Association of the Volumes of Limbic Brain Structures with the Development of Psychoneurological Disorders in Patients with Ischemic Stroke

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Abstract

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0 =10.9; β = –4.27; p = 0.04) and in-creased salivary α-amylase activity (β0 = –3.55; β = 2.68e–05; p = 0.02). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0 = 3.41; β = –0.99; p = 0.047), smaller temporal pole volume (β0 = 3.41; β = –3.12; p = 0.06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0 = 3.41; β = –0.05; p = 0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

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About the authors

N. V. Ierusalimsky

Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences

Email: nata_gul@ihna.ru
Russian Federation, Moscow; Moscow

T. A. Druzhkova

Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department

Email: nata_gul@ihna.ru
Russian Federation, Moscow

M. Y. Zhanina

Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences

Email: nata_gul@ihna.ru
Russian Federation, Moscow; Moscow

E. E. Vladimirova

M. P. Konchalovsky City Clinical Hospital

Email: nata_gul@ihna.ru
Russian Federation, Moscow

N. N. Eremina

M. P. Konchalovsky City Clinical Hospital

Email: nata_gul@ihna.ru
Russian Federation, Moscow

A. B. Guekht

Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department; Pirogov Russian National Research Medical University

Email: nata_gul@ihna.ru
Russian Federation, Moscow; Moscow

N. V. Gulyaeva

Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences

Author for correspondence.
Email: nata_gul@ihna.ru
Russian Federation, Moscow; Moscow

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2. Fig. 1. Design of the study. NIHSS, scale of the US National Institutes of Health; HADS, Hospital Scale of Anxiety and Depression; MoCA, Montreal Cognitive Scale; HAM, Hamilton Depression Scale; BDI, Beck Depression scale; MRI, magnetic resonance imaging; 1-365, days after AI.

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3. Fig. 2. Dynamics of changes in NIHSS indices in the groups of patients without PKN (a), with PKN (b), without PDR (c) and with PDR (d). Statistical differences between time points were evaluated using the Friedman criterion with the posteriori Dann criterion: *p < 0.05, **p < 0.01, ***p < 0.001. The values on the charts are represented as median and span.

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4. Fig. 3. Dynamics of changes in scores on psychometric scales. At each point in time, groups with and without PCN were compared and dynamics for each group was estimated. The scales used were: MoCA (a), HADS (b), HAM (c), BDI (d). Statistical differences between the groups were evaluated using the Mann—Whitney criterion for the MoCA, HADS, HAM scales and the unpaired t-criterion for the BDI scale: #p < 0.1, *p < 0.05, **p < 0.01. Statistical differences in dynamics within groups were evaluated using the Wilcoxon criterion for the MoCA, HADS, HAM scales and the paired t-criterion for the BDI scale: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The data in graphs a, b and c are presented as a median with a span. The data in graph g is represented as M ± SEM.

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5. Fig. 4. Dynamics of cortisol levels in hair in groups with and without PCN. Statistical differences were assessed using the Mann—Whitney criterion. #p < 0.1, *p < 0.05, **p < 0.01. The data is presented as a median with a span.

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6. Fig. 5. Relative volumes of the temporal pole (a) and supramarginal gyrus (b) in groups with and without PCN. Statistical differences between the groups were assessed using the unpaired t-test: *p < 0.05. All data is presented as M ± SEM. The location of the temporal pole and supramarginal gyrus (b) is shown.

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7. Fig. 6. Multiple logistic regression and ROC analysis of predictors influencing the development of PCN.

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8. Fig. 7. Dynamics of psychoemotional status in groups with and without PDR on the HADS (a), HAM (b), BDI (c) and MoCA (d) scales. Statistical differences between the groups were assessed using the unpaired t-test for the HADS and HAM scales and the Mann—Whitney test for the BDI scales and MoCA: #p < 0.1, *p < 0.05, **p < 0.01, ****p < 0.001. Statistical differences for dynamics within the same groups were evaluated using the paired t-test for the HADS, HAM scales and the Wilcoxon criterion for the BDI and MoCA scales: #p < 0.1, *p < 0.05, **p < 0.01. The data in graphs a, b are presented as M ± SEM. The data in graphs c and d are presented as a median with a span.

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9. Figure 8. Dynamics of α-amylase content in saliva (a) and IL-6 in blood serum (b) in groups with and without PDR. Statistical differences between the groups were assessed using the Mann—Whitney criterion for α-amylase in saliva (a), and according to the unpaired t-test for IL-6 in blood serum: *p < 0.05, **p < 0.01. Statistical differences in dynamics were assessed using the Wilcoxon criterion for α-amylase in saliva and according to the paired t-criterion for IL-6 in blood serum: #p < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001. The data in graph a is presented as a median with a span. The data in graph b is represented as M ± SEM.

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10. Fig. 9. Relative volumes of the entorhinal cortex (a), temporal pole (b) and hippocampus (c) in groups of patients with and without PD. Statistical differences between the groups were assessed using the unpaired t-test: *p < 0.05, **p < 0.01. All data is presented as M ± SEM. The location of the entorhinal cortex, temporal pole and hippocampus (d) is shown.

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11. Fig. 10. Multiple logistic regression and ROC analysis of the effect of changes in the volume of the temporal pole and the level of α-amylase on the development of PDR.

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