Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

Bellia, Fabio; Vismara, Matteo; Annunzi, Eugenia; Cifani, Carlo; Benatti, B.; Dell’Osso, Bernardo; D’Addario, Claudio

doi:10.1016/j.jpsychires.2020.10.040

Cited by 19 publications

(15 citation statements)

References 269 publications

(242 reference statements)

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“…7 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini, 1, 64100 Teramo, Italy. 8 Department of Psychiatry, Department of Biomedical and Clinical Sciences "Luigi Sacco", Psychiatry Unit 2, ASST Sacco-Fatebenefratelli, Via G.B. Grassi, 74, 20157 Milan, Italy.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…As yet, many studies have focused on the inherited component of OCD. However, the available data identifying DNA sequence-based causes are inconclusive with sometimes conflicting results [8]. Environmental risk factors (e.g., stressful life events, trauma and impoverished social context), known to be relevant in the development of OCD [9][10][11], can modify genes transcription regulation via epigenetic mechanisms [12].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

et al. 2022

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Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies.

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Section: Supplementary Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

et al. 2022

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“…Within the CSTC circuit, defects in neurotransmission involving serotonin, catecholamine/dopamine and glutamate appear to contribute to OCD (Stein et al, 2019). Indeed, several genetic polymorphisms have been linked to OCD involving serotonin signaling (in the genes SLC6A4, HTR2A, HTR2C, HTR1B, TPH1, TPH2), catecholamine/dopamine system (COMT, SLC6A3, MAOA, DRD2, DRD3, DRD4), and glutamate system (SLC1A1, GRIN2B, GRIK2, GRIK3) (Bellia et al, 2021). Some SNPs among the PCOS-IVs in the present study play roles in neurotransmitter systems.…”

Section: Discussionmentioning

confidence: 99%

“…It is a chronic, debilitating psychiatric illness, characterized by obsessions (intrusive and disturbing thoughts), compulsions (repetitive behaviors), or both. OCD appears to involve the cortico-striato-thalamo-cortical (CSTC) circuit, as well as the fronto-limbic, fronto-parietal, and cerebellar networks (Stein et al, 2019 ; Bellia et al, 2021 ). Within the CSTC circuit, defects in neurotransmission involving serotonin, catecholamine/dopamine and glutamate appear to contribute to OCD (Stein et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Polycystic Ovary Syndrome and Risk of Five Common Psychiatric Disorders Among European Women: A Two-Sample Mendelian Randomization Study

Jin

Chen

et al. 2021

Front. Genet.

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Background: Observational studies have implied an association between polycystic ovary syndrome (PCOS) and psychiatric disorders. Here we examined whether PCOS might contribute causally to such disorders, focusing on anxiety disorder (AD), bipolar disorder (BIP), major depression disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ).Methods: Causality was explored using two-sample Mendelian randomization (MR) with genetic variants as instrumental variables. The genetic variants were from summary data of genome-wide association studies in European populations. First, potential causal effects of PCOS on each psychiatric disorder were evaluated, and then potential reverse causality was also assessed once PCOS was found to be causally associated with any psychiatric disorder. Causal effects were explored using inverse variance weighting, MR-Egger analysis, simulation extrapolation, and weighted median analysis.Results: Genetically predicted PCOS was positively associated with OCD based on inverse variance weighting (OR 1.339, 95% CI 1.083–1.657, p = 0.007), simulation extrapolation (OR 1.382, 95% CI 1.149–1.662, p = 0.009) and weighted median analysis (OR 1.493, 95% CI 1.145–1.946, p = 0.003). However, genetically predicted OCD was not associated with PCOS. Genetically predicted PCOS did not exert causal effects on AD, BIP, MDD, or SCZ.Conclusions: In European populations, PCOS may be a causal factor in OCD, but not AD, BIP, MDD, or SCZ.

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“…Different methylation profiles were found in the promoter regions of the MAOA, GABA, MOG, BDNF, LEPR, OXTR, SLC6A4, and SLC6A3 genes in studies of DNA methylation comparing OCD patients and controls. 11 The balance between HAT/ HDAC is thought to be related to neuron death, with diseases occurring when this balance is disrupted. 12,13 Neuron cell death, causing amyloid precursor protein (APP) activation in AD and amyotrophic lateral sclerosis (ALS), was shown to be associated with HDAC levels in in vitro model studies.…”

Section: Introductionmentioning

confidence: 99%

Link between obsessive-compulsive disorder and polymorphisms in HDAC genes

Dondu¹,

Caliskan

Boyacioglu

2022

Braz. J. Psychiatry

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Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

Cited by 19 publications

References 269 publications

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Polycystic Ovary Syndrome and Risk of Five Common Psychiatric Disorders Among European Women: A Two-Sample Mendelian Randomization Study

Link between obsessive-compulsive disorder and polymorphisms in HDAC genes

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