ArticleEBioMedicine2017
Sexually Dimorphic Changes of Hypocretin (Orexin) in Depression.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder.Annals of medicine · 2026Article
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- TTNPB Promotes Human Pluripotent Stem Cell-to-Neural Stem Cell Transition via Modulation of Chromatin Accessibility and the S-(5'-adenosyl)-L-homocysteine/Choline Metabolic Network.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.Nature communications · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sleep deprivation engages the orexin/hypocretin system to regulate food reward seeking.The international journal of neuropsychopharmacology · 2025Article
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Hallmarks of Cancer Cachexia: Sexual Dimorphism in Related Pathways.International journal of molecular sciences · 2025Review
- Common and sex-specific differences in hypothalamic subunit volumes and their links with depressive symptoms in treatment-naïve patients with major depressive disorder.Brain structure & function · 2025Article
- Alzheimer's disease with depression: clinical characteristics and potential mechanisms involving orexin and brain atrophy.Translational psychiatry · 2025Article
- Effects of Traumatic Brain Injury on the Orexin/Hypocretin System.Neurotrauma reports · 2025Review
- Hypocretin in the nucleus accumbens shell modulates social approach in female but not male California mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Interaction between corticotropin-releasing factor, orexin, and dynorphin in the infralimbic cortex may mediate exacerbated alcohol-seeking behavior.Neurobiology of stress · 2024Article
- Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment.International journal of molecular sciences · 2024Review
- Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.Heliyon · 2024Review
- Understanding the Biological Relationship between Migraine and Depression.Biomolecules · 2024Review
- Sex and Sleep Disruption as Contributing Factors in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Review
- Mild Traumatic Brain Injury Affects Orexin/Hypocretin Physiology Differently in Male and Female Mice.Journal of neurotrauma · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects.
methodsWe quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat.
resultsi) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats.
conclusionsThe clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.