Hunting for another way to treat bugbear of depression

In Ireland, about 450,000 people – or one in 10 – are depressed at any one time, according to Aware.ie. And researchers are seeking to understand lesser-studied aspects of depression, which they hope can lead to developing better treatments.

"When you ask depressed people about getting better, they say they want to go back to their 'normal' selves, to be able to enjoy things again," says Prof Aaron Heller of the University of Miami's psychology department.

Heller studies the resonance of emotion. While most depression studies focus on how strong an emotion is, fewer tend to look at the length of time an emotion lingers in the brain.

“What we’re studying is the reason why some people can see a beautiful sunset, enjoy a meal or a relationship and not savour that emotion,” he says.

Not being able to hold on to “positive affect” after something good happens is a hallmark of depression, according to Heller and his colleagues.

In July, as part of a research team at the University of Wisconsin-Madison, Heller investigated the mechanics behind retaining happy emotions.

"The key finding is that neural activity, unfolding over the course of seconds, translates to behavioural differences in minutes and even hours in the real world," he says.

In the experiment, participants played a game that gave small money rewards. After winning, each person gave a number of reports on how they were feeling. The experiment was then repeated in a laboratory, this time hooking people up to a functional magnetic resonance imaging (fMRI) machine to scan brain activity.

Each time a person won, the scans showed the ventral striatum, a small structure in the front of the brain, lighting up for just a couple of seconds. The more seconds this region activated at the point of winning money, the longer the positive emotion lasted, “for minutes and even hours afterwards”.

Heller says he hopes the study will improve treatment options beyond the “blunt hammer” of normal antidepressants, which “wash the brain in serotonin”.

Increasing serotonin

Declan McLoughlin is a research professor of psychiatry at Trinity College Dublin. He agrees that depression treatment is becoming more sophisticated than simply increasing a person's serotonin, a chemical long associated with depression.

"Treatments for depression have not changed radically for about 50 years," he says. "There's been so much investment in the last 20 or 30 years on pursuing drugs like Prozac, resulting in a slew of antidepressants which had no particular great advantage over the ones that were invented in the 1950s."

He says Heller’s paper is important for learning about how emotion works, but there’s a barrier to using it for treatment: the study used healthy subjects rather than depressed people. “That’s a whole different ball game,” he says. “It’s a big step from a study like that, say to a clinical population study, which could tap into this for therapeutic processes.”

Recently, treatments have looked at drugs that work on another part of the brain associated with learning and memory. One such drug is ketamine, an anaesthetic that is used as a recreational drug. Research has found that sub-anaesthetic doses have rapid-onset antidepressant effects.

“It’s not just because it makes you feel ‘high’ or anything like that, it seems to be a genuine antidepressant effect and this can last for a few days after a single dose,” says McLoughlin.

Traditional antidepressants typically take two weeks to take effect, and therapy isn’t fast-acting. Unfortunately, this leads many to stop treatment and relapse.

“There’s a lot of interest in providing some insight into perhaps another way of how to treat depression in a way that may be more rapid-acting,” says the professor.

Generally, drug treatment is often not necessary for less severe depression. “Most people are quite resilient, really” and most mild symptoms resolve themselves, McLoughlin says. Therapy helps more at early stages.

If things progress, antidepressant drugs are prescribed, but 30 per cent of people end up being treated for treatment-resistant depression. At that stage, electroconvulsive therapy (formerly electroshock therapy) is still considered the “gold standard”, and about 400 people per year in Ireland receive it.

“What any successful treatment of depression seems to do is change the way the brain works in a subtle sort of way,” says McLoughlin. “That has to do with altering the ability in the brain to just be a bit more plastic in response to experience, and improving connections between nerve cells.”

Declan McLoughlin is currently looking for healthy volunteers for a depression study. For more information, email thekeepwellstudy@gmail.com

THE HIPPOCAMPUS: REBOOTING THE NETWORK

The brain isn’t a collection of structures that work on their own, performing specific functions. As Prof Declan McLoughlin of Trinity College Dublin puts it, neuroscience views disorders such as depression as “network problems”, involving a collection of regions working, or not working, together.

“Pretty much all brain regions are interconnected with other brain regions, so a problem in one brain region will have an impact on others,” he says.

That said, some structures do have more prominent parts to play in some functions and disorders. There are “important nodes” involved in depression, the professor says, such as the hippocampus.

The hippocampus is a horseshoe-shaped structure found near the centre and base of the brain.

It has huge implications for the storing of long-term memories and is damaged by diseases such as Alzheimer’s. It also plays an important role in emotional responses and is physically different in depressed people.

“Structural imaging studies show the hippocampus is actually smaller in people who are depressed than in non-depressed controls,” says Prof McLoughlin. “It’s smaller in individuals who have had adverse life experiences like deprivation and abuse, compared to those who haven’t had those life experiences.”

It’s not surprising, then, that many depression treatments generally strengthen the connections and size of the hippocampus.

“We know some treatments, like ECT for example, alter the volume of the hippocampus and increase the volume for short periods. Precisely why that is, we don’t know exactly.”