New mechanism discovered for depression

20 August 2015
Dr Suresh Muthukumaraswamy
Dr Suresh Muthukumaraswamy

Research into the action of ketamine on the brain has revealed neural pathways that will help scientists develop fast-acting medications for treating depression.
The discovery was made by Rutherford Fellow, Dr Suresh Muthukumaraswamy, who is a senior research fellow in both the School of Pharmacy and Psychology at the University of Auckland. He is also a member of the University’s Centre for Brain Research.

His research focusses on brain imaging and using the latest technology in brain imaging to understand and treat brain disorders.
The technique used in this research was magnetoencephalography (MEG) measuring the brain’s magnetic fields in combination with the latest in computational models.

His findings were published today in the Journal of Neuroscience.
“Our interest is in the mechanism of action that ketamine uses to be active in the human brain,” says Dr Muthukumaraswamy. “That will give us a target for other compounds.”

The research data was collected by colleagues while Dr Muthukumaraswamy was based at the University of Cardiff and they tested the ketamine in healthy volunteers to see what parts of the brain it affects.

“We know that ketamine is active in the frontoparietal circuit of the brain and disconnects these two parts,” he says. “In depression those two parts of the brain work overtime in an over-connected way. By disconnecting those two parts of the brain and stopping that over-connectivity, may be how ketamine works as an antidepressant.”

“Unlike other anti-depressants, ketamine is very fast acting, but other clinical trials have found that the ketamine-induced anti-depression effect only lasts a week or so,” he says. “It’s important as a mechanism to identify potential biomarkers of antidepressant activity in human patients, but for other reasons, we cannot use it for treatment.”

He says ketamine (that was developed in the 1960s) is off-patent now and is primarily used as an anaesthetic and sometimes for chronic pain. Only low doses of ketamine are needed, compared to anaesthetics, to create those anti-depressant effects.

“It’s not licenced for depression because it is still very experimental in that role,” says Dr Muthukumaraswamy. “Ketamine’s anti-depressant properties were discovered relatively recently and did well in clinical trials. Unfortunately, ketamine is also a drug of abuse, as it’s mildly hallucinogenic and it is unclear if it could be used in routine clinical practise,” he says.

The research team investigated what effect ketamine was having on the brain to work so quickly. Further work is needed to explore this mechanism, he says.

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