Marmoset study gives insights into loss of pleasure in depression



'Anhedonia’ (the loss of pleasure) is one of the key symptoms of depression. An important component of this symptom is an inability to feel excitement in anticipation of events; however the brain mechanisms underlying this phenomenon are poorly understood.

Understanding the brain circuits that underlie specific aspects of anhedonia is of major importance, not only because anhedonia is a core feature of depression but also because it is one of the most treatment-resistant symptoms.
- Laith Alexander

Now, in a study involving marmosets, scientists at the University of Cambridge have identified the region of the brain that contributes to this phenomenon, and shown that the experimental antidepressant ketamine acts on this region, helping explain why this drug may prove effective at treating anhedonia.

Depression is a common and debilitating condition which is recognised as a leading cause of disability worldwide. A survey published in 2016 found that 3.3 out of every 100 UK adults had experienced depression in the week before being interviewed.

A key symptom of depression is anhedonia, typically defined as the loss of ability to experience pleasure. However, anhedonia also involves a lack of motivation and lack of excitement in anticipation of events. All these aspects have proven difficult to treat. One major issue slowing down progress in developing new treatments is that the brain mechanisms that give rise to anhedonia remain largely unknown.

“Imaging studies of depressed patients have given us a clue about some of the brain regions that may be involved in anhedonia, but we still don't know which of these regions is causally responsible,” says Professor Angela Roberts from the Department of Physiology, Development and Neuroscience at the University of Cambridge.

“A second important issue is that anhedonia is multi-faceted – it goes beyond a loss of pleasure and can involve a lack of anticipation and motivation, and it’s possible that these different aspects may have distinct underlying causes.”

In fact, even when existing therapies do work, the reasons why they are effective are not always clear, making it difficult to target these therapies to individuals. 

Using marmosets, a type of non-human primate, Professor Roberts and MBPhD student Laith Alexander, along with other colleagues, including those at the Wolfson Brain Imaging Centre and Translational Neuroimaging Laboratory, have shown how over-activity in a specific area of the brain’s frontal lobe blunts the excitement seen when anticipating a reward and the motivation to work for that reward. Their results are published in the journal Neuron.

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Reproduced courtesy of the University of Cambridge

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