Anhedonia: joylessness affects many mentally ill people

"When I met my partner, I had the happiest six months of my life". I had just gotten my first job and was able to support my family." For the young woman who calls herself Sarisa on the Internet platform Reddit, this feeling now seems worlds away. For months, she continues, she has lost all zest for life. "When I imagine that I could feel like this for the rest of my life, I toy with the idea of killing myself." Sarisa is not alone in her despair and helplessness on Reddit: under the keyword "anhedonia," hundreds of users of the forum describe their inability to feel anything. They tell each other what they have already tried to regain a zest for life, and encourage each other.

The term anhedonia is the counterpart of the Greek word "hēdonē’" meaning joy or pleasure. The French psychologist Theodule Armand Ribot coined the term for a pathological joylessness at the end of the 19. Century. One affects many people with mental disorders and sometimes places an extreme burden on those affected. The modern term no longer refers only to a loss of enjoyment of pleasurable experiences, but also to a diminished interest in bringing about appropriate experiences.

This article is featured in Spectrum – The Week, 34/2020

Joylessness is thus clearly distinguished from sadness. Brain research shows that positive and negative emotions are not simply two sides of the same coin. "Rather, it seems to be a matter of two different dimensions, each based on its own neuronal systems," explains Henrik Walter. He is a professor of psychiatry, psychiatric neuroscience and neurophilosophy at the Charite Hospital in Berlin and heads the Mind and Brain research area at the Department of Psychiatry and Psychotherapy.

Many people with mental illness suffer from anhedonia. Joylessness is even a core symptom of depression.

Sufferers usually have a worse prognosis: their condition is often more severe and less likely to respond to typical antidepressants.

Researchers are now testing several medications and specific psychotherapy procedures to help relieve anhedonia.

With his research group, he is investigating the basis of joy of life and its absence. Her current project, called ELAN, aims to contribute to a better understanding of the neuronal mechanisms of anhedonia. This is not a uniform complaint, but can affect different functions of thinking, feeling and acting and thus different neuronal circuits. Roughly, it can be divided into two subtypes: anticipatory anhedonia, which is characterized by the absence of anticipation, and consummatory anhedonia, which is accompanied by an actual lack of pleasure and enjoyment. Henrik Walter and his colleagues even assume four components: In addition to pleasure at the moment of experience, anticipation may be disturbed, the motivation to seek out a potentially pleasurable situation may be disturbed, and the retrospective evaluation of how rewarding the experience was may be disturbed.

Imagine, for example, that you want to go to the movies. To make the decision, joyful anticipation is first needed. You are curious about the movie and hope you will enjoy it. Then the motivation must be sufficient to put up with a certain amount of effort. Finally, one must organize the visit, get ready, leave the house, and invest money in tickets and possibly overpriced popcorn. During the film, at best, you are exhilarated, eager to see the next twist or gripped by the tragedy of the story. At the end, you weigh up – usually unconsciously – whether the experience was worth the effort and whether you would like to repeat it in the near future. If one or more of these functions are disturbed, anhedonia occurs: fun falls by the wayside, life loses its spice.

An aspect of many illnesses

Anhedonia is one of the three core symptoms of depression, along with depressed mood and lack of drive. In addition, people with schizophrenia as well as those with bipolar disorder also often develop anhedonia. Reduced desire can also occur in post-traumatic stress disorder, eating disorders, anxiety disorders and addictive disorders. Even in some neurological disorders, anhedonia occurs, most notably in patients with Alzheimer’s dementia, Parkinson’s disease, and occasionally in those with brain injuries.

