Insulin resistance could be an ‘early red flag’ for mood disorders: research
Research suggests insulin resistance may trigger mood disorders in some young people, not the other way around, offering hope for those who don’t respond to traditional treatments.
There are times when Samuel Hockey’s world grows a little darker and shrinks, and everyday tasks become impossible feats.
“There’ll be moments where I cannot physically get out of bed or move or do tasks such as brushing my teeth or making a meal,” he said. “You take for granted how much effort those things can take.”
It’s such an engulfing feeling that “snapping out of it” is not an option. Something much deeper is at play.
“There is nothing there to help me to move,” he said. “Quite often I’ll find myself in a state of numbness or disassociation to protect myself from feeling too much or going through the rollercoaster of emotions and complexity that are synonymous with a mood disorder.
“You can’t change it. You almost have to wait it out. And that’s a challenge and an educational thing not just for me but also my loved ones.”
Mr Hockey has been diagnosed with complex mood disorder and anxiety. It began before he was a teenager and has remained part of his life for two decades.
“It was an absolute draining journey to finally reach a point where I’m able to actually know what I’m experiencing and put a name to it and be educated through my clinicians on how that works, and then further educate my loved ones.”
Mr Hockey is one of a small portion of people who don’t respond to traditional treatments. However, he’s come to realise that there are certain things that make him feel worse.
“I fall within that 30 per cent of people with mood disorders where my mood is largely driven by my circadian rhythm and the regulation or dysregulation that comes with that,” he said.
It’s an understanding that’s captivated him and driven him to want to know more. It’s also part of the reason why he is now a youth mental health expert as well as a masters of research student at Macquarie University.
It is people like Mr Hockey who have also caught the attention of researchers at the University of Sydney’s Brain and Mind Centre. Mood disorders can be influenced by several things, but these researchers believe that, for a small group of people like Mr Hockey, their condition may be driven largely by changes in the body rather than the brain.
Sarah McKenna is a post doctoral researcher and clinical psychologist with the Brain and Mind Centre and led a cross-sectional cohort study to the connection between early metabolic dysfunction and depression or bipolar disorder.
“There are really high rates of cardiovascular disease and metabolic dysfunction in people with mood disorders, and it hasn’t really gotten any better in the last decade or so, and we don’t really understand why it’s happening,” Dr McKenna said.
“Our team has found signs of insulin resistance at really young stages, far earlier than previously thought.
“So, there might be something more complicated happening. We think a good explanation is circadian disturbances, which we know are really common in young people with mood disorders, and if you have sleep-wake disturbances you are at an increased risk of metabolic dysfunction.”
For the study, Dr McKenna and her team reviewed 751 young people, recruited from early intervention mental health services between 2004 and 2024, who were classified in either the more common hyperarousal-anxious depression subgroup or the circadian-bipolar spectrum subgroup. Then they compared metabolic markers in patients from both groups.
They found those in the less traditional circadian-bipolar spectrum subgroup had significantly elevated fasting glucose compared to those in the other subgroup.
“As the larger hyperarousal-anxious depression subgroup is the most generic type, and weight gain is also a characteristic of the circadian-bipolar subgroup, we then differentiated those with the hyperarousal-anxious subtype on the basis of low versus high BMI,” researchers wrote in their academic paper.
“The ‘circadian-bipolar’ group had higher fasting glucose, fasting insulin, and HOMA2-IR (a measure of insulin resistance), than those in the hyperarousal-anxious-depression group with low BMI.”
Dr McKenna said those findings led her to conclude that insulin resistance could be an “early red flag” for metabolic and mental health problems rather than the other way around.
It’s a concept Ian Hickie, who is also with the university’s Brain and Mind Centre, has been investigating.
Professor Hickie’s most recent research also concludes that insulin resistance and disrupted sleep-wake cycles can appear before mood symptoms develop in some people.
“We have been thinking of sleep cycle disruptions as a symptom of mood disorders and metabolic changes as a side-effect of medication,” he said. “But our research suggests that the sleep disruption and metabolic changes may actually come first.”
His research suggests that about 30 per cent of young people who seek help for mental health could be affected, leading him to suggest a simple blood test could help to identify those at greater risk of developing a mood disorder and associated comorbidities earlier.
“We wanted to know if there are processes that are running throughout the body that are not only affecting brain function but affecting other fundamental mechanisms too, like regulation of the body clock and its impact on the cortisol systems … and also on the insulin release systems that leads to insulin resistance and, further down the track, gaining weight and the possibility of developing diabetes,” Professor Hickie said.
“A lot of people with mood disorders have insulin resistance before treatment starts.
“This is not picked up because healthcare providers only measure blood sugar and not insulin.”
It’s a prospect that could lead researchers to consider new screening and treatment options for the affected group. It could also prevent patients from being prescribed medication they may not respond well to.
“If they’re at risk of developing these conditions, then when they are exposed to other medications they may be particularly likely then to gain weight and go on to develop diabetes,” Professor Hickie said. “So this is the group we want to intervene in early to prevent really bad outcomes, metabolically as well as psychiatrically.”
Mr Hockey was one of those patients who responded poorly to his treatment as a teen. It triggered his insulin resistance, resulting in him becoming borderline diabetic. That meant he had to take even more medication, leading to weight gain and, later, an eating disorder.
He believes if his biomarkers for insulin sensitivity had been identified via a blood test earlier, it could have prevented not only the metabolic damage but also those other impacts.
“Having access to such a simple screening, I could have eased the unfair value I have placed on myself – because so much of that self-judgment stemmed from physical changes, my inability to find motivation for even the simplest of tasks, and the ‘confidence’ to invest and feel valued in relationships,” he said.
“I assumed these shifts were personal failings rather than the consequences of unstable insulin and its affects on my mood disorder.”
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