Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume

Wu, Hao; Zhong, Yuan; Xu, Huazhen; Ding, Huachen; Yuan, Shiting; Wu, Yun; Liu, Gang; Liu, Na; Chun, Wu

doi:10.3389/fpsyt.2022.853613

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…It is increased in expression in blood in high anxiety in our work. The gene had been previously described to be hypomethylated in panic disorders patients, which is consistent with higher expression of the gene [11,12]. GAD1 in our studies modestly predicts clinically severe anxiety state in all patients in the independent testing cohort (AUC 58%, p = 0.04), with results being somewhat better in women (AUC 65%, p = 0.03).…”

Section: Convergent Functional Evidence (Cfe)supporting

confidence: 89%

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

et al. 2023

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Anxiety disorders are increasingly prevalent, affect people’s ability to do things, and decrease quality of life. Due to lack of objective tests, they are underdiagnosed and sub-optimally treated, resulting in adverse life events and/or addictions. We endeavored to discover blood biomarkers for anxiety, using a four-step approach. First, we used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states. Second, we prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety. Fourth, we tested these candidate biomarkers for clinical utility, i.e. ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects. We showed increased accuracy of individual biomarkers with a personalized approach, by gender and diagnosis, particularly in women. The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. Finally, we identified which of our biomarkers are targets of existing drugs (such as a valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. We also used our biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide. Given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications, there is a urgent need for more precise and personalized approaches like the one we developed.

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Section: Convergent Functional Evidence (Cfe)supporting

confidence: 89%

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

et al. 2023

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“…In this study, we attempted to reconcile the heterogenous VBM findings of past studies with shared symptoms using CNM. In accordance with studies applying CNM to other psychiatric and neurological disorders [20-22, 32, 33], we identified a common anxiety network associated with spatially heterogenous abnormalities revealed by VBM [34][35][36]. This anxiety network was defined by hub regions in the bilateral amygdala and included positive connectivity among regions consistently implicated in psychiatry disorders, such as the ventrolateral prefrontal cortex, insula, and cingulate cortex [22,37].…”

Section: Discussionsupporting

confidence: 79%

Heterogeneous Brain Atrophy Sites in Anxiety Disorders Map to a Common Brain Network

Yang,

Xu,

Wang

et al. 2024

Depression and Anxiety

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Background. Heterogeneous findings among anxiety disorder studies have hindered elucidation of the underlying pathophysiology and the development of mechanism-based therapies. Purpose. To determine whether structural MRI findings in anxiety disorder studies converge on a common network with therapeutic significance. Materials and Methods. In this retrospective study, a systematic literature search of PubMed and Web of Science databases was performed to identify coordinates of gray matter atrophy in patients with anxiety disorder. Atrophy coordinates were then mapped to an anxiety network constructed from the resting-state functional MRI (rs-fMRI) data of 652 healthy participants using “coordinate network mapping” and validated by specificity tests. The causal association of this network to anxiety symptoms was tested in a cohort of patients with brain lesions and emergent anxiety symptoms. The potential therapeutic utility of this anxiety network was then assessed by examining the clinical efficacy of network-targeted repetitive transcranial magnetic stimulation (rTMS) among a separate anxiety disorder cohort. Statistical analyses of images were performed using nonparametric tests and corrected for family-wise error. Results. Sixteen studies comprising 453 patients with anxiety (245 females; mean age±SD, 31.4±8.71 years) and 460 healthy controls (238 females; 31.7±10.08 years) were included in the analysis. Atrophy coordinates were mapped to an anxiety network with a hub region situated primarily within the superficial amygdala. Lesions associated with emergent anxiety symptoms exhibited stronger connectivity within this anxiety network than lesions not associated with anxiety (t=2.99; P=.004). Moreover, the connectivity strength of rTMS targets in the anxiety network was correlated with the improvements of anxiety symptom after treatment (r=.42, P=.02). Conclusions. Heterogeneous gray matter atrophy among patients with anxiety disorder localize to a common network that may serve as an effective therapeutic target.

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Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

Zou¹,

Qiu²,

Zhou³

et al. 2023

World J Psychiatry

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A condition of exposure to multiple stressors resulting in a mixed clinical picture spanning conventional categories without meeting any of them in full, encompasses a risk for a list of comorbidities preventing appropriate prevention and treatment. New transformative transdiagnostic approaches suggest changes spanning conventional categories. They base their systems of classification on biomarkers as well as on brain structural and functional dysregulation as associated with behavioral and emotional symptoms. These new approaches received critiques for not being specific enough and for suggesting a few biomarkers for psychopathology as a whole. Therefore, they put the value of differential diagnosis at risk of avoiding appropriate derived prevention and treatment. Multiplicity of stressors has been considered mostly during and following catastrophes, without considering the resulting mixed clinical picture and life event concomitant stressors. We herewith suggest a new category within the conventional classification systems: The Complex Stress Reaction Syndrome, for a condition of multiplicity of stressors, which showed a mixed clinical picture for daily life in the post coronavirus disease 2019 era, in the general population. We argue that this condition may be relevant to daily, regular life, across the lifespan, and beyond conditions of catastrophes. We further argue that this condition may worsen without professional care and it may develop into a severe mental health disorder, more costly to health systems and the suffering individuals. Means for derived prevention and treatment are discussed.

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Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume

Cited by 3 publications

References 35 publications

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

Heterogeneous Brain Atrophy Sites in Anxiety Disorders Map to a Common Brain Network

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

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