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10-Minute Neuroscience: Depression

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24 June 2025
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10-Minute Neuroscience: Depression
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In this video, I discuss the neuroscience of depression. First, I cover the serotonin hypothesis, which suggests depression is caused by low levels of serotonin in the brain, and I explain why this hypothesis does not fully explain what’s happening in the brain to cause depression. Then, I cover several other hypotheses, including those that focus on dysregulation in the HPA axis, immune system dysfunction, and impaired neuroplasticity and neurogenesis (linked to low levels of BDNF). Along the way, I also explain the mechanisms behind some common antidepressants, such as SSRIs.

Key points:

00:00 Introduction
1:01 Serotonin hypothesis
3:48 Flaws with serotonin hypothesis
4:57 HPA axis dysregulation
6:19 Immune system dysfunction
7:30 Neuroplasticity, neurogenesis, and BDNF

REFERENCES:

Dean J, Keshavan M. The neurobiology of depression: An integrated view. Asian J Psychiatr. 2017 Jun;27:101-111. doi: 10.1016/j.ajp.2017.01.025. Epub 2017 Jan 29. PMID: 28558878.

Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008 Oct 16;455(7215):894-902. doi: 10.1038/nature07455. PMID: 18923511; PMCID: PMC2721780.

López-Muñoz F, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des. 2009;15(14):1563-86. doi: 10.2174/138161209788168001. PMID: 19442174.

López-Muñoz F, Alamo C, Juckel G, Assion HJ. Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part I: monoamine oxidase inhibitors. J Clin Psychopharmacol. 2007 Dec;27(6):555-9. doi: 10.1097/jcp.0b013e3181bb617. PMID: 18004120.

Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2023 Aug;28(8):3243-3256. doi: 10.1038/s41380-022-01661-0. Epub 2022 Jul 20. PMID: 35854107; PMCID: PMC10618090.

Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, Mohr DC, Schatzberg AF. Major depressive disorder. Nat Rev Dis Primers. 2016 Sep 15;2:16065. doi: 10.1038/nrdp.2016.65. PMID: 27629598.

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