A cortico-amygdala neural substrate for endocannabinoid modulation of fear extinction

Neuron, Год журнала: 2023, Номер 111(19), С. 3053 - 3067.e10

Опубликована: Июль 21, 2023

Язык: Английский

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The definition of treatment resistance in anxiety disorders: a Delphi method‐based consensus guideline

World Psychiatry, Год журнала: 2024, Номер 23(1), С. 113 - 123

Опубликована: Янв. 12, 2024

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials innovative therapeutic interventions. However, an explicit definition treatment-resistant anxiety (TR-AD) informing such is currently lacking. We used Delphi method-based consensus approach to provide internationally agreed, consistent clinically useful operational criteria for TR-AD in adults. Following summary the current state knowledge based on international guidelines available systematic review, survey free-text responses 29-item questionnaire relevant aspects TR-AD, online meeting, panel 36 multidisciplinary experts stakeholders voted anonymously written statements three rounds. Consensus was defined as ≥75% agreeing statement. The agreed set 14 recommendations providing detailed pharmacological and/or psychotherapeutic treatment, well potential staging model. also evaluated further regarding epidemiological subgroups, comorbidities biographical factors, terminology vs. "difficult-to-treat" preferences attitudes persons these future research directions. This expected serve systematic, practical guideline aid designing mechanistic studies facilitate purposes. effort could ultimately lead development more effective evidence-based stepped-care algorithms patients disorders.

Язык: Английский

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Epilepsy: Mitochondrial connections to the ‘Sacred’ disease

Mitochondrion, Год журнала: 2023, Номер 72, С. 84 - 101

Опубликована: Авг. 13, 2023

Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms epilepsy makes diagnosis challenging. Diagnosis and monitoring childhood add to the need non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms epileptogenesis are not fully understood, evidence mitochondrial involvement is substantial. Seizures affect 35%-60% patients diagnosed with diseases. Mitochondrial dysfunction pathophysiological in various epilepsies, including those non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads altered neuronal bioenergetics, metabolism neurological complications, Iron-dependent lipid peroxidation initiates ferroptosis, a death pathway that aligns morphology found neurodegenerative diseases (NDDs). Studies mouse genetic models seizure phenotypes where function an essential selenoprotein (GPX4) targeted suggest roles ferroptosis epilepsy. GPX4 pivotal NDDs, selenium protects interneurons ferroptosis. Selenium central nervous system micronutrient trace element. Low serum concentrations other elements minerals, iron, noted diagnosing supplements alleviate intractable seizures children reduced GPX activity. Copper cuproptosis, like iron link NDDs. Connecting these mechanistic pathways selenoproteins provides new insights into treating seizures, pointing using medicines prodrugs lipoic acid treat potential alternative therapeutic approaches transcranial magnetic stimulation (transcranial), photobiomodulation vagus nerve stimulation.

Язык: Английский

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The effect of subjective exercise experience on anxiety disorder in university freshmen: the chain-mediated role of self-efficacy and interpersonal relationship

Frontiers in Psychology, Год журнала: 2024, Номер 15

Опубликована: Фев. 21, 2024

Background Anxiety disorder is a significant concern in the context of mental health among university students. This study aimed to examine impact subjective exercise experience on anxiety freshmen and verify mediating role self-efficacy interpersonal relationships between them. Methods A total 1,308 Chinese underwent an investigation using Subjective Exercise Experience Scale (SEES), Generalized Disorder (GAD-7), General Self-Efficacy (GSES), Interpersonal Relationship Comprehensive Diagnostic (IRIDS). Results The outcomes this are as follows: (1) Boys exhibited marginally greater performance physical activity assessments compared girls while displaying somewhat lower scores than measures disorders, self-efficacy, relationship tests. Of these, 63.39% were diagnosed with mild anxiety, 51.73% moderate 10% severe anxiety; (2) had negative correlation ( r = −0.36, p < 0.01), direct (β −0.112, t −11.776, 0.01). Furthermore, positively predicted 0.125, 13.236, 0.01) 0.395, 12.359, Self-efficacy substantial 0.724, 12.172, disorders −0.148, −8.387, positive predictive effect −0.081, −10.441, 0.01); (3) identified important mediators disorder. intermediary accounted for 18.84% effect. Specifically, through (2.90%), (1.45%), chain (14.49%). Conclusion has students’ relationships, Moreover, interactions serve intermediaries experiences disorders. These findings have immense importance advancing well-being theoretical foundation formulating intervention strategies. However, certain limitations, such specificity sample use self-reported data. Further research could enhance size utilize various assessment techniques validate these findings.

