Neuropeptide Modulation in Stress and Anxiety Disorders
Summary
The regulation of stress and anxiety involves a complex interplay of chemical messengers known as neuropeptides, which fine-tune neuronal circuits across key limbic and brainstem regions. Among the most extensively studied are neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), substance P and pro-opiomelanocortin (POMC)-derived peptides. These molecules act on G-protein-coupled receptors within the amygdala, hippocampus, bed nucleus of the stria terminalis (BNST) and locus coeruleus to either amplify or dampen the behavioural and endocrine responses to threat. Dysregulation of neuropeptide systems contributes to maladaptive fear, heightened vigilance and sustained anxiety, while targeted modulation holds promise for novel therapeutics. Advances in genetic, transcriptomic and pharmacological approaches have revealed sex-specific expression patterns, receptor heteromerisation and epigenetic reprogramming that shape individual vulnerability to stress-triggered disorders. By elucidating how neuropeptides orchestrate neuronal excitability, synaptic plasticity and hypothalamic–pituitary–adrenal axis feedback, researchers are defining pathways for precision interventions that restore resilience without overtly sedating central circuits.
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Neuropeptide Modulation in Stress and Anxiety Disorders publication trend
The graph below shows the total number of articles in neuropeptide modulation in stress and anxiety disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Neuropeptide: A small protein-like signalling molecule released by neurons to modulate brain function and behaviour.
Neuropeptide Y (NPY): A 36-amino-acid peptide involved in appetite, stress resilience and anxiolysis through Y-receptor subtypes.
Corticotropin-releasing hormone (CRH): A hypothalamic peptide that triggers the stress hormone cascade via the HPA axis.
Bed nucleus of the stria terminalis (BNST): A forebrain structure central to sustained anxiety and contextual fear processing.
Locus coeruleus: A brainstem nucleus of noradrenergic neurons critical for arousal, vigilance and stress adaptation.
References
- Enhancing Cognitive Functions and Neuronal Growth through NPY1R Agonist and Ketamine Co-Administration: Evidence for NPY1R-TrkB Heteroreceptor Complexes in Rats. Cells (2024).
- Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons. European Neuropsychopharmacology (2023).
- Valence-dependent effects of neuropeptide Y on the expression of conditioned fear and anxiety-like behavior: Involvement of the bed nucleus of the stria terminalis. Neuropharmacology (2024).
- Prostaglandin E2 Induces Long-Lasting Inhibition of Noradrenergic Neurons in the Locus Coeruleus and Moderates the Behavioral Response to Stressors. Journal of Neuroscience (2023).
- Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders. Biomolecules (2020).
- Allele-specific programming of Npy and epigenetic effects of physical activity in a genetic model of depression. Translational Psychiatry (2013).
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