title: Increased doublecortin (DCX) expression and incidence of DCX-immunoreactive multipolar cells in the subventricular zone-olfactory bulb system of suicides.
abstract: Postmortem studies have confirmed the occurrence of adult hippocampal neurogenesis in humans and implicated this process in antidepressant response, yet neurogenesis in other regions remains to be examined in the context of depression. Here we assess the extent of subventricular zone-olfactory bulb (SVZ-OB) neurogenesis in adult humans having died by suicide. Protein expression of proliferative and neurogenic markers Sox2, proliferating cell nuclear antigen, and doublecortin (DCX) were examined in postmortem SVZ and OB samples from depressed suicides and matched sudden-death controls. In the SVZ, DCX-immunoreactive (IR) cells displayed phenotypes typical of progenitors, whereas in the olfactory tract (OT), they were multipolar with variable size and morphologies suggestive of differentiating cells. DCX expression was significantly increased in the OB of suicides, whereas SVZ DCX expression was higher among unmedicated, but not antidepressant-treated, suicides. Although very few DCX-IR cells were present in the control OT, they were considerably more common in suicides and correlated with OB DCX levels. Suicides also displayed higher DCX-IR process volumes. These results support the notion that OB neurogenesis is minimal in adult humans. They further raise the possibility that the differentiation and migration of SVZ-derived neuroblasts may be altered in unmedicated suicides, leading to an accumulation of ectopically differentiating cells in the OT. Normal SVZ DCX expression among suicides receiving antidepressants suggests a potentially novel mode of action of antidepressant medication. Given the modest group sizes and rarity of DCX-IR cells assessed here, a larger-scale characterization will be required before firm conclusions can be made regarding the identity of these cells.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada.
authors.forename: Marissa E
authors.initials: ME
authors.lastname: Maheu
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Devorak
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Freibauer
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Davoli
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada ; Department of Psychiatry, McGill University Montreal, QC, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute Montreal, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada ; Department of Psychiatry, McGill University Montreal, QC, Canada.
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
keywords: adult neurogenesis; antidepressants; depression; human postmortem; olfactory bulb