Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype
Abstract Background Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a co...
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2024-10-01
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| Online Access: | https://doi.org/10.1186/s12888-024-06207-y |
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| author | Maja Pantovic-Stefanovic Jelena Karanovic Vladimir Jurisic Bojana Dunjic-Kostic Milica Nesic Sara Dodic Marta Gostiljac Marija Puric Dusanka Savic Pavicevic Maja Ivkovic |
| author_facet | Maja Pantovic-Stefanovic Jelena Karanovic Vladimir Jurisic Bojana Dunjic-Kostic Milica Nesic Sara Dodic Marta Gostiljac Marija Puric Dusanka Savic Pavicevic Maja Ivkovic |
| author_sort | Maja Pantovic-Stefanovic |
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| description | Abstract Background Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes. Methods The study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio. Results The HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role. Conclusions To our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course. |
| format | Article |
| id | doaj-art-658e14ea222d4ff893d7aa1d7f9a5e44 |
| institution | OA Journals |
| issn | 1471-244X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj-art-658e14ea222d4ff893d7aa1d7f9a5e442025-08-20T02:18:35ZengBMCBMC Psychiatry1471-244X2024-10-0124111210.1186/s12888-024-06207-yMood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotypeMaja Pantovic-Stefanovic0Jelena Karanovic1Vladimir Jurisic2Bojana Dunjic-Kostic3Milica Nesic4Sara Dodic5Marta Gostiljac6Marija Puric7Dusanka Savic Pavicevic8Maja Ivkovic9Department for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaCentre for Human Molecular Genetics, Faculty of Biology, University of BelgradeFaculty of Medical Scinces, University of KragujevacFaculty of Medicine, University of BelgradeDepartment for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaDepartment for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaDepartment for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaDepartment for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaCentre for Human Molecular Genetics, Faculty of Biology, University of BelgradeDepartment for Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of SerbiaAbstract Background Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes. Methods The study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio. Results The HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role. Conclusions To our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course.https://doi.org/10.1186/s12888-024-06207-yHTR2A rs6313Mood disordersUnipolar depressionBipolar disorderGene-environment interactions |
| spellingShingle | Maja Pantovic-Stefanovic Jelena Karanovic Vladimir Jurisic Bojana Dunjic-Kostic Milica Nesic Sara Dodic Marta Gostiljac Marija Puric Dusanka Savic Pavicevic Maja Ivkovic Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype BMC Psychiatry HTR2A rs6313 Mood disorders Unipolar depression Bipolar disorder Gene-environment interactions |
| title | Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype |
| title_full | Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype |
| title_fullStr | Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype |
| title_full_unstemmed | Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype |
| title_short | Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype |
| title_sort | mood disorders and 5 htr2a genetic variants the moderator effect of inflammation on expression of affective polarity phenotype |
| topic | HTR2A rs6313 Mood disorders Unipolar depression Bipolar disorder Gene-environment interactions |
| url | https://doi.org/10.1186/s12888-024-06207-y |
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