RESUMEN
Preliminary evidence suggests that BDNF (brain derived neurotrophic factor) rs6265 genetic polymorphism, BDNF gene promotor methylation and BDNF serum levels might play an important role in the pathogenesis of affective disorders. As studies testing the BDNF system across molecular levels are sparse, this study aimed at investigating the BDNF val66met genotype, BDNF DNA methylation changes and peripheral BDNF serum levels in acute and remitted phases of MDD (major depressive disorder) and BD (bipolar disorder) and healthy controls. We found a significant difference of methylation levels at CpG site 1-1-1 and 3-1-1 between MDD and healthy controls (p < 0.003) with MDD patients showing significantly higher methylation levels. CpG 5-2-1 revealed a statistically significant difference between MDD and healthy controls and MDD and BD (p = 0.00003). Similar to the results of the methylation analysis a significant difference between MDD and healthy controls was found in BDNF serum levels (p = 0.002) with significantly lower BDNF serum levels in MDD compared to healthy controls. A difference between the samples from admission and discharge from hospital of both BDNF gene methylation and serum levels could not be detected in the present study and no influence of the BDNF val66met genotype on neither methylation nor BDNF serum level.
Asunto(s)
Trastorno Bipolar/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Metilación de ADN , Trastorno Depresivo Mayor/sangre , Adulto , Biomarcadores/sangre , Trastorno Bipolar/genética , Trastorno Bipolar/terapia , Factor Neurotrófico Derivado del Encéfalo/genética , Islas de CpG , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/terapia , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Admisión del Paciente , Alta del Paciente , Regiones Promotoras Genéticas , Inducción de RemisiónRESUMEN
Gene-environment-development interactions are suggested to play a crucial role in psychiatric disorders. However, it is not clear if there are specific risk gene interactions with particular pre-, peri-, and postnatal risk factors for distinct disorders, such as adult attention-deficit-/hyperactivity disorder (aADHD) and bipolar disorder (BD). In this pilot study, the first aim was to investigate retrospective self-reports of pre-, peri-, and postnatal complications and risk factors from 126 participants (aADHD, BD, and healthy controls) and their mothers. The second aim was to investigate possible interaction between the previously published common risk gene variants of ADHD in the ADGRL3 (=LPHN3) gene (rs2305339, rs1397548, rs734644, rs1397547, rs2271338, rs6551665, and rs2345039) and shared risk gene variants of aADHD and BD in the DGKH gene (DGKH rs994856/rs9525580/rs9525584 GAT haplotype) and pre-, peri-, and postnatal risk factors in comparison to a healthy control group. After correction for multiple comparison, the following pre-, peri-, and postnatal risk factors remained statistically significant (p ≤ 0.0036) between healthy controls and ADHD and BD patients as one group: unplanned pregnancies, psychosocial stress of the mother during pregnancy, mode of delivery, shared decision-making regarding medical procedures during the delivery, perinatal bonding, number of crybabies, and quality of mother-child and father-child relationship. There were no significant environment-gene interactions. In our preliminary data, similar risk factors were found to be significantly associated with both disorders in comparison to healthy controls. However, larger and longitudinal studies and standardized and validated instruments to get a better understanding of the interaction of pre-, peri-, and postnatal complications and mental health in the offspring are needed.
