Rapid synaptic and gamma rhythm signature of mouse critical period plasticity.

Early-life experience enduringly sculpts thalamocortical (TC) axons and sensory processing. Here, we identify the very first synaptic targets that initiate critical period plasticity, heralded by altered cortical oscillations. Monocular deprivation (MD) acutely induced a transient (<3 h) peak in EEG γ-power (~40 Hz) specifically within the visual cortex, but only when the critical period was open (juvenile mice or adults after dark-rearing, Lynx1-deletion, or diazepam-rescued GAD65-deficiency). Rapid TC input loss onto parvalbumin-expressing (PV) inhibitory interneurons (but not onto nearby pyramidal cells) was observed within hours of MD in a TC slice preserving the visual pathway - again once critical periods opened. Computational TC modeling of the emergent γ-rhythm in response to MD delineated a cortical interneuronal gamma (ING) rhythm in networks of PV-cells bearing gap junctions at the start of the critical period. The ING rhythm effectively dissociated thalamic input from cortical spiking, leading to rapid loss of previously strong TC-to-PV connections through standard spike-timing-dependent plasticity rules. As a consequence, previously silent TC-to-PV connections could strengthen on a slower timescale, capturing the gradually increasing γ-frequency and eventual fade-out over time. Thus, ING enables cortical dynamics to transition from being dominated by the strongest TC input to one that senses the statistics of population TC input after MD. Taken together, our findings reveal the initial synaptic events underlying critical period plasticity and suggest that the fleeting ING accompanying a brief sensory perturbation may serve as a robust readout of TC network state with which to probe developmental trajectories.

The effect of intra spinal administration of cerium oxide nanoparticles on central pain mechanism: An experimental study.

This study investigated Cerium oxide nanoparticles (CeONPs) effect on central neuropathic pain (CNP). The compressive method of spinal cord injury (SCI) model was used for pain induction. Three groups were formed by a random allocation of 24 rats. In the treatment group, CeONPs were injected above and below the lesion site immediately after inducing SCI. pain symptoms were evaluated using acetone, Radian Heat, and Von Frey tests weekly for six weeks. Finally, we counted fibroblasts using H&E staining. We evaluated the expression of Cx43, GAD65 and HDAC2 proteins using the western blot method. The analysis of results was done by PRISM software. At the end of the study, we found that CeONPs reduced pain symptoms to levels similar to those observed in normal animals. CeONPs also increased the expression of GAD65 and Cx43 proteins but did not affect HDAC2 inhibition. CeONPs probably have a pain-relieving effect on chronic pain by potentially preserving GAD65 and Cx43 protein expression and hindering fibroblast infiltration.

The GABA shunt contributes to ROS homeostasis in guard cells of Arabidopsis.

γ-Aminobutyric acid (GABA) accumulates rapidly under stress via the GABA shunt pathway, which has been implicated in reducing the accumulation of stress-induced reactive oxygen species (ROS) in plants. γ-Aminobutyric acid has been demonstrated to act as a guard-cell signal in Arabidopsis thaliana, modulating stomatal opening. Knockout of the major GABA synthesis enzyme Glutamate Decarboxylase 2 (GAD2) increases the aperture of gad2 mutants, which results in greater stomatal conductance and reduces water-use efficiency compared with wild-type plants. Here, we found that the additional loss of GAD1, GAD4, and GAD5 in gad2 leaves increased GABA deficiency but abolished the more open stomatal pore phenotype of gad2, which we link to increased cytosolic calcium (Ca2+ ) and ROS accumulation in gad1/2/4/5 guard cells. Compared with wild-type and gad2 plants, glutamate was ineffective in closing gad1/2/4/5 stomatal pores, whereas lowering apoplastic calcium, applying ROS inhibitors or complementation with GAD2 reduced gad1/2/4/5 guard-cell ROS, restored the gad2-like greater stomatal apertures of gad1/2/4/5 beyond that of wild-type. We conclude that GADs are important contributors to ROS homeostasis in guard cells likely via a Ca2+ -mediated pathway. As such, this study reveals greater complexity in GABA's role as a guard-cell signal and the interactions it has with other established signals.

