Sex Differences in Human Brains May Help Explain Mental Health Risks

Efforts to identify sex differences in human brains have sparked debate about what, if anything, lies behind apparent differences in behaviour and mental health.

A new examination of imaging data gathered through the Human Connectome Project (HCP) has revealed what may be the largest sex-related variations yet found in microscopic structures located deep in the brains of men and women.

Drawing on what is known about where the strongest contrasts occur, the international research team says the results may improve understanding of why many neurological conditions seem to affect the sexes differently.

"The brain regions and measures that showed the largest differences are also strongly associated with mental health disorders," says senior author Richard Watts, a data scientist at the University of Canterbury in New Zealand.

"This finding may help explain why men and women are at different risk for specific disorders, such as anxiety and mood disorders, autism, and attention-deficit hyperactivity disorder."

Sex differences in human brains

Despite distinctions that can appear clear-cut, male and female humans are remarkably alike for an ape species.

Sorting the statistical subtleties of sex into tidy categories is famously difficult. Scientists must therefore seek increasingly precise methods to determine whether conditions including autism and anxiety disorders genuinely correlate with sex, or whether conclusions are being shaped by numerous biases.

In the past, neuropsychiatric differences between men and women have largely been attributed to differences in brain volume. This has suggested that such variation may reflect size rather than genuine differences in neural wiring.

Although brain size undoubtedly has an important influence on human behaviour, some studies that control for both sex and brain volume still identify a remaining effect that is not easily explained away.

Human Connectome Project imaging findings

Watts and colleagues therefore examined MRI scans from more than 1,000 people taking part in the HCP Young Adult study. They investigated the microstructures of subcortical brain regions and compared them with participants’ self-reported sex and mental health status.

Using an advanced diffusion MRI method, which charts how water moves through the distinctive cellular architecture of different brain tissues, the researchers found small yet significant differences between male and female subgroups. These persisted after adjustments for age, BMI and total brain volume.

Measures based on participants’ own evaluations of their emotional and behavioural states also suggested a link between neurological structures involved in memory, attention and emotion, and disorders concerning mood, attention and personality.

"Previous work has concentrated on sex-related differences in the volumes of brain regions, but by using more advanced imaging technology our team, which includes colleagues at the University of California San Diego, has discovered there are much bigger differences in the cellular structure of these regions, with only a small overlap found between the sexes," says Watts.

Rather than merely placing men and women into pathological categories, the research creates an opportunity to examine the complex effects of hormones and their receptors on the neurological landscape within the brain.

Gender, biological factors and future studies

Participants were asked about their gender rather than their biological sex, but could select only one of two responses: male or female. This restricted comparisons of brain structure across other gender identities.

Further research may establish how a spectrum of gender and sexuality relates to personality, mood and emotional states. Such work could support more individualised diagnoses or treatment choices.

"We would like to be able to separate the effects of biological factors, such as hormones and genetics, and the effects of environmental factors, such as how we are socialized to think and behave differently as a man or a woman in societies that have very different expectations of each gender," says Watts.

The research was published in PNAS.