Depression ages the brain, first human trials suggest: Damage appears 10 years early

Depression may speed up brain aging, according to the first human study to test the theory.

Researchers at Yale University used a new brain scanning technique to show that synaptic density – the amount of connections in the brain – started thinning out 10 years earlier in people with depression – at 40 years old rather than 50.

That could mean earlier memory loss, brain fog, slowing speech, and even earlier onset of age-related diseases like Alzheimer’s.

Lead author Dr Irina Esterlis says the research could bring us closer to explaining why women, who are twice as likely than men to suffer from depression, have triple the risk of Alzheimer’s compared to their male counterparts.

She adds that it could also help us develop and approve drugs to target the hippocampus, the brain region affected in both disorders – such as ketamine, the ‘club drug’ which this week gained support from an FDA advisory committee to treat depression.

The study is small, with just 10 people, but Dr Esterlis says it is the green light they were looking for to set up a large-scale years-long study with many more people. 

For the first time, scientists have seen in humans that depression may age the brain 

‘We have never been able to measure before in living people because we never had a tool,’ Dr Esterlis, who will present the study at the world’s largest science conference this week, told

The potential of this new, promising tool is significant.

With time, Dr Esterlis says, we could screen people with depression for tell-tale signs of brain aging that could turn sinister.

‘There’s a lot we can do, we just need more time because all those studies take time,’ Dr Esterlis warns.

The reason it has been so hard to see whether depression ages the brain in humans is because brain scans can only see so much.

MRI scans can map out regions of the brain but they can’t project a live-stream of the complex, rapid changes happening on a constant basis.  

One of the most important aspects of the brain is also the most elusive: synapses.  

Synapses are the connections between neurons, allowing information to travel around and across the brain’s regions.

There are about 100 billion neurons in the brain, each connected to about 10,000 others. 

As we experience different things – anything – those connections change, form, break down or strengthen. 

Simultaneously, as we age, we are losing synaptic connections – which is both helpful (it focuses useful connections, getting rid of pointless ones) and frustrating (making multi-tasking and recalling words harder).   

For decades, neuroscientists have suspected that synaptic density can tell us a lot about a person’s mental and cognitive health. 

But until now, we’ve had to open up the brain to find out.

The new tool developed by Yale in 2016 broke new ground, allowing scientists to map out synapses in living humans without dissection.

The technique is a type of PET imaging.

Researchers at Yale’s PET Center designed a radioactive molecule that would bind to proteins found only in synapses.

They could then track that molecule, watching where it gathers and where it doesn’t, showing where synaptic density is higher or lower.  

It uniquely allows researchers to measure synaptic density in living people, and to cross-reference brain scans with patient interviews, offering a rounded perspective of their physical and mental health. 

Now, Dr Esterlis, a PTSD and depression researcher, has put the tool to use with her co-author, who has a special interest in aging.

They gathered 10 people with major depressive disorder with an average age of 40 years old, and a group of controls with an average age of 36. 

The small study delivered the results they had expected: synapse density was two to three percent lower in people with chronic depression. 

It will be years before we fully understand the link. Alzheimer’s and depression are slow-burning conditions that develop over a long course of time. 

But Dr Esterlis says this study offers a glimpse into what we may find.  

‘Potentially we could help people with depression, and we could spot individuals who have density in the hippocampus who maybe will go on to have Alzheimer’s.

‘We could see if we could prevent Alzheimer’s disease.’

As for how we might use this information, there are numerous clinical trials to develop drugs to target Alzheimer’s pathology – many backed by Big Pharma companies, hoping to find the goldmine drug. 

Separately, there are efforts to develop new methods for treating the growing number of people with depression. 

Just this week, an FDA advisory committee approved a ketamine-like treatment to do just that. 

Dr Esterlis says the drug – a horse tranquilizer better known in clubs than clinics – has promise.

‘Ketamine has been shown to reverse synaptic density in animals who are depressed.’

The issue is that it targets systems other than the hippocampus too. 

But there are other agents that may do the same thing.

‘Maybe we could use those to delay the onset of Alzheimer’s.’