The work, led by Toronto scientist Dr. Jeffrey Meyer, concludes that high levels of a chemical called monoamine oxidase A, or MAO-A, may be to blame.
The protein is known to break down other brain chemicals such as serotonin, norepinephrine and dopamine which help to maintain normal mood.
Rates of depression in women in perimenopause — the period leading up to menopause — are unusually high.
In fact, previous studies have suggested that first-time depressions in women in this period of life reach 16 to 17 per cent and a similar percentage of women develop milder depressive symptoms.
This study, published in the journal JAMA Psychiatry, was conducted by an international team of scientists led by Meyer.
Meyer is the head of the neurochemical imaging program in mood disorders at the University of Toronto's Centre for Addiction and Mental Health.
He says he got the idea to study the potential role of MAO-A in perimenopause depression because of clinical work he does at the centre.
"I work in a mood disorders clinic one day a week outside of my research," says Meyer, who holds a Canada Research Chair in the neurochemistry of major depression.
"And what is striking is that about a third of the people who come through for concerns about having clinical depression are women in this age range. So they're disproportionately represented in the mood clinics."
A common characteristic of women going through perimenopause is the propensity to cry easily. And that too is associated with high levels of MAO-A in the prefrontal cortex, the front of the brain.
Levels of MAO-A in the brain are known to rise as levels of estrogen drop — which happens during perimenopause. Meyer says that the fluctuation of estrogen at this time of life is five-fold greater than earlier in life.
He and his co-authors used positron emission tomography, or PET scans, to image the brains of 58 healthy women — 19 of reproductive age, 27 in perimenopause and 12 who had gone through menopause.
They found that on average the perimenopausal women had 34 per cent more MAO-A present in their brains than the younger women and 16 per cent more than the women who had gone through menopause.
This type of study cannot prove cause and effect. It can only note an association between perimenopause and increased levels of this brain chemical. But earlier work by Meyer has linked high levels of MAO-A to major depressive disorder, depressed mood related to alcohol dependence and smoking cessation and post-partum depression.
Meyer says there is already an anti-depressant on the market — moclobemide or Manerix — that specifically targets production of MAO-A. Based on these results, he says, it would make sense to study it in perimenopausal women suffering from depression to see if it should be the drug option of choice for this group.
But he is currently working on studying the effect of a supplement combination that could potentially stave off excess MAO-A production, thereby potentially preventing the onset of depression in women going through perimenopause.
Financial support for the research came from the Canadian Institutes of Health Research, the Brain and Behaviour Research Foundation, the Canada Foundation for Innovation and the Ontario Ministry of Research and Innovation.