scholarly journals Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

2016 ◽  
Vol 113 (52) ◽  
pp. E8472-E8481 ◽  
Author(s):  
Swapnali Barde ◽  
Joelle Rüegg ◽  
Josée Prud’homme ◽  
Tomas J. Ekström ◽  
Miklos Palkovits ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Epigenetic Modification ◽  
Anterior Cingulate ◽  
Mrna Levels ◽  
Mood Regulation ◽  
Major Depressive ◽  
Release Of Noradrenaline ◽  
Transcript Levels

Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL1–3, are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region- and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL3 antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation.

scholarly journals Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Jiaqi Zhou ◽  
Miao Li ◽  
Xueying Wang ◽  
Yuwen He ◽  
Yan Xia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Clinical Improvement ◽  
Drug Response ◽  
Epigenetic Modification ◽  
Antidepressant Treatment ◽  
Future Research ◽  
Major Depressive

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.

Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder

2016 ◽  
Vol 22 (1) ◽  
pp. 113-119 ◽  
Author(s):  
J Ernst ◽  
A Hock ◽  
A Henning ◽  
E Seifritz ◽  
H Boeker ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Anterior Cingulate ◽  
Major Depressive

Prefrontal cortex function in remitted major depressive disorder

2012 ◽  
Vol 43 (6) ◽  
pp. 1219-1230 ◽  
Author(s):  
N. L. Nixon ◽  
P. F. Liddle ◽  
G. Worwood ◽  
M. Liotti ◽  
E. Nixon
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Negative Feedback ◽  
Affective State ◽  
Recurrence Risk ◽  
Anterior Cingulate ◽  
Major Depressive ◽  
Negative Experience

BackgroundRecent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence.MethodBaseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patientsversuscontrols and recurrenceversusnon-recurrenceversuscontrol groups.ResultsAnalysis of patients (n = 20)versuscontrols (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.ConclusionsConvergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.

scholarly journals Regionally specific alterations in functional connectivity of the anterior cingulate cortex in major depressive disorder

2012 ◽  
Vol 42 (10) ◽  
pp. 2071-2081 ◽  
Author(s):  
C. G. Davey ◽  
B. J. Harrison ◽  
M. Yücel ◽  
N. B. Allen
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Frontal Cortex ◽  
Caudate Nucleus ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Major Depressive ◽  
Close Link

BackgroundDepression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.MethodEighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.ResultsThe depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.ConclusionsThe results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

scholarly journals Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures

2019 ◽  
Vol 50 (10) ◽  
pp. 1653-1662 ◽  
Author(s):  
Mathew A. Harris ◽  
Xueyi Shen ◽  
Simon R. Cox ◽  
Jude Gibson ◽  
Mark J. Adams ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Case Control ◽  
Anterior Cingulate ◽  
Interactive Effects ◽  
Polygenic Risk Score ◽  
Major Depressive ◽  
Polygenic Risk ◽  
High Genetic Risk ◽  
Effective Diagnosis

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

Rostral Anterior Cingulate Glutamine/Glutamate Disbalance in Major Depressive Disorder Depends on Symptom Severity

2019 ◽  
Vol 4 (12) ◽  
pp. 1049-1058 ◽  
Author(s):  
Lejla Colic ◽  
Felicia von Düring ◽  
Dominik Denzel ◽  
Liliana Ramona Demenescu ◽  
Anton R. Lord ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Symptom Severity ◽  
Anterior Cingulate ◽  
Major Depressive

scholarly journals DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kathryn L. Humphreys ◽  
Sarah R. Moore ◽  
Elena Goetz Davis ◽  
Julie L. MacIsaac ◽  
David T. S. Lin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Major Depressive Disorder ◽  
Genetic Variability ◽  
Depressive Disorder ◽  
Hpa Axis ◽  
Early Adulthood ◽  
Familial Risk ◽  
Major Depressive ◽  
Cpg Sites ◽  
First Onset

Abstract The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.

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