Depression, Anhedonia, and the Brain

Anhedonia, which refers to decreased ability to experience pleasure in normally pleasurable things, is a core symptom of depression; in fact, you can get a diagnosis of major depressive disorder without depressed mood if you have anhedonia. Anhedonia is a part of the melancholic features specifier for depression, as opposed to atypical features, which involves mood reactivity to pleasurable stimuli. It can also be one of the negative symptoms of schizophrenia. People with major depressive disorder who experience anhedonia tend to respond less favourably to treatment than those who don’t.

While serotonin circuits in the brain play a role in mood, dopamine and the nucleus accumbens region play a big role in pleasure and reward. I was curious to see what science has to say about how anhedonia happens in the brain, and this post is the result.

Pleasure and anhedonia

Anhedonia can affect different aspects of how we relate to pleasure. The reward pathway involves three phases: anticipatory (the motivation to seek out rewards), consummatory (finding experiences pleasurable in the moment), and satiety (learning after the consummatory phase). The graphic below illustrates these phases. The appetitive phase is dominated by wanting a reward experience, the consummatory phase is dominated by liking the experience, and the satiety phase is dominated by learning to associate consumption with pleasure. We make predictions for future experiences based on these learned associations.

In people with depression, there tends to be a reduction in capacity in the wanting and liking phases, as well as impairment in reward learning. Essentially, the whole kit and caboodle is affected, although some studies have shown that the liking phase isn’t impaired to the extent that the wanting and learning phases are.

That actually corresponds fairly well with my own experience. Something that’s normally yummy to eat may still taste reasonably good when I’m anhedonic, but I’m not very interested in seeking that reward out in the first place or trying to repeat it once it’s happened.

Pleasure and the brain

There are multiple areas of the brain that are involved in the appetitive/wanting phase, including areas of the cortex (the more advanced part of the brain) and the limbic system (a more primitive part of the brain). The consummative/liking phase appears to be more focused in a small area of the nucleus accumbens, which is part of the limbic system.

Both dopamine and opioid circuits play a role (the brain makes natural opioids known as endorphins). The neurotransmitters glutamate and acetylcholine may also play a role, which might explain some of the benefit that the drugs ketamine and scopolamine have shown in people with depression.

I’ve included the diagram below, not because I expect the details of it to be meaningful to anyone, but rather to give a general sense that reward circuitry is complex and there are a whole lot of different places where things could go wrong. The complexity is one of the reasons why there’s a lot that science hasn’t figured out yet; another issue is that animal models don’t necessarily translate that well to the human experience of anhedonia.

The nucleus accumbens

A recent study found changes in functional connectivity of the nucleus accumbens, a key part of the reward system, in people with major depressive disorder vs. healthy control subjects. Neural activity involves both wiring and firing, and functional connectivity is the firing part. Researchers observed reduced connectivity to several brain regions. In particular, people with more severe anhedonia had reduced functional connectivity between the nucleus accumbens and an area called the anterior cingulate cortex compared to people with less severe anhedonia.

Medications

Some researchers have suggested that the amotivation that SSRI (selective serotonin reuptake inhibitor) antidepressants can cause is related to the way that they affect the striatum, an area of the brain that’s involved in reacting to both aversive and pleasurable stimuli. It can be a good thing if antidepressants are lowering our reactivity to negative stimuli, but not so good if they’re also lowering our reactivity to positive stimuli.

For me, the pattern of anhedonia over time has been consistent with it being illness-related rather than being negatively affected by medication.

What does any of this mean?

The TL;DR is that anhedonia in depression is complicated, and science has some ideas but hasn’t figured it out yet. I feel like anhedonia is something that can make a substantial difference in quality of life. It’s not as painful in the moment as low mood, but it can suck all the light right out of life. It seems like a difficult thing to address, too, because the absence of positive feelings doesn’t give you a lot to seek your teeth into. When doing supposedly positive things doesn’t generate a reward, continuing to do them seems a bit like pissing in the wind, which is perhaps why I’ve never found the CBT concept of behavioural activation to be particularly useful for me.

Is anhedonia something you experience, and if so, what is that like for you?

References

• Liu, R., Wang, Y., Chen, X., Zhang, Z., Xiao, L., & Zhou, Y. (2021). Anhedonia correlates with functional connectivity of the nucleus accumbens subregions in patients with major depressive disorder. NeuroImage: Clinical, 30, 102599.
• Rømer Thomsen, K., Whybrow, P. C., & Kringelbach, M. L. (2015). Reconceptualizing anhedonia: Novel perspectives on balancing the pleasure networks in the human brain. Frontiers in Behavioral Neuroscience, 9, 49.
• Sternat, T., & Katzman, M. A. (2016). Neurobiology of hedonic tone: The relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse. Neuropsychiatric disease and treatment, 2016(12), 2149-2164.