Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 460 - 460

Published: Jan. 31, 2023

The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in brain and periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. net effect depends on their local concentration, cellular environment, well complex positive negative feedback loops. imbalance between beneficial harmful kynurenines was implicated pathogenesis various neurodegenerative disorders, psychiatric illnesses metabolic including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- microvascular complications cardio- cerebrovascular disease, peripheral vascular chronic renal diabetic retinopathy, autonomic neuropathy cognitive impairment. It established that low-grade inflammation, which coincides with DM, can affect function KP and, conversely, modulate immune response. This review provides detailed summary findings concerning status Trp–KYN based animal, human microbiome studies. We highlight importance molecular interplay deranged (functionally qualitatively) Trp development insulin resistance. emerges novel target search preventive therapeutic interventions DM.

Language: Английский

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Treatment-Resistant Depression Revisited: A Glimmer of Hope

Journal of Personalized Medicine, Journal Year: 2021, Volume and Issue: 11(2), P. 155 - 155

Published: Feb. 23, 2021

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response approximately one third these patients, remission obtained in 30% patients. This known as Treatment-Resistant Depression (TRD). The burden TRD exponentially increases the longer it persists, with higher risk impaired functional social functioning, vast losses quality life significant somatic morbidity suicidality. Different approaches have been suggested utilized, but results not encouraging. In this review article, we present new identify correct potential TRD, thereby reducing its prevalence overall disease entity. We will address contributory factors most which can be investigated many laboratories routine tests. discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation thyroid gonadal dysfunction. role Vitamin D contributing depression. Pharmacogenomic testing being increasingly used determine Single Nucleotide Polymorphisms Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As immune system recognized potentially major factor measurement C-reactive protein (CRP) select biomarkers, where available, guide combination treatments anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. focus on established emerging test procedures, biomarkers non-biologic assessments apply personalized medicine effectively manage resistance general specifically.

Language: Английский

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Risk Factors of Postpartum Depression

Cureus, Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 31, 2022

Postpartum depression (PPD) is a widespread mental health problem and one of the prime causes maternal suffering ill health. On global level, prevalence disorder about 10 to 15%. Symptoms generally appear within first four six weeks, which high-risk period. However, it may develop up year post-delivery. PPD presents with symptoms classical depression, including mood fluctuations, bouts crying, lack interest in child, even thoughts suicide. not only has adverse effects on mother’s but also hampers growth development child. It formation healthy mother-child bond, turn impact feeding practices. The social environment infant during few months primarily provided by mother, thus child’s development. increases susceptibility malnutrition. Research postpartum garnered momentum last years. masses are still largely unaware its implications. There an inadequacy awareness risk factors PPD. cross-cultural differences manifestations appropriate preventive measures have been extensively studied. Some for similar those classic depression; however, obstetrical pediatric involved. This literature review aims assess currently known PPD, their strength association, probable mechanisms help identify group enable implementation or facilitate early diagnosis. identified spanned sociodemographic, biological, psychological, obstetric domains. These included socioeconomic standing, marital relationship, history psychiatric illness, support, gestational diabetes, vitamin D deficiency, immigration status, delivery method, violence abuse, birth experience, biological epigenetic markers. numerous strong weak associations A previous depressive pregnancy, spousal support were most powerful factors. Other significant include complications low stressful life events. Studies age chronic illness as inconclusive. roles genetic markers, cultural factors, insufficiency require further investigation.

