Multidimensional Analysis of Major Depression: Association Between BDNF Methylation, Psychosocial and Cognitive Domains.
Ontology highlight
ABSTRACT:
SUBMITTER: Velasquez MM
PROVIDER: S-EPMC8712447 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThere is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD.MethodsWe recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing.ResultsBDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD.ConclusionsOur results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.
| S-EPMC8323304 | biostudies-literature
Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.
| S-EPMC6007393 | biostudies-literature
Project description:BackgroundThe interplay among lifetime adversities and the genetic background has been previously examined on a variety of measures of depression; however, only few studies have focused on major depression disorder (MDD) in adolescence.MethodsUsing clinical data and DNA samples from mouthwash gathered from an epidemiological study on the prevalence of mental disorders in youths between 12 and 17 years old, we tested the statistical interaction between a set of psychosocial adversities experienced during childhood (CAs) with two common polymorphisms in the brain-derived neurotrophic factor (BDNF) (Val66Met) and SLC6A4 (L/S) genes on the probability of suffering MDD in adolescence.ResultsGenotype or allele frequencies for both polymorphisms were similar between groups of comparison (MDD N = 246; controls N = 270). The CAs factors: Abuse, neglect, and family dysfunctions; parental maladjustment, parental death, and to have experienced a life-threatening physical illness were predictors of clinical depression in adolescents. Remarkably, the cumulative number of psychosocial adversities was distinctly associated with an increase in the prevalence of depression but only in those Val/Val BDNF individuals; while the possession of at least a copy of the BDNF Met allele (i.e., Met +) was statistically linked with a "refractory" or resilient phenotype to the noticeable influence of CAs.ConclusionLiability or resilience to develop MDD in adolescence is dependent of a complex interplay between particular environmental exposures and a set of plasticity genes including BDNF. A better understanding of these factors is important for developing better prevention and early intervention measures.
| S-EPMC3967543 | biostudies-literature
Project description:OBJECTIVE:Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). METHODS:Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. RESULTS:Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. CONCLUSION:BDNF genotyping may be informative for anticipating chronicity in major depression.
| S-EPMC3590431 | biostudies-literature
Project description:BackgroundCognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.MethodsThis is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; N = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.Results508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (B = 5.17, s.e. = 2.21, p = 0.019) and functional impairment (B = 4.82, s.e. = 1.79, p = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.ConclusionsWe replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.
| S-EPMC10520589 | biostudies-literature
Project description:Major depressive disorder (MDD) is a complex psychiatric condition with strong genetic predisposition. The association of MDD with genetic polymorphisms, such as Val66Met (rs6265), in the brain derived neurotrophic factor (BDNF), have been reported in many studies and the results were conflicting. In this study, we performed a systematic literature search and conducted random-effects meta-analysis to evaluate genetic variants in BDNF with MDD. A gene-based analysis was also conducted to investigate the cumulative effects of genetic polymorphisms in BDNF. A total of 28 studies from 26 published articles were included in our analysis. Meta-analysis yielded an estimated odds ratio (OR) of 0.96 (95% CI: 0.89-1.05; P = 0.402) for Val66Met (rs6265), 0.83 (95% CI: 0.67-1.04; P = 0.103) for 11757C/G, 1.16 (95% CI: 0.74-1.82; P = 0.527) for 270T/C, 1.03 (95% CI: 0.18-5.75; P = 0.974) for 712A/G and 0.98 (95% CI: 0.85-1.14; P = 0.831) for rs988748. The gene-based analysis indicated that BDNF is not associated with MDD (P > 0.21). Our updated meta- and novel gene-based analyses provide no evidence of the association of BDNF with major depression.
| S-EPMC3725128 | biostudies-literature
Project description:ObjectiveTo examine the relationship of negative emotions with suicidal ideation during 12 weeks of Problem Adaptation Therapy (PATH) versus Supportive Therapy of Cognitively Impaired Older Adults (ST-CI), hypothesizing that improved negative emotions are associated with reduced suicidal ideation, PATH improves negative emotions more than ST-CI, and improved negative emotions, rather than other depression symptoms, predict reduction in suicidal ideation.MethodsIn a randomized controlled trial of two home-delivered psychosocial interventions, 74 older participants (65-95 years old) with major depressive disorder and cognitive impairment were recruited in collaboration with community agencies. The sample reported less intense feelings than suicidal intention. Interventions and assessments were conducted in participants' homes. PATH focuses on improving emotion regulation, whereas ST-CI focuses on nonspecific therapeutic factors, such as understanding and empathy. Improved negative emotions were measured as improvement in Montgomery Asberg's Depression Rating Scales' (MADRS) observer ratings of sadness, anxiety, guilt, hopelessness, and anhedonia. Suicidal ideation was assessed with the MADRS Suicide Item.ResultsMADRS Negative Emotions scores were significantly associated with suicidal ideation during the course of treatment (F[1,165] = 12.73, p = 0.0005). PATH participants had significantly greater improvement in MADRS emotions than ST-CI participants (treatment group by time: F[1,63.2] = 7.02, p = 0.0102). Finally, improved negative emotions, between lagged and follow-up interview, significantly predicted reduction in suicidal ideation at follow-up interview (F[1, 96] = 9.95, p = 0.0022).ConclusionFindings thatimprovement in negative emotions mediates reduction in suicidal ideation may guide the development of psychosocial interventions for reduction of suicidal ideation (clinicaltrials.gov; NCT00368940).
| S-EPMC5429870 | biostudies-literature
Project description:Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV) at the promoters of the brain-derived neurotrophic factor (BDNF) gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray® system (SEQUENOM), and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.
| S-EPMC3166055 | biostudies-literature
Project description:AimsFew studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders.MethodsBased on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs.ResultsLiving alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD.ConclusionsRisk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.
| S-EPMC4748002 | biostudies-literature
Project description:IntroductionBrain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD). In present study, we aimed to assess the possible association between POCD and BDNF rs6265 polymorphisms.Methods124 patients aged 60 years or older scheduled for elective surgery under general anesthesia and 25 age- and gender-matched healthy volunteers were recruited. POCD was identified using a neuropsychological test battery administered preoperatively, 7 days, and 3 months after surgery. Genotyping of rs6265 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis.Results99 patients and 25 healthy controls were finally enrolled in the analysis. 29(29.3%) and 18(18.2%) of 99 patients had POCD at 7 days and 3 months after surgery, respectively. The patients carrying a G allele at the rs6265 locus showed a lower risk for POCD than an A allele carriers on postoperative 7 days, but not 3 months after surgery (OR = 0.67; 95% CI: 0.47-0.96; p = .017; OR = 0.69; 95% CI: 0.42-1.13; p = .14, respectively). The risk of POCD at 7 days following surgery was significantly lower in additive model (OR = 0.41; 95% CI: 0.2-0.84; p = .015) and dominant model (OR = 0.35; 95% CI: 0.13-0.96; p = .042).ConclusionWe tentatively demonstrate that BDNF rs6265 polymorphisms might be associated with occurrence of POCD at 7 days after surgery and the A > G mutant at the rs6265 locus be likely a protective factor for early POCD in Chinese Han population.
| S-EPMC7559622 | biostudies-literature