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Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

ABSTRACT: Depression is a common, recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide. Up to 15%-40% of cases do not respond to diverse pharmacological treatments and, thus, can be defined as treatment-resistant depression (TRD). The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment. Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD. Specifically, the N-methyl-D-aspartic acid receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), which are targeted by ketamine and esketamine, are proposed as promising pathways. A literature search was performed to identify studies on the genetics of the glutamatergic system in depression, focused on variables related to NMDARs and AMPARs. Our review highlights GRIN2B, which encodes the NR2B subunit of NMDAR, as a candidate gene in the pathogenesis of TRD. In addition, several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation. These genes encoding glutamatergic receptors could, therefore, be candidate genes for understanding the etiopathogenesis of TRD, as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

SUBMITTER: Saez E

PROVIDER: S-EPMC9331449 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

Saez Estela E Erkoreka Leire L Moreno-Calle Teresa T Berjano Belen B Gonzalez-Pinto Ana A Basterreche Nieves N Arrue Aurora A

World journal of psychiatry 20220719 7

Depression is a common, recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide. Up to 15%-40% of cases do not respond to diverse pharmacological treatments and, thus, can be defined as treatment-resistant depression (TRD). The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment. Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD. Specifi ...[more]

PMID: 36051601

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Project description:ObjectiveReal-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade.Data sourcesA literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022. Bibliographies of all relevant identified systematic reviews and relevant conference proceedings from 2020 to 2022 were manually hand-searched.Study selectionReal-world studies, including cohort, cross-sectional, case-control, chart review and registry studies, published in English and reporting outcomes in adults with TRD, were included.Data extractionExtracted data included study and baseline disease characteristics, treatment type, treatment response, clinical outcomes and health-related quality of life.ResultsTwenty studies were included. Criteria for TRD varied, but patients typically experienced long-lasting depression (range 1.4 to 16.5 years). Across studies, mean disease severity scores demonstrated moderate to severe depression, reflecting a high burden of disease at baseline. Remission rates were typically low but generally increased with longer follow-up durations. However, the heterogeneity of interventions, follow-up durations (range 2 weeks to 9.4 years) and assessment tools precluded their quantitative synthesis. Studies were frequently limited by low sample size (range 14 to 411 patients) and health-related quality of life was infrequently assessed.ConclusionsThere is a lack of clinical consensus regarding the definition, assessment and monitoring of TRD in real-world practice. Nevertheless, TRD carries a high burden of illness and there is an unmet need for faster and more effective treatments. To better understand the personal burden of affected patients, future studies would benefit from standardisation of severity assessment and measures of treatment effectiveness, as well as greater consideration of health-related quality of life.

Project description:Since African swine fever virus (ASFV) genotype II reached Europe in 2007 and has widely spread, causing important economic losses to the pig production sector. To guide policy and management actions, robust quantitative evidence about possible explanatory variables associated with ASF in domestic pigs and Eurasian wild boar (Sus scrofa) is needed. To this aim, a systematic literature review of the scientific evidence available on variables analysed through quantitative methods investigating their possible association with ASF occurrence was carried out in 2021 and updated in 2024. Information on article metadata, study settings, and details of the analysed variables were extracted from the identified articles. The variables were structured in categories and subcategories, and their frequencies were evaluated, as well as the proportions of the studied variables that proved significant in each subcategory. The literature search retrieved 569 articles, resulting in 48 inclusions in the review after application of the selection criteria. The categories of variables most often significantly associated with the occurrence of ASF in domestic pigs were related to the ASF virus infection pressure in the area, socio-economic factors (mainly human population density and poverty), the pig farming system (pig or farm density and certain biosecurity practises), and wild boar habitats. For wild boars, these were also variables related to ASFV infection pressure in the area, wild boar habitats (mainly climatic conditions, vegetation, waterbodies), and socio-economic factors (especially human population and poverty-related variables). Despite the many studies of variables possibly associated with ASF occurrence, the review identified a gap in quantitative observational studies focusing on manageable variables, i.e., those related to specific biosecurity measures applied to pig farms and during hunting. To allow for a meta-analysis of the results, these studies should be performed according to standardised protocols using harmonised data collections.

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Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

Publications

Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

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