Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures

Molecules, Год журнала: 2024, Номер 29(5), С. 964 - 964

Опубликована: Фев. 22, 2024

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance monoamine hypothesis, resulting slow progress. Traditional ADs have undesirable traits like delayed onset action, limited efficacy, severe side effects. Recently, two categories fast-acting antidepressant compounds surfaced, dissociative anesthetics S-ketamine its metabolites, as well psychedelics such lysergic acid diethylamide (LSD). This led to research drug receptors they target. review provides breakthroughs achievements structure depression-related novel based on these. Cryo-electron microscopy (cryo-EM) enabled researchers identify structures membrane receptors, including N-methyl-D-aspartate receptor (NMDAR) 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution can be used for using virtual screening (VDS). Moreover, unique effects 5-HT1A various brain regions, pivotal roles α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPAR) tyrosine kinase 2 (TrkB) regulating synaptic plasticity, emphasize their potential therapeutic targets. Using information, series highly selective were designed different role MDD. molecules favorable characteristics rapid low adverse reactions. offers guidance methodological framework structure-based design ADs.

Язык: Английский

---

Associations between soluble urokinase plasminogen activator receptor (suPAR) concentration and psychiatric disorders – A systematic review and meta-analysis

Brain Behavior and Immunity, Год журнала: 2024, Номер 120, С. 327 - 338

Опубликована: Июнь 9, 2024

There is some evidence of an association between inflammation in the pathogenesis mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) a biomarker chronic inflammation, which provides more stable index systemic than widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations individuals with psychiatric disorder, determine if these are altered comparison healthy participants. Comprehensive literature searches from inception October 2023 were conducted five relevant databases (PubMed, Web Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses performed compare standardised mean difference blood levels (i.e. plasma or serum) for any disorder relative controls. Separate schizophrenia other psychotic and depressive disorder. Risk bias was assessed using Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding at high risk bias, either serum separately. The search identified 149 records. Ten full-text screened eligibility 9 review. Primary revealed no significant compared controls (k = 7, SMD 0.42, 95 % CI [−0.20, 1.04]). However, those had elevated 3, 0.61, [0.34, 0.87]). Similarly, secondary showed when excluded 6, 0.54, [−0.14, 1.22]), but found 0.98, [0.39, 1.58]). Furthermore, analysed 5, 0.84, [0.38, 1.29]), while measuring did not find 2, -0.61, [−1.27, 0.04]). For plasma, also When only considered, observed groups, although significantly detected moderate severe controls, samples found. A similar finding reported findings suggest inflammatory dysregulation may contribute pathology Future longitudinal required fully elucidate role this marker psychopathology

Язык: Английский

---

Immune dysregulation in psychiatric disorders with and without exposure to childhood maltreatment: A transdiagnostic stratified meta-analysis

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Childhood maltreatment (CM), i.e. physical, psychological, or sexual abuse and neglect, affects approximately one third of the general population is an important risk factor for all major psychiatric disorders. Exposure to CM also has a profound impact on immune function, with both factors independently implicated in development prognosis different mental This study aims 1) assess differences markers among adults diagnosed disorders without history 2) explore role as mediating abnormalities patients compared non-psychiatric controls. A PRISMA-compliant systematic search PubMed, Web Science Embase databases was performed until October 24th, 2024 original studies that assessed trauma-stratified adult (PROSPERO ID CRD42021273059). We modelled random-effects meta-analyses compare levels pro-inflammatory (PIM), anti-inflammatory (AIM) cellular (CIM) between traumatized (CM + ) non-traumatized (CM-) individuals, investigated exposure Secondary analyses were diagnostic subgroups individual markers. Study quality Newcastle Ottawa Scale. included data from 53 n = 12,141 mood (MD), schizophrenia spectrum (SSD), substance use (SUD), eating (ED) anxiety (AD). uncovered consistent transdiagnostic blood-based molecules (OR 1.186; 95 % CI 1.030-1.365, p 0.018) effect not observed controls same studies. did find evidence specific trauma-induced composite scores separate subgroups, except PIM SUD 2.324, 1.043-5.182, 0.039). Interleukin 6 (IL-6) identified significant mediator diagnosis adulthood 1.609; 1.100-2.353, 0.014), while increases C-reactive protein (CRP) 10 (IL-10) appear be trauma-specific. Our findings confirm increased molecular patients. IL-6 emerged crucial mediator, suggesting leads alterations predisposing individuals conditions. meta-analysis highlights potentially mechanism contributing vulnerability towards illness later life.

