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Major depressive disorder; MDD

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:583
Name:Major depressive disorder; MDD
Associated with:4 targets
1 immuno-relevant ligand
Database Links
Disease Ontology: DOID:1470
OMIM: 608516

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
5-HT2A receptor
5-HT3B
Role:  5-HT3B has been associated with major female depression in genetic analyses.
Comments:  This polymorphism occurs at a significantly reduced frequency in female patients suffering from major depression and also patients with bipolar disorder, consistent with a protective influence of the variant allele.
References:  9
Mutations:  5-HT3B is associated with 1 mutation. Click here for details
KCa2.3
Drugs:  Apamin has positive effects in a mouse model of depression.
Side effects:  High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum.
Therapeutic use:  KCa2.3 blockers have been proposed for the treatment of depression.
References:  1,3,5
Kir4.1
Role:  K+ buffering. There is a putative link between Kir4.1 and depression
Drugs:  Tricyclic anti-depressants.
Side effects:  Seizure.
References:  8

Ligands

GtoPdb Disease Summaries - Ligands

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  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
sirukumab
Immuno Disease Comments: Phase 2 clinical candidate for MDD (see NCT02473289).
Clinical Use: Phase 3 clinical trials assessing sirukumab for RA have been completed or are still ongoing (Oct 2017). Click here to link to ClinicalTrials.gov's listing of Phase 3 sirukumab trials. Other trials are collecting data in additional inflammatory conditions including lupus nephritis [7], cutaneous lupus erythematosus, systemic lupus erythematosus and giant cell arteritis.
Research is beginning to indicate that the disease pathophysiology of depression may have an immune component [2,4,6], and reviewed in [10]. In particular, IL-6 has been identified as a susceptibility gene for major depressive disorder (MDD), with the promoter polymorphism rs1800797 showing a marginally significant correlation with cortical IL-6 expression [11]. This and other work (including [6]) has led to clinical trial of sirukumab as an adjunct to conventional antidepressant therapy in patients with MDD (see Phase 3 trial NCT02473289). | View clinical data

References

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1. Blank T, Nijholt I, Kye MJ, Spiess J. (2004) Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr Drug Targets CNS Neurol Disord, 3 (3): 161-7. [PMID:15180477]

2. Du Preez A, Leveson J, Zunszain PA, Pariante CM. (2016) Inflammatory insults and mental health consequences: does timing matter when it comes to depression?. Psychol Med, 46 (10): 2041-57. [PMID:27181594]

3. Galeotti N, Ghelardini C, Caldari B, Bartolini A. (1999) Effect of potassium channel modulators in mouse forced swimming test. Br J Pharmacol, 126 (7): 1653-9. [PMID:10323599]

4. Hepgul N, Cattaneo A, Agarwal K, Baraldi S, Borsini A, Bufalino C, Forton DM, Mondelli V, Nikkheslat N, Lopizzo N et al.. (2016) Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression. Neuropsychopharmacology, 41 (10): 2502-11. [PMID:27067128]

5. Lam J, Coleman N, Garing AL, Wulff H. (2013) The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases. Expert Opin Ther Targets, 17 (10): 1203-20. [PMID:23883298]

6. Money KM, Olah Z, Korade Z, Garbett KA, Shelton RC, Mirnics K. (2016) An altered peripheral IL6 response in major depressive disorder. Neurobiol Dis, 89: 46-54. [PMID:26804030]

7. Rovin BH, van Vollenhoven RF, Aranow C, Wagner C, Gordon R, Zhuang Y, Belkowski S, Hsu B. (2016) A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis. Arthritis Rheumatol, 68 (9): 2174-83. [PMID:27110697]

8. Su S, Ohno Y, Lossin C, Hibino H, Inanobe A, Kurachi Y. (2007) Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline. J Pharmacol Exp Ther, 320 (2): 573-80. [PMID:17071817]

9. Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Takao H, Minabe Y, Nakatani N, Higuchi T et al.. (2006) Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression. Biol Psychiatry, 60 (2): 192-201. [PMID:16487942]

10. Young JJ, Bruno D, Pomara N. (2014) A review of the relationship between proinflammatory cytokines and major depressive disorder. J Affect Disord, 169: 15-20. [PMID:25128861]

11. Zhang C, Wu Z, Zhao G, Wang F, Fang Y. (2016) Identification of IL6 as a susceptibility gene for major depressive disorder. Sci Rep, 6: 31264. [PMID:27502736]