ABSTRACT
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.
Subject(s)
Bipolar Disorder/blood , Brain-Derived Neurotrophic Factor/blood , DNA Methylation , Depressive Disorder, Major/blood , Adult , Biomarkers/blood , Bipolar Disorder/genetics , Bipolar Disorder/therapy , Brain-Derived Neurotrophic Factor/genetics , CpG Islands , Depressive Disorder, Major/genetics , Depressive Disorder, Major/therapy , Female , Humans , Longitudinal Studies , Male , Middle Aged , Patient Admission , Patient Discharge , Promoter Regions, Genetic , Remission InductionABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/etiology , Attention Deficit Disorder with Hyperactivity/genetics , Bipolar Disorder/etiology , Bipolar Disorder/genetics , Adult , Female , Humans , Middle Aged , Parent-Child Relations , Pilot Projects , Pregnancy , Prenatal Exposure Delayed Effects , Risk Factors , Young AdultABSTRACT
Changes of sphingolipid metabolism were suggested to contribute to the patho-etiology of major depression (MD) and bipolar disorder (BD). In a pilot study we assessed if lipid allostasis manifested in pathological plasma concentrations of bioactive lipids i.e. endocannabinoids, sphingolipids, ceramides, and lysophosphatidic acids. METHODS: Targeted and untargeted lipidomic analyses were performed according to GLP guidelines in 67 patients with unipolar or bipolar disorders (20-67â¯years, 36 male, 31 female) and 405 healthy controls (18-79â¯years, 142â¯m, 263â¯f), who were matched according to gender, age and body mass index. Multivariate analyses were used to identify major components, which accounted for the variance between groups and were able to predict group membership. RESULTS: Differences between MD and BP patients versus controls mainly originated from ceramides and their hexosyl-metabolites (C16Cer, C18Cer, C20Cer, C22Cer, C24Cer and C24:1Cer; C24:1GluCer, C24LacCer), which were strongly increased, particularly in male patients. Ceramide levels were neither associated with the current episode, nor with the therapeutic improvement of the Montgomery Åsberg Depression Rating Scale (MARDS). However, long-chain ceramides were linearly associated with age, stronger in patients than controls, and with high plasma levels of diacyl- and triacylglycerols. Patients receiving antidepressants had higher ceramide levels than patients not taking these drugs. There was no such association with lithium or antipsychotics except for olanzapine. CONCLUSION: Our data suggest that high plasma ceramides in patients with major depression and bipolar disorder are indicative of a high metabolic burden, likely aggravated by certain medications.