Biological Underpinnings of Anxiety and Well-Being
DOI:
https://doi.org/10.61173/4b8mnj90Keywords:
Anxiety Disorders, Psychological Well-being, Neurobiological MechanismsAbstract
While well-being has emerged as a crucial factor in determining resilience and health, anxiety disorders are among the most common mental health diseases in the world, significantly increasing disability and associated risk. In order to investigate the common and unique neurobiological underpinnings of anxiety and wellbeing across biomarkers, brain circuits, genetic factors, and intervention outcomes, this study synthesises research from after 2019. While dopaminergic reward pathways and striatal activity promote well-being through positive affect and resilience, anxiety is caused by amygdala hyperactivity, HPA axis instability, and decreased prefrontal control. Their orientations differ—vigilance versus reward engagement—despite having similar corticolimbic networks. Dopaminergic polymorphisms are linked to wellbeing, while serotonergic and Hypothalamic-Pituitary-Adrenal (HPA) variations are linked to anxiety, according to genetic data. System plasticity is demonstrated by interventions like mindfulness, Cognitive Behavioral Therapy (CBT), and Selective Serotonin Reuptake Inhibitors (SSRIs). The findings, which are backed by longitudinal, cross-cultural, and developmental studies, collectively imply that anxiety and well-being are related but separate, highlighting the potential of precision medicines that lessen threat sensitivity while increasing reward responsiveness.
References
[1] Sawiak S. J., Froudist-Walsh S., Bullmore E. T.:The neurobiological architecture of trait anxiety: Meta-analytic evidence from structural MRI. Neuroscience & Biobehavioral Reviews 113, 83–94 (2020)
[2] Lomas T., Waters L., Williams P., Oades L., Kern M. L.:Third wave positive psychology: Broadening towards complexity. The Journal of Positive Psychology 16(5), 660–674 (2021)
[3] Shackman A. J., Fox A. S.:Dispositional negativity: An integrative psychological and neurobiological perspective. Psychological Bulletin 147(1), 1–34 (2021)
[4] Baggio T., Grecucci A., Crivello F., Joliot M., Tzourio C., et al.:Resting-state connectivity patterns associated with trait anxiety in adolescence. Scientific Reports 15, 9711 (2025)
[5] Barros V., Trezza B. M., Vicente C. S., Crippa J. A. S., Loureiro S. R.:State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA): Psychometric properties in a large sample of the Brazilian population. Frontiers in Psychology 13, 843174 (2022)
[6] De la Peña-Arteaga V., Martin-Pascual M. Á., Álvarez- Méndez J. C., Pujol J., Soriano-Mas C.:Trait anxiety is associated with resting-state connectivity of attentional networks. European Neuropsychopharmacology 78, 38–47 (2024)
[7] Saviola F., Pappaianni E., Monti A., Grecucci A., Jovicich J., De Pisapia N.:Trait and state anxiety are mapped differently in the human brain. Scientific Reports 10, 11112 (2020)
[8] King L. A., Heffernan M. E., Krull J. L., Jackson J. J.:The neural correlates of well-being: A systematic review. Psychological Bulletin 145(10), 988–1024 (2019)
[9] Van Zyl L. E., Gaffaney J., van der Vaart L., Dik B. J., Donaldson S. I.:Addressing the criticisms and critiques of positive psychology: Recommendations for improving the science and practice of the field. Frontiers in Psychology 16, 1548612 (2025)
[10] Costa A., Caltagirone C., Oliveri M.:The neural correlates of hedonic and eudaimonic happiness: An fMRI study. Scientific Reports 9, 1–9 (2019)
[11] Richter A., Röcke C., Riediger M.:Brain imaging studies of emotional well-being: A scoping review. Frontiers in Psychology 14, 1328523 (2024)
