Why do men and women suffer stress differently?
The answer could have much to do with how the male and female brains respond to sex hormones - a complex process that remains something of an enigma to scientists.
An estimated 636,000 Kiwis were affected by mood and anxiety disorders, and rates appeared to be on the rise, said Dr Karl Iremonger, an award-winning Otago University brain researcher now leading a $958,000 study supported by the Marsden Fund.
Yet women were nearly twice as likely as men to suffer from anxiety, which was now affecting female health more severely than even heart disease and kidney failure.
"Stress is one of the major factors that can lead to the onset of mental health conditions such as depression, anxiety and post-traumatic stress disorder," Iremonger said.
"Females and males respond differently to acute stress - and this is thought to give rise to sex differences in stress adaptation, stress resilience and subsequent risk for developing stress-related mental health conditions."
It was now known that the sex hormones testosterone and oestrogen played an important role in modifying neural pathways in the brain, both when developing and when it was mature.
But what wasn't clear, Iremonger said, was what specific circuits in the brain were targeted by sex hormones to control stress sensitivity.
"Secondly, we don't understand the exact changes in the brain that result from exposure to these different sex hormones.
"The key question we want to answer, is where in the brain are sex differences in stress responses manifested and what underpins these changes."
Researchers speculated that one part of the brain that was essential for controlling stress hormone levels - the paraventricular nucleus of the hypothalamus - may be regulated differently between males and females.
Unravelling those mechanisms wouldn't be easy, as the brain structure was packed with many different types of neurons linked to stress responses.
In the new study, Iremonger and his team would use brain tissue from male and female mice to analyse single cells and how their activity patterns differed.
The scientists could also tease out effects by adding certain chemicals, such as noradrenaline.
"Recording the patterns of activity of brain cells is extremely difficult, as a single brain cell is only 0.02mm in diameter," he said.
"Because of their small size, we need powerful microscopes, sensitive amplifiers and delicate micro-manipulators."
But, if successful, the study could yield crucial insights.
"Understanding how the brain controls stress responses will be key in understanding mental health conditions that are associated with stress," he said.
"Understanding the differences in the brain between males and females may also give insight into why stress responses are different and why stress-associated disorders affect men and women differently."
How blood pressure affects our brain
High blood pressure, or hypertension, is the most common cardiovascular disease affecting Kiwis, and with an ageing population these numbers are likely to increase.
Maori, whose rates were 50 per cent higher than Pakeha, were especially at risk.
"Characterising the relationship between blood pressure and brain blood flow is critical if we are to understand how best to treat hypertension to ensure a healthy brain," said Dr Fiona McBryde, of the University of Auckland's Faculty of Medical and Health Sciences.
McBryde's study, also supported with a Marsden Fund grant, will explore how the brain protects itself from low blood flow, and what effect hypertension has.
She described the brain as our most "expensive organ", given its high demand for energy and oxygen that demanded an ongoing and uninterrupted supply of blood.
On top of this was the requirement to push blood up to what, for most of the day, was the highest point of our body.
"The textbook view is that the blood vessels supplying the brain will automatically relax or constrict as the supply blood pressure varies, such that blood flow remains constant; this is called 'cerebral autoregulation'," she explained.
"This theory predicts that other mechanisms step in to protect flow only when the supply blood pressure reaches extremely high or low levels."
But one problem was that this view was based on data where brain blood flow was estimated in groups of patients with high or low resting blood pressures.
"Thus, it does not reflect what happens in you or I as our blood pressure naturally varies throughout the day.
"My research interest is in how the brain protects its own blood flow on a minute-to minute and day-to-day basis."
If blood flow to the brain was too low, this could cause neurological problems, notably stroke.
"More insidiously, it seems that even small reductions in brain blood flow over long periods of time may contribute to conditions such as vascular dementia.
"We know that high blood pressure is one of the main risk factors for developing neurological conditions such as dementia, which may be partly explained by the recent finding that patients with high blood pressure often have lower brain blood flow than normal.
"What we don't know is whether the ability to protect brain blood flow may already be impaired in subjects with high blood pressure, and what the impact of giving medications to lower blood pressure might be."
Her laboratory has developed a new technique that allows scientists to directly measure the blood flow to the brain during controlled falls in blood pressure.
"This lets us measure how the brain responds to a fall in the 'supply pressure' – we believe that the brain will sense this as a threat to blood flow, and send signals via nerves to the cardiovascular system - the heart, kidneys and blood vessels - to cause a reflex increase in blood pressure to compensate.
"Thus, in this situation we would say that our brain acts 'selfishly' by demanding high blood pressure to the body, in order to protect its own blood supply."
As with all cutting-edge research, McBryde and her team were pushing the boundaries of what could be measured.
New technology used wireless telemetry devices to record blood pressure and other cardiovascular variables, letting them make their recordings in freely moving subjects.
"Our laboratory is also one of the few in the world capable of making long-term recordings of the nerve signals from the brain which communicate with the cardiovascular system – this is one of the main pathways by which the brain can tell the body to increase blood pressure, and protect its blood flow."
While the project was essentially blue-skies research, early findings had already challenged the assumption that brain blood vessels were the sole regulators of brain blood flow.
"We propose that instead the brain needs to recruit the cardiovascular system on a near-continual basis in order to maintain its blood flow," she said.
"A better understanding of how brain blood flow is protected in diseases such as hypertension is important going forward - the tools to let us assess brain blood flow are increasingly available even in hospitals, and perhaps brain blood flow should be a consideration when prescribing medications to treat and control blood pressure."