title: Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry.
abstract: It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is growing evidence for hemispheric lateralization in brain systems regulating arousal and emotion. Here we tested the hypotheses that individual variations in basal morning and afternoon/evening cortisol levels would be associated with the degree of hemispheric asymmetry in hippocampal microstructure. Fifty healthy adults aged 19 to 86 years were included in the analyses. Diffusion-weighted imaging was acquired from all subjects. Hippocampal mean diffusivity (MD) and volume was extracted. Cortisol measures were based on 5 morning and 3 afternoon/evening saliva samples. Higher left relative to right hippocampus MD was associated with higher basal cortisol levels. Associations were anatomically specific and not attributable to hippocampal volume asymmetry. No correlation between hippocampal volume and MD was observed, suggesting that MD and volume index distinct biological properties of the hippocampus. Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point to an important relationship between the limbic system and neuroendocrine function in terms of left-right asymmetries, raising additional questions about how the limbic system is related to neuroendocrine functions.
authors: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark. kathrine@drcmr.dk
authors: Kathrine Skak
authors: KS
authors: Madsen
authors: Terry L
authors: TL
authors: Jernigan
authors: Pernille
authors: P
authors: Iversen
authors: Vibe G
authors: VG
authors: Frokjaer
authors: Gitte M
authors: GM
authors: Knudsen
authors: Hartwig R
authors: HR
authors: Siebner
authors: William F C
authors: WF
authors: Baaré
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006624:Hippocampus / Q000033:anatomy & histology* / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012463:Saliva / Q000737:chemistry
chemical_list: D006854:Hydrocortisone