the Korean population. METHODS: The original SCAARED was translated into Korean and administered to community adult population (N = 119) ages 18-45 years old in South Korea. The internal consistency and test-retest reliability of the SCAARED were evaluated. In addition, its factor structure was examined using confirmatory and exploratory factor analysis. Concurrent validity was evaluated by comparing SCAARED with the Depression, Anxiety and Stress Scale-21 (DASS), the Beck's Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI). Test-retest reliability was evaluated one week after the first assessment. RESULTS: The SCAARED showed good internal consistency (Cronbach's α = 0.945) and test-retest reliability (γ = 0.883). The SCAARED had significant correlation with DASS-21 subscales (γ = 0.655-0.701), BAI (γ = 0.788) and STAI subscales (γ = 0.548-0.736), confirming good concurrent validity. The results of the Exploratory Factor Analysis showed four factors comparable to the original SCAARED (Generalized anxiety, Somatic/Panic/Agoraphobia, Social anxiety, and Separation anxiety). The area under the curve of the receiver operating characteristic of total and each of the factor scores ranged from 0.724 to 0.942. CONCLUSIONS: The Korean version of the SCAARED is a reliable and valid instrument to screen for anxiety disorders in the Korean adult populations.

Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study.

BACKGROUND: Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD. METHODS: This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits. RESULTS: We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores (r=-0.315, p = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 (p < 0.001) with 80.65% sensitivity and 62.79% specificity at a cutoff value of 33.93 pg/ml. Conversely, we noticed elevated serum IL-2 levels in GAD patients than in HCs (14.81 ± 2.88 pg/ml vs. 8.08 ± 1.1 pg/ml); however, it failed to maintain any significant association with GAD-7 scores, implying that IL-2 might not be involved in GAD pathogenesis. The lower AUC value (0.640; p > 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD. CONCLUSION: This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.

Temporal network of experience sampling methodology identifies sleep disturbance as a central symptom in generalized anxiety disorder.

BACKGROUND: A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. METHODS: A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. RESULTS: In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. CONCLUSIONS: This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Association between watching eating broadcasts like mukbang and cookbang and generalized anxiety disorder among Korean adolescents.

BACKGROUND: Anxiety disorders are common during adolescence; therefore, detecting anxiety disorders among adolescents and providing appropriate treatment are crucial. Studies have suggested that watching online audiovisual broadcasts like mukbang and cookbang (hereafter mukbang), where hosts eat or cook food, may influence anxiety disorders. However, there is insufficient research on the association between watching mukbang and generalized anxiety disorder (GAD). Therefore, we investigated the association between watching mukbang and GAD among Korean adolescents. METHODS: We analyzed 51,764 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-Based Survey (KYRBS). The participants were asked how frequently they watched mukbang per week over the past 12 months. Anxiety disorders were assessed using the generalized anxiety disorder-7 (GAD-7) questionnaire. A multiple logistic regression analysis was performed after adjusting for confounding variables. RESULTS: The prevalence of GAD was higher among adolescents who watched mukbang compared to those who did not (aOR: 1.100, 95% CI: 1.026-1.180, P = 0.008 in male participants; aOR: 1.090, 95% CI: 1.003-1.185, P = 0.042 in female participants). The frequency of watching mukbang showed a dose-dependent relationship with a greater likelihood of GAD in female adolescents. CONCLUSION: This study's results showed that watching mukbang is associated with GAD in Korean adolescents. Proper interventions for mental health are needed for adolescents who watch mukbang.

Prevalence and correlates of generalized anxiety disorder and perceived stress among Sudanese medical students.

BACKGROUND: Generalized Anxiety Disorder (GAD) causes significant disturbance in an individual's well-being and activity. Whereby, interfering with the dynamic progress in life. Also, anxiety is a product of stress and a major predictor of academic performance. This study aimed to assess the prevalence of Generalized Anxiety Disorder (GAD), measure levels of anxiety and perceived stress, evaluate the academic profile, identify lifestyle characteristics, and explore the relationship between these factors. METHODS: In this cross-sectional study, 340 Sudanese medical students filled out online questionnaires, composed of the sociodemographic and lifestyle characteristics, academic profile, Generalized Anxiety Disorder-2 scale (GAD-2), and Perceived Stress Scale-10 (PSS-10). Descriptive and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 20.0 for data analysis. RESULTS: Of 340 medical students, 3.8% of them were diagnosed with GAD, while 29.1% scored ≥ 3 in GAD-2, indicating a possible diagnosis. The study found that 9.7% of the participants used addictive substances, with 42% of them having high GAD-2 scores. Moreover, high anxiety levels were associated with high-stress scores (p-value = 0.000). Also, high GAD-2 scores were significantly associated with students who spent less than 10,000 SDG (18 USD) weekly, spent more time on entertainment using smart devices (p-value = 0.004), and had an unhealthy diet (p-value = 0.004). Low anxiety levels were associated with better sleep quality (p-value = 0.00), satisfaction with religious practices (p-value = 0.00), and increased leisure/hobby time (p-value = 0.018). High-stress levels were observed in females (p-value = 0.035), those with lower academic performance satisfaction levels, and increased hours of smart device usage for entertainment (p-value = 0.001). Reduced stress levels were associated with being ≥ 23 years old, increased leisure/hobby time (p-value = 0.002), satisfaction with religious practices [F(3, 166.6) = 10.8, p-value = 0.00)], and having a healthy diet (p-value = 0.006). CONCLUSION: The low prevalence of GAD corresponded with previous literature, but 29.1% of medical students had a high probability of having GAD. The study emphasizes on providing accessible mental health services for medical students and interventions addressing modifiable risk factors.