Insulin Resistance and Mood Disorder Interactions
Summary
Insulin resistance is increasingly recognised as a key physiological factor influencing the onset, severity and treatment response of mood disorders, most notably major depressive disorder and bipolar disorder. At its core, insulin resistance denotes a diminished cellular response to circulating insulin, leading to compensatory hyperinsulinaemia and disrupted glucose homeostasis. In the central nervous system, insulin modulates neurotransmitter systems, neuroinflammation, synaptic plasticity and hypothalamic–pituitary–adrenal axis balance. Impairment of these processes has been linked to an atypical mood disorder phenotype marked by increased fatigue, psychomotor changes, altered appetite and sleep disturbances. Bidirectional interactions between metabolic and affective systems are underpinned by chronic low-grade inflammation, oxidative stress and gut–brain axis alterations, which may exacerbate both insulin resistance and depressive symptoms. The emergence of a “metabolic” depressive subtype has prompted interest in stratified interventions, encompassing lifestyle modification, insulin-sensitising medications and targeted anti-inflammatory strategies, with the aim of improving both metabolic and mood outcomes on a global scale.
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Insulin Resistance and Mood Disorder Interactions publication trend
The graph below shows the total number of articles in insulin resistance and mood disorder interactions across all publications each year (not limited to Nature Index journals).
Technical terms
Insulin resistance: A state in which cells fail to respond adequately to insulin, leading to impaired glucose uptake and compensatory hyperinsulinaemia.
Major depressive disorder: A psychiatric condition characterised by persistent low mood, loss of interest or pleasure and a range of cognitive and somatic symptoms.
HOMA-IR (Homeostasis Model Assessment of Insulin Resistance): A calculated index derived from fasting glucose and insulin levels, used to estimate insulin sensitivity.
Thiazolidinediones: A class of insulin-sensitising drugs that activate peroxisome proliferator-activated receptor-gamma (PPARγ) to improve insulin action and modulate inflammation.
Selective serotonin-noradrenaline reuptake inhibitors: Antidepressant agents that block the neuronal reuptake of serotonin and noradrenaline, thereby enhancing monoaminergic neurotransmission.
References
- Consolidating evidence on the role of insulin resistance in major depressive disorder. Current Opinion in Psychiatry (2023).
- Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder. Pharmacological Reports (2024).
- Changes in insulin resistance following antidepressant treatment mediate response in major depressive disorder. Journal of Psychopharmacology (2022).
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