Mood disorders and 5-HTR2A genetic variants - the moderator effect of inflammation on expression of affective polarity phenotype.
Humans
Male
Female
Receptor, Serotonin, 5-HT2A
/ genetics
Depressive Disorder, Major
/ genetics
Adult
Phenotype
Inflammation
/ genetics
Bipolar Disorder
/ genetics
Middle Aged
Gene-Environment Interaction
Polymorphism, Single Nucleotide
/ genetics
Mean Platelet Volume
Platelet Count
Genotype
Blood Platelets
HTR2A rs6313
Bipolar disorder
Gene-environment interactions
Mood disorders
Unipolar depression
Journal
BMC psychiatry
ISSN: 1471-244X
Titre abrégé: BMC Psychiatry
Pays: England
ID NLM: 100968559
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
25
06
2024
accepted:
22
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 39472813
doi: 10.1186/s12888-024-06207-y
pii: 10.1186/s12888-024-06207-y
doi:
Substances chimiques
Receptor, Serotonin, 5-HT2A
0
HTR2A protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
747Informations de copyright
© 2024. The Author(s).
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