Dimensional Traits of Schizotypy Associated With Glycine Receptor <i>GLRA1</i> Polymorphism: An Exploratory Candidate-Gene Association Study

Vora, Anvi; Fisher, Amanda; New, Antonia S.; Hazlett, Erin A.; McNamara, Margaret; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin A.; Goldman, David; Siever, Larry J.; Roussos, Panos; Perez‐Rodriguez, M. Mercedes

doi:10.1521/pedi_2017_31_303

Cited by 7 publications

(2 citation statements)

References 40 publications

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“…By finding the closest DE expressed protein coding genes to DE ncRNAs between HFP and LFP chickens we were able to identify 21 putative eRNAs (Table 1). Among possible targets of these eRNA candidates are ARHGEF38 and SH3YL1, which have been linked to bipolar disorder and suicide [47,48], GLRA1 and MCTP2 were found to be associated with schizophrenia [49,50], and CHIR-B3, MHCIA7, MHCIY as well as MICA are genes involved in the immune system [51]. Thus, further experiments, like overexpression studies, will help to clarify the involvement of particular ncRNAs in FP.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

et al. 2020

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Background: Feather pecking (FP) in laying hens reduces animal welfare and leads to economic losses for the layer industry. FP is considered a heritable condition that is influenced by dysregulation of neurotransmitter homeostasis, the gut microbiome, and the immune system. To identify genes and biological pathways responsible for FP behavior we compared the brain transcriptomes of 48 hens divergently selected for FP. In addition, we tested if high feather peckers (HFP) and low feather peckers (LFP) respond differently to light since light has been shown to trigger FP behavior. Results: Of approximately 48 million reads/sample an average of 98.4% were mapped to the chicken genome (GRCg6a). We found 13,070 expressed genes in the analyzed brains of which 423 showed differential expression between HFP and LFP. Genes of uncertain function and non-coding RNAs were overrepresented among those transcripts. Functional analyses revealed the involvement of cholinergic signaling, postsynaptic activity, membrane channels, and the immune system. After the light stimulus, 28 genes were found to be differentially expressed. These included an interaction cluster of core components of the circadian clock. However, differences in the response to light between HFP and LFP were not detectable. Conclusions: Genes involved in cholinergic signaling, channel activity, synaptic transmission, and immune response were found to be involved in FP behavior. We propose a model in which the gut microbiota modulates the immune system, which in turn affects cholinergic signaling. This might have an influence on monoamine signaling with possible involvement of GABA or glutamate signaling.

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Section: Discussionmentioning

confidence: 99%

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

et al. 2020

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“…Treatment-Resistant Schizophrenia and Glycine Signaling subunit (GLRA1) gene, and dimensional schizotypy, specifically with the disorganized symptoms cluster (199). Further support for a role of the glycinergic system comes from a genetic-metabolomic study (200), which showed that 5-oxoproline, aspartate, and glutamate, known to affect NMDAR function, were significantly elevated in patients with rare variants in genes encoding for the glycine cleavage system.…”

Section: Genetics Of Glycinergic Pathway In Schizophreniamentioning

confidence: 99%

Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia

Bartolomeis¹,

Manchia

Marmo³

et al. 2020

Front. Psychiatry

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Treatment-resistant schizophrenia (TRS) or suboptimal response to antipsychotics affects almost 30% of schizophrenia (SCZ) patients, and it is a relevant clinical issue with significant impact on the functional outcome and on the global burden of disease. Among putative novel treatments, glycine-centered therapeutics (i.e. sarcosine, glycine itself, D-Serine, and bitopertin) have been proposed, based on a strong preclinical rationale with, however, mixed clinical results. Therefore, a better appraisal of glycine interaction with the other major players of SCZ pathophysiology and specifically in the framework of dopamineglutamate interactions is warranted. New methodological approaches at cutting edge of technology and drug discovery have been applied to study the role of glycine in glutamate signaling, both at presynaptic and post-synaptic level and have been instrumental for unveiling the role of glycine in dopamine-glutamate interaction. Glycine is a non-essential amino acid that plays a critical role in both inhibitory and excitatory neurotransmission. In caudal areas of central nervous system (CNS), such as spinal cord and brainstem, glycine acts as a powerful inhibitory neurotransmitter through binding to its receptor, i.e. the Glycine Receptor (GlyR). However, glycine also works as a coagonist of the N-Methyl-D-Aspartate receptor (NMDAR) in excitatory glutamatergic neurotransmission. Glycine concentration in the synaptic cleft is finely tuned by glycine transporters, i.e. GlyT1 and GlyT2, that regulate the neurotransmitter's reuptake, with the first considered a highly potential target for psychosis therapy. Reciprocal regulation of dopamine and glycine in forebrain, glycine modulation of glutamate, glycine signaling interaction with postsynaptic density proteins at glutamatergic synapse, and human genetics of glycinergic pathways in SCZ are tackled in order to highlight the exploitation of this neurotransmitters and related molecules in SCZ and TRS.

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Current Knowledge on Gene-Environment Interactions in Personality Disorders: an Update

Bulbena-Cabré

Nia

Perez‐Rodriguez

2018

Curr Psychiatry Rep

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Research supports that susceptibility genes to BPD or its underlying traits may be expressed under certain environmental conditions such as physical or childhood sexual abuse. Epigenetic modifications of neurodevelopment- and stress-related genes are suggested to underlie the relationship between early life adversary and borderline personality disorder. Only limited studies have investigated the role of gene-environment interactions and epigenetic changes in the genesis of antisocial, schizotypal, and avoidant personality disorders. Considering the lack of pharmacological treatment for most personality disorders, the emerging evidence on the critical role of G×E and epigenetic changes in the genesis of personality disorders could help develop more biologically oriented therapeutic approaches. Future studies should explore the potential of this new therapeutic dimension.

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Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study

Cited by 7 publications

References 40 publications

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia

Current Knowledge on Gene-Environment Interactions in Personality Disorders: an Update

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