Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome

Faculty Reviews, Journal Year: 2022, Volume and Issue: 11

Published: April 28, 2022

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase menstrual cycle characterized by moderate to severe physical, affective, or behavioral symptoms that impair daily activities quality life. PMS PMDD have recently raised great interest in research community for their considerable global prevalence. The etiology PMS/PMDD is complex. Ovarian reproductive steroids (estradiol progesterone) considered pathogenetic effectors, but key feature seems be an altered sensitivity GABAergic central inhibitory system allopregnanolone, a neurosteroid derived from progesterone produced after ovulation. Also, reduced availability serotonin involved. New insights point role genetic epigenetic modifications hormonal neurotransmitter pathways, inflammation potential link between peripheral neurological integrated responses stressors. Thus, new therapeutic approaches include inhibition receptors brain (i.e., with ulipristal acetate), conversion its metabolite allopregnanolone dutasteride, possible modulation action on sepranolone. Further needed better understand interaction inflammatory molecules (cytokines, interleukins, C-reactive protein, reactive oxygen species) systems women PMS/PMDD. If confirmed, neuroinflammation could lead both develop targeted anti-inflammatory therapies define prevention strategies associated chronic risk Finally, observed association psychological diseases may guide prompt adequate interventions achieve

Language: Английский

---

Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 26, 2023

The pathophysiology of major depressive disorder (MDD) is thought to result from impaired connectivity between key brain networks. Gamma-aminobutyric acid (GABA) the inhibitory neurotransmitter in brain, working primarily via GABA

Language: Английский

---

GABAA receptors as targets for treating affective and cognitive symptoms of depression

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(9), P. 586 - 600

Published: Aug. 3, 2023

Language: Английский

---

Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 161 - 161

Published: Feb. 6, 2025

Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts affected patients. Few treatments have received regulatory approval treatment-resistant depression (TRD). Methods: A systematic search of United States and European Union trials registries was conducted identify Phase II, III, or IV trials, last update posted on after 1 January 2020, that were evaluating medications TRD. For both the US EU registries, condition term "treatment resistant depression" associated lower-level terms (per registry protocol) used. registry, secondary using "depressive disorders" modifying "inadequate" also performed capture registrations not tagged as Two additional searches in "suicide" "anhedonia" transdiagnostic targets investigational medications. Trials categorized based primary mechanism action trial's medication. Results: Fifty TRD, 20 anhedonia, 25 suicide identified. Glutamate system modulation currently most compounds development, including antagonists allosteric modulators NMDA receptors, AMPA metabotropic type 2/3 glutamate intracellular effector molecules downstream signaling. Psychedelics seen greatest surge among mechanistic past 5 years, however, psilocybin particular garnering significant attention. Other mechanisms included GABA modulators, monoamine anti-inflammatory/immune-modulating agents, an orexin 2 receptor antagonist. Conclusions: These investigations offer substantial promise more efficacious potentially personalized medication approaches Challenges detecting efficacy TRD include heterogeneity within population stemming from presumed variety biological dysfunctions underlying disorder, comorbid disorders, chronic psychosocial stressors, enduring effects prior serotonergic antidepressant treatments.

Language: Английский

---

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5495 - 5495

Published: May 23, 2021

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after stimulus is no longer present. In addition corticosteroids (e.g., cortisol), neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms restore homeostasis. Chronic, repeated exposure stress impairs responsivity of HPA and dampens levels, participating etiopathology psychiatric disorders, such as major depressive disorder (MDD) post-traumatic (PTSD). MDD PTSD patients present abnormalities regulation, altered cortisol levels or failure suppress release dexamethasone suppression test. Herein, we review neurophysiological role both a potent positive GABAergic neuromodulator but also its capacity inhibiting axis. The function recapitulate stress-induced pathophysiology, including PTSD, potential treatment target biomarker for these disorders discussed.

