New investigational agents for the treatment of major depressive disorder

Pochwat, Bartłomiej; Krupa, Anna; Siwek, Marcin; Szewczyk, Bernadeta

doi:10.1080/13543784.2022.2113376

Cited by 8 publications

(7 citation statements)

References 135 publications

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“…Dysfunction of glutamatergic neurotransmission is well established in depression [ 33 ]. Targeting the regulation of glutamate and glutamatergic-related pathways may contribute to the development of novel antidepressants (such as esketamine, approved by the FDA for the treatment of treatment-resistant depression) [ 34 , 35 , 36 ]. The interaction between PrP c and glutamate receptors represents a new direction in neuropsychiatric research.…”

Section: The Function Of the Prion Protein (Prp C ...mentioning

confidence: 99%

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

Chrobak,

Pańczyszyn-Trzewik,

Król

et al. 2024

IJMS

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Mood disorders are highly prevalent and heterogenous mental illnesses with devastating rates of mortality and treatment resistance. The molecular basis of those conditions involves complex interplay between genetic and environmental factors. Currently, there are no objective procedures for diagnosis, prognosis and personalization of patients’ treatment. There is an urgent need to search for novel molecular targets for biomarkers in mood disorders. Cellular prion protein (PrPc) is infamous for its potential to convert its insoluble form, leading to neurodegeneration in Creutzfeldt-Jacob disease. Meanwhile, in its physiological state, PrPc presents neuroprotective features and regulates neurotransmission and synaptic plasticity. The aim of this study is to integrate the available knowledge about molecular mechanisms underlying the impact of PrPc on the pathophysiology of mood disorders. Our review indicates an important role of this protein in regulation of cognitive functions, emotions, sleep and biological rhythms, and its deficiency results in depressive-like behavior and cognitive impairment. PrPc plays a neuroprotective role against excitotoxicity, oxidative stress and inflammation, the main pathophysiological events in the course of mood disorders. Research indicates that PrPc may be a promising biomarker of cognitive decline. There is an urgent need of human studies to elucidate its potential utility in clinical practice.

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Section: The Function Of the Prion Protein (Prp C ...mentioning

confidence: 99%

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

Chrobak,

Pańczyszyn-Trzewik,

Król

et al. 2024

IJMS

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“…The racemic ketamine comprises both esketamine and arketamine, which could potentially result in increased effectiveness and a distinct safety profile in the clinical setting, in comparison to esketamine ( 9 ). Furthermore, there is evidence that TRD patients might benefit from ketamine ( 10 ). These findings provide compelling evidence supporting the use of ketamine for its rapid-acting antidepressant effects in MDD.…”

Section: Introductionmentioning

confidence: 99%

Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression

Kwaśny,

Cubała,

Włodarczyk

2024

Front. Psychiatry

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BackgroundAnhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties.MethodsThis post-hoc analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment.ResultsResults show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p<0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p’s<0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up.DiscussionThere is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.

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“…Recently, the research hotspot has been the identification of non‐monoamine‐based antidepressants. Most clinically used are antidepressants synthetic compounds, such as selective 5‐hydroxytryptamine reuptake inhibitors (SSRIs) 4 . Although the currently applied treatment regime alleviates depression, the symptoms are not completely resolved in about 50% of the cases and the remission rates in individuals who failed initial treatment are even worse 2,5 .…”

Section: Introductionmentioning

confidence: 99%

Engeletin alleviates depression‐like phenotype by increasing synaptic plasticity via the BDNF‐TrkB‐mTORC1 signalling pathway

Xu,

Zhang,

et al. 2023

J Cellular Molecular Medi

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Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first‐line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side‐effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural Smilax glabra rhizomilax derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity‐linked protein expressions and the brain‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB)‐ mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA‐12 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant‐like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF‐TrkB‐mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity‐linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF‐TrkB‐mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.

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New investigational agents for the treatment of major depressive disorder

Cited by 8 publications

References 135 publications

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression

Engeletin alleviates depression‐like phenotype by increasing synaptic plasticity via the BDNF‐TrkB‐mTORC1 signalling pathway

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