Lifetime major depression and grey-matter volume

Abstract

Background: There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS). Methods: We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities. Results: Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype. Limitations: This study was limited by its cross-sectional design. Conclusion: Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.

Structural brain changes with lifetime trauma and re-experiencing symptoms is 5-HTTLPR genotype-dependent

“…The most robust finding was observed with subregions in prefrontal cortex (PFC) (rostral and caudal middle frontal and lateral orbitofrontal), superior, inferior and medial (precuneus) parietal, as well as middle temporal cortex, whose volumes were smaller in the T + R SS participants. These findings were notably independent of psychiatric comorbidity and quite distinct from abnormalities associated with lifetime major depression recently reported in this Esprit population (Ancelin et al, 2019). This suggests a specific enduring effect of lifetime trauma on brain structure.…”

“…lifetime major depression and anxiety disorder, head injury, and cardiovascular ischaemic pathologies. Given the frequent report of heterosis for 5-HTTLPR due to multiple sources of interacting effect (epistasis, sex, childhood adversity …) (Ancelin & Ryan, 2018), the modifying effect of 5-HTTLPR was evaluated by stratification into three genotypes (LL, SL, and SS) as described (Ancelin et al, 2019(Ancelin et al, , 2017. To account for the multiple brain regions examined, we adjusted the significance levels using the false discovery rate (FDR) method (Benjamini & Hochberg, 1995).…”

“…All the neuroimaging scans were acquired using the same scanner and analysed as described previously (Ancelin et al, 2019). Briefly, a 1.5 T GE Signa Imaging system (General Electric Medical Systems, Milwaukee, WI) was used to acquire a contiguous AC-PC aligned axial IR-prepared SPGR T1-weighed sequence for volumetric estimations (TR = 12, TE = 2.8, IT = 6000, matrix, size = 256 x 256, pixel spacing = 0.9375 x 0.9375 mm, NEX = 1, slice thickness = 1.0 mm).…”

“…Blood samples were collected at baseline, enabling DNA extraction and 5-HTTLPR genotyping and data was validated using replicate independent genotyping of buccal DNA extracted from the same participants (Ancelin et al, 2019(Ancelin et al, , 2017.…”

Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

“…In particular, two large studies with a combined sample size of 1767 patients failed to demonstrate volumetric differences in the hippocampus between depressed and non-depressed individuals. 1,46 There are some difficulties in interpreting these results. Shen et al used a composite of self-reported symptoms and hospital admission data to estimate probable MDD, rather than an operational MDD diagnosis based on strict structured clinical interviews.…”