Antidepressant Strategies in Stress-Induced Behavioral Disorders

Stress-induced behavioural disorders encompass a spectrum of conditions in which chronic or acute stress leads to persistent changes in mood, cognition and physiological function. Traditional antidepressant strategies have centred on modulation of monoamine neurotransmitters, notably serotonin and noradrenaline, to restore chemical balance in key brain regions. However, limitations such as delayed onset of effect and incomplete remission have driven the exploration of novel approaches. These include agents that enhance neurotrophic support, regulate the hypothalamic–pituitary–adrenal (HPA) axis, and target neuroinflammatory pathways. Nutraceuticals, such as polyphenols and flavonols, have garnered attention for their antioxidant and anti-inflammatory properties. Rapid-acting interventions, from ketamine derivatives to neuromodulation techniques, seek to recalibrate synaptic plasticity and neurogenesis more swiftly. Emerging delivery systems aim to improve central nervous system bioavailability and reduce peripheral side effects. Together, these multifaceted strategies reflect a transition towards personalised treatments that address the diverse biological sequelae of stress.

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Antidepressant Strategies in Stress-Induced Behavioral Disorders publication trend

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Technical terms

Hypothalamic–pituitary–adrenal (HPA) axis: A neuroendocrine system that governs stress responses by regulating release of corticotrophin-releasing hormone, adrenocorticotropic hormone and cortisol or corticosterone.

Neurogenesis: The process by which new neurons are generated from neural stem or progenitor cells, particularly within the hippocampal dentate gyrus, contributing to mood regulation.

Synaptic plasticity: The capacity of synapses to strengthen or weaken over time in response to increases or decreases in their activity, underlying learning, memory and mood adaptation.

Exosome: A small extracellular vesicle secreted by cells that can transfer proteins, lipids and nucleic acids to recipient cells, mediating intercellular communication.

Flavonol: A subclass of flavonoids found in fruits and vegetables, characterised by antioxidant and anti-inflammatory effects that may support neuronal health and resilience.

References

1. Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model. Pharmaceutics (2023).
2. Oligodendrocyte‐derived exosomes‐containing SIRT2 ameliorates depressive‐like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK‐3β pathway in depressed mice. CNS Neuroscience & Therapeutics (2024).
3. Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder. International Journal of Molecular Sciences (2023).