Depression is not just feeling depressed. Not being able to enjoy things? There is a word for that. It comes from the Greek. If you've heard of a hedonist, put the two letters that denote "not that thing" in front--"an", and we're almost there! Anhedonia. Welcome to The Frontier Psychiatrists, a daily health-themed newsletter written by Owen Scott Muir, M.D., DFAACAP. I practice medicine at Fermata in NYC and Acacia Clinics in Sunnyvale, CA. I still see patients…you can click this link to book a consultation.1
During the pandemic, many of us learned what it was like to have one of our senses go away. Covid-19 creates a problem with your sense of smell, called anosmia-- the inability to smell. When it comes to the ability to feel pleasure or joy, it's like our sense of smell. You take it for granted until you can't because you get an illness. Just like COVID-19 can make your sense of smell vanish, depression can make your sense of pleasure vanish.
This can be a real problem. A lot of us learned what it was like to have our sense of smell go away for the first time in the pandemic, food didn't taste the same, when you can't smell, and also can't taste. Not the same way anyway. Taste is the heady admixture of smell and sensory information from your tongue, and that's not obvious until one of those systems goes offline.
The strange thing about depression, and anhedonia, is that it's very much like a lack of a sense of smell. It impacts so many domains of life that we might not imagine required "a sense of pleasure." The ability to get out of bed in the morning, promptly? Some of that is driven by the sense of pleasure of seeing the sunlight in the morning. Even when you're going to the bathroom— peeing!— the sense of pleasure, powered by the release of dopamine in the nucleus accumbens, makes that worth your time. Having a cup of coffee, that is enriched, by both that sense of smell, and that sense of pleasure.
The strange thing about depression, as an illness, is that even in the absence of a depressed mood, the loss of a sense of pleasure is a cardinal symptom of the disorder. Similarly, some people who got COVID-19 only lost their sense of smell! “It's a mild case, no fever, etc….just losing your sense of smell.” Some people with depression don't feel sad. But they do lose that sense of pleasure. It's pervasive, but it's an important thing to know and can be taken away by the biology of depression. That is anhedonia.
If you can't feel good? It might not be that things aren't good, it might be a problem with your brain. That problem, we know something about it, because it might be depression. We've spent enough time studying that to have some sense of what might be helpful. But similar to Covid, if you don't know it exists, you might write it off as something else. It's a virus, maybe I have the flu, maybe I have a cold, or maybe it's something else?
Depression, with that loss of a sense of pleasure, which we call anhedonia, might be something else.
Now, for the nerdy science part of the article.
Addressing anhedonia is an active area of inquiry and a new class of medicines targeting the Kappa Opioid Receptor2 is in development (this is NOT the mu-opioid receptor causing so much trouble with opioids of the past!)
Although the kappa receptor has been less than a successful target in the field of addiction research3, it has been demonstrated in fancy PET trials by very fancy scientists (including J. John Mann, who gave me a lumbar puncture at age 20 as part of a research trial4) that binding to this receptor modulated anhedonia.5
Given anhedonia has a long track record of being a risk factor for suicide6, it is a crucial symptom domain to target:
The association between anhedonia and current suicidal ideation remained significant when controlling for depression and psychiatric disorders.7
There is more than simply a depressed mood to depression.
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Dalefield ML, Scouller B, Bibi R, Kivell BM. The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies. Front Pharmacol. 2022 Jun 20;13:837671. doi: 10.3389/fphar.2022.837671. PMID: 35795569; PMCID: PMC9251383.
Banks ML. The Rise and Fall of Kappa-Opioid Receptors in Drug Abuse Research. Handb Exp Pharmacol. 2020;258:147-165. doi: 10.1007/164_2019_268. PMID: 31463605; PMCID: PMC7756963.
Oquendo MA, Placidi GP, Malone KM, Campbell C, Keilp J, Brodsky B, Kegeles LS, Cooper TB, Parsey RV, van Heertum RL, Mann JJ. Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression. Arch Gen Psychiatry. 2003 Jan;60(1):14-22. doi: 10.1001/archpsyc.60.1.14. PMID: 12511168.
Smart, K., Yttredahl, A., Oquendo, M. A., Mann, J. J., Hillmer, A. T., Carson, R. E., & Miller, J. M. (2021). Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography. Translational Psychiatry, 11(1), 1-9. https://doi.org/10.1038/s41398-021-01729-5
Winer ES, Drapeau CW, Veilleux JC, Nadorff MR. The Association between Anhedonia, Suicidal Ideation, and Suicide Attempts in a Large Student Sample. Arch Suicide Res. 2016;20(2):265-72. doi: 10.1080/13811118.2015.1025119. Epub 2015 Jul 27. PMID: 26214573.
Ducasse, D., Loas, G., Dassa, D., Gramaglia, C., Zeppegno, P., Guillaume, S., Olié, E., & Courtet, P. (2018). Anhedonia is associated with suicidal ideation independently of depression: A meta‐analysis. Depression and Anxiety, 35(5), 382–392. https://doi.org/10.1002/da.22709
Thank you for this.
I would add that anhedonia (the inability to feel pleasure), like anosmia (the inability to smell), is not visible to others and, therefore, does not always garner as much empathy. While empathy for such 'invisible' maladies seems to be on the rise, many are still blind to them.
I've been diagnosed with depression with anhedonia and I've had very little sense of smell all my life, so this works both ways