Язык: Английский

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Anxiety Disorders

Cambridge University Press eBooks, Год журнала: 2025, Номер unknown, С. 181 - 200

Опубликована: Янв. 2, 2025

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The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets

Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108825 - 108825

Опубликована: Фев. 1, 2025

Язык: Английский

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Preclinical Behavioral and Pharmacological Treatments for Enhancing Fear Extinction in Adolescence

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106090 - 106090

Опубликована: Март 1, 2025

Adolescence is a window of vulnerability for the development anxiety disorders but also opportunity treatments to minimize long-term impact such disorders. Current first-line treatments, primarily exposure-based cognitive-behavioral therapy (CBT), have limited efficacy in adolescents. The urgent need more effective interventions underscored by frequent reports extinction impairments adolescents as well rising rates youth, particularly post-COVID-19. Preclinical research on learned fear may contribute developing better treatment approaches this age group. Unfortunately, still largely under-explored area. However, both pharmacological and behavioral augmentation strategies can be used enhance learning consolidation. Here we describe work exploring adjuncts, focusing pre-clinical with rodents. Much date shows striking developmental differences response various only few shown Further, recent experience stress reduces these adolescence. This review highlights necessity tailored strategies, especially when it comes that address drug responses stressful experiences efficacy.

Язык: Английский

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Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024

F1000Research, Год журнала: 2025, Номер 14, С. 275 - 275

Опубликована: Март 7, 2025

1) Introduction Cognitive enhancers, also known as nootropics, aim to improve cognitive functions, such memory and attention. Despite their potential benefits, the challenges include scientific validation, ethical considerations, regulatory hurdles. This bibliometric study analyzes literature from Scopus identify key trends, influential authors, research gaps, providing guidance for future research. 2) Methods employs a review methodology gather data database on Neuroaid, analyzing it using Biblioshiny VOSviewer software. The focus was Ginkgo Biloba niche-theme enhancer agent based data, both quantitative qualitative analyses. 3) Results discussion biloba, 'maidenhair tree’ order Ginkgoales, appeared 290 million years ago. Chinese Japanese culture has been cultivated thousands of years. tree is valued its resilience therapeutic properties, often used in traditional medicine respiratory blood circulation issues. 4) Conclusions enhancers aims provide comprehensive systematic existing literature, highlighting gaps. findings this will contribute better understanding current state inform conducted December 2024.

Язык: Английский

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Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder

Molecular Psychiatry, Год журнала: 2024, Номер 29(7), С. 2105 - 2116

Опубликована: Фев. 27, 2024

Posttraumatic stress disorder (PTSD) is a psychiatric associated with traumatic memory, yet its etiology remains unclear. Reexperiencing symptoms are specific to PTSD compared other anxiety-related disorders. Importantly, reexperiencing can be mimicked by retrieval-related events of fear memory in animal models memory. Recent studies revealed candidate PTSD-associated genes that were related the cyclic adenosine monophosphate (cAMP) signaling pathway. Here, we demonstrate tight linkage between facilitated cAMP and analyzing loss- gain-of-cAMP effects on mice transcriptomes memory-activated female patients symptoms. Pharmacological optogenetic upregulation or downregulation transduction enhanced impaired, respectively, retrieval subsequent maintenance mice. In line these observations, integrative mouse human transcriptome analysis reduced mRNA expression phosphodiesterase 4B (PDE4B), an enzyme degrades cAMP, peripheral blood showing more severe hippocampus after retrieval. lower PDE4B levels correlated decreased DNA methylation locus within PDE4B, suggesting involvement mechanism PTSD. These findings raise possibility facilitation mediating enhances thereby playing key role as functional index

Язык: Английский

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Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 8, 2024

Abstract The ventromedial prefrontal cortex (vmPFC; rodent infralimbic (IL)), is posited to be an important locus of fear extinction-facilitating effects the dopamine (DA) bio-precursor, L-DOPA, but this hypothesis remains formally tested. Here, in a model impaired extinction (the 129S1/SvImJ inbred mouse strain; S1), we monitored extracellular DA dynamics via vivo microdialysis IL during and following L-DOPA administration. Systemic caused sustained elevation levels increased neuronal activation subpopulation neurons. enabled learning promoted retention at one not ten days after training. Conversely, direct microinfusion into produced long-term (an effect that was insensitive ɑ-/ß-adrenoreceptor antagonism). However, intra-IL delivery D1-like or D2 receptor agonist did facilitate extinction. Using ex multi-electrode array recordings, along with quantification immediate early genes signalling markers mPFC, found evidence reduced DA-evoked mPFC network responses S1 as compared extinction-competent C57BL/6J mice were partially driven by D1 activation. Together, our data demonstrate locally increasing sufficient produce lasting rescue finding systemic levels, had only transient on extinction, suggests failed reach threshold level opposing behavioural other brain regions. Collectively, findings provide further insight neural basis extinction-promoting clinically relevant animal model, possible implications for therapeutically targeting system anxiety trauma-related disorders.

Язык: Английский

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