Association of Cortical Atrophy Patterns With Clinical Phenotypes and Histopathological Findings in Patients With Rasmussen Syndrome DOI
Tobias Bauer, Nina R. Held, Lennart Walger

и другие.

Neurology, Год журнала: 2025, Номер 104(10)

Опубликована: Май 2, 2025

Automated MRI analyses have identified variable patterns of cortical atrophy in Rasmussen syndrome. In this study, we aim to identify imaging phenotypes syndrome, clinically characterize these phenotypes, and validate imaging-based approach through histopathologic analysis. For retrospective case-control individuals with syndrome diagnosed according the European Consensus Statement at least one 3D T1-weighted scan (<20 years after onset) were from University Hospital Bonn (1995-2023). Healthy controls selected databases Bonn, Charité Berlin, Human Connectome Project. Disease epicenters, describing brain regions highly connected regions, mapped individually using network-based modeling. Subtypes k-means clustering. Neuropsychological test results neuropathologic biopsies ascertained, correlations between subtype-specific maps normative (enhancing neuro genetics meta analysis [ENIGMA] neuromaps toolbox) used profiles epicenter susceptibility. The study incorporated 54 (median age MRI: 18 years, range 2-61, 65% female) 270 healthy 26.5 3-61, 49% female). Four distinct subtypes (temporoparietal, centrotemporal, frontal, bilateral). Individuals centrotemporal subtype younger onset 5.5 years) than temporoparietal 11.5 p = 0.02) frontal 6 subtypes. Most severe neuropsychological impairment was observed for subtypes, occurred preferentially hubs (r -0.28, 0.006; r -0.30, 0.02). susceptibility associated higher thickness -0.57, 0.005), lower myelin content 0.47, 0.02), cerebral blood flow 0.42, 0.03), volume 0.57, 0.006), oxygen metabolism 0.01). Brain showing strong inflammation taken likely whereas weaker came less epicenters (p 0.04). Using as a model, mapping individual disease evidence. With further validation, could potentially be guide biopsy site selection, inform treatment decisions, improve outcome prognoses.

Язык: Английский

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders DOI Creative Commons

Thian‐Sze Wong,

Guangzhi Li, Shiliang Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 3, 2023

Neuropsychiatric disorders are multifactorial with diverse aetiological factors. Identifying treatment targets is challenging because the diseases resulting from heterogeneous biological, genetic, and environmental Nevertheless, increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge molecular mechanisms structural information GPCRs will be advantageous for developing effective drugs. This review provides an overview role various neurodegenerative psychiatric diseases. Besides, we highlight emerging opportunities novel GPCR address recent progress development.

Язык: Английский

Процитировано

66
Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions? DOI
Marjorie R. Levinstein,

Reece C. Budinich,

Jordi Bonaventura

и другие.

American Journal of Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Ketamine is a racemic compound and medication comprised of (S)-ketamine (R)-ketamine enantiomers its metabolites. It has been used for decades as dissociative anesthetic, analgesic, recreational drug. More recently, ketamine, enantiomers, metabolites have or are being investigated the treatment refractory depression, well comorbid disorders such anxiety, obsessive-compulsive, opioid use disorders. Despite complex pharmacology, ketamine referred to an N-methyl-d-aspartate (NMDA) receptor antagonist. In this review, authors argue that ketamine's pharmacology should be redefined include receptors endogenous system. They also highlight potential mechanism action depression attributed bifunctional, synergistic interactions involving NMDA receptors.

Язык: Английский

Процитировано

3
Arketamine, a new rapid-acting antidepressant: A historical review and future directions DOI Creative Commons
Jichun Zhang, Wei Yao, Kenji Hashimoto

и другие.

Neuropharmacology, Год журнала: 2022, Номер 218, С. 109219 - 109219

Опубликована: Авг. 14, 2022

The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine causes rapid onset and sustained antidepressant actions in treatment-resistant patients with major depressive disorder (MDD) other psychiatric disorders, such as bipolar post-traumatic stress disorder. is a racemic mixture consisting of (R)-ketamine (or arketamine) (S)-ketamine esketamine), (S)-enantiomer having greater affinity for the NMDAR. In 2019, an esketamine nasal spray by Johnson & was approved USA Europe depression. contrast, increasing number preclinical studies show that arketamine has potency longer-lasting antidepressant-like effects than rodents, despite lower binding Importantly, side effects, i.e., psychotomimetic dissociative abuse liability, are less those animals humans. An open-label study demonstrated MDD. A phase 2 clinical trial MDD underway. This designed to review brief history novel arketamine, molecular mechanisms underlying its actions, future directions. article part Special Issue on 'Ketamine Metabolites'.

