A hyperadrenergic state in hypertension is associated with depressive symptoms and impaired stress-modulated vasomotor responses: evidence for chronic stress as a common aetiology for a hypertension/depression phenotype

Background Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism explaining the link between hypertension and affective disorders. Aims We investigated whether these stress-sensitive comorbidities may be dependent on basal noradrenergic activity and wheth...

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Main Authors: Bushra Farukh, Luca Faconti, Ryan J. McNally, Calum D. Moulton, Allan H. Young, Phil J. Chowienczyk
Format: Article
Language:English
Published: Cambridge University Press 2025-09-01
Series:BJPsych Open
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Online Access:https://www.cambridge.org/core/product/identifier/S205647242500064X/type/journal_article
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Summary:Background Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism explaining the link between hypertension and affective disorders. Aims We investigated whether these stress-sensitive comorbidities may be dependent on basal noradrenergic activity and whether vascular responses to centrally acting stimuli vary according to noradrenergic activity. Method We examined the relation of affective disorders and stress-mediated vascular responses to plasma concentrations of normetanephrine, a measure of noradrenergic activity, in subjects with primary hypertension (n = 100, mean ± s.d. age 43 ± 11 years, 54% male). The questionnaires Patient Health Questionnaire-9 (PHQ-9), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDSSR-16) and Generalized Anxiety Disorder-7 (GAD-7) were used for evaluation of symptoms of depression and anxiety. Forearm blood flow (strain gauge plethysmography) was used to assess vascular responses to mental stress and to device-guided breathing (DGB), interventions that respectively increase or decrease noradrenergic activity in the prefrontal cortex and locus coeruleus. Results Low mood and high anxiety were two- to threefold higher for hypertensive subjects in the highest compared with the lowest normetanephrine tertiles (each P < 0.005). Forearm vasodilator responses to mental stress and vasoconstrictor responses to DGB were attenuated in those with high compared with low normetanephrine (28.3 ± 21% v. 47.1 ± 30% increases for mental stress and 3.7 ± 21% v. 18.6 ± 15% decreases for DGB for highest versus lowest tertiles of normetanephrine, each P ≤ 0.01). Conclusions A hyperadrenergic state in hypertension is associated with mood disturbance and impaired stress-modulated vasomotor responses. This association may be mediated by chronic stress impinging on pathways regulating central arousal and peripheral sympathetic nerve activity.
ISSN:2056-4724