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

Sáez, E. Rodríguez; Erkoreka, Leire; Moreno-Calle, T.; Berjano, Belen; González-Pinto, Ana; Basterreche, Nieves; Arrúe, Aurora

doi:10.5498/wjp.v12.i7.884

Cited by 10 publications

(5 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cognitive impairment is not a specific disease but a symptom, and studies have shown that AD is the most common cause of cognitive impairment in older individuals 9 . Mild cognitive impairment (MCI), which can be reversible or does not progress over time, is the best chance for the secondary prevention of AD 1,10 .…”

Section: Introductionmentioning

confidence: 99%

“…Cognitive impairment is not a specific disease but a symptom, and studies have shown that AD is the most common cause of cognitive impairment in older individuals. 9 Mild cognitive impairment (MCI), which can be reversible or does not progress over time, is the best chance for the secondary prevention of AD. 1,10 According to the World Health Organization's (WHO) Study on Global Aging and Adult Health, the true overall prevalence of MCI in China, Ghana, India, Mexico, Russia, and South Africa was 15.3% based on the criteria set by the National Institute on Aging/Alzheimer's Association (NIAAA).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cognitive status and its risk factors in patients with hypertension and diabetes in a low‐income rural area of China: A cross‐sectional study

Guo,

Liang,

Ren

et al. 2023

Int J Geriat Psychiatry

View full text Add to dashboard Cite

ObjectivesThe proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non‐communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas.MethodsA multi‐stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self‐designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi‐square test, ANOVA and multiple linear regression analysis.ResultsA total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87–3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16–2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34–0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U‐curve, the group with an annual income of 6000–7999 RMB had a maximum OR of 1.93 (95%CI 0.12–2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = −2.28, 95% CI–4.18–0.39, p = 0.018).ConclusionsParticipants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cognitive status and its risk factors in patients with hypertension and diabetes in a low‐income rural area of China: A cross‐sectional study

Guo,

Liang,

Ren

et al. 2023

Int J Geriat Psychiatry

View full text Add to dashboard Cite

show abstract

“…As for MDD, no directly related pathway was available in the KEGG database. Therefore, we selected four main pathways (Dopaminergic synapse (hsa04728), Glutamatergic synapse (hsa04724), Serotonergic synapse (hsa04726), and GABAergic synapse (hsa04727)) that have been implicated in MDD, serving as reference points [43][44][45][46] . Overall, after eliminating duplicate entries, we assembled a total of 288 genes associated with the four pathways representing MDD.…”

Section: Identification Of Longevity-associate Genes In Major Depress...mentioning

confidence: 99%

“…Therefore, in the case of MDD, the four KEGG pathways Dopaminergic synapse (hsa04728), Glutamatergic synapse (hsa04724), Serotonergic synapse (hsa04726), and GABAergic synapse (hsa04727) were selected to act as its reference points. We chose these four pathways to represent the MDD "pathway" because there is extensive evidence that dysregulation of these four pathways is associated with its development [43][44][45][46] . Using the KEGGREST package, we collected from the KEGG database the genes associated with each of the following pathways: Longevity regulating pathway (hsa04211), Cocaine addiction (hsa05030), Amphetamine addiction (hsa05031), Morphine addiction (hsa05032), Nicotine addiction (hsa05033), Dopaminergic synapse (hsa04728), Glutamatergic synapse (hsa04724), Serotonergic synapse (hsa04726), and GABAergic synapse (hsa04727).…”

Section: Comparison Of Kegg Longevity Regulating Pathway With Npds Re...mentioning

confidence: 99%

Molecular signatures of premature aging in Major Depression and Substance Use Disorders

Onisiforou,

Zanos,

Georgiou

2024

Sci Data

View full text Add to dashboard Cite

Major depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability to cognitive decline and other forms of dementia. This study utilized advanced systems bioinformatics to identify aging “signatures” in MDD and SUDs and evaluated the potential for known lifespan-extending drugs to target and reverse these signatures. The results suggest that inhibiting the transcriptional activation of FOS gene family members holds promise in mitigating premature aging in MDD and SUDs. Conversely, antidepressant drugs activating the PI3K/Akt/mTOR pathway, a common mechanism in rapid-acting antidepressants, may accelerate aging in MDD patients, making them unsuitable for those with comorbid aging-related conditions like dementia and Alzheimer’s disease. Additionally, this innovative approach identifies potential anti-aging interventions for MDD patients, such as Deferoxamine, Resveratrol, Estradiol valerate, and natural compounds like zinc acetate, genistein, and ascorbic acid, regardless of comorbid anxiety disorders. These findings illuminate the premature aging effects of MDD and SUDs and offer insights into treatment strategies for patients with comorbid aging-related conditions, including dementia and Alzheimer’s disease.

show abstract

“…NR2B has been identified to form the glutamate-binding pocket of NMDARs, indicating that ( R,S )-ketamine may interact directly with NR2B to modulate channel gating [17]. A reduction in human NR2B subunit expression was found in the prefrontal cortex (PFC) of patients with MDD as compared to controls [18], and 3 potentially functional SNPs that are considered risk variables for MDD and predictors of TRD were identified in the NR2B gene GRIN2B [19]. Furthermore, NR2B on principal cortical neurons is necessary for ( R,S )-ketamine’s effects in mice [20].…”

Section: Introductionmentioning

confidence: 99%

(R,S)-ketamine’s rapid-acting antidepressant effects are modulated by NR2B-containing NMDA receptors on adult-born hippocampal neurons

Bulthuis,

McGowan,

Ladner

et al. 2023

Preprint

View full text Add to dashboard Cite

Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, anN-methyl-D-aspartate (NMDA) antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the NR2B subunit of the NMDA receptor (NMDAR) on interneurons in the medial prefrontal cortex (mPFC), no study has investigated the influence of NR2B-expressing adult-born granule cells (abGCs). In this study, we examined whether (R,S)-ketamine’s efficacy depends upon these adult-born hippocampal neurons using a genetic strategy to selectively ablate the NR2B subunit of the NMDAR from Nestin+cells. To validate our findings, we also used several other transgenic lines including one in which NR2B was deleted from an interneuron (Parvalbumin (PV)+) population. We report that in male mice, NR2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamine’s effects on behavioral despair in the forced swim test (FST) and on hyponeophagia in the novelty suppressed feeding (NSF) paradigm, as well on fear behavior following contextual fear conditioning (CFC). In female mice, NR2B expression is necessary for effects on hyponeophagia in the NSF. We also find that ablating neurogenesis increases fear expression in CFC, which is buffered by (R,S)-ketamine administration. In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing NR2B partially modulate (R,S)-ketamine’s rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamine’s antidepressant actions.

show abstract

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

Cited by 10 publications

References 94 publications

Cognitive status and its risk factors in patients with hypertension and diabetes in a low‐income rural area of China: A cross‐sectional study

Cognitive status and its risk factors in patients with hypertension and diabetes in a low‐income rural area of China: A cross‐sectional study

Molecular signatures of premature aging in Major Depression and Substance Use Disorders

(R,S)-ketamine’s rapid-acting antidepressant effects are modulated by NR2B-containing NMDA receptors on adult-born hippocampal neurons

Contact Info

Product

Resources

About