Hormonal Regulation of Mood Disorders

Hormonal regulation of mood disorders encompasses the intricate interplay between systemic endocrine signals and central nervous system processes that govern emotional states. Key hormones such as cortisol, oestrogens, progesterone and testosterone modulate neuronal excitability and synaptic plasticity through the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes. Adipokines including leptin and adiponectin further influence mood by regulating energy homeostasis, neurogenesis and neuroinflammation. Dysregulation of these hormonal pathways can precipitate symptoms of depression and anxiety, manifesting as alterations in appetite, sleep, cognition and stress resilience. Moreover, interactions between metabolic hormones and classical neurotransmitter systems underscore a bidirectional relationship: for example, impaired leptin signalling disrupts hippocampal and prefrontal circuitry, while inflammatory mediators released under chronic stress feed back on endocrine function. Sex differences in hormone receptor expression and downstream gene transcription contribute to variations in prevalence and presentation of mood disorders globally, highlighting the need for personalised therapeutic strategies.

Research from Nature Portfolio

Analyses in rodent models of comorbid obesity and chronic stress have elucidated the role of leptin receptor signalling in mood regulation. Experimental exposure to a high-fat diet combined with chronic unpredictable mild stress induces pronounced depression-like behaviours, anxiety-like responses and cognitive deficits. These behavioural changes correspond with a down-regulation of the long-form leptin receptor in the hippocampus and hypothalamus, implicating impaired leptin/LepRb pathways in the pathogenesis of mood disturbances within a metabolic challenge context.

Hormonal Regulation of Mood Disorders publication trend

The graph below shows the total number of articles in hormonal regulation of mood disorders across all publications each year (not limited to Nature Index journals).

Technical terms

LepRb: The long-form leptin receptor that mediates central leptin signalling and influences mood regulation.

HPA axis: Hypothalamic–pituitary–adrenal axis, the principal stress response system coordinating cortisol release.

Anhedonia: A core symptom of depression characterised by loss of interest or pleasure in normally rewarding activities.

AMPK: AMP-activated protein kinase, a cellular energy sensor involved in metabolic and inflammatory pathways.

PPM1F: A Mg2+/Mn2+-dependent protein phosphatase that modulates p300 activity and influences neuronal signalling.

References

1. The Effects of High-fat-diet Combined with Chronic Unpredictable Mild Stress on Depression-like Behavior and Leptin/LepRb in Male Rats. Scientific Reports (2016).
2. Influence of leptin and its receptors on individuals under chronic social stress behavior. Frontiers in Endocrinology (2024).
3. Sex differences in the association between serum α-Klotho and depression in middle-aged and elderly individuals: A cross-sectional study from NHANES 2007–2016. Journal of Affective Disorders (2023).
4. Medial prefrontal cortical PPM1F alters depression‐related behaviors by modifying p300 activity via the AMPK signaling pathway. CNS Neuroscience & Therapeutics (2023).