[12] Yaribeygi H., Panahi Y., Sahraei H., Johnston T. P., Sahebkar A.:Cortisol and its regulation in anxiety disorders: A review of the evidence and implications. Journal of Cellular Physiology 236(10), 6572–6589 (2021)
[13] Lange J., Erhardt-Lehmann A.:HPA system in anxiety disorder patients treated with cognitive behavioural therapy: A review. Biomarkers in Neuropsychiatry 12, 100116 (2024) Dean&Francis ISSN 2959-6149
[14] Lei A. A., Gonzalez A., Kwan S.:Chronic stress-associated depressive disorders: The impact of HPA axis dysregulation and neuroinflammation on the hippocampus—A mini review. International Journal of Molecular Sciences 26(7), 2940 (2025)
[15] Sic A., Bogicevic M., Brezic N., Nemr C., Knezevic N. N.:Chronic stress and headaches: The role of the HPA axis and autonomic nervous system. Biomedicines 13(2), 463 (2025)
[16] Langhammer T., Biggs E., Campbell A., et al.:Restingstate functional connectivity in anxiety disorders: A systematic review and meta-analysis. Molecular Psychiatry Advance online publication (2024)
[17] Varkevisser T., Gladwin T. E., Kaldewaij R.:Amygdala fMRI—A critical appraisal of the extant literature. Neuroscience Insights 19, 26331055241270591 (2024)
[18] Godlewska B. R., Browning M., Norbury R., Cowen P. J., Harmer C. J.:Early changes in emotional processing as a marker of clinical response to SSRI treatment in generalized anxiety disorder. Translational Psychiatry 10, 186 (2020)
[19] Kotoula V., Evans J. W., Punturieri C. E., Zarate C. A. Jr.:The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression. Frontiers in Neuroimaging 2, 1110258 (2023)
[20] Yang Z., Oathes D. J., Linn K. A., et al.:Connectome-wide functional analysis of the amygdala in major depressive disorder: Altered connectivity between core limbic structures following antidepressant treatment. Translational Psychiatry 11, 49 (2021)
[21] Radua J., Vieta E., Shinohara R., et al.:Reward system dysfunction in major depressive disorder and other mood disorders: A meta-analysis of neuroimaging studies. JAMA Psychiatry 78(4), 387–397 (2021)
[22] Weinstein A. M.:Reward, motivation and brain imaging in human healthy participants – A narrative review. Frontiers in Behavioral Neuroscience 17, 1123733 (2023)
[23] Calabro F. J., Murata Y., Luna B.:Striatal dopamine supports reward expectation and learning. NeuroImage 275, 119698 (2023)
[24] Wingo A. P., Almli L. M., Stevens J. S., et al.:Genome-wide association study of positive emotion identifies a link to reward circuitry. Nature Human Behaviour 4, 269–278 (2020)
[25] Tunbridge E. M., Harrison P. J., Weinberger D. R.:Which dopamine polymorphisms are functional? Systematic review and meta-analyses of human dopamine transporter and receptor gene variants. Biological Psychiatry 85(2), 154–162 (2019)
[26] Baetu I., Neguţ A.:Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes: Behavioral and cognitive associations. Behavioral Genetics 45(3), 247–259 (2015)
[27] Kok B. E., Singer T., Engert V.:Longitudinal changes in brain function and behavior in a social mental training intervention. Science Advances 7(15), eabb4986 (2021)
[28] Hölzel B. K., Carmody J., Vangel M., et al.:Mindfulnessbased stress reduction is associated with increased gray matter density in brain regions involved in learning and memory processes, emotion regulation, and perspective taking. Psychiatry Research: Neuroimaging 191(1), 36–43 (2011)
[29] Yue W. L., Lu Y. T., Chen Z. Q., et al.:Mindfulness-based therapy improves brain functional reconfiguration efficiency in older adults with sleep difficulties. Translational Psychiatry 13, 181 (2023) (Open Access Text) Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting. Springer Nature will add OpenAccess standard text here during typesetting.
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