Relación entre el estrés y la adversidad en la vida temprana con la metilación de DDR1 en el trastorno mental grave

Identifier:  TDX:4049

Handle: https://hdl.handle.net/20.500.11797/TDX4049

Authors:  García Ruiz, Beatriz

Abstract:
The main objective of this doctoral thesis was to evaluate whether altered DNA methylation (DNAm) in CpG dinucleotides in the DDR1 gene is related to the presence of a severe mental disorder in association with factors such as stress and childhood trauma. DDR1 DNAm patterns in peripheral leukocytes from patients with early psychosis, bipolar disorder, and healthy individuals were studied. In addition, the association of DNAm to stress (psychological/physiological) and inflammation in early psychosis, and to childhood trauma and suicidal behavior in bipolar disorder was explored. Likewise, the relationship of DDR1 DNAm with its expression was studied in the brain tissue of patients with schizophrenia and bipolar disorder. In the patient groups, mDNA was altered compared to their respective controls, both in leukocytes and in brain tissue. In peripheral leukocytes, DNAm was associated with stress and inflammation in early psychosis. In bipolar disorder, childhood trauma was associated with DDR1 DNAm and suicidal behavior. However, no relationship was found between DNAm and suicidal behavior. Finally, DDR1 DNAm was associated with gene and isoform expression in schizophrenia and bipolar disorder in brain tissue. Taken together, these results suggest that changes in DDR1 DNAm in blood and brain might be related to etiological processes underlying early psychosis, schizophrenia, and bipolar disorder, including inflammatory and immunologic mechanisms, or be a consequence of these.