Candidate gene study reveals DRD1 and DRD2 as putative interacting risk factors for youth depression

Corrales, Eyleen; Navarro, Arcadi; Cuenca, Patricia; Campos, Domingo

doi:10.1016/j.psychres.2016.07.032

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…D2 receptors are associated with Gi proteins to inhibit production of the cAMP. Nevertheless, recently, it was suggested that an imbalance of D1R/D2R heteromers could be related to depressive symptoms in youngsters (Corrales et al 2016 ). Putative D1/D2 receptor heterodimers have been suggested to regulate diacylglycerol and IP 3 signaling by activating Gq (Rashid et al 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IP3R1 Complex

et al. 2017

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Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). Aim of this work was to investigate possible changes in IP3Rs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IP3Rs (IP3R1s) and σ1Rs at mRNA and protein levels. Haloperidol treatment did not alter expression of other types of IP3Rs. Calcium release from endoplasmic reticulum (ER) mediated by increased amount of IP3R1s elevated cytosolic calcium and generated ER stress. IP3R1s were bound to σ1Rs, and translocation of this complex from ER to nucleus occurred in the group of cells treated with haloperidol, which was followed by increased nuclear calcium levels. Haloperidol-induced changes in cytosolic, reticular, and nuclear calcium levels were similar when specific σ1 blocker -BD 1047- was used. Changes in calcium levels in nucleus, ER, and cytoplasm might be responsible for alterations in cellular plasticity, because length of neurites increased and number of neurites decreased in haloperidol-treated differentiated NG-108 cells.

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Section: Introductionmentioning

confidence: 99%

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IP3R1 Complex

et al. 2017

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“…Genetic factors may promote or even cause the occurrence of depression (21). A systematic review found that major histocompatibility complex, class I-related gene polymorphisms, and glutamate decarboxylase (GAD) genes ( GAD1 and GAD2 ) contributed to the development of depression (22).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the underling mechanism of ketamine for antidepressant effects in treatment‑refractory affective disorders via molecular profile analysis

Qiao

Sun

et al. 2019

Exp Ther Med

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Ketamine elicits a rapid antidepressant effect in treatment-refractory affective disorders. The aim of the present study was to elucidate the underlying mechanism of this effect and to identify potential targets of ketamine for antidepressant effects. GSE73798 and GSE73799 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in hippocampus or striatum samples treated with ketamine, phencyclidyne or memantine compared with a saline or normal group at 1, 2, 4 and 8 h. The overlapping DEGs were the DEGs in both hippocampus and striatum samples. Kyoto Encyclopedia of Genes and Genomes and BioCyc databases were used to perform functional annotation and pathway analyses. Protein-protein interactions (PPIs) were predicted using Search Tool for the Retrieval of Interacting Genes/Proteins version 9.1 for the DEGs in the striatum samples treated with ketamine, phencyclidine or memantine compared with normal samples. Reverse transcription-quantitative polymerase chain reaction was performed to determine mRNA levels. Perilipin 4 (Plin4) , serum/glucocorticoid regulated kinase 1 (Sgk1) , kruppel like factor 2 (Klf2) and DDB1 and CUL4 associated factor 12 like 1 (Dcaf12l1) were the overlapping DEGs in the striatum samples treated with the three drugs at different time points. The mRNA expression levels of Plin4, Sgk1 and Klf2 were significantly higher (P<0.05), and the mRNA expression level of Dcaf12l1 was significantly lower in the striatum samples of the ketamine-treated group compared with the control group in an in vivo experiment. Both Sgk1 and Klf2 were enriched in the ‘forkhead box O (FoxO) signaling pathway’, and Sgk1 was additionally enriched in the ‘mechanistic target of rapamycin kinase (mTOR) signaling pathway’. PPI networks of DEGs in the striatum samples treated with ketamine, phencyclidine and memantine compared with normal samples were constructed, and Klf2 was involved in more pairs and was therefore a gene hub in the three networks. The four genes, Plin4, Sgk1, Klf2 and Dcaf12l1 , were differentially expressed in all of the groups that treated with the three drugs and their expression levels were verified in in vivo experiments. The FoxO and mTOR signaling pathways may be involved in the underlying mechanism of the antidepressant effects of ketamine, and Plin4, Sgk1, Klf2 and Dcaf12l1 may be potential biomarkers for depression in N-methyl-D-aspartic acid receptor antagonist treatment.

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“…Pearson-Fuhrhop et al [ 41 ] explored the effect of dopamine genetic risk scores for polymorphisms in five genes involved in the dopaminergic system (including 1 SNP in the DRD1 gene, located on the 5’UTR) on depressive symptoms and in a subsample of healthy participants, analyzed with the CES-D scale, this association was significant. Corrales et al analyzed 170 SNPs in 21 candidate dopaminergic and serotonergic genes (including other 5 SNPs in DRD1 gene, one of them located on the 5’UTR) in a sample of healthy children and adolescents from Costa Rica, assessed for depressive symptoms using the Child Depression Inventory (CDI) and none of these polymorphisms were significant [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

A Functional Polymorphism in the DRD1 Gene, That Modulates Its Regulation by miR-504, Is Associated with Depressive Symptoms

Jiménez

Pereira-Morales

Forero

2018

Psychiatry Investig

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ObjectiveThe aim of this study was to examine a possible association between depressive symptoms and a functional polymorphism (rs686) that modulates the regulation of DRD1 gene by miR-504.MethodsA total of 239 young Colombian subjects were evaluated with the Patient Health Questionnaire-9 (PHQ-9) scale and genotyped for the rs686 polymorphism. A linear regression model, corrected by age and gender, was used.ResultsA significant association between the rs686 polymorphism and PHQ-9 scores was found, under a dominant genetic model (p=0.0094).ConclusionThese results provide novel evidence about the growing role of inherited variants in binding sites for brain-expressed miRNAs on depressive symptomatology.

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Candidate gene study reveals DRD1 and DRD2 as putative interacting risk factors for youth depression

Cited by 11 publications

References 43 publications

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IP3R1 Complex

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IP3R1 Complex

Investigation of the underling mechanism of ketamine for antidepressant effects in treatment‑refractory affective disorders via molecular profile analysis

A Functional Polymorphism in the DRD1 Gene, That Modulates Its Regulation by miR-504, Is Associated with Depressive Symptoms

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