Does Myelin Contribute to Sex Differences in Depression?

According to the World Health Organization, suicide is the fourth leading cause of death of 15- to 29-year-olds. About 1.9 million people between the ages of three and 17 are diagnosed with depression, and women are disproportionately affected over men.

A study published in Neuropsychopharmacology in July of this year shows that patterns of myelination differ between male and female adolescents experiencing depression. Myelin is cellular membrane wrapped around nerve fibres in the brain. Myelin keeps nerve fibres healthy and optimizes the speed of passing information between neurons. Myelin is a large component of the brain's white matter. It's what gives it its characteristic white colour.

The study, led by Dr. Tiffany Ho and Lucinda Sisk, used multimodal magnetic resonance imaging to measure myelin in areas of the brain previously associated with depression, the uncinate fasciculus and the corpus callosum genu. Female adolescents experiencing depression had more myelin in these tracts compared to female participants without depression. Myelin in males with depression and without depression did not differ.

Why It's Important to Study Teen Depression

Adolescence ranges from ages 10 to 19 and represents the phase of life between childhood and adulthood. It is a unique stage in human development and an important time for laying the foundations of good health, writes the World Health Organization. It's also an important time to study to understand how the emergence of depression influences white matter.

"By focusing on a period (...) where depression has more recently emerged and where teens are otherwise healthy," says Dr. Ho, "we're able to pinpoint with more specificity that these white matter changes we're seeing (...) are related to emotion regulation and cognitive processing." Because of all the developmental changes within the brain during adolescence, it's also a time when the brain is particularly sensitive to positive and negative inputs.

One hypothesis explaining the increase in myelin with depression is stress acceleration. A predominant perspective on early adversity and mental illness has been that these negative experiences impair brain function, write Drs. Bridget Callaghan and Nim Tottenham of Columbia University in an article published in Current Opinions in Behavioral Sciences. But numerous theories now predict that adversity may lead to a reprioritization away from a developmental strategy favouring a slow developmental pace towards one that promotes adult-like functioning. What we're seeing here may be another example of stress acceleration, says Sisk. We would expect to see this gradual increase in myelination across adolescence. Perhaps that process is getting sped up in individuals who have experienced stressors.

What Else We've Learned About Myelin and Stress

Myelination changes in response to stress in animals. The research lab of Dr. Daniela Kaufer at the University of California, Berkeley published a study early this year where pre-adolescent male and female rats were exposed to short periods of stress. The researchers then measured indicators of myelin in brain regions associated with emotion regulation.

In adolescence, myelin in the prefrontal cortex of female rats increased in animals exposed to the pre-adolescent stress. Myelin in other areas decreased. There were no myelin differences in males in the prefrontal cortex, but myelin increased in other areas, like the amygdala and the hippocampus. In this study, myelin differences after just one bout of pre-adolescent stress persisted into adulthood. The authors concluded, "Experiencing a single acute severe stress as a juvenile alters myelin and [the cells that produce myelin] in a sex and region-specific manner, with lasting impacts."

Why This Research Matters

Understanding the biology underlying sex differences in depression is complicated. Stress acceleration is one hypothesis. But there are many other factors that may contribute, and it is likely they all interact in important ways to manifest into diagnosable symptoms of depression. "I hope that by demonstrating that there are these different patterns of myelination in youth who are experiencing depression," says Sisk, "that might usher in more research investigating (...) myelination during adolescence and how those patterns differ as a function of stress exposure and psychopathology experience."

It's important to remember that myelination is an experience-dependent process, too. How myelin wraps around a nerve fibre in the brain changes in response to the needs of neural circuits. And there's evidence suggesting myelin can change well into a person's thirties. Differences in myelination in teens with depression could indicate that this is a target for intervention, says Dr. Ho. Myelination being experience-dependent suggests that there are ways to alter these trajectories earlier in development and earlier in the disease course. That can help keep this disorder from being recurrent and plaguing the individual in the long term.

Depression Essential Reads

3 Things Not to Say to Someone Struggling With Depression

101 Activities to Boost Your Mood

Dr. Tiffany Ho is an assistant professor of psychiatry at the University of California, San Francisco. Lucinda Sisk is a Ph.D. student at Yale.