Brain Volume-Related Polymorphisms of the Glycogen Synthase Kinase-3β Gene and Their Effect on Antidepressant Treatment in Major Depressive Disorder

2019 ◽  
Vol 78 (3) ◽  
pp. 136-144 ◽  
Author(s):  
Naotaka Sunada ◽  
Yoshiteru Takekita ◽  
Shinpei Nonen ◽  
Masataka Wakeno ◽  
Yosuke Koshikawa ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Jiarun Yang ◽  
Siyuan Ke ◽  
Zhengxue Qiao ◽  
Xiuxian Yang ◽  
Xiaohui Qiu ◽  
...  

Background: Recent studies suggest that glycogen synthase kinase (GSK)-3β is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3β polymorphism (rs6438552, rs334558, and rs2199503) and negative life events in the pathogenesis of major depressive disorder (MDD).Methods: DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A chi-square method was employed to assess the gene-environment interaction (G × E).Results: Differences in rs6438552, rs334558, and rs2199503 genotype distributions were observed between MDD patients and controls. Significant G × E interactions between allelic variation of rs6438552, rs334558, and rs2199503 and negative life events were observed. Individuals with negative life events and carrying genotypes of rs6438552 A+, rs334558 A+, and rs2199503G+ have increased the risk of depression.Conclusions: These results indicate that interactions between the GSK-3β rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.


2012 ◽  
Vol 24 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Dong Hoon Oh ◽  
Seon-Cheol Park ◽  
Yong Chon Park ◽  
Seok Hyeon Kim

Objective: We showed previously that glycogen synthase kinase-3β (GSK-3β) levels are significantly elevated in the hippocampi of patients with major depressive disorder (MDD). However, the exact cause of this elevation and its function are unknown. Recent animal studies have suggested a mechanism involving the N-methyl-d-aspartate (NMDA) NR2B–GSK-3β loop.Methods: To investigate the existence of an NR2B–GSK-3β loop in the hippocampi of patients with MDD, we examined the expression of NR2B. We also attempted to identify markers that correlate with NR2B levels in the hippocampus, using the Stanley Neuropathology Consortium Integrative Database (SNCID). The SNCID is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets.Results: We found that hippocampal levels of NR2B and DLGAP1 mRNA were higher in the MDD group (n = 8) than in unaffected controls (n = 12) (p < 0.05). NR2B expression levels were correlated with the expression levels of NR2A, NR1, DLGAP1, GSK-3β and nitric oxide synthase 1, as well as with the number of calretinin-immunoreactive neurons in the hippocampus in all subjects in the SNC (n = 42, p < 0.001).Conclusion: The results of our study show the possible involvement of excessive activation of the NR2B–GSK-3β loop in the overexpression of GSK-3β in the hippocampi of patients with MDD.


2017 ◽  
Vol 41 (S1) ◽  
pp. S529-S529
Author(s):  
B. Grancini ◽  
B. Dell’Osso ◽  
L. Cremaschi ◽  
F. De Cagna ◽  
B. Benatti ◽  
...  

IntroductionMajor depressive disorder (MDD) is a prevalent burdensome disease, which frequently remains untreated. The duration of untreated illness (DUI) is modifiable parameter and a valid predictor of outcome. Previous investigation in patients with MDD revealed a DUI of different years, while recent reports have documented a reduction of DUI across time, in patients with different psychiatric disorders.Objectives/aimsThe present study was aimed to investigate potential differences in terms of DUI and related variables in patients with MDD across time.MethodsAn overall sample of 188 patients with MDD was divided in two subgroups on the basis of their epoch of onset (onset before and after year 2000). DUI and other onset-related variables were assessed through a specific questionnaire and compared between the two subgroups.ResultsThe whole sample showed a mean DUI of approximately 4.5 years, with a lower value in patients with more recent onset compared to the other subgroup (27.1 ± 42.6 vs. 75.8 ± 105.2 months, P < .05). Moreover, patients with onset after 2000 reported higher rates of onset-related stressful events and lower ones for benzodiazepines prescription (65% vs. 81%; P = 0.02; 47% vs. 30%; P = 0.02).ConclusionsThe comparison of groups with different epochs of onset showed a significant reduction in terms of DUI and benzodiazepines prescription, and a higher rate of onset-related stressful events in patients with a more recent onset. Reported findings are of epidemiologic and clinical relevance in order to evaluate progress and developments in the diagnostic and therapeutic pathways of MDD in Italian and other countries.Disclosure of interestThe authors have not supplied their declaration of competing interest.


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