γ-Aminobutyric acid (GABA) is a widely distributed non-protein amino acid that serves as a crucial inhibitory neurotransmitter in the brain, regulating various physiological functions. As a result of its potential benefits, GABA has gained substantial interest in the functional food and pharmaceutical industries. The enzyme responsible for GABA production is glutamic acid decarboxylase (GAD), which catalyzes the irreversible decarboxylation of glutamate. Understanding the crystal structure and catalytic mechanism of GAD is pivotal in advancing our knowledge of GABA production. This article provides an overview of GAD\'s sources, structure, and catalytic mechanism, and explores strategies for enhancing GABA production through fermentation optimization, metabolic engineering, and genetic engineering. Furthermore, the effects of GABA on the physiological functions of animal organisms are also discussed. To meet the increasing demand for GABA, various strategies have been investigated to enhance its production, including optimizing fermentation conditions to facilitate GAD activity. Additionally, metabolic engineering techniques have been employed to increase the availability of glutamate as a precursor for GABA biosynthesis. By fine-tuning fermentation conditions and utilizing metabolic and genetic engineering techniques, it is possible to achieve higher yields of GABA, thus opening up new avenues for its application in functional foods and pharmaceuticals. Continuous research in this field holds immense promise for harnessing the potential of GABA in addressing various health-related challenges.

UNASSIGNED: Generalized anxiety disorder (GAD) (Chittodvega) is one among many types of mental disorders explained in Ayurveda. It can be defined as a Chitta (mind) + Udvega (anxiety)= Chittodvega- Anxious status of a mind. Celastrus paniculatus also known as Jyotishmati. stimulates and improves the digestive fire and metabolism at a cellular level ( Jatharagni and Majja dhatwagni). It can be correlated to GAD. GAD is characterized by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. It affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects. In modern medicine the first-line psychological and pharmaceutical treatments are selective serotonin reuptake inhibitors (SSRIs) like sertraline (SNRIs).
UNASSIGNED: To evaluate the comparative efficacy of Jyotishmati versus sertraline in the management of Chittodvega.
UNASSIGNED: In this randomized active controlled double blind equivalence trial a total of 70 patients will be enrolled and divided into two equal groups. Patients between 20-50 years age of either gender having symptoms of Chittodvega and a Hamilton anxiety rating (HAM-A) scale score less than 24 (i.e., mild to moderate) will be selected for the study. In Group A, sertraline capsules 25 mg for first 7 days and then dose increased to 50 mg at bedtime for next 53 days and in Group B Jyotishmati Capsules 500 mg will be given twice a day after food with water for 60 days.
UNASSIGNED: The patients will be assessed on the HAM-A scale, serum cortisol and WHO Quality of Life on day 0, 30, 60 and 90 and data will be analyzed using paired and unpaired t-tests for continuous variables and chi-square tests for categorical variables to evaluate whether treatments are equivalent.
UNASSIGNED: CTRI No. REF/2023/07/069880 Date - 15/09/2023.

This study examined the usefulness of drama and music therapies as communication strategies for reducing symptoms of post-traumatic stress disorder (PTSD) and generalised anxiety disorder (GAD) among school children (aged 10-16) who were victims of the 2022 floods in Nigeria. The researchers randomly assigned the children to control (n = 122) drama therapy (n = 120) and music therapy (n = 120) groups. The result of the study revealed that after the intervention, school children in the drama and music therapies (unlike those in the control group) reported a significant reduction in their PTSD and GAD symptoms; the reduction achieved statistical significance (p = 0.001, ηp2 = 0.48). Further results revealed a significant interactive effect of gender (p = 0.001) with boys reporting a significant reduction more than girls. The results showed that drama therapy contributed more to reducing PTSD symptoms, while music therapy contributed more to reducing GAD symptoms. The difference did not achieve statistical significance (p = 0.23). The researchers conclude that both drama and music therapies were associated with reduced symptoms, indicating the interventions may be beneficial therapies.

UNASSIGNED: The Global Psychotrauma Screen (GPS) is a brief transdiagnostic screener that covers a broad range of trauma-related disorders as well as risk factors known to influence the course of symptoms.
UNASSIGNED: We analyzed data from African war refugees in Australia (n = 70), including the GPS, the Structured Clinical Interview for DSM-5 Disorders (SCID-5), the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and the Brief Resilience Scale (BRS).
UNASSIGNED: Using the Youden\'s J Index to examine the clinical validity of the GPS subscales measuring PTSD, dissociation, depression, and generalized anxiety disorder (GAD), we found that a PTSD subscale score of 3 or higher, and a depression and dissociation subscale score of 1 or higher, was optimally efficient for detecting a probable diagnosis (Youden\'s J = 0.76, J = 0.72, and J = 0.90, respectively) with high sensitivity and specificity. We were unable to test the GPS clinical validity for GAD due to the low GAD occurrence. The GPS resilience item was not related to the total score (r = 0.02), indicating low convergent validity for resilience. Risk factors, including current stressors and childhood trauma history, were related to more severe GPS symptom scores, while lack of resilience, social support, and history of mental illness were not.
UNASSIGNED: We conclude that the GPS may be a useful screening tool for PTSD, depression, and the dissociative subtype in refugees.

