A common laxative may do more than aid digestion: it could sharpen memory and attention in people with a history of depression.
People with depression and other mental illnesses often complain of brain fog or problems with cognition, including difficulties with thinking, planning tasks, and memory.
New research from the University of Birmingham and University of Oxford has found an existing licensed drug currently used to treat chronic constipation could tackle these often-overlooked cognitive symptoms.
In a small trial, participants who had previously had depressive episodes took either 2mg Prucalopride or a placebo for seven to 10 days. Prucalopride stimulates a specific serotonin receptor – 5-HT4 R – in the gut and brain to help increase bowel movements.
Participants’ executive function, short- and long-term memory, and emotional cognition were measured through a series of tasks, before and after taking the active drug or placebo.
Researchers found those taking prucalopride performed faster and more accurately on tests of executive function and memory than those on the placebo.
“Our current thinking is that stimulating 5-HT4 receptors boosts neural circuits involved in learning and memory, especially the hippocampus and connected frontal networks,” says Angharad de Cates, National Institute for Health and Care Research Clinical Lecturer at the Institute for Mental Health, University of Birmingham.
“Mechanistically, this may involve increased acetylcholine release, enhanced hippocampal synaptic plasticity, and broader modulation of glutamate and other neurotransmitter systems that support cognition.”
The cognitive benefits were seen after participants had been taking prucalopride for about a week, but as researchers did not test what happened when treatment stopped, they cannot say whether the improvements continue once the drug is withdrawn.
Prucalopride was “generally well tolerated,” with participants not reporting “any serious gut complaints, because prucalopride works as a laxative gently stimulating bowel movements,” de Cates added. Those given the drug did, however, report a slight decrease in appetite after treatment.
These findings are promising, but preliminary, de Cates notes: “This was a first study of young to middle-aged adults with depression in remission. We need further research to validate these findings in older adults and in people with more complex medical and psychiatric histories.”
But de Cates believes this study provides solid proof-of-concept for future studies in people with current symptoms of mental illness, particularly in terms of the potential for broad cognitive benefits.
“This is especially relevant because cognitive problems are common across many mental illnesses, including depression, but are poorly targeted by current treatments,” she adds.
Previous research has shown that 5-HT4 receptor agonists may reduce the risk of depression, with another recent study coauthored by de Cates finding that a similar 5-HT4R drug had promise for people with active depression but not taking medication, particularly in relation to mood symptoms.
This study offers a potential new direction for treatment development, and the team is continuing their work in this area.
The study has been published in Psychological Medicine.
Source: University of Birmingham
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