Anhedonia (the loss of pleasure) is a major characteristic of clinical depression and one of its hardest-to-treat symptoms. Now, researchers from the University of Cambridge think they have located the region of the brain responsible for anhedonia and identified a possible cure – all thanks to the help of a bunch of adorable marmosets. Their research is published in the journal Neuron.
Depression is an unpleasant and pervasive disorder, affecting over 300 million people worldwide. A 2016 study found that 3.3 percent of UK adults had experienced depression in the week before being surveyed. Anhedonia, a feature of depression, is not just the loss of pleasure but the loss of motivation and anticipatory excitement in the lead up to events. But scientists aren't entirely sure why it occurs.
"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," Professor Angela Roberts, of the University of Cambridge, said in a statement.
"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."
With two tasks and the help of some marmoset monkeys, Roberts and her team were able to determine the region of the brain associated with anhedonia. Marmosets are often used in studies examining brain disorders because, unlike rats, their frontal lobes are incredibly similar to ours.
"Studying [the symptoms of depression] in non-human primates, such as marmosets, can help bridge the gap between findings from rodent studies and the clinic," Roberts explained.
In the first task, the animals were trained to respond to two sounds. One anticipated a marshmallow treat. The other did not. Over time, the marmosets learned to associate the first with food and became aroused when it was played – their blood pressure would increase and they would jerk their head in anticipation. Unsurprisingly, the marshmallow-less second sound did not provoke quite as much excitement.
The researchers then gave some of the marmosets a drug to temporarily over-activate a part of the brain called "area 25". The others (the controls) were given a saline solution. The drug-impaired monkeys displayed less anticipation than the controls, even if they were just as quick to eat the marshmallows.
For the second task, the researchers attempted to frustrate the marmosets by making it harder to retrieve the treats. On first go, they won their reward by pressing a colored shape on a touchscreen. But over the course of the task, they had to press it more and more to get their marshmallow. Each marmoset eventually gave up, deciding the proverbial carrot was not worth the effort. However, the drug-impaired monkeys were much quicker to quit.
This suggests "area 24" is tightly linked to anhedonia. But that's not all. The researchers were able to identify a possible treatment – the experimental antidepressant ketamine. When the drug-impaired marmosets were administered the antidepressant 24 hours before the task, they displayed the usual levels of anticipatory excitement. It was as if the ketamine overrides the anhedonia-inducing drug, an observation backed up by PET scans that showed brain circuits functioning normally.
This is an animal study and the results will need to be replicated in human subjects, but they are hugely promising for the millions of people worldwide who suffer from depression.