Hippocampal volume and total cell numbers in major depressive disorder

Abstract

Neuroimaging consistently reveals smaller hippocampal volume in recurrent or chronic major depressive disorder (MDD). The underlying cellular correlates of the smaller volume are not clearly known. Postmortem tissues from 17 pairs of depressed and control subjects were obtained at autopsy, and informant-based retrospective psychiatric assessment was performed. Formalin-fixed left temporal lobes were sectioned (40 μm), stained for Nissl substance, and every 60th section selected throughout the entire hippocampus. Total volume of the hippocampal formation was calculated, and total numbers of pyramidal neurons (in hippocampal fields CA1, CA2/3, hilus), dentate gyrus (DG) granule cells, and glial cells were estimated stereologically. While hippocampal volume in all MDD subjects was not significantly smaller versus control subjects, in recurrent/chronic MDD, total volume decreased with duration of depressive illness (r=−0.696, p<0.026). There was no significant difference between MDD and controls in total number or density of pyramidal neurons/granule cells or glial cells in CA1, CA2/3, hilus, or DG. However, CA1 pyramidal neuron density increased with duration of illness in recurrent/chronic MDD (r=0.840, p<0.002). Granule cell (r=0.971, p<0.002) and glial cell numbers (r=0.980, p<0.001) increased with age in those taking antidepressant medication (n=6). Increasing DG granule cell and glial cell numbers with age in antidepressant-treated subjects may reflect proliferative effects of antidepressant medications. Decreasing total volume and increasing CA1 pyramidal neuron density with duration of illness in recurrent/chronic MDD lends support to the neuropil hypothesis of MDD.

Dentate gyrus volume and memory performance in major depressive disorder

“…Furthermore, a recent in-vivo MRI study we performed (Huang et al, 2013) and post-mortem studies (Boldrini et al, 2013), reported increased DG volume and increased DG granule cell and glial cell numbers (Cobb et al, 2013) in MDD patients treated with antidepressants. These findings are consistent with the suggestion that stimulating DG neurogenesis with antidepressants might play an important role in reversing HC volume reduction in MDD patients.…”

GABAergic Control of Depression-Related Brain States

“…In some studies volume reductions of the hippocampus were shown to correlate with duration of untreated illness, suggesting that they may represent long-term consequences rather than predict illness onset (Cobb et al, 2013; MacQueen et al, 2003; Sheline, Sanghavi, Mintun, & Gado, 1999). However, a recent meta analysis of studies investigating first episode depression has found volume losses that are consistent with the neurotrophic deficit hypothesis of MDD (Cole, Costafreda, McGuffin, & Fu, 2011).…”

“…Some studies suggest that brain volume reduction in MDD is due to loss of neurons and/or glia (Drevets, Price, & Furey, 2008; Miguel-Hidalgo & Rajkowska, 2002). However, more recent data suggest that brain volume reduction in MDD is predominantly due to reductions in neuropil rather than cell numbers (Cobb et al, 2013). …”

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder

“…A meta-analysis of 32 magnetic resonance imaging (MRI) studies suggests about a 4 percent smaller left hippocampal volume in patients with a history of multiple episodes of depression or duration of illness exceeding 2 years (McKinnon et al, 2009). Our group recently published a stereological assessment of the volume of the postmortem hippocampus in chronic/recurrent depression and noted that total volume was decreased with increasing duration of illness (Cobb et al, 2013). We sought to determine whether the change in volume in MDD was due to altered neuronal or glial number, density or soma size.…”