title: Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder.
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.
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Mamdani
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rollins
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Morgan
authors.affiliation: Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Barchas
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Schatzberg
authors.affiliation: Molecular and Behavioral Neurosciences Institute, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Watson
authors.affiliation: Molecular and Behavioral Neurosciences Institute, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Akil
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Bunney
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Vawter
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Sequeira
mesh_terms: D000704:Analysis of Variance; D001921:Brain / Q000473:pathology; D002102:Cadaver; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology*; D004210:Dissection; D005260:Female; D005821:Genetic Techniques; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics* / Q000473:pathology*