Язык: Английский

Процитировано

71
Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options DOI Open Access
Ane Larrea, Laura Sánchez-Sánchez, Eguzkiñe Díez-Martín

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(6), С. 1727 - 1727

Опубликована: Март 17, 2024

Major Depressive Disorder (MDD) is one of the most disabling diseases in world. MDD traditionally diagnosed based on a patient’s symptoms, which can lead to misdiagnosis. Although pathogenic mechanisms are unknown, several studies have identified mitochondrial dysfunction as central factor onset and progression MDD. In context MDD, alterations metabolism imbalances energy production oxidative stress, contributing disorder´s underlying pathophysiological mechanisms. Consequently, identification key biomarker for early accurate diagnosis represents significant challenge. Faced with limits traditional treatments antidepressants, new pharmacological therapeutic targets being investigated such ketamine/esketamine, psychedelics, or anti-inflammatories. All these drugs show potential antidepressant effects due their speed action ability modulate neuroplasticity and/or motor processing. parallel, non-pharmacological studied, like Transcranial Magnetic Stimulation (TMS) Deep Brain (DBS), recognized neuronal activity offer treatment alternatives. As cellular directly related respiration, aim this review examining link between assessing how biomarkers could provide more objective precise diagnostic tool, exploring other addition specific focus emerging targets. Finally, detailed analysis strengths, weaknesses, opportunities, threats approaches was carried out, highlighting challenges that must be addressed.

Язык: Английский

Процитировано

10
A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens DOI
Johnathan M. Borland

Frontiers in Neuroendocrinology, Год журнала: 2025, Номер unknown, С. 101175 - 101175

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability DOI Creative Commons
Marjorie R. Levinstein,

Meghan L. Carlton,

Tommaso Di Ianni

и другие.

Biological Psychiatry, Год журнала: 2022, Номер 93(12), С. 1118 - 1126

Опубликована: Дек. 24, 2022

Язык: Английский

Процитировано

35
GLP-1 agonists and risk of suicidal thoughts and behaviours: Confound by indication once again? A narrative review DOI Creative Commons
Robertas Strumila, Aistė Lengvenytė,

Sebastien Guillaume

и другие.

European Neuropsychopharmacology, Год журнала: 2024, Номер 87, С. 29 - 34

Опубликована: Июль 27, 2024

Glucagon-like peptide-1 (GLP-1) agonists have been successfully used in clinical practice for the treatment of diabetes and obesity, offering significant benefits. However, concerns regarding their potential link to psychiatric side effects, like suicidal thoughts behaviours (STB) emerged. This narrative review investigates complex interplay between GLP-1 STB, focusing on biological stress induced by rapid weight loss, psychological social consequences, similar mechanism with addiction, evaluative lens Bradford Hill criteria causality. While can contribute substantial health improvements, they also introduce stressors. Disruptions homeostasis from quick reduction elevate cortisol norepinephrine levels, heightening risk for, or exacerbation STB. Psychological factors, including unfulfilled expectations identity changes after compound these risks. Utilizing reveals insufficient evidence a direct causal Yet, indirect effects related metabolic disturbances associated loss call cautious approach. Used carefully targeted populations may even emerge as protective agents against Therefore, it is crucial monitor patients during screen preexisting mental conditions. If detected, appropriate management should be applied. Future studies aim at optimizing dosing schedules mitigate adverse further investigate possible STB prevention.

Язык: Английский

Процитировано

8
Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors DOI
Ivone Gomes, Achla Gupta, Elyssa B. Margolis

и другие.

Molecular Pharmacology, Год журнала: 2024, Номер 106(5), С. 240 - 252

Опубликована: Авг. 26, 2024

Ketamine is a glutamate receptor antagonist that was developed over 50 years ago as an anesthetic agent. At subanesthetic doses, ketamine and some metabolites are analgesics fast-acting antidepressants, presumably through targets other than receptors. We tested its for activity allosteric modulators of opioid receptors expressed recombinant in heterologous systems with native rodent brain; signaling examined by measuring GTP binding,

Язык: Английский

Процитировано

8
The serotonin hypothesis of depression: both long discarded and still supported? DOI Open Access
Joanna Moncrieff, Ruth Cooper, Tom Stockmann

и другие.

Molecular Psychiatry, Год журнала: 2023, Номер 28(8), С. 3160 - 3163

Опубликована: Июнь 15, 2023

Язык: Английский

Процитировано

12
Aticaprant: (a κ-opioid receptor antagonist) for major depressive disorder DOI Creative Commons
Elliot Hampsey, Luke A. Jelen, Allan H. Young

и другие.

Expert Opinion on Emerging Drugs, Год журнала: 2024, Номер 29(3), С. 193 - 204

Опубликована: Апрель 29, 2024

Major depression is a common, disabling mental health condition associated with the highest disease burden for any neuropsychiatric disorder worldwide, according to WHO. Due imperfect efficacy and tolerability profiles of existing treatments, investigational compounds in novel treatment classes are needed. Opioid-receptor antagonists potential new class treatments currently under investigation. depressive first overviewed. Existing both their mechanisms action place within antidepressant space, discussed herein. Then, profile Aticaprant wider context kappa-opioid antagonism focus. Early evidence indicates that may possess desirable pharmacodynamic pharmacokinetic properties. A lack convincing data at time writing precludes definitive statement on its as an antidepressant.

Язык: Английский

Процитировано

5