Brain grey matter volume alterations associated with antidepressant response in major depressive disorder

AbstractPrevious reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n=1157) and white matter integrity (n=1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β=-0.182, p=0.005). We also found reductions in FA in association/commissural fibres (β=-0.184, pcorrected=0.010) and thalamic radiations (β=-0.159, pcorrected=0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β=-0.194, pcorrected=0.025), superior thalamic radiation (β=-0.224, pcorrected=0.009) and forceps major (β=-0.193, pcorrected=0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.

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P.4.008 Larger grey matter volume reductions are related to longer duration of major depressive disorder

European Neuropsychopharmacology ◽

10.1016/s0924-977x(12)70095-0 ◽

2012 ◽

Vol 22 ◽

pp. S90

Author(s):

M. Serra-Blasco ◽

M.J. Portella ◽

J. De Diego-Adeliño ◽

Y. Vives-Gilabert ◽

B. Gómez-Ansón ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Grey Matter ◽

Grey Matter Volume ◽

Major Depressive ◽

Matter Volume

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Integrative omics analysis identifies differential biological pathways that are associated with regional grey matter volume changes in major depressive disorder

Psychological Medicine ◽

10.1017/s0033291720002676 ◽

2020 ◽

pp. 1-12

Author(s):

Zhiqiang Sha ◽

Layla Banihashemi

Keyword(s):

Major Depressive Disorder ◽

Grey Matter ◽

Enrichment Analysis ◽

Biological Pathways ◽

Transmembrane Transport ◽

Grey Matter Volume ◽

Volume Changes ◽

Major Depressive ◽

Matter Volume ◽

Integrative Omics

Abstract Background Major depressive disorder (MDD) is accompanied by alterations in grey matter volume. However, the biological processes associated with regional structural perturbations remain elusive. Methods We applied integrative omics analysis to investigate specialized transcriptome signatures and translational determinants associated with regional grey matter variations in 2737 MDD patients relative to 3098 controls by summarizing the results from gene co-expression network analysis of Allen human brain transcriptome profiles in six donors, enrichment analysis of gene-sets and cellular structure from rodents and mediation analysis of BrainSpan proteome profile in six donors. Results We found convergent alterations of grey matter volume in MDD were associated with transcriptome profiles enriched for synaptic transmission, metabolism, immune processes and transmembrane transport. Genes with abnormal expression in post-mortem tissue in MDD were also associated with transcriptome signatures. Further gene co-expression network and enrichment analysis of MDD-related genes in these signatures revealed the modules with higher neuronal expression were enriched in the medial temporal cortex and temporo-parietal junction with genes differentially associated with neuronal development and metabolism. Also, the modules with higher non-neuronal (e.g. astrocyte and oligodendrocyte) expression were concentrated in the rostral and dorsal anterior cingulate cortex and were separately associated with immune response and transmembrane transport. Moreover, proteins as the gene expression products mediated the association between transcriptome signatures and brain volume changes in the visual and dorsolateral prefrontal cortex. Conclusions Our multidimensional analyses offer a novel approach to detect specific biological pathways that capture regional structural variations in MDD, which suggests structural endophenotypes associated with MDD.

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Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

CNS Spectrums ◽

10.1017/s1092852912000430 ◽

2012 ◽

Vol 17 (2) ◽

pp. 76-86 ◽

Cited By ~ 11

Author(s):

David Mischoulon ◽

Stefania Lamon-Fava ◽

Jacob Selhub ◽

Judith Katz ◽

George I. Papakostas ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Mthfr C677t ◽

Response Rates ◽

Mthfr Gene ◽

Methionine Synthase ◽

Antidepressant Response ◽

Major Depressive ◽

Fluoxetine Treatment ◽

Intent To Treat

AbstractObjectiveTo examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response.MethodsWe screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20–60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined.ResultsPrevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C = 41%, C/T = 47%, T/T = 11%, A/A = 66%, A/G = 29%, G/G = 4%). In the fluoxetine-treated subsample (n = 49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response.ConclusionThe C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples.

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