How anhedonia and depression are related is well studied. Those who lack joie de vivre have an increased risk of developing depression. Patients with marked anhedonia also have a worse prognosis. This was shown, among other things, by data from a team led by psychologist Dana McMakin, then at the University of Pittsburgh. Their study involved 334 depressed adolescents. They had all received an antidepressant that belongs to the selective serotonin reuptake inhibitor (SSRI) drug class. The drug had no effect on any of them. The scientists therefore randomly assigned the young patients to a new therapy: for six months, they either received another SSRI, or they were given the drug and also underwent cognitive behavioral therapy. Nearly 40 percent of participants ended up feeling so much better that they no longer met diagnostic criteria for depression. The rest differed from the recovered patients in one feature in particular: anhedonia. As the only symptom, it predicted a worse outcome. Subjects in whom joylessness was particularly pronounced recovered more slowly. In addition, those affected had fewer depression-free days, and on average their illness was more severe. Further research suggests that anhedonic depressives relapse more often and have a higher risk of death. Thus, adolescents who actually attempt suicide experience more severe anhedonia than those who merely contemplate it.

Some people seem to be naturally more prone to anhedonia. A hereditary component probably exists. Stressful life circumstances also contribute to the development of anhedonia. Here’s how chronic stress can affect the mesolimbic system in the brain. This has an effect on motivation and learning processes controlled by reward via the neurotransmitter dopamine. Dysfunction is found in depressed individuals, as well as in healthy individuals with a history of depression and in young adults with traumatic childhood experiences. The so-called negative symptoms of schizophrenia, which are often also characterized by anhedonia, are, according to a common hypothesis, due to a lack of dopamine in the mesocortical part of the reward system, i.e. in connections to the cerebral cortex. Mesolimbic as well as mesocortical areas are involved in anhedonia, according to current knowledge.

Depression associated with anhedonia often cannot be alleviated with standard medications. Indeed, depressed mood is the main focus of depression treatment. Antidepressants mostly target the neurotransmitter serotonin. However, because anhedonia appears to be associated with changes in dopaminergic signaling pathways in the brain, scientists are now testing appropriate medicines. Pramipexole, a drug used in Parkinson’s disease, binds to dopamine receptors, mimicking the action of the neurotransmitter. It selectively stimulates D2 and D3 receptors, which are found in the nucleus accubens and the striatum. In Parkinson’s patients, pramipexole reduces more than just motor symptoms. The drug was also effective against anxiety, depression and joylessness, which the patients often suffer from. In an initial series of treatments with chronically depressed and bipolar patients with pronounced anhedonia, the drug showed effect: high-dose pramipexole in addition to the previous medication improved symptoms in three-quarters of the participants. However, these preliminary successes need to be confirmed by further clinical studies.

With medicine to pleasure?

Henrik Walter believes it is plausible that drugs that interfere with the dopamine system may be more suitable for treating anhedonia than classic antidepressants. "Common antidepressants do not increase the ability to enjoy, but can actually decrease it. For example, they impair libido and the ability to have an orgasm."The study situation is currently too thin, however, to be able to make a recommendation. And the drugs carry dangers, too. "Dopamine agonists can potentially worsen depression and, in the worst case, trigger psychosis," cautions Ulrich Hegerl, a psychiatrist and chairman of the German Depression Aid Foundation. "In Germany alone, more than four million people live with depression; one should not raise false hopes there."Jan Dreher, psychiatrist and head physician at the Konigshof Clinic in Krefeld, Germany, has a similar opinion. "It is possible that drugs that act on the dopamine system improve anhedonia," he explains. "However, since they have been shown to be ineffective for general depressive symptomatology, I don’t think much is gained by doing so. In clinical practice, we consider the clinical picture as a whole."

In a review paper published in 2019, a team led by Bing Cao of Peking University addressed the issue of which drugs can be used to counteract anhedonia. The authors screened 17 studies on the effects of a total of 14 medications in adults with depression. Most antidepressants alleviate the symptoms only marginally. Substances that affect the neurotransmitter melatonin, and thus also the sleep-wake rhythm, fared comparatively well. The anesthetic ketamine, which is used "off label" in Germany as an adjunctive treatment for treatment-resistant depression, was particularly effective against anhedonia in one of the studies considered: the improvement was most marked in the first three days after infusion.

