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Major depressive disorder (MDD): overview and research tools

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                          Explore the heterogeneity of major depressive disorder and find the best tools to study this complex disorder. 

                          Overview

                          • What is major depressive disorder (MDD)?
                          • Molecular mechanisms involved in MDD
                          • Role of biomarkers in MDD
                          • References

                          What is major depressive disorder (MDD)?

                          Major depressive disorder (MDD) is a clinically and biologically heterogeneous disorder, which is thought to originate from the interaction of susceptibility genes and noxious environmental events such as chronic stress. Although MDD is one of the most common debilitating mental disorders, its etiology and pathophysiology remain unclear.

                          The clinical heterogeneity in MDD together with a lack of knowledge on the pathophysiology hinder the diagnosis and the effective treatment of this disorder. Currently, MDD is diagnosed using a symptom-based approach; there is no non-invasive and quantitative test available1.

                          The investigation of mechanisms underlying MDD has been complicated by the following obstacles:

                          • the lack of a suitable animal model of depression
                          • the inclusion of a set of biologically and clinically heterogeneous disorders in MDD
                          • the presence of different subtypes and the continual change of MDD subgrouping
                          • the high incidence of comorbidities of MDD with other physical or psychiatric disorders
                          • the lack of specificity and sensitivity rates of a single biomarker1

                          Molecular mechanisms underlying MDD

                          Several possible pathophysiological mechanisms of depression have been suggested, including altered neurotransmission, hypothalamus-pituitary-adrenal (HPA) axis abnormalities involved in chronic stress, inflammation, reduced neuroplasticity, and network dysfunction2.

                          Both glutamatergic and GABAergic neurotransmissions seem to play an important role in the pathogenesis of MDD. Accumulating evidence has demonstrated that the dysfunction of glutamatergic neurotransmission, particularly via N-methyl-d-aspartate (NMDA) receptors, contributes to the neurobiology of MDD. Several studies have revealed an altered expression of NMDA receptor subtypes and impaired NMDA receptor-mediated intracellular signaling pathways in brain circuits of patients with MDD. Furthermore, NMDA receptor antagonists, particularly ketamine, have been shown to exhibit rapid antidepressant effects in treatment-resistant depression in clinical studies3.

                          Inhibitory neurotransmitter γ-aminobutyric acid (GABA) has also been implicated in the pathophysiology of MDD. Studies have demonstrated a reduction in GABA levels in the brain, decreased expression of GABAergic interneuron markers, and alterations in GABAA and GABAB receptor levels in patients with MDD and chronically stressed animals4,5.

                          Study the involvement of NMDA receptors, GABA, and other key players in MDD with our interactive poster.

                          Download our MDD poster


                          To support your research in MDD, we’ve compiled a list of our best-selling antibodies against key targets in MDD.

                          Gene name

                          Target name

                          Recommended abID

                          Publications

                          Applications

                          Suitable for

                          CLDN5

                          Claudin 5

                          ab131259

                          Yamazaki Y 2020,

                          Wu LP 2019,

                          Li C 2019
                          (17 in total)

                          WB, IHC-P

                          Mouse, Human

                          GRIN2A

                          NMDAR2A

                          ab124913

                          Guo B 2019,

                          Lin L 2019,
                          Ge M 2019 (18 in total)

                          WB

                           Mouse, Rat, Human

                          TNFAIP3

                          A2 / TNFAIP3

                          ab92324

                          Sabry M 2019,
                          Yoon CI 2019,

                          Liu K 2018
                          (15 in total)

                          ICC/IF, WB, IHC-P, Flow Cyt

                          Mouse, Human

                          NR3C1

                          Glucocorticoid receptor

                          ab183127

                          Hu S 2019,
                          Hu S 2019 (a)

                          WB, IHC-P, ICC/IF, Flow Cyt

                          Mouse, Rat, Human

                          HTR1A

                          5HT1A receptor

                          ab85615

                          Cui WQ 2019,
                          Sobrido-Cameán D 2019,

                          Chen Y 2019

                          (15 in total)

                          WB, IHC-P, ICC/IF

                          Mouse, Rat, Human

                          RELN

                          Reelin

                          ab230820

                          NA

                           IHC-P

                           Mouse, Rat, Human

                          Role of biomarkers in MDD

                          The diagnosis of MDD currently relies on clinical examination and subjective evaluation of depressive symptoms. No approved biomarker is available as part of the diagnostic criteria despite multiple studies that have been carried out to assess various biomarkers for MDD. Identification of biomarkers in MDD could help facilitate the diagnosis of the disorder, choose the optimal treatment, and predict the treatment response as well as the course of the disorder6.

                          Suggested biomarkers for MDD include growth factors, cytokines and other inflammatory markers, oxidative stress markers, endocrine markers, energy balance hormones, genetic and epigenetic features, and neuroimaging6.

                          The most investigated growth factor in MDD is BDNF, which regulates neural plasticity, migration, and survival in the central and peripheral nervous systems. Multiple studies and meta-analyses have consistently reported that plasma and serum BDNF levels are reduced in patients with depression but can be normalized by antidepressant drugs or electroconvulsive therapy6.

                          In the table below, we summarize potential biomarkers for MDD.

                          Biomarker candidate

                          Source

                          Biomarker levels compared to healthy individuals

                          Product recommendations

                          BDNF

                          Serum and plasma

                          Decreased

                          BDNF recombinants, BDNF ELISA kits

                          IL-1

                          Serum and peripheral mRNA expressions

                          Increased

                          IL-1 recombinants, IL-1 ELISA kits

                          IL-6

                          Serum and peripheral mRNA expressions

                          Increased

                          IL-6 recombinants, IL-6 ELISA kits

                          TNF

                          Serum and peripheral mRNA expressions

                          Increased

                          TNF recombinants, TNF ELISA kits

                          MDA

                          -

                          Increased

                          MDA ELISA kit

                          HPA activity

                          -

                          Increased

                          NA

                          Cortisol response to DEX/CRH

                          -

                          Increased

                          NA

                          Hippocampus volume

                          -

                          Decreased

                          NA

                          BDNF: brain-derived neurotrophic factor, IL: interleukin, TNF: Tumor necrosis factor, MDA: malondialdehyde, HPA: hypothalamus-pituitary-adrenal, DEX/CRH: dexamethasone/corticotropin-releasing hormone.

                          References:

                          1. Pitsillou, E. et al. The cellular and molecular basis of major depressive disorder: towards a unified model for understanding clinical depression. Mol Biol Rep. 47, 753-770 (2020).
                          2. Dean, J., Keshavan, M. The neurobiology of depression: An integrated view. Asian J Psychiatr. 27, 101-111 (2017).
                          3. Amidfar, M., et al. The role of NMDA receptor in neurobiology and treatment of major depressive disorder: Evidence from translational research. Prog Neuropsychopharmacol Biol Psychiatry. 94, 109668 (2019).
                          4. Fogaça, M.V., Duman, R.S. Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions. Front Cell Neurosci. 13:87 (2019).
                          5. Luscher, B., Shen, Q., Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16, 383-406 (2011).
                          6. Hacimusalar, Y., Eşel, E. Suggested Biomarkers for Major Depressive Disorder. Noro Psikiyatr Ars. 55, 280-290 (2018).





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