Anhedonia accompanies a range of neuropsychiatric conditions.
Most people will, at some point in their life, lose interest in things that used to excite them.
Anhedonia, however, takes this loss to its limits; it becomes impossible to draw enjoyment from things that once elicited excitement, such as music, sex, food, and conversation.
It may even play a part in an individual’s desire to indulge in risky behaviors, such as skydiving.
Over recent years, anhedonia has received increased attention. Part of the reason for this is that it predicts how well someone with depression will respond to treatment.
Because treating depression is so challenging, any additional insight is welcome. There is evidence to suggest that the presence of anhedonia increases the risk of committing suicide, so if the link is proven, recognizing and dealing with anhedonia could save lives.
What does anhedonia feel like?
To gain a better understanding of what anhedonia feels like, the following is an excerpt from a firsthand account.
“For the past 7 years, I have had the smallest flickering of emotions, what I feel on a daily basis is practically nil. I have no desires to truly speak of, as nothing I do is rewarding or satisfying. This is the core of my anhedonia, a symptom of major depression.”
“Essentially, I gain nothing from my daily life; my world is cold and, as such, it makes life seem the same way. Everything I look at, everything I do, looks and feels the same.”
What’s happening in the brain?
As with the investigation of any emotional response, the story is not a simple one. The brain’s circuitry is dense, convoluted, and incredibly busy.
Anhedonia is not simply a reduced appreciation of the taste of chocolate; the underlying reward mechanisms are impaired.
This might involve alterations in levels of interest, motivation, anticipation, expectation, and effort prediction, all of which are complex in their own right, and all of which are processed by different but overlapping neural circuits.
Anhedonia and reward
There is evidence that many individuals with anhedonia can experience pleasure in a similar way to the rest of the population — it’s just that there is something amiss as far as motivation, anticipation, and reward are concerned.
Anhedonia seems to interfere with reward mechanisms.
For people with anhedonia, the reward process has come unhinged. Finding which part of this process has become unshackled is a difficult job.
In order to understand the interplay between the different aspects of pleasure, I will relay an example. If we experience something and enjoy it — eating a new type of candy, for instance — we might want to do it again.
However, if the candy costs $1,000 per piece, we might not bother. Or, similarly, if it is known to cause cancer, we will probably give it a miss.
If the candy is free and safe, however, we will tuck in. If we are required to walk to the next room to get a piece, we will probably make the effort. But, if it is stationed half a mile away, we might pause for thought. And, if it’s in the next town, we will forgo the pleasure.
But even if the candy is healthful, placed on the table next to us, and free of charge, we might take a piece even if we have just eaten a three-course meal.
Desire, motivation, and the pleasure we derive from things are fluid.
Although this particular example is simplistic, it shows how our brains make computations about risks, rewards, and payoffs using multiple brain regions, often without our conscious input.
With this in mind, where should we start? Well, for many years, a part of the basal ganglia called the nucleus accumbens has been referred to as the “pleasure center.”
Unsurprisingly, it is implicated in anhedonia. Recent studies have shown that other brain areas are also involved, including:
- the prefrontal cortex, which is involved in planning and personality expression
- the amygdala, which processes emotions and is involved in decision-making
- the striatum, which is the area that houses the nucleus accumbens, implicated in the reward system
- the insula, which is thought to be important in consciousness and self-awareness
The prefrontal cortex seems important in high-level processing of rewards, including cost-benefit analysis and decision-making. Its connections to the ventral striatum seem to be particularly important in motivation and therefore anhedonia.
The role of neurotransmitters
Neurotransmitter imbalances have also been investigated in relation to anhedonia. Dopamine is of particular interest due to its involvement in reward pathways as well as the fact that it is expressed in high quantities in the nucleus accumbens.
In fact, reduced dopamine expression in the ventral striatum of depressed people was found to correlate well with anhedonia severity but not depressive symptoms overall.
Dopamine’s relationship with anhedonia and reward is a complex one, though. Reduced dopamine levels in different parts of the brain can have different effects.
As an example, increased dopamine in the insula has the opposite effect on effort-based decision-making to increased dopamine in the ventral striatum. So, dopamine is unlikely to tell the whole story.
GABA (an inhibitory neurotransmitter), glutamate (an excitatory neurotransmitter), serotonin, and opioids may also play their part.
For instance, people with depression who also have pronounced anhedonia seem to have reduced GABA levels. And, depressed people with reduced opioid activity experience less pleasure during positive interactions.
A possible role for inflammation
Depression and inflammation have been linked for some time. Scientists have measured increased levels of inflammatory compounds in people with depression. These chemical hallmarks include cytokines and C-reactive proteins.
Cytokines (shown here) may be involved in anhedonia.
A study of people with depression, published in the journal Molecular Psychiatry in 2015, found that increased levels of C-reactive protein were associated with reduced connectivity between the ventral striatum and ventromedial prefrontal cortex (which is important in motivation) and increased anhedonia.
Other studies have produced similar findings, so inflammation appears to be involved in both depression and anhedonia.
Although a link between anhedonia and inflammation seems, perhaps, unexpected, it makes sense when one peels back the layers. Cytokines can influence neurotransmitter metabolism and brain activity.
Also, cytokines promote so-called sickness behavior — including lethargy, malaise, loss of appetite, sleepiness, and sensitivity to pain — all of which have parallels in depression. And, people who undergo cytokine treatment for cancer often report depressive symptoms.
Although we do not have a full understanding of the origins of anhedonia, the research to date tells us that it is multifaceted and — quite possibly — different from person to person.
At present, there are no treatments aimed at anhedonia. It is commonly treated alongside the condition that it is part of — for instance, selective serotonin reuptake inhibitors are often prescribed for individuals with depression.
There is a growing body of evidence that standard depression treatments do little for anhedonia and, worse still, may add to the problem by causing emotional blunting, sexual anhedonia, and anorgasmia, or the inability to orgasm.
This negative interaction might be because serotonin inhibits dopamine release in certain brain regions, potentially interfering with the reward, motivation, and pleasure circuitry.
On a positive note, there has been recent interest in the anesthetic ketamine as a potential anti-anhedonic medication. Ketamine has shown promise as a treatment for depression, quickly reducing symptoms in both major depressive disorder and bipolar disorder.
A study that was published in the journal Nature in 2014 specifically set out to see whether it could also have an effect on anhedonia. Trials in rodents had already generated interesting results, but this was the first time that ketamine had been investigated in humans.
Specifically, the study looked at treatment-resistant bipolar disorder. The authors concluded that “ketamine rapidly reduced the levels of anhedonia.”
In fact, the reduction occurred within 40 minutes and lasted up to 14 days following a single injection. Interestingly, the reduction occurred without a similar reduction in depressive symptoms.
Ketamine blocks N-Methyl-D-aspartate receptors, thereby preventing them from being activated by glutamate. This infers that glutamate, an excitatory neurotransmitter, might play a role in anhedonia.
There is still a long way to go before the many strands of anhedonia are fully understood. However, our knowledge is slowly growing, and, with time, there is hope of a solution to this highly intrusive and debilitating malady.
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