Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder
Abstract Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocyte...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-03-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01905-1 |
| _version_ | 1818644988786900992 |
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| author | Natalia Rodríguez Luisa Lázaro Ana E. Ortiz Astrid Morer Albert Martínez-Pinteño Alex G. Segura Patricia Gassó Sergi Mas |
| author_facet | Natalia Rodríguez Luisa Lázaro Ana E. Ortiz Astrid Morer Albert Martínez-Pinteño Alex G. Segura Patricia Gassó Sergi Mas |
| author_sort | Natalia Rodríguez |
| collection | DOAJ |
| description | Abstract Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocytes of pediatric patients with OCD (N = 102) compared to controls (N = 47). We examined gene expression in primary cultures of peripheral monocytes from participants, under basal conditions and under exposure to lipopolysaccharide (LPS) to stimulate immune response. Whole-genome expression was assessed in 8 patients and 8 controls. Differentially expressed genes were identified followed by protein-protein interaction network construction and functional annotation analysis to identify the genes and biological processes that are altered in the monocytes of OCD patients. We also explored the expression levels of selected genes in monocytes from the other participants using qPCR. Several changes in gene expression were observed in the monocytes of OCD patients, with several immune processes involved under basal conditions (antigen processing and presentation, regulation of immune system and leukocyte cell adhesion) and after LPS stimulation (immune and inflammatory response, cytokine production and leukocyte activation). Despite the qPCR analysis provided no significant differences between patients and controls, high correlations were observed between the expression levels of some of the genes and inflammatory markers (i.e., T helper 17 and regulatory T cell levels, total monocyte and proinflammatory monocyte subset levels, and the cytokine production by resting and stimulated monocytes) of the study participants. Our findings provide more evidence of the involvement of monocyte dysregulation in early-onset OCD, indicating a proinflammatory predisposition and an enhanced immune response to environmental triggers. |
| first_indexed | 2024-12-17T00:23:36Z |
| format | Article |
| id | doaj.art-404f3abd55e549919b103f4a0fc7d431 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-17T00:23:36Z |
| publishDate | 2022-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-404f3abd55e549919b103f4a0fc7d4312022-12-21T22:10:31ZengNature Publishing GroupTranslational Psychiatry2158-31882022-03-0112111010.1038/s41398-022-01905-1Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorderNatalia Rodríguez0Luisa Lázaro1Ana E. Ortiz2Astrid Morer3Albert Martínez-Pinteño4Alex G. Segura5Patricia Gassó6Sergi Mas7Department of Basic Clinical Practice, University of BarcelonaDepartment of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de BarcelonaDepartment of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de BarcelonaDepartment of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de BarcelonaDepartment of Basic Clinical Practice, University of BarcelonaDepartment of Basic Clinical Practice, University of BarcelonaDepartment of Basic Clinical Practice, University of BarcelonaDepartment of Basic Clinical Practice, University of BarcelonaAbstract Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocytes of pediatric patients with OCD (N = 102) compared to controls (N = 47). We examined gene expression in primary cultures of peripheral monocytes from participants, under basal conditions and under exposure to lipopolysaccharide (LPS) to stimulate immune response. Whole-genome expression was assessed in 8 patients and 8 controls. Differentially expressed genes were identified followed by protein-protein interaction network construction and functional annotation analysis to identify the genes and biological processes that are altered in the monocytes of OCD patients. We also explored the expression levels of selected genes in monocytes from the other participants using qPCR. Several changes in gene expression were observed in the monocytes of OCD patients, with several immune processes involved under basal conditions (antigen processing and presentation, regulation of immune system and leukocyte cell adhesion) and after LPS stimulation (immune and inflammatory response, cytokine production and leukocyte activation). Despite the qPCR analysis provided no significant differences between patients and controls, high correlations were observed between the expression levels of some of the genes and inflammatory markers (i.e., T helper 17 and regulatory T cell levels, total monocyte and proinflammatory monocyte subset levels, and the cytokine production by resting and stimulated monocytes) of the study participants. Our findings provide more evidence of the involvement of monocyte dysregulation in early-onset OCD, indicating a proinflammatory predisposition and an enhanced immune response to environmental triggers.https://doi.org/10.1038/s41398-022-01905-1 |
| spellingShingle | Natalia Rodríguez Luisa Lázaro Ana E. Ortiz Astrid Morer Albert Martínez-Pinteño Alex G. Segura Patricia Gassó Sergi Mas Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder Translational Psychiatry |
| title | Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder |
| title_full | Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder |
| title_fullStr | Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder |
| title_full_unstemmed | Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder |
| title_short | Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder |
| title_sort | gene expression study in monocytes evidence of inflammatory dysregulation in early onset obsessive compulsive disorder |
| url | https://doi.org/10.1038/s41398-022-01905-1 |
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