Search

Introduction Hippocampus (HC) volume reductions have been a consistent finding in major depression (MDD). One possible mechanism that contribute to these reductions might be the inhibition of hippocampal neurogenesis through increased glucocorticoid stimulation following the chronic activation of the hypothalamo-pituitary stress axis (HPA) [1,2]. This is also supported by the fact that the resulting volume reductions can be partially reversed with antidepressant treatment [1,2] Furthermore, preclinical studies suggest that the effect of HPA dysregulation on hippocampal volume reduction, neurogenesis and their reversal by antidepressant response vary across hippocampal regions and are especially present in CA1, CA3 (atrophy of dendrites) and dentate gyrus (neurogenesis) [2]. Compatibly with this hypothesis, genetic variants influencing the endocrine stress axis in MDD, such as the FKBP5 glucocorticoid receptor regulator, were shown to be associated with brain structural changes, especially in the presence of environmental stressors such as early life stress (ELS) [3,4]. In accordance with the above mentioned findings we hypothesized that there might be a differential effect of early life stress on hippocampal subfields volumes in MDD patients with different allelic variants of FKBP5. To answer this question, we investigated whether patients exposed to childhood adversity and carrying the high-risk T allele of the rs1360780 polymorphism of FKBP5 showed smaller hippocampal volumes compared to C homozygous patients. Since CA1, CA3 and the dentate gyrus are especially affected by HPA axis alterations, we decided to focus on these hippocampal subfields. Methods We processed structural MRI data from 65 healthy controls (HC) and 91 MDD patients with automated hippocampal subfields segmentation using Freesurfer 5.3 for whole brain segmentation, followed by hippocampal subfields segmentation using Freesurfer 6 developer version. A quality check was performed using the ENIGMA hippocampal subfield protocols. We selected the following subfields for analysis: granule cells/molecular layer/dentate gyrus (GCMLDG), CA1, CA3, whole hippocampus (WH). ELS was evaluated with the Childhood Trauma Questionnaire Short Form. At least one mild expression of sexual abuse (subscale score > 7), emotional abuse (subscale score > 12) or physical abuse (subscale score > 9) was seen as having had a history of childhood abuse. We predicted the volume of each subfield using generalized linear scale response models, testing for the significance of between-group (diagnosis, ELS, allele status, age, sex, site, total intractranial volume) and within-group (side) factors. Results MDD patients showed reduced volume in all the subfields and in the total HC (p Conclusion In MDD, volume of CA1, CA3, DG and total HC was reduced. Patients with a high-risk variant in a glucocorticoid receptor regulator gene display smaller CA1 volumes in presence of ELS.

Diffusion-weighted imaging (DWI) is an advanced magnetic resonance imaging technique, based on the analysis of thermallydependent movement of water molecules in the extracellular space. This method allows to examine pathological changes at the cellular level which are not visible on conventional magnetic resonance (MR). Apparent diffusion coefficient (ADC) is a mathematically calculated value indicating the diffusion. Reduced ADC value demonstrates a restricted diffusion while increased ADC value indicates a facilitated diffusion. Aim: The aim of this study was to assess changes in ADC values within normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in patients with MS before initiating the treatment with IFN-Beta and already in the course of treatment, in comparison with a control group. Material and Methods: The study comprised 84 patients divided into three groups: patients with MS before initiating the therapy with IFN-Beta (MS0, n = 28: 22 women, 6 men; average age: 28.8), patients with MS after at least one year of treatment with IFN-Beta (MS1, n = 28: 22 women, 6 men; average age: 30.2) and a control group of patients with no intracranial pathology (CG, n = 28: 20 women, 8 men; average age: 29.8). ADC was measured in 11 regions of interest (ROIs), as follows: 1, 2 − cerebellum at the level of dentate nuclei, 3 − pons, 4, 5 − thalamus, 6, 7 − caudate nuclei, 8, 9 − frontal white matter regions, 10, 11 − fronto-parietal white matter at the convexity. The results were compared between the groups. The study was performed using a 1.5T GE MRI scanner. DWI sequence was performed with the following parametres: b = 0 and b = 1000, TR=8000, TE=81.2, slice thickness = 4mm. Results: In the examined areas of brain, in ROIs: 8 and 9 the ADC values were statistically significantly higher in MS0 group in comparison with CG (p< 0.01). There were no significant differences in ADC values in ROIs: 8 and 9 between MS1 and CG. However, in ROI 6 the ADC values were significantly lower (p< 0.01), while in ROIs: 10 and 11 significantly higher (p< 0.01) in MS1 group in comaprison with CG. No other statistically significant differences were found between groups: MS0 and CG, MS1 and CG, as well as MS0 and MS1. Conclusions: Increased ADC values in NAWM of the frontal lobes in patients with MS before initiating the treatment with IFN-Beta may indicate early axonopathy, in the course of which diffusion is facilitated. Normalization of ADC values in this region after several months of treatment with IFN-Beta as well as decrease in ADC values in NAGM of right caudate nucleus may indicate a decrease of the diffusion and delay in the axonal damage as a result of immunomodulatory treatment.