Язык: Английский

---

Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study

BMC Psychiatry, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 20, 2024

Abstract Background Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed assess role interleukin-2 (IL-2) interleukin-10 (IL-10) in pathophysiology development Methods This study recruited 50 GAD patients diagnosed according DSM-5 criteria 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all subjects. The socio-demographic clinical characteristics population were determined using pre-structured questionnaires or interviews, cytokine serum levels estimated commercially available ELISA kits. Results We observed reduced IL-10 compared HCs (33.69 ± 1.37 pg/ml vs. 44.12 3.16 pg/ml). Also, significant negative correlation between altered GAD-7 scores ( r =-0.315, p = 0.039). Moreover, measurement exhibited good predictive value receiver operating (ROC) analysis with an area under curve (AUC) 0.793 < 0.001) 80.65% sensitivity 62.79% specificity at cutoff 33.93 pg/ml. Conversely, noticed elevated IL-2 than (14.81 2.88 8.08 1.1 pg/ml); however, it failed maintain any association scores, implying might not be involved pathogenesis. lower AUC (0.640; > 0.05) ROC further supported associated Conclusion provides new insights into complex interplay anti-inflammatory Based on present findings, can assume but may However, research larger size longitudinal design required confirm diagnostic efficacy IL-10.

Язык: Английский

---

Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 2, 2024

In recent times, the pathogenesis of generalized anxiety disorder (GAD) and influence pro- anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research GAD patients, is limited. Here, we aim to assess role interleukin-17A (IL-17A) interleukin-23A (IL-23A) in pathophysiology development GAD. This investigation included 50 patients 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed with assessed symptom severity using DSM-5 GAD-7 scales. The serum concentrations IL-17A IL-23A were determined commercially available ELISA kits. exhibited elevated levels (77.14 ± 58.30 pg/ml) (644.90 296.70 compared HCs (43.50 25.54 pg/ml 334.40 176.0 pg/ml). We observed a positive correlation between disease changes (IL-23A: r = 0.359, p 0.039; IL-17A: 0.397, 0.032). These findings indicate that may be associated ROC analysis revealed moderately higher AUC values 0.824 0.710), demonstrating their potential discriminate HCs. Also, sensitivity both relatively 80.49% 77.27%). According present findings, there an association peripheral altered play directing early risk developing recommend further ascertain exact performance as assessment markers

Язык: Английский

---

Neuroinflammation and mental health outcomes in adolescents living with HIV

Current Opinion in HIV and AIDS, Год журнала: 2024, Номер 19(6), С. 355 - 360

Опубликована: Июль 10, 2024

Adolescents living with HIV show chronic inflammation, which in turn has been linked to mental health outcomes the general population. The increased risk for issues adolescents may thus be driven by HIV-related inflammation. In this review, we discuss associations between peripheral and central nervous system inflammation HIV.

Язык: Английский

---

Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12634 - 12634

Опубликована: Авг. 10, 2023

Over the past few decades, extensive research has shed light on immune alterations and significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to integrity both brain intestinal barriers, may play a crucial role origin peripheral central inflammation these pathologies. Sphingosine-1-phosphate (S1P) is bioactive lipid that regulates response permeability barriers. Notably, S1P-based drugs, such as fingolimod ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease nervous system (CNS), ulcerative colitis, inflammatory condition colon, respectively. Although precise mechanisms action are still under investigation, effectiveness drugs pathologies sparks debate extending their use psychiatry. This comprehensive review aims delve into molecular through which S1P modulates brain/intestinal barrier functions. Furthermore, it will specifically focus diseases, with primary objective uncovering potential innovative therapies based signaling.

Язык: Английский

---

Systemic concentrations of IL-18, TFG-, RANTES, ICAM-1 and uPAR as combined pathway-related factors may help in identification of patients suffering from depressive disorder

Archives of Medical Science, Год журнала: 2024, Номер 20(1), С. 348 - 353

Опубликована: Фев. 2, 2024

1. Ruiz NAL, Del Ángel DS, Brizuela NO, et al. Inflammatory process and immune system in major depressive disorder. Int J Neuropsychopharmacol 2022; 25: 46–53. Google Scholar

Язык: Английский

---

Mesenchymal Stem Cells Improve Depressive Disorder via Inhibiting the Inflammatory Polarization of Microglia

Journal of Psychiatric Research, Год журнала: 2024, Номер 179, С. 105 - 116

Опубликована: Сен. 8, 2024

Язык: Английский

---

Serum TNFα and IL-17A levels may predict increased depressive symptoms: findings from the Shika Study cohort project in Japan

BioPsychoSocial Medicine, Год журнала: 2024, Номер 18(1)

Опубликована: Окт. 2, 2024

Язык: Английский

---