Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review

Overview

Journal Brain Sci

Publisher MDPI

Date 2024 Jan 22

PMID 38248265

Authors

Musi Xie

Ying Huang

Wendan Cai

Bingqi Zhang

Haonan Huang

Qingwei Li

Pengmin Qin

Junrong Han

Affiliations

Soon will be listed here.

Abstract

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical-cortical interactions in arousal, few have explored the relationship between subcortical-cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression.

Citing Articles

Stress, Anxiety and Depressive Symptoms, Burnout and Insomnia Among Greek Nurses One Year After the End of the Pandemic: A Moderated Chain Mediation Model.

Pachi A, Sikaras C, Melas D, Alikanioti S, Soultanis N, Ivanidou M J Clin Med. 2025; 14(4).

PMID: 40004676 PMC: 11856992. DOI: 10.3390/jcm14041145.

Sleep duration in adolescence buffers the impact of childhood trauma on anxiety and depressive symptoms.

Coote T, Barrett E, Grummitt L BMC Public Health. 2025; 25(1):437.

PMID: 39905366 PMC: 11792485. DOI: 10.1186/s12889-025-21621-x.

Multimodal state-dependent connectivity analysis of arousal and autonomic centers in the brainstem and basal forebrain.

Pourmotabbed H, Martin C, Goodale S, Doss D, Wang S, Bayrak R bioRxiv. 2024; .

PMID: 39605337 PMC: 11601260. DOI: 10.1101/2024.11.11.623092.

References

Veith R, Lewis N, LINARES O, BARNES R, Raskind M, Villacres E . Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch Gen Psychiatry. 1994; 51(5):411-22. DOI: 10.1001/archpsyc.1994.03950050071008. View

Wijdicks E . The Ascending Reticular Activating System. Neurocrit Care. 2019; 31(2):419-422. DOI: 10.1007/s12028-019-00687-7. View

Mendlewicz J . Sleep disturbances: core symptoms of major depressive disorder rather than associated or comorbid disorders. World J Biol Psychiatry. 2009; 10(4):269-75. DOI: 10.3109/15622970802503086. View

Volkers A, Tulen J, Van den Broek W, Bruijn J, Passchier J, Pepplinkhuizen L . Motor activity and autonomic cardiac functioning in major depressive disorder. J Affect Disord. 2003; 76(1-3):23-30. DOI: 10.1016/s0165-0327(02)00066-6. View

Murphy S, Elklit A, Chen Y, Ghazali S, Shevlin M . Sex differences in PTSD symptoms: A differential item functioning approach. Psychol Trauma. 2018; 11(3):319-327. DOI: 10.1037/tra0000355. View

Kong X, Kong R, Orban C, Wang P, Zhang S, Anderson K . Sensory-motor cortices shape functional connectivity dynamics in the human brain. Nat Commun. 2021; 12(1):6373. PMC: 8568904. DOI: 10.1038/s41467-021-26704-y. View

Wong M, Kling M, Munson P, Listwak S, Licinio J, Prolo P . Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci U S A. 2000; 97(1):325-30. PMC: 26662. DOI: 10.1073/pnas.97.1.325. View

Laureys S . The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci. 2005; 9(12):556-9. DOI: 10.1016/j.tics.2005.10.010. View

Setzer B, Fultz N, Gomez D, Williams S, Bonmassar G, Polimeni J . A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state. Nat Commun. 2022; 13(1):5442. PMC: 9481532. DOI: 10.1038/s41467-022-33010-8. View

10.

Schumann A, Andrack C, Bar K . Differences of sympathetic and parasympathetic modulation in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017; 79(Pt B):324-331. DOI: 10.1016/j.pnpbp.2017.07.009. View

11.

Arora I, Bellato A, Ropar D, Hollis C, Groom M . Is autonomic function during resting-state atypical in Autism: A systematic review of evidence. Neurosci Biobehav Rev. 2021; 125:417-441. DOI: 10.1016/j.neubiorev.2021.02.041. View

12.

Neumeister A, Nugent A, Waldeck T, Geraci M, Schwarz M, Bonne O . Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls. Arch Gen Psychiatry. 2004; 61(8):765-73. DOI: 10.1001/archpsyc.61.8.765. View

13.

Wang C, Wu H, Chen F, Xu J, Li H, Li H . Disrupted functional connectivity patterns of the insula subregions in drug-free major depressive disorder. J Affect Disord. 2018; 234:297-304. DOI: 10.1016/j.jad.2017.12.033. View

14.

Pintor L, Torres X, Navarro V, Martinez de Osaba M, Matrai S, Gasto C . Corticotropin-releasing factor test in melancholic patients in depressed state versus recovery: a comparative study. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(5):1027-33. DOI: 10.1016/j.pnpbp.2007.03.002. View

15.

Plotsky P, Owens M, Nemeroff C . Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am. 1998; 21(2):293-307. DOI: 10.1016/s0193-953x(05)70006-x. View

16.

Grant M, Weiss J . Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry. 2001; 49(2):117-29. DOI: 10.1016/s0006-3223(00)00936-7. View

17.

Schmidt F, Pschiebl A, Sander C, Kirkby K, Thormann J, Minkwitz J . Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls. Neuropsychobiology. 2016; 73(1):1-9. DOI: 10.1159/000441190. View

18.

Herrera C, Cadavieco M, Jego S, Ponomarenko A, Korotkova T, Adamantidis A . Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness. Nat Neurosci. 2015; 19(2):290-8. PMC: 5818272. DOI: 10.1038/nn.4209. View

19.

Goodale S, Ahmed N, Zhao C, de Zwart J, Ozbay P, Picchioni D . fMRI-based detection of alertness predicts behavioral response variability. Elife. 2021; 10. PMC: 8104962. DOI: 10.7554/eLife.62376. View

20.

Agelink M, Boz C, Ullrich H, Andrich J . Relationship between major depression and heart rate variability. Clinical consequences and implications for antidepressive treatment. Psychiatry Res. 2002; 113(1-2):139-49. DOI: 10.1016/s0165-1781(02)00225-1. View