Rates of clinical anxiety have increased during COVID and post-quarantine in youth, with older adolescent girls and youth with minorized racial, gender, and sexuality identities most vulnerable. Given that increased anxiety to a threatening/uncertain environment is adaptive, it is important to conceptualize anxiety from a balanced perspective, evaluating its functionality. For adolescents continuing to struggle with re-integration into their social environments and school avoidance, an exposure framework is necessary to encourage approach behaviors to recalibrate the social environment as safe. Disproportion between demand for services and available providers increased greatly due to the pandemic. Evidence-based treatments for anxiety can be delivered via telehealth, in school, or in primary care settings.

Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics.

UNASSIGNED: Generalized anxiety disorder (GAD) is a suboptimally managed chronic recurring psychiatric condition with a lifetime prevalence of 2.6% in Japan. We assessed the current status of GAD management in Japan.
UNASSIGNED: This was an observational, cross-sectional study conducted through an anonymous web-based survey in Japan from December 12-16, 2022. Psychiatrists and psychosomatic medicine physicians who agreed to participate and saw ≥10 outpatients in the previous month were eligible. Survey questionnaire comprised 37 single/multiple choice, numerical entry, or open-ended questions in Japanese.
UNASSIGNED: Among 509 participants (493 psychiatrists and 16 psychosomatic medicine physicians), 96.9% were aware of GAD. On average, 12.4 outpatients and 1.0 inpatient were diagnosed with GAD per physician per month. Of 433 physicians having patients diagnosed with GAD, 46.9% used operational diagnostic tools; among these, DSM-5 diagnostic criteria were used by 81.5% physicians. The majority (54.7%) of participants did not use a self-administered rating scale; depression scales were used more than anxiety scales. Among these 433 physicians, 96.8% used selective serotonin reuptake inhibitors for GAD management, and 79.2% used it as the first choice; of 431 physicians who prescribed drug therapy, 54.3% gave antidepressant monotherapy as first choice. The most frequent symptom in patients diagnosed with GAD was excessive anxiety/worry (96.5%); depression was the most commonly reported comorbidity (84.3%) as per physicians aware of GAD (N=508).
UNASSIGNED: This study illustrates that although GAD awareness is high among Japanese psychiatric specialists, GAD is not frequently diagnosed using operational diagnostic approaches. Due to a lack of Japanese guidelines for GAD diagnosis and treatment, diverse international guidelines are followed, with similar treatment paradigms as that of depression. This may not be an optimal approach given cultural/geographical differences. These findings highlight the need for uniform diagnosis and treatment recommendations for GAD management in Japan.
UNASSIGNED: UMIN-CTR: UMIN000049572.

Interpersonal problems are common in individuals with generalized anxiety disorder (GAD) and improved interpersonal functioning is an important goal in treatment. In the metacognitive model of worry and generalized anxiety disorder, emotional distress and psychological dysfunction are related to two distinct types of worry. Particular emphasis is put on meta-worry which refers to \"worry about worrying\" or appraisal of worrying as threatening in itself. Meta-worry impairs effective mental regulation and might therefore be an important predisposition to self-regulate via others and thereof interpersonal problems. In the current study, we tested the prediction that meta-worry is uniquely associated with interpersonal problems in two samples. The first consisted of 135 individuals with analogue GAD and the second of 56 individuals with a diagnosis of GAD. Using hierarchical linear regressions controlling for anxiety, depression and worry, meta-worry showed a unique relationship with interpersonal problems in both samples. These findings indicate that meta-worry may be relevant to formulate and treat interpersonal problems in individuals with GAD.

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.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s11032-024-01460-1.

Generalized anxiety disorder (GAD) is a prevalent and chronic mental health condition, associated with considerable individual and economic burden. Despite the availability of effective treatments, many individuals do not access support. The current study explores treatment histories, barriers to help-seeking, and cognitive behavioral therapy (CBT) treatment preferences for individuals with clinically significant GAD symptoms. The utility of Health Belief Model (HBM) in predicting help-seeking is also examined. A cross-sectional design with 127 participants (Mage = 29.17; SD = 11.86; 80.3% female) was used. Sixty-two percent of participants reported previously seeking psychological treatment, and approximately 28% received CBT in the first instance. The most influential treatment barriers were a desire to solve the problem on one\'s own (M = 1.96, SD = 0.96), followed by affordability (M = 1.75, SD = 1.15) and feeling embarrassed or ashamed (M = 1.75, SD = 1.06). The most preferred treatment modes were in-person individual treatment (M = 7.59, SD = 2.86) followed by remote treatment via videoconferencing (M = 4.31, SD = 3.55). Approximately 38% of the variance in intention to seek treatment was associated with the HBM variables, with perceived benefit of treatment being the strongest predictor. Results have the potential to inform mental health service delivery by reducing treatment barriers and aligning public health campaigns with benefits of psychological treatments.