The associations of <i>CNR1</i> SNPs and haplotypes with vulnerability and treatment response phenotypes in Han Chinese with major depressive disorder: A case–control association study

Yang, Chenghao; Nolte, Ilja M.; Ma, Yanyan; An, Xuguang; Bosker, Fokko J.; Li, Jie

doi:10.1002/mgg3.1752

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…The CUX2 gene exhibited the greatest positive correlation and high expression in the primary sensory and visual cortex. As a key component of the endocannabinoid system, the CNR1 contributed to the support of the molecular architecture of processing reward and perception of certain basic emotions, and was even regarded as a promising genetic predictor for diagnosis of MDD and treatment response to antidepressants (Icick et al, 2015 ; Yang, Nolte, et al, 2021 ; Yao et al, 2018 ). For example, previous research has shown that variations in CNR1 modulated the striatal response to emotional faces (Anderson, Collins, Chin, et al, 2020 ; Mecca et al, 2021 ; Tsuboi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Compressed primary‐to‐transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder

Xiao,

Zhao,

Zang

et al. 2023

Human Brain Mapping

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Major depressive disorder (MDD) has been shown to involve widespread changes in low‐level sensorimotor and higher‐level cognitive functions. Recent research found that a primary‐to‐transmodal gradient could capture a cortical hierarchical organization ranging from perception and action to cognition in healthy subjects, but a prominent gradient dysfunction in MDD patients. However, whether and how this cortical gradient is linked to subcortical impairments and whether it is reflected in the microscale neurotransmitter systems and cell type‐specific transcriptional signatures remain largely unknown. Data were acquired from 323 MDD patients and 328 sex‐ and age‐matched healthy controls derived from the REST‐meta‐MDD project, and the human brain neurotransmitter systems density maps and gene expression data were drawn from two publicly available datasets. We investigated alterations of the primary‐to‐transmodal gradient in MDD patients and their correlations with clinical symptoms of depression and anxiety, as well as their paralleled subcortical impairments. The correlations between MDD‐related gradient alterations and densities of the neurotransmitter systems and gene expression information were assessed, respectively. The results demonstrated that MDD patients had a compressed primary‐to‐transmodal gradient accompanied by paralleled alterations in subcortical regions including the caudate, amygdala, and thalamus. The case–control gradient differences were spatially correlated with the densities of the neurotransmitter systems including the serotonin and dopamine receptors, and meanwhile with gene expression enriched in astrocytes, excitatory and inhibitory neuronal cells. These findings mapped the paralleled subcortical impairments in cortical hierarchical organization and also helped us understand the possible molecular and cellular substrates of the co‐occurrence of high‐level cognitive impairments with low‐level sensorimotor abnormalities in MDD.

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Section: Discussionmentioning

confidence: 99%

Compressed primary‐to‐transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder

Xiao,

Zhao,

Zang

et al. 2023

Human Brain Mapping

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“…Longer AAT repeat expansions can produce a Z-shaped DNA conformation, thereby potentially downregulating gene transcription [ 111 ]. In this context, the CNR1 SNPs rs6454674 and rs806367 have been indicated to increase vulnerability to major depressive disorder and resistance to antidepressant treatment [ 114 ]. However, a recent meta-analysis did not reveal an association between CNR1 rs1049353 or AAT repeat polymorphism with depression risk [ 115 ].…”

Section: Genetic Factors Associated With Depression In Idiopathic Par...mentioning

confidence: 99%

Genetic Insights into the Molecular Pathophysiology of Depression in Parkinson’s Disease

et al. 2023

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Background and Objectives: Parkinson’s disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies. Materials and Methods: we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression. Results: in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene, SLC6A4, tryptophan hydrolase-2 gene, TPH2), dopamine metabolism and neurotransmission (dopamine receptor D3 gene, DRD3, aldehyde dehydrogenase 2 gene, ALDH2), neurotrophic factors (brain-derived neurotrophic factor gene, BDNF), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene, TEF), the sodium-dependent neutral amino acid transporter B(0)AT2 gene, SLC6A15), and PARK16 genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (SLC6A3), monoamine oxidase A (MAOA) and B (MAOB) genes, catechol-O-methyltransferase gene (COMT), CRY1, and CRY2 have not been related to PD depression. Conclusions: the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.

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“…The haplotype comprising rs806366, rs806367, rs806368, and rs806370 SNPs was associated with the vulnerability to develop MDD and resistance to antidepressant therapy. They hypothesized that CNR1 genetic polymorphisms are associated with a higher probability of developing MDD and within depressed patients with a higher likelihood of resistance to antidepressant treatment [234] (Table 6).…”

Section: Clinical Studiesmentioning

confidence: 99%

“…In WT mice, LY2828360 blocked morphine-induced reward in a CPP paradigm, whereas morphine-induced reward was absent in CB2r KO mice. LY2828360 partially attenuated naloxone-precipitated opioid withdrawal in morphine-dependent WT mice, whereas this withdrawal was markedly exacerbated in CB2r KO mice [474] Animals Maternally deprived adolescent rats Maternally deprived adolescent rats exhibited ↑ AEA in the NAcc, the Cpu nucleus, and the mesencephalon Maternally deprived adult rats, showed ↑ AEA and 2-AG in the NAcc, and ↑ 2-AG in the CPu nucleus [177,273,275] [193,195,196,230,231,233,269,271,271, 276,375,376,396,397,430,434] [134] [234,271,396] [234] [234,269,270,375,396,430,434,451,460,470] [396]…”

Section: Authorsmentioning

confidence: 99%

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro

Gasparyan

Navarrete

et al. 2022

IJMS

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The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

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The associations of CNR1 SNPs and haplotypes with vulnerability and treatment response phenotypes in Han Chinese with major depressive disorder: A case–control association study

Cited by 6 publications

References 49 publications

Compressed primary‐to‐transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder

Compressed primary‐to‐transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder

Genetic Insights into the Molecular Pathophysiology of Depression in Parkinson’s Disease

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

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