Language: Английский

---

Steroid Hormone Sensitivity in Reproductive Mood Disorders: On the Role of the GABAA Receptor Complex and Stress During Hormonal Transitions

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 7

Published: Jan. 18, 2021

Women worldwide are two to three times more likely suffer from depression in their lifetime than men. Female risk for depressive symptoms is particularly high during the reproductive years between menarche and menopause. The term “Reproductive Mood Disorders” refers disorders triggered by hormonal fluctuations transitions including perimenarchal phase, pre-menstrual pregnancy, peripartum period perimenopausal transition. Here we focus on mood manifesting adult life. We propose a research agenda that draws together several investigates which genetic, endocrinological, neural, psychosocial factors can explain phases of women. Based current it assumed some women experience an increased sensitivity not only steroids (estrogen progesterone), but also stress-related steroids. integrate both dynamics into concept “steroid hormone sensitivity,” expanding “reproductive sensitivity.” suggest differential response stress steroid system corticosteroids, neurosteroids, like allopregnanolone GABA-A Receptor complex, as well (epi)genetic serotonergic GABAergic signaling, moderators or mediators changes physiological, affective, cognitive outcomes disorders. point lack role increasing woman's level at her within etiology Reproductive Disorders. Drawing evidence various seek present basis development effective pharmacological, social, psychological treatment interventions prevention strategies susceptible these This could pave way new medical teaching practice- such type Practice Gynecological Psychoneuroendocrinology- with aim working ultimately offering integrative forms support yet available suffering transitions. In history have been left alone this challenge.

Language: Английский

---

GABAkines – Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAA receptors

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 234, P. 108035 - 108035

Published: Nov. 16, 2021

Language: Английский

---

A systematic review of treatment for patients with burning mouth syndrome

Cephalalgia, Journal Year: 2021, Volume and Issue: 42(2), P. 128 - 161

Published: Aug. 18, 2021

Background Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains challenge to clinicians due its poorly understood pathogenesis and inconsistent response various treatments. Aim This review aimed study the short- (≤3 months) long-term (>3 effectiveness sustainable benefit of different burning treatment strategies associated side effects. Materials methods Randomised controlled trials compared with placebo or other interventions minimum follow up 2 months were searched from PubMed, Embase Cochrane database (published July 2020). Results Twenty-two studies selected based on inclusion exclusion criteria analysed. Nine categories identified: Anticonvulsant antidepressant agents, phytomedicine alpha lipoic acid supplements, low-level laser therapy, saliva substitute, transcranial magnetic stimulation, cognitive behaviour therapy. Cognitive topical capsaicin clonazepam, therapy demonstrated favourable outcome in both assessment. Phytomedicines reported short-term pain score reduction. The pooled effect (ALA) improvement was low, but positive effects increased long term Conclusion A more significant volume terms sample size, multi-centres, multi-arm comparison therapeutic agents longitudinal follow-up recommended establish standardised protocol. Further are required assess analgesic benefits clonazepam capsaicin, alternative medicines neurodegenerative prevention capability psychology support treating reducing systemic adverse drug reactions. Registration International Prospective Register Systematic Reviews (PROSPERO): Protocol ID - CRD42020160892.

Language: Английский

---

Allopregnanolone: An overview on its synthesis and effects

Journal of Neuroendocrinology, Journal Year: 2021, Volume and Issue: 34(2)

Published: June 1, 2021

Allopregnanolone, a 3α,5α-progesterone metabolite, acts as potent allosteric modulator of the γ-aminobutyric acid type A receptor. In present review, synthesis this neuroactive steroid occurring in nervous system is discussed with respect to physiological and pathological conditions. addition, its neuroprotective effects are also reported. Interestingly, levels steroid, well effects, sex-dimorphic, suggesting possible gender medicine based on for neurological disorders. However, allopregnanolone presents low bioavailability extensive hepatic metabolism, limiting use drug. Therefore, synthetic analogues or different therapeutic strategy able increase have been proposed overcome any pharmacokinetic issues.

Language: Английский

---

The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders

Pharmacology Biochemistry and Behavior, Journal Year: 2022, Volume and Issue: 213, P. 173321 - 173321

Published: Jan. 15, 2022

Language: Английский

---