Corticosteroid-Induced Neuropsychiatric Effects

Corticosteroids, whether prescribed as anti-inflammatory or immunosuppressive agents, exert profound effects on the central nervous system. Their actions on glucocorticoid receptors are especially prominent in regions such as the hippocampus, amygdala and prefrontal cortex, which together regulate mood, cognition and stress responses. Adverse neuropsychiatric outcomes encompass a spectrum from mild anxiety and insomnia through mood disturbances—depression, mania or euphoria—to frank psychotic episodes and cognitive impairments. The likelihood and severity of these effects depend on dose, duration, individual susceptibility and interactions with other medications. Underlying mechanisms include dysregulation of the hypothalamic–pituitary–adrenal axis, altered neurotransmitter balance (notably in dopaminergic, serotonergic and glutamatergic systems), increased neuroinflammation and oxidative stress, and direct impacts on neuronal excitability and survival. Presentation may be acute, emerging within days of initiation, or delayed, arising after weeks to months of therapy. Recognition is often poor, leading to underreporting and delayed management. Timely identification, dose reduction or withdrawal of corticosteroids and, when necessary, adjunctive psychiatric interventions are central to minimising long-term sequelae and restoring functional wellbeing.

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Corticosteroid-Induced Neuropsychiatric Effects publication trend

The graph below shows the total number of articles in corticosteroid-induced neuropsychiatric effects across all publications each year (not limited to Nature Index journals).

Technical terms

Glucocorticoid receptor: Intracellular protein that binds corticosteroids and regulates gene expression affecting metabolism, inflammation and neuronal function.

Hypothalamic–pituitary–adrenal axis: A hormonal feedback system that controls cortisol secretion and mediates stress responses.

Neuroinflammation: Activation of immune-related cells within the brain, contributing to neuronal dysfunction and mood changes.

Oxidative stress: Cellular damage caused by an excess of reactive oxygen species relative to antioxidant defences.

Hippocampal-dependent functions: Cognitive processes, notably memory formation and consolidation, that rely on the hippocampus.

References

1. Molecular, Pathophysiological, and Clinical Aspects of Corticosteroid-Induced Neuropsychiatric Effects: From Bench to Bedside. Biomedicines (2024).
2. Adverse cognitive effects of glucocorticoids: A systematic review of the literature. Steroids (2023).