Lactococcus lactis CNCM I-5388 versus NCDO2118 by its GABA hyperproduction ability, counteracts faster stress-induced intestinal hypersensitivity in rats.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by its main symptom, visceral hypersensitivity (VH), which is aggravated by stress. Gut-brain interactions and gut bacteria may alleviate IBS symptoms, including VH. γ-amino butyric acid (GABA), produced notably by lactic acid bacteria (LAB), shows promising result in IBS symptoms treatment. In bacteria, GABA is generated through glutamate decarboxylase (GAD) metabolism of L-glutamic acid, maintaining intracellular pH. In mammals, GABA acts as an inhibitory neurotransmitter, modulating pain, stress, and anxiety. Therefore, utilizing GABA-producing LAB as a therapeutic approach might be beneficial. Our previous work showed that a GABA-producing Lactococcus lactis strain, NCDO2118, reduced VH induced by acute stress in rats after a 10-day oral treatment. Here, we identified the strain CNCM I-5388, with a four-fold higher GABA production rate under the same conditions as NCDO2118. Both strains shared 99.1% identical GAD amino acid sequences and in vitro analyses revealed the same optimal pH for GAD activity; however, CNCM I-5388 exhibited 17 times higher intracellular GAD activity and increased resistance to acidic pH. Additionally, in vivo experiments have demonstrated that CNCM I-5388 has faster anti-VH properties in rats compared with NCDO2118, starting from the fifth day of treatment. Finally, CNCM I-5388 anti-VH effects partially persisted after 5-day treatment interruption and after a single oral treatment. These findings highlight CNCM I-5388 as a potential therapeutic agent for managing VH in IBS patients.

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Senegenin regulates the mechanism of insomnia through the Keap1/Nrf2/PINK1/Parkin pathway mediated by GAD67.

GAD67 impacts insomnia as a key enzyme catalysing the conversion of glutamate (Glu) to gamma-aminobutyric acid (GABA). Senegenin enhances neuroprotection and is used widely to treat insomnia and other neurological diseases. This study aimed to investigate how senegenin regulates insomnia through a GAD67-mediated signalling pathway. We measured GAD67 expression levels in insomnia patients and evaluated the expression levels of GAD67 and Keap1/Nrf2/Parkin/PINK1-related cytokines following GAD67 lentiviral transfection in PC12 cells and in rat models. We also assessed cellular reactive oxygen species (ROS) and mitochondrial membrane potential levels. Additionally, EEG/EMG was used to analyse the sleep phases of rats and to assess memory and exploration functions. Pathological changes and the expression of GAD67 and sleep-related proteins in the hippocampus were examined. The results showed that GAD67 expression was increased in insomnia patients, ROS levels were elevated, and the mitochondrial membrane potential was decreased in the GAD67-KD group. Insomnia rats exhibited changes in sleep rhythm, learning, and exploration dysfunction, pathological changes in the CA1 region of the hippocampus, and differential expression of GAD67 and sleep-related factors. Inhibitory neurofactor expression levels were decreased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Conversely, excitatory factor expression levels were increased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Senegenin intervention modulated cytokine expression levels. In conclusion, GAD67 negatively regulates insomnia, and senegenin can regulate insomnia by mediating the expression of cytokines in the GAD67-regulated Keap1/Nrf2/Parkin/PINK1 pathway.

Antibodies against glutamic acid decarboxylase in intravenous immunoglobulin preparations can affect the diagnosis of type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulins (IVIgs) contain various autoantibodies, including those against glutamic acid decarboxylase (GADAb), a valuable biomarker of type 1 diabetes mellitus. Passive transfer of GADAb from IVIgs to patients poses a risk of misdiagnosis, and information on the specific titres of GADAb and their impact on diagnostic accuracy remains limited. This study aimed to provide further insights into the origin of GADAb detected in patient serum following IVIg infusion. MATERIALS AND METHODS: GADAb titres in IVIg products from Japan and the United States were measured using enzyme-linked immunosorbent assay-based assays. For reliable quantification, GADAb titres in pooled plasma were quantified and compared with those in the IVIg products. The determined titres were used to estimate the likelihood of passively detecting acquired GADAb in individuals receiving IVIgs. RESULTS: GADAbs were prevalent in IVIg products; however, the titres varied significantly among different lots and products. Importantly, IVIg-derived GADAb was estimated to remain detectable in patient serum for up to 100 days following a dosage of 2000 mg/kg. CONCLUSION: Clinicians should consider that IVIg preparations may contain GADAb, which can lead to false-positive results in serological assays. Careful interpretation of the assay results is key to the definitive diagnosis of type 1 diabetes mellitus.

The natural history of lifetime psychiatric disorders in patients with obsessive-compulsive disorder followed over half a century.

