Efforts to uncover sex differences between human brains have given rise to a debate over what – if anything at all – accounts for apparent distinctions in our behavior and mental health.

A recent analysis of imaging data collected as a part of the Human Connectome Project (HCP) has delivered what could be the largest sex-related variations in microscopic structures deep within the brains of men and women.

Extrapolating from what's known about the locations of the most significant contrasts, the international team of researchers behind the study claims the findings could help us better understand why many neurological conditions appear to be weighted by sex.

"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."

In spite of what may seem like clear-cut distinctions, male and female humans are surprisingly similar for a species of ape.

Separating the statistical molehills of sexuality into neat piles is notoriously messy, leaving scientists to search for ever-more precise ways to tell whether conditions such as autism or anxiety disorder really do correlate with sex, or if we're guided by a slew of biases.

Neuropsychiatric differences between men and women have in the past been largely put down to variations in brain volume, suggesting differences are more likely to be a reflection of size than actual wiring.

While there's little doubt that neurological real estate influences a significant amount of human behavior, some studies that account for sex and brain size still find a residual effect that can't be easily dismissed.

So Watts and his team used the MRI scans of more than 1,000 participants in the HCP Young Adult study to investigate the microstructures of their subcortical brain regions and match them with their self-reported sex and mental health status.

Using an advanced diffusion MRI technique that mapped the movement of water through the unique cellular architecture of different brain tissues, the researchers identified small but significant differences between male and female sub-groups that remained even after they'd adjusted for age, BMI, and overall brain volume.

Measures based on the participants' own assessments of their emotional and behavioral states also hinted at a relationship between the neurological structures responsible for memory, attention, and emotion and disorders involving 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.

Far from simply pigeon-holing men and women into pathological boxes, the research opens the way for exploring the complex influence of hormones and their receptors on the neurological tapestry inside our heads.

Participants were asked about their gender, not their biological sex, but were only given two options: male or female, limiting brain structure comparisons for other gender identities.

Future studies may continue to identify how a spectrum of gender and sexuality correlates with states of personality, mood, and emotion, informing diagnoses or choices of therapy on a more individualized basis.

"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.

This research was published in PNAS.