Retinoic Acid Signaling in Affective Disorders
Summary
Retinoic acid (RA), the principal active metabolite of vitamin A, exerts wide-ranging effects on neuronal development, synaptic plasticity and neuroendocrine regulation. Within the adult brain, RA modulates gene expression through retinoic acid receptors, influencing neuroinflammation, neurotransmitter systems and homeostatic synaptic adjustments. Dysregulation of RA signalling has been implicated in affective disorders through several convergent pathways: perturbation of hypothalamic–pituitary–adrenal (HPA) axis function, impaired glucocorticoid receptor feedback, altered hippocampal synaptic gene expression and shifts in excitatory–inhibitory balance. Clinical and preclinical studies reveal abnormalities in peripheral retinoid homeostasis among individuals with major depressive disorder, while experimental models demonstrate that both endogenous RA binding proteins and pharmacological isomers such as 13-cis-retinoic acid can precipitate depression-like and anxiety-like phenotypes. Together, these findings highlight retinoid signalling as a nexus connecting nutritional status, molecular regulation of stress circuits and emotional behaviour, with implications for biomarker development and novel therapeutic approaches.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Retinoic Acid Signaling in Affective Disorders publication trend
The graph below shows the total number of articles in retinoic acid signaling in affective disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Retinoic acid (RA): bioactive metabolite of vitamin A that regulates gene transcription via nuclear retinoic acid receptors.
Retinoid homeostasis: balance of synthesis, metabolism and distribution of retinoids in the body.
Hypothalamic–pituitary–adrenal (HPA) axis: neuroendocrine system controlling stress responses and glucocorticoid release.
Glucocorticoid receptor (GR): nuclear receptor mediating feedback inhibition in the HPA axis.
Cellular retinoic acid-binding protein 1 (Crabp1): intracellular protein that modulates RA availability and signalling.
References
- Retinoid homeostasis in major depressive disorder. Translational Psychiatry (2023).
- Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression. International Journal of Molecular Sciences (2021).
- Chronic Administration of 13-cis-retinoic Acid Induces Depression-Like Behavior by Altering the Activity of Dentate Granule Cells. Neurotherapeutics (2021).
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.