OBJECTIVE: Few long-term studies have examined the life-time prevalence of comorbid psychiatric conditions in patients with obsessive-compulsive disorder (OCD). We therefore studied the frequency of comorbid psychiatric disorders, and their relation to onset and prognosis, in patients with OCD who were followed for almost half a century. METHODS: During 1947-1953, 285 OCD patients were admitted as inpatients to a university hospital in Gothenburg, Sweden. Among those, 251 (88%) accepted a structured comprehensive psychiatric examination in 1954-1956. In 1989-1993, 176 survivors were eligible and 144 (response rate 82%) were re-examined. The same psychiatrist performed both examinations. OCD was diagnosed according to the Schneider criteria, and other mental disorders according to DSM-IV. Mean follow-up since onset was 47 years. RESULTS: The lifetime frequency of depressive disorders was 84.7% (major depression 43.8%), generalized anxiety disorder (GAD) 71.5%, panic anxiety disorder 47.9%, agoraphobia 52.1%, specific phobias 64.6%, social phobia 47.9%, paranoid conditions 40.3% (29.1% paranoid ideation), psychotic disorders 15.3%, alcohol abuse 13.2% (men 39%, women 3%) and substance abuse 17.4%. Specific phobia most often started before OCD, while depression had a varied onset in relation to OCD. Social phobia, agoraphobia, GAD, alcohol and substance abuse, psychotic disorders and paranoid conditions most often started after OCD. Presence of GAD, psychotic disorder and substance abuse worsened prognosis of OCD. CONCLUSION: Comorbid psychiatric conditions are common in OCD patients, and have onset throughout the course. OCD signals vulnerability for other psychiatric conditions, which are important to detect in clinical practice as they negatively affect the outcome.

Truncation of the calmodulin binding domain in rice glutamate decarboxylase 4 (OsGAD4) leads to accumulation of γ-aminobutyric acid and confers abiotic stress tolerance in rice seedlings.

GABA (Gamma-aminobutyric acid) is a non-protein amino acid widely known as major inhibitory neurotransmitter. It is synthesized from glutamate via the enzyme glutamate decarboxylase (GAD). GAD is ubiquitous in all organisms, but only plant GAD has ability to bind Ca2+/calmodulin (CaM). This kind of binding suppresses the auto-inhibition of Ca2+/calmodulin binding domain (CaMBD) when the active site of GAD is unfolded resulting in stimulated GAD activity. OsGAD4 is one of the five GAD genes in rice genome. It was confirmed that OsGAD4 has ability to bind to Ca2+/CaM. Moreover, it exhibits strongest expression against several stress conditions among the five OsGAD genes. In this study, CRISPR/Cas9-mediated genome editing was performed to trim the coding region of CaMBD from the OsGAD4 gene, to remove its autoinhibitory function. DNA sequence analysis of the genome edited rice plants revealed the truncation of CaMBD (216 bp). Genome edited line (#14-1) produced 11.26 mg GABA/100 g grain, which is almost nine-fold in comparison to wild type. Short deletion in the coding region for CaMBD yielded in mutant (#14-6) with lower GABA content than wild type counterpart. Abiotic stresses like salinity, flooding and drought significantly enhanced GABA accumulation in #14-1 at various time points compared to wild-type and #14-6 under the same stress conditions. Moreover, upregulated mRNA expression in vegetative tissues seems correlated with the stress-responsiveness of OsGAD4 when exposed to the above-mentioned stresses. Stress tolerance of OsGAD4 genome edited lines was evidenced by the higher survival rate indicating the gene may induce tolerance against abiotic stresses in rice. This is the first report on abiotic stress tolerance in rice modulated by endogenous GABA. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01460-1.

GAD1 ameliorates glioma progression through regulating cuproptosis via RAS/MAPK pathway.

Glioma represents a primary malignant tumor occurring in the central nervous system. Glutamate decarboxylase (GAD1) plays a significant role in tumor development; however, its function of GAD1 and underlying mechanisms in glioma progression remain unclear. Differentially expressed genes (DEGs) obtained from the GSE12657 and GSE15209 datasets that intersected with cuproptosis-related genes and pivot genes were identified using comprehensive bioinformatics methods. The elesclomol (ES) treatment was used to induce cuproptosis in U251 cells, which was validated by detecting intracellular copper levels and cuproptosis marker expression. Lentivirus-mediated gene overexpression was performed to explore the effects of GAD1 using functional assays in vitro and in a mouse xenograft model. The RAS agonist ML098 was used to verify the effect of GAD1 on the RAS/MAPK pathway in glioma cells. A total of 87 cuproptosis-related DEGs and seven hub genes were obtained, with five genes upregulated and two were downregulated in gliomas. Overexpression of GAD1 inhibited proliferation, invasion, and migration, promoted apoptosis of glioma cells, and suppressed tumorigenesis in vivo. In addition, GAD1 overexpression enhanced the sensitivity of glioma cells to cuproptosis. Additionally, ML098 treatment attenuated the inhibitory effect of GAD1 overexpression on the malignant phenotype of ES-treated cells. GAD1 plays an anti-oncogenic role in glioma by regulating apoptosis via inhibition of the RAS/MAPK pathway.