Language: Английский

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Phenomenology, Epidemiology and Aetiology of Postpartum Psychosis: A Review

Brain Sciences, Journal Year: 2021, Volume and Issue: 11(1), P. 47 - 47

Published: Jan. 4, 2021

Postpartum psychoses are a severe form of postnatal mood disorders, affecting 1–2 in every 1000 deliveries. These episodes typically present as acute mania or depression with psychosis within the first few weeks childbirth, which, life-threatening psychiatric emergencies, can have significant adverse impact on mother, baby and wider family. The nosological status postpartum remains contentious; however, evidence indicates most to be manifestations bipolar disorder vulnerability puerperal trigger. While childbirth appears potent trigger precise mechanisms by which occurs poorly understood. This review examines current respect potential aetiology childbirth-related triggers psychosis. Findings date implicated neurobiological factors, such hormones, immunological dysregulation, circadian rhythm disruption genetics, important pathogenesis this disorder. Prediction models, informed prospective cohort studies high-risk women, required identify those at greatest risk

Language: Английский

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The role of selenium in depression: a systematic review and meta-analysis of human observational and interventional studies

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Jan. 20, 2022

Abstract The results of human studies are inconsistent regarding selenium and depressive disorders. Therefore, we aimed to conduct a systematic review meta-analysis observational interventional provided an overview the role in depression. Three databases including Medline, Scopus, Web Science were searched on June 30, 2020 updated April 12, 2021. Also, electronical WHO Global Index Medicus ClinicalTrials.gov. No time or language restrictions used for search. A random effects model was pool effect sizes. In total, 20 included review, 15 meta-analysis. There no significant differences serum levels between patients with depression healthy subjects (WMD: 2.12 mg/L; 95% CI: − 0.11, 4.36; I 2 = 98.0%, P < 0.001). correlation found scores (r: 0.12; 0.33, 0.08; 73.5%, 0.010). Nevertheless, there negative association high intake risk postpartum (OR: 0.97; 0.95, 0.99; 0.0%, 0.507). addition, supplementation significantly reduced symptoms 0.37; 0.56, 0.18; 0.959). Taken these together, seems have protective against can be considered as beneficial adjuvant therapy Further necessary draw definitive conclusions.

Language: Английский

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Association between sleep disorders during pregnancy and risk of postpartum depression: a systematic review and meta-analysis

Archives of Women s Mental Health, Journal Year: 2023, Volume and Issue: 26(2), P. 259 - 267

Published: Feb. 4, 2023

Language: Английский

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Identifying risk factors for postpartum depression in Mashhad, Iran, 2017–2024: a population-based case-control study

Archives of Public Health, Journal Year: 2025, Volume and Issue: 83(1)

Published: March 3, 2025

Postpartum depression (PPD) is a common and debilitating disorder affecting mothers worldwide. This study aimed to identify risk factors the frequency of PPD in Mashhad, Iran. A population-based case-control was conducted using data from Sina Health Information System (SINAEHR) March 1, 2017, June 20, 2024. The Edinburgh Depression Scale used cases (score > 12) controls ≤ 12). Bivariate multivariate logistic regression analyses were performed determine associated with PPD. Among 108,952 women evaluated, 3,407 (3.03%) diagnosed matched an equal number controls. Significant for included maternal age 20 years (OR = 1.76, 95% CI: 1.31–2.36), history abortion 1.25, 1.15–1.42), cesarean delivery 1.22, 1.11–1.34), preterm 1.99, 1.67–2.37), twin births 2.10, 1.41–3.24), drug use 5.76, 2.90–11.33). Psychological strongly PPD, including anxiety 2.48, 2.06–2.93), domestic violence 4.08, 2.43–6.59), 5.31, 4.58–6.61), psychological distress 4.94, 3.91–6.23). identified multiple showing strongest associations. These findings highlight importance screening mental health issues providing targeted support high-risk during pregnancy postpartum period prevent manage effectively.

