Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study - PubMed (original) (raw)

Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study

Natalie M Zahr et al. Neuroimage Clin. 2019.

Abstract

The profile of brain structural dysmorphology of individuals with Alcohol Use Disorders (AUD) involves disruption of the limbic system. In vivo imaging studies report hippocampal volume loss in AUD relative to controls, but only recently has it been possible to articulate different regions of this complex structure. Volumetric analysis of hippocampal regions rather than total hippocampal volume may augment differentiation of disease processes. For example, damage to hippocampal subfield cornu ammonis 1 (CA1) is often reported in Alzheimer's disease (AD), whereas deficits in CA4/dentate gyrus are described in response to stress and trauma. Two previous studies explored the effects of chronic alcohol use on hippocampal subfields: one reported smaller volume of the CA2+3 in alcohol-dependent subjects relative to controls, associated with years of alcohol consumption; the other, smaller volumes of presubiculum, subiculum, and fimbria in alcohol-dependent relative to control men. The current study, conducted in 24 adults with DSM5-diagnosed AUD (7 women, 53.7 ± 8.8) and 20 controls (7 women, 54.1 ± 9.3), is the first to use FreeSurfer 6.0, which provides state-of-the art hippocampal parcellation, to explore the sensitivity of hippocampal sufields to alcoholism. T1- and T2- images were collected on a GE MR750 system with a 32-channel Nova head coil. FreeSurfer 6.0 hippocampal subfield analysis produced 12 subfields: parasubiculum; presubiculum; subiculum; CA1; CA2+3; CA4; GC-ML-DG (Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)); molecular layer; hippocampus-amygdala-transition-area (HATA); fimbria; hippocampal tail; hippocampal fissure; and whole volume for left and right hippocampi. A comprehensive battery of neuropsychological tests comprising attention, memory and learning, visuospatial abilities, and executive functions was administered. Multiple regression analyses of raw volumetric data for each subfields by group, age, sex, hemisphere, and supratentorial volume (svol) showed significant effects of svol (p < .04) on nearly all structures (excluding tail and fissure). Volumes corrected for svol showed effects of age (fimbria, fissure) and group (subiculum, CA1, CA4, GC-ML-DG, HATA, fimbria); CA2+3 showed a diagnosis-by-age interaction indicating older AUD individuals had a smaller volume than would be expected for their age. There were no selective relations between hippocampal subfields and performance on neuropsychological tests, likely due to lack of statistical power. The current results concur with the previous study identifying CA2+3 as sensitive to alcoholism, extend them by identifying an alcoholism-age interaction, and suggest an imaging phenotype distinguishing AUD from AD and stress/trauma.

Keywords: Alcohol Use Disorder (AUD); Attention; Executive functions; Hippocampal subfields; Hippocampal subregions; Hippocampus; Learning and memory; Visuospatial.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Figures

Fig. 1

Fig. 1

Axial, coronal, and sagittal slices through the hippocampus demonstrating parcellation of a fully processed set of images from a 65 year-old control man. Subfields are color-coded.

Fig. 2

Fig. 2

Scatterplots of control (white circles) and AUD (black square) performance on neuropsychological composite scores; mean and SD indicated by lines.

Fig. 3

Fig. 3

Scatterplots of control (circles) and AUD (squares) svol-corrected volumes for each hippocampal subfield; mean and SD indicated by lines. Each region is color-coded according to segmentation shown in inset.

Fig. 4

Fig. 4

Age-by-diagnosis plots of each svol-corrected and left + right summed hippocampal subfield for controls (white circles) and AUD participants (black squares).

Supplementary Fig. 1

Supplementary Fig. 1

Volumes of hippocampal fimbria and fissure (a CSF-filled space) as a function of AUD-related seizures (no – self-report of no seizures; yes – self-report of AUD-related seizures).

Supplementary Fig. 2

Supplementary Fig. 2

Correlation between fimbria volume and performance on WMSr-visual recognition 2 raw score.

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References

    1. Aas M., Haukvik U.K., Djurovic S., Tesli M., Athanasiu L., Bjella T., Hansson L., Cattaneo A., Agartz I., Andreassen O.A., Melle I. Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders. J. Psychiatr. Res. 2014;59:14–21. - PubMed
    1. Bengochea O., Gonzalo L.M. Effect of chronic alcoholism on the human hippocampus. Histol. Histopathol. 1990;5:349–357. - PubMed
    1. Beresford T.P., Arciniegas D.B., Alfers J., Clapp L., Martin B., Du Y., Liu D., Shen D., Davatzikos C. Hippocampus volume loss due to chronic heavy drinking. Alcohol. Clin. Exp. Res. 2006;30:1866–1870. - PubMed
    1. Boen E., Westlye L.T., Elvsashagen T., Hummelen B., Hol P.K., Boye B., Andersson S., Karterud S., Malt U.F. Smaller stress-sensitive hippocampal subfields in women with borderline personality disorder without posttraumatic stress disorder. J. Psychiatry Neurosci. 2014;39:127–134. - PMC - PubMed
    1. Braak E., Braak H. Alzheimer's disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon's horn. Acta Neuropathol. 1997;93:323–325. - PubMed

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