Impact of Baseline Anxiety on Well-being in People with Post-COVID-19 Condition: A Secondary Analysis.

BACKGROUND: Post-COVID-19 condition (PCC) is associated with a host of psychopathological conditions including prominent anxiety symptoms. However, it is not known what effect anxious symptoms have on measures of well-being in individuals living with PCC. This study aims to evaluate anxiety's association with measures of well-being in people with PCC. METHODS: This is a post hoc analysis utilizing data from a placebo-controlled, randomized, double-blind clinical trial assessing the effect of vortioxetine on cognitive impairment in individuals with PCC (NCT05047952). Baseline data with respect to anxiety and well-being were collected using the Generalized Anxiety Disorder Scale, 7-Item (GAD-7), and the World Health Organization (WHO) Well-Being Index, 5-Item (WHO-5), respectively. A generalized linear model (GLM) analysis on baseline GAD-7 and WHO-5 scores was conducted with age, sex, employment status, education level, previous major depressive disorder (MDD) diagnosis, and confirmed COVID-19 cases as covariates. RESULTS: Data was analyzed in a sample of 144 participants (N = 144). After controlling for the aforementioned covariates, the results found that GAD-7 and WHO-5 scores had a significant negative correlation (ß = -0.053, p = <0.001), signifying that increased anxiety had adverse effects on the overall well-being of individuals with PCC. CONCLUSION: Herein, we observed a clinically meaningful level of anxiety in individuals with PCC. We also identified a robust correlation between anxiety in PCC and measures of general well-being. Our results require replication, providing the impetus for recommending screening and targeting anxious symptoms as a tactic to improve general well-being and outcomes in individuals with PCC.

Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts.

Opioid addiction is a global problem that has been exacerbated in the USA and Europe by the COVID-19 pandemic. The globus pallidus (GP) plays a prominent neurobiological role in the regulation of behaviour as an output station of the striato-pallidal system. GABAergic large projection neurons are the main neuronal type in the external (EGP) and internal (IGP) parts of the GP, where addiction-specific molecular and functional abnormalities occur. In these neurons, glutamate decarboxylase (GAD) with isoforms GAD 65 and 67 is a key enzyme in GABA synthesis, and experimental studies suggest GAD dysregulation in the GP of heroin addicts. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of large GP neurons by densitometric evaluation of their GAD 65/67-immunostained thick dendrites. The study revealed a bilaterally decreased fibres density in the EGP paralleled by the increase in the IGP in 11 male heroin addicts versus 11 healthy controls (significant U-test P values). The analysis of confounding variables found no interference of age, brain volume, and duration of formalin fixation with the results. Our findings suggest a dysregulation of GABAergic activity in the GP of heroin addicts, which is consistent with experimental data from animal models and plays potentially a role in the disturbed function of basal ganglia circuit in opioid addiction.

Impairment of the GABAergic system in the anterior insular cortex of heroin-addicted males.

Opioid addiction is a global problem, causing the greatest health burden among drug use disorders, with opioid overdose deaths topping the statistics of fatal overdoses. The multifunctional anterior insular cortex (AIC) is involved in inhibitory control, which is severely impaired in opioid addiction. GABAergic interneurons shape the output of the AIC, where abnormalities have been reported in individuals addicted to opioids. In these neurons, glutamate decarboxylase (GAD) with its isoforms GAD 65 and 67 is a key enzyme in the synthesis of GABA, and research data point to a dysregulation of GABAergic activity in the AIC in opioid addiction. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the AIC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. The study showed bilaterally increased neuropil density in layers III and V in 13 male heroin-addicted males compared to 12 healthy controls, with significant U-test P values for layer V bilaterally. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings suggest a dysregulation of GABAergic activity in the AIC in opioid addiction, which is consistent with experimental data from animal models and human neuroimaging studies.

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.

Antioxidant intake and its relationship with generalized anxiety disorder among adults.

