Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial6

PSYCHONEUROENDOCRINOLOGY

卷:124

Article

Kalafatakis, Konstantinos^{1,2,3,10,11,12,13}  Russell, Georgina M.¹  Ferguson, Stuart G.⁴  Grabski, Meryem^5,6  Harmer, Catherine J.^7,8  Munafo, Marcus R.⁶  Marchant, Nicola⁹  Wilson, Aileen^2,3  Brooks, Jonathan C.^2,3  Thakrar, Jamini^2,3,9  Murphy, Patrick^1,9  Thai, Ngoc J.^2,3  Lightman, Stafford L.⁹ 

[1] Univ Bristol, Sch Clin Sci, Labs Integrat Neurosci & Endocrinol, Bristol BS1 3NY, Avon, England

[2] Univ Bristol, Clin Res & Imaging Ctr, Bristol BS2 8DX, Avon, England

[3] Univ Hosp Bristol NHS Fdn Trust, Bristol BS2 8DX, Avon, England

[4] Univ Tasmania, Sch Med, Hobart, Tas 7000, Australia

[5] UCL, Div Psychol & Language Sci, Clin Psychopharmacol Unit, London WC1E 6BT, England

[6] Univ Bristol, Sch Psychol Sci, MRC Integrat Epidemiol Unit, Bristol BS8 1TU, Avon, England

[7] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England

[8] Oxford Hlth NHS Fdn Trust, Oxford OX3 7JX, England

[9] Univ Hosp Bristol NHS Fdn Trust, Bristol Royal Infirm, Bristol BS2 8HW, Avon, England

[10] Vet Hosp Athens, 417 NIMTS, Athens, Greece

[11] Univ Ioannina, Ioannina, Greece

[12] Univ Crete, Iraklion, Greece

[13] Univ Bristol, Bristol, Avon, England

关键词: Glucocorticoids;    Ultradian rhythm;    FMRI;    Mood;    Psychophysiology;   

DOI  :  10.1016/j.psyneuen.2020.105096

来源: Elsevier

【 摘 要 】

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.

【 授权许可】

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