Smaller Cornu Ammonis 2–3/Dentate Gyrus Volumes and Elevated Cortisol in Multiple Sclerosis Patients with Depressive Symptoms

Abstract

Background The hippocampus is likely involved in mood disorders but in vivo evidence for the role of anatomically distinct hippocampal subregions is lacking. Multiple sclerosis (MS), an inflammatory disease of the CNS, is linked to a high prevalence of depression as well as hippocampal atrophy and may thus provide important insight into the pathological correlates of medical depression. Here, we examine the role of subregional hippocampal volume for depression in relapsing-remitting (RR) MS. Methods Anatomically defined hippocampal subregional volumes (Cornu Ammonis 1 (CA1), CA2–CA3 and the Dentate Gyrus (CA23DG), Subiculum, Entorhinal Cortex) were measured using a high resolution T2-weighted magnetic resonance imaging (MRI) sequence in 29 RRMS patients and 20 matched healthy controls. Diurnal salivary cortisol was assessed at awakening, 4pm and 9pm on two consecutive days. Subjects also completed the Beck Depression Inventory (BDI-II). Results MS patients showed smaller hippocampal volumes compared to controls, particularly in the CA1 and Subiculum subregions. In addition, MS patients with depressive symptoms (BDI-II > 13) also showed smaller CA23DG volumes and higher cortisol levels. Within the MS group, CA23DG volume was correlated with depressive symptoms and cortisol levels. There were no associations with number of previous steroid treatments, global atrophy, or disease duration. Conclusions This report provides in vivo evidence for selective association of smaller CA23DG subregional volumes in the hippocampus with cortisol hypersecretion and depressive symptoms in MS.

Pattern separation performance is decreased in patients with early multiple sclerosis

“…Given that dentate gyrus morphological abnormalities have been described in MS (Gold et al, 2010;, and given the particular importance of the dentate gyrus for pattern separation, our results provide additional neuropsychological support for an early dentate gyrus disruption during the course of MS. This selective vulnerability of dentate granular neurons at the early stage of MS could be related to a differential pattern of microglial activation in the dentate gyrus compared to other hippocampal subfields (Di Filippo et al, 2016;Planche et al, 2017), but the exact underlying molecular mechanisms remain unclear.…”

“…Therefore, MRI studies in patients with MS have reported controversial results, possibly due to different postprocessing techniques, and have highlighted a differential vulnerability either of CA1 Sicotte et al, 2008) or of CA3/CA4/dentate gyrus (Gold et al, 2010;. Therefore, whether the concept of an early selective vulnerability of the dentate gyrus is true in patients with early MS remains to be demonstrated.…”

Cognitive and neuropsychiatric disease manifestations in MS

“…Other studies found that depressed, but not euthymic patients have more severe atrophy of the frontal and parietal lobes (Bakshi et al, 2000). Interestingly, a study which has estimated hippocampal subregional volumes has demonstrated that depressed MS patients experience tissue loss in the cornu ammonis 2-3 (CA2-CA3) and the dentate gyrus (Gold et al, 2010). Using diffusion tensor MRI, abnormal diffusivity indexes in the normal appearing WM and GM of the left temporal lobe have been found in depressed vs. non-depressed patients (Feinstein et al, 2010).…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Pathological studies show demyelination and neuronal loss throughout the hippocampal formation [92,93]. Recent evidence suggests that there may be subregional susceptibility to distinct MS disease processes linked to depression and cognitive impairment in the hippocampus [94,95]. Although changes in these distinct gray matter areas are well documented, few current studies are targeting MR outcome measures to assess specific treatment effects on these key brain areas.…”