Antioxidant intake may contribute to the prevention of numerous diseases, particularly those related to stress-induced psychiatric and stress disorders. The current study aimed to assess the relationship between daily antioxidant intake (DAI) and Generalized Anxiety Disorder (GAD) in adults. It also sought to investigate the correlation between the type of diet in conjunction with DAI and the scores on GAD 7-Item Scale in adults. A cross-sectional design was used to examine if DAI was lower in individuals with GAD; followed by an interventional study of 40 adults with severe GAD, who were exposed to higher DAI for a period of 6 weeks. The results indicated that participants with severe GAD had significantly lower levels of DAI compared to healthy controls (p < 0.001). After 6 weeks of antioxidant supplementation, a significant decrease in GAD-7 scores of participants was observed (p < 0.001). The study found a significant negative relationship between DAI and GAD.

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.

A meta-analysis on the efficacy of low-intensity cognitive behavioural therapy for generalised anxiety disorder.

BACKGROUND: Low-intensity cognitive behavioural therapy (LICBT) has been recommended as a primary intervention in the tiered care for mild to moderate generalised anxiety disorder. However, LICBT for generalised anxiety disorder are markedly diverse and efficacy data on various outcomes have not been systematically reviewed. This meta-analysis aimed to synthesise effect sizes of three NICE-recommended LICBT for generalised anxiety disorder: non-facilitated self-help, guided self-help, and psychoeducational groups. METHODS: A systematic literature review of randomised controlled trials (RCTs) examining LICBT for generalised anxiety disorder in the last 23 years (2000-2023) was conducted. Efficacy data for anxiety, depression, and worry outcomes were separately meta-analysed. The study was reported following the PRISMA guidelines. RESULTS: The systematic review identified 12 RCTs out of 1205 papers. The three meta-analyses consisted of 12 (anxiety), 11 (depression), and 9 (worry) effect sizes respectively, including total sample sizes of 1201 (anxiety), 1164 (depression), and 908 (worry). The adjusted effect sizes for reductions in anxiety (g = -0.63), depression (g = -0.48), and worry (g = -0.64) were all in the medium range, favouring LICBT over control conditions. Between-study heterogeneity was significant on anxiety and worry, with no specific moderators identified by meta-regression. CONCLUSIONS: LICBT has shown promise as an effective and efficient treatment modality for individuals with generalised anxiety disorder. Future research comparing various LICBT subtypes and treatment components will further inform clinical practice. TRIAL REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; record ID CRD42021285590).

Subjective and objective cognitive functioning in untreated late-life depression: An exploration centered on comorbid generalized anxiety disorder.

BACKGROUND: Late-Life Depression (LLD) is a prevalent mental health disorder that is often accompanied by cognitive impairments. The objective of this study is to investigate the influence of coexisting Generalized Anxiety Disorder (GAD) on both subjective and objective cognitive abilities in untreated LLD individuals. METHODS: A total of 77 participants aged 60 years and above were recruited for this study, comprising 31 individuals with Major Depressive Disorder (LLD group), 46 with MDD and coexisting Generalized Anxiety Disorder (LLDA group), and 54 healthy controls (HC). Prior to the study, all patients had abstained from psychotropic medication for a minimum of two weeks. Comprehensive neuropsychological assessments were administered to all participants. RESULTS: The LLDA group exhibited substantial disparities in memory, attention, processing speed,executive function,overall cognitive functioning, and subjective cognitive functioning when compared to the HC group. The LLD group displayed deficits in memory, SCWT-W in attention, SCWT-C in processing speed,overall cognitive functioning, and subjective cognitive functioning in comparison to the healthy controls. Although the LLD group achieved lower average scores in executive function, TMTA in processing speed, and DSST in attention than the HC group, no significant distinctions were identified between these groups in these domains. Linear regression analysis unveiled that anxiety symptoms had a significant impact on subjective cognitive deficits among MDD patients, but exhibited a milder influence on objective cognitive performance. After adjusting for the severity of depression, anxiety symptoms were found to affect TMTA in processing speed and subjective cognitive functioning in LLD patients. CONCLUSION: Late-Life Depression (LLD) exhibits pervasive cognitive impairments, particularly in individuals with generalized anxiety disorder, presenting a crucial target for future therapeutic interventions. Among elderly individuals with depression, anxiety symptoms significantly impact subjective cognitive functioning, suggesting its potential utility in distinguishing between depression-associated cognitive decline and pre-dementia conditions.

From lab bench to hope: a review of gene therapies in clinical trials for Parkinson's disease and challenges.

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.