Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions

G-protein-coupled receptors (GPCRs) play an integral role in the neurobiology of psychiatric disorders. Almost all neurotransmitters involved in psychiatric disorders act through GPCRs, and GPCRs are the most common targets of therapeutic drugs currently used in the treatment of psychiatric disorder...

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Autores principales:	Roudabeh Vakil Monfared, Wedad Alhassen, Tri Minh Truong, Michael Angelo Maglalang Gonzales, Vincent Vachirakorntong, Siwei Chen, Pierre Baldi, Olivier Civelli, Amal Alachkar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	GPCRs psychiatric disorders transcriptomics age-dependent expression Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/427ce6a776f4444da7c73d7c71cf9123
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spelling	oai:doaj.org-article:427ce6a776f4444da7c73d7c71cf91232021-11-25T17:09:53ZTranscriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions10.3390/cells101129672073-4409https://doaj.org/article/427ce6a776f4444da7c73d7c71cf91232021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2967https://doaj.org/toc/2073-4409G-protein-coupled receptors (GPCRs) play an integral role in the neurobiology of psychiatric disorders. Almost all neurotransmitters involved in psychiatric disorders act through GPCRs, and GPCRs are the most common targets of therapeutic drugs currently used in the treatment of psychiatric disorders. However, the roles of GPCRs in the etiology and pathophysiology of psychiatric disorders are not fully understood. Using publically available datasets, we performed a comprehensive analysis of the transcriptomic signatures of G-protein-linked signaling across the major psychiatric disorders: autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD). We also used the BrainSpan transcriptomic dataset of the developing human brain to examine whether GPCRs that exhibit chronological age-associated expressions have a higher tendency to be dysregulated in psychiatric disorders than age-independent GPCRs. We found that most GPCR genes were differentially expressed in the four disorders and that the GPCR superfamily as a gene cluster was overrepresented in the four disorders. We also identified a greater amplitude of gene expression changes in GPCRs than other gene families in the four psychiatric disorders. Further, dysregulated GPCRs overlapped across the four psychiatric disorders, with SCZ exhibiting the highest overlap with the three other disorders. Finally, the results revealed a greater tendency of age-associated GPCRs to be dysregulated in ASD than random GPCRs. Our results substantiate the central role of GPCR signaling pathways in the etiology and pathophysiology of psychiatric disorders. Furthermore, our study suggests that common GPCRs’ signaling may mediate distinct phenotypic presentations across psychiatric disorders. Consequently, targeting these GPCRs could serve as a common therapeutic strategy to treat specific clinical symptoms across psychiatric disorders.Roudabeh Vakil MonfaredWedad AlhassenTri Minh TruongMichael Angelo Maglalang GonzalesVincent VachirakorntongSiwei ChenPierre BaldiOlivier CivelliAmal AlachkarMDPI AGarticleGPCRspsychiatric disorderstranscriptomicsage-dependent expressionBiology (General)QH301-705.5ENCells, Vol 10, Iss 2967, p 2967 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GPCRs psychiatric disorders transcriptomics age-dependent expression Biology (General) QH301-705.5
spellingShingle	GPCRs psychiatric disorders transcriptomics age-dependent expression Biology (General) QH301-705.5 Roudabeh Vakil Monfared Wedad Alhassen Tri Minh Truong Michael Angelo Maglalang Gonzales Vincent Vachirakorntong Siwei Chen Pierre Baldi Olivier Civelli Amal Alachkar Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
description	G-protein-coupled receptors (GPCRs) play an integral role in the neurobiology of psychiatric disorders. Almost all neurotransmitters involved in psychiatric disorders act through GPCRs, and GPCRs are the most common targets of therapeutic drugs currently used in the treatment of psychiatric disorders. However, the roles of GPCRs in the etiology and pathophysiology of psychiatric disorders are not fully understood. Using publically available datasets, we performed a comprehensive analysis of the transcriptomic signatures of G-protein-linked signaling across the major psychiatric disorders: autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD). We also used the BrainSpan transcriptomic dataset of the developing human brain to examine whether GPCRs that exhibit chronological age-associated expressions have a higher tendency to be dysregulated in psychiatric disorders than age-independent GPCRs. We found that most GPCR genes were differentially expressed in the four disorders and that the GPCR superfamily as a gene cluster was overrepresented in the four disorders. We also identified a greater amplitude of gene expression changes in GPCRs than other gene families in the four psychiatric disorders. Further, dysregulated GPCRs overlapped across the four psychiatric disorders, with SCZ exhibiting the highest overlap with the three other disorders. Finally, the results revealed a greater tendency of age-associated GPCRs to be dysregulated in ASD than random GPCRs. Our results substantiate the central role of GPCR signaling pathways in the etiology and pathophysiology of psychiatric disorders. Furthermore, our study suggests that common GPCRs’ signaling may mediate distinct phenotypic presentations across psychiatric disorders. Consequently, targeting these GPCRs could serve as a common therapeutic strategy to treat specific clinical symptoms across psychiatric disorders.
format	article
author	Roudabeh Vakil Monfared Wedad Alhassen Tri Minh Truong Michael Angelo Maglalang Gonzales Vincent Vachirakorntong Siwei Chen Pierre Baldi Olivier Civelli Amal Alachkar
author_facet	Roudabeh Vakil Monfared Wedad Alhassen Tri Minh Truong Michael Angelo Maglalang Gonzales Vincent Vachirakorntong Siwei Chen Pierre Baldi Olivier Civelli Amal Alachkar
author_sort	Roudabeh Vakil Monfared
title	Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
title_short	Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
title_full	Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
title_fullStr	Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
title_full_unstemmed	Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions
title_sort	transcriptome profiling of dysregulated gpcrs reveals overlapping patterns across psychiatric disorders and age-disease interactions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/427ce6a776f4444da7c73d7c71cf9123
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Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions

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