Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder

ObjectiveThe main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism inSLC6A4on chromosome 17q11.2. Secondarily, we also hypothesised that 5-HTTLPR may be a risk factor for MDD.MethodsQuantitative magnetic resonance imaging (MRI) of the hippocampus was studied in 23 inpatients suffering from MDD and in 33 healthy controls. Normalised volumetric MRI data of hippocampus were assessed with adjustment for total brain volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from twoSLC6A4promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits.ResultsHealthy controls had a smaller relative hippocampal volume (relative to brain size) but a larger total brain volume compared with patients with MDD. For patients compared with healthy controls, atrophy was found in the right temporal lobe and pons medulla. Allele and genotype frequencies were strikingly different from the previous study that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found.ConclusionsThe present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients and the serotonin transporter polymorphism.

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Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder

Translational Psychiatry ◽

10.1038/tp.2015.134 ◽

2015 ◽

Vol 5 (9) ◽

pp. e636-e636 ◽

Cited By ~ 51

Author(s):

F Mamdani ◽

B Rollins ◽

L Morgan ◽

R M Myers ◽

J D Barchas ◽

...

Keyword(s):

Major Depressive Disorder ◽

Prefrontal Cortex ◽

Depressive Disorder ◽

Telomere Length ◽

Dorsolateral Prefrontal Cortex ◽

Brain Regions ◽

Cellular Aging ◽

Post Mortem ◽

Major Depressive ◽

Dorsolateral Prefrontal

Abstract Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N=40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P<0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings.

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