Language: Английский

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Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism

Nutrients, Journal Year: 2022, Volume and Issue: 14(6), P. 1229 - 1229

Published: March 14, 2022

Recent studies have reported a strong association between gestational diabetes mellitus (GDM) and postpartum depression (PPD), but little is known about the underlying physiological mechanism. In this study, GDM rat model was used to evaluate direct effect of on PPD explore After parturition, dams were divided into two groups: blood glucose not recovered group (GH group) (GL group). Fasting plasma (FPG), cortisol (COR) serotonin (5-hydroxytryptamine, 5-HT) metabolism continuously monitored during lactation period, until postnatal day 21. evaluated by behavioral tests. At endpoint, expression key enzymes Trp metabolic pathway in colon brain tissues analyzed immunohistochemistry western blot. The microbe composition colonic contents determined 16S rDNA gene sequencing. results showed that induced depression-like behavior rats. HPA axis hormone did show typical stress state depression, level 5-HT decreased significantly serum, prefrontal cortex hippocampus, Kyn/Trp ratio increased serum cortex, implying switch tryptophan (Trp) from kynurenine (Kyn) pathway. Indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme Kyn metabolism, up-regulated brain, which an important reason for switch. This accelerated decrease hydroxylase (TPH), production pathway, colon. displayed significant changes gut microbiome profiles, correlated with depression. Firmicutes Bacteroidetes decreased. Lactobacillus Bacteroides negatively positively level, whereas Clostridium XlVa Ruminococcus level. These suggest disrupts both microbiota, provide putative basis PPD.

Language: Английский

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Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy

Psychopharmacology, Journal Year: 2023, Volume and Issue: 240(9), P. 1841 - 1863

Published: Aug. 11, 2023

Abstract This article describes the critical role of neurosteroids in postpartum depression (PPD) and outlines landmark pharmacological journey brexanolone as a first-in-class neurosteroid antidepressant with significant advantages over traditional antidepressants. PPD is neuroendocrine disorder that affects about 20% mothers after childbirth characterized by symptoms including persistent sadness, fatigue, dysphoria, well disturbances cognition, emotion, appetite, sleep. The main pathology behind reduction neurosteroids, referred to withdrawal, concept pioneered our preclinical studies. We developed replacement therapy (NRT) rational approach for treating other conditions related deficiency, unveiling power novel anxiolytic-antidepressants. neurosteroid, (BX), progesterone-derived allopregnanolone rapidly relieves anxiety mood deficits activating GABA-A receptors, making it transformational treatment PPD. In 2019, FDA approved BX, an intravenous formulation allopregnanolone, NRT treat clinical studies, BX significantly improved within hours administration, tolerable side effects headache, dizziness, somnolence. identified molecular mechanism neuronal PPD-like milieu. involves activation both synaptic extrasynaptic which promote tonic inhibition serve key target conditions. Neurosteroids offer several antidepressants, rapid onset, unique mechanism, lack tolerance upon repeated use. Some limitations include aqueous solubility, limited accessibility, hospitalization treatment, oral product, serious adverse events at high doses. However, unmet need synthetic address this condition supersedes these limitations. Recently, we hydrophilic superior profile drug delivery. Overall, approval major milestone field neurotherapeutics, paving way development depression, epilepsy, status epilepticus. Graphical abstract

Language: Английский

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Prevalence and risk factors of postpartum depressive symptoms at 42 days among 2462 women in China

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 350, P. 706 - 712

Published: Jan. 21, 2024

Postpartum depression is a common and serious mental health problem that affecting an increasing percentage of the world's population. We aimed to evaluate prevalence postpartum depressive symptoms in Beijing, China, during COVID-19 pandemic identify several potential risk factors. This was cross-sectional observational study conducted at Peking University First Hospital from 2020 2021. Women who delivered had reviews 42 days after delivery were invited complete Chinese version Edinburgh Postnatal Depression Scale (EPDS) under guidance trained nurses. A score ≥10 used as threshold depression. t-tests, chi-square tests or Mann–Whitney U applied. multivariate logistic regression analysis assess factors for symptoms. total 2462 mothers included this study, 20.2 % whom considered have Multivariate showed formula feeding (OR = 2.219, 95 CI: 1.300–3.786, P 0.013), preterm birth 1.619, 1.108–2.367, cervical insufficiency 3.022, 1.200–7.615, 0.019) history 6.519, 1.537–27.659, 0.011) associated with high There developed regions China pandemic. More attention should be given PPD, follow-up care needed.

Language: Английский

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