Bipolar: Men More Likely To Have Mania, Women Depression

Brain Scan Study Reveals Why Bipolar Disorder Hits Men and Women Differently

A new study suggests that differences in how men’s and women’s brains process chemicals and structure in a key emotional circuit may explain why bipolar I disorder often shows up as intense mania in men but prolonged depression in women.

Researchers in China analyzed brain scans from 109 adults experiencing an acute episode of bipolar I disorder — the severe form marked by full-blown manic highs and crushing depressive lows. The findings, published last week in the journal BMC Psychiatry, point to “lateralization” differences — meaning one side of the brain dominates more than the other — in a network called the cortico-striatal-cerebellar circuit. This circuit helps regulate mood, reward, motivation, and cognitive control.

Men in the study were far more likely to be in a manic episode (31 out of 49) than women (17 out of 60). Women, by contrast, were more often depressed (43 out of 60). These patterns align with what doctors see in clinics worldwide: women with bipolar I tend to suffer more depressive episodes, while men experience more manic ones and higher rates of substance abuse.

Using advanced MRI and magnetic resonance spectroscopy (MRS) — a technique that measures brain chemicals like glutamate (Glx), N-acetylaspartate (NAA), and choline (Cho) — the team found clear sex-based asymmetries.

Men showed stronger left-side dominance in several markers, including higher laterality indices for anterior cingulate cortex volume, NAA levels (a sign of neuron health), basal ganglia choline, and glutamate-related compounds (all with statistical significance at P < 0.007). Women, however, had greater left-side dominance only in basal ganglia volume.

When researchers built predictive models using machine learning (XGBoost algorithm), these asymmetry patterns proved powerful. In men, brain lateralization correctly predicted manic episodes with 80.3% accuracy (AUC = 0.803). In women, it predicted depressive episodes at 82.4% accuracy (AUC = 0.824). Models that ignored left-right differences performed significantly worse.

The most important predictor for mania in males was asymmetry in glutamate levels in the anterior cingulate cortex, the authors noted. For depressive episodes in females, imbalances in NAA and choline in the same regions carried the heaviest weight.

The anterior cingulate cortex acts like an emotional “conflict monitor,” while the basal ganglia handles reward and motivation — pathways long tied to bipolar swings. The study suggests sex hormones, dopamine sensitivity, and stress responses may amplify these left-right imbalances differently in men and women.

All participants were medication-free for at least two weeks before scanning to avoid drug effects clouding results. Researchers took extra steps to scan highly manic patients safely, including shorter scan blocks and real-time monitoring.

Experts say the work adds a missing piece to understanding bipolar’s stubborn sex differences. While the study was done in one hospital and needs replication in diverse populations, it opens doors to tailored treatments — perhaps targeting brain asymmetry or specific chemicals based on a patient’s sex and dominant symptoms.

These findings highlight that bipolar I disorder isn’t one-size-fits-all, said lead researcher Ran-chao Wang of the study’s institution (as summarized in the journal). Sex-specific neuro-metabolic patterns could guide more precise interventions in the future.

The full open-access study is available here: https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-07537-1

ManiaInsights.com covers the latest science on mood disorders with clarity and compassion. If you or a loved one is in crisis, contact the National Suicide Prevention Lifeline at 988.

Editor’s note: My personal anecdotal evidence shows this theory to be true. I have met hundreds of people with bipolar disorder in group support sessions with DBSA. The vast majority of women seem to face depression, and men seem more likely to experience mania and manic episodes.

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