Levels of joylessness

In addition to the different components, one also distinguishes domains of anhedonia. Roughly, they can be divided into physical and social manifestations. In social anhedonia, there is a reduced enjoyment of conversations, meetings, and other contacts. Sufferers sometimes withdraw completely. Physical anhedonia, on the other hand, consists of the inability to enjoy physical stimuli – such as a massage, sex, or good food. A common questionnaire that captures both aspects is the Social Anhedonia Scale/Physical Anhedonia Scale. By agreeing or disagreeing with statements such as "I like to laugh at jokes with others" or "When I walk past a bakery, the smell of fresh bread often makes me hungry," he gauges which domain is prominent in the individual patient’s mind.

Research shows that the two aspects reflect unique proportions, but they often occur together. People with schizophrenia sometimes have long-term problems forming consistent interpersonal relationships and also enjoy physical pleasures less. Depressives with anhedonia symptoms suffer more often from loss of appetite and social withdrawal than those in whom depressed mood is the primary concern. Some, in turn, only lose pleasure in certain areas of life. Researchers hope that identifying such subtypes of depression will allow for more targeted treatment in the future.

Ketamine helps some people with depression even when common antidepressants fail. How it manages to do so is still largely unclear. Its effect in the habenulae, two thin bundles of nerve fibers in the diencephalon, could be decisive. In experiments with monkeys, rewards revved up the dopaminergic system, while at the same time neuronal activity in the habenulae decreased. The reverse was true when an expected reward failed: the dopaminergic neurons fired less, while the habenulae cells became more active. "The habenulae are closely linked to the reward system. They obviously form a counterweight, a kind of anti-reward system," says psychiatrist Volker Arolt of Munster University Hospital. In depression, this system is probably out of sync, and ketamine contributes to a normalization of overactive habenulae. "However, ketamine can be addictive. That’s why it should only be administered under medical supervision," notes Ulrich Hegerl. In addition, the effect does not last long, which is why the treatment must be repeated regularly. The authors of the review point out that the validity is limited due to the small number and varying methodologies of the studies considered. They see it as a starting point for further research into effective drugs for anhedonia.

A program that promotes positive feelings

And what about the second pillar of the treatment of depression, psychotherapy? Established psychotherapies for depression primarily seek to dispel dark thoughts and feelings and to lift the mood. According to a survey conducted in Belgium in 2015, practitioners usually set themselves the goal of combating negative sensations. The majority of the patients interviewed, on the other hand, wanted the restoration of a positive attitude to life. One approach that takes this into account was tested by a team led by Michelle Craske at the University of California at Los Angeles in 2019. The researchers compared a psychotherapeutic program designed to promote positive emotions with one designed primarily to drive away negative ones. The former, "Positive Affect Treatment," should improve three components in depression and anxiety patients: Anticipation, Pleasure, and Reward Learning.

The initial phase of the program is designed to create joyful anticipation. It’s based on the "reinforcer loss model" of depression that U.S. psychologist Peter Lewinsohn established in the 1970s. According to this, the disease is caused by a lack of positive experiences and is perpetuated by a vicious cycle of lethargy and social withdrawal. This is where you can start therapeutically. Patients should do things they used to enjoy, even if they don’t feel like it: Meeting friends, singing in the choir or baking a cake. This technique is also used in cognitive behavioral therapy and shows good results. The learned avoidance behavior is reduced, and the patient gets the chance to have pleasant experiences again. This paves the way out of depression; gradually the joy of life returns, according to the basic idea. In Positive Affect Treatment, the patient is asked to keep an accurate record of his or her mood before and after the experience. In the psychotherapy session that follows, he deals again with the emotional facets of what happened: What does it feel like to hug a good friend?? What does the sound of a favorite song trigger in me?? The successful baking might even make me a little proud? As a result, he learns to focus his attention more and more on positive aspects of the experience.

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