Substantial Reorganization of Structural Brain Networks Among Young Adults at High Risk for BD

Psychological concept vector illustration.
This study recruited individuals aged 12-30 years who had first-degree relatives with BD I or II and those with no family history of mental illness.

Individuals with high genetic risk for bipolar disorder (BD) were found to have substantial reorganization of structural brain networks during adolescence and young adulthood, according to results of a study, published in AJP in Advance.

This study recruited individuals aged 12-30 years who had first-degree relatives with BD I or II (n=97) and those with no family history of mental illness (n=86). Participants underwent diffusion magnetic resonance imaging at baseline and at a 2-year follow-up. Changes to whole-brain structural networks were evaluated on the basis of familial BD risk.

Those at risk and controls were 59% and 53% girls or women, aged mean 21.12 (SD, 5.24) and 22.41 (SD, 4.04) years, intellectual quotient was 115.42 (SD, 10.98) and 117.40 (SD, 10.19), and 57% and 31% had any disorder diagnosed at baseline (P <.001), respectively.

At follow-up, a substantial reorganization in structural connectivity was observed, with 6.5% of total edges significantly stronger and 8.8% significantly weaker (P <.001). These changes occurred among most individuals in both groups.

In general, effects were stronger among women and girls and tended to decrease with age.

There was a significant group-by-time effect (P =.007), predominantly in left-side inferior and lateral structures. Edge weights of this network were increased in strength among controls and decreased among those at high-risk for BD. There was a significant time effect, in which the strength of the network increased with age among controls (t, 3.4; P =.0007) but not among those at high risk for BD.

The effect of age on edge weights was predominantly linear, with only 0.71% of edges having a nonlinear age-weight effect, of which 100 had a concave up and 86 a concave down relationship. The nonlinearity of edges was consistent from baseline to follow-up (r, 0.56; P <.001) but was more consistent among the controls (r, 0.60) than the high-risk group (r, 0.54; P <.05).

During the study, 5 of the high-risk group experienced an episode of mania or hypomania, formally converting to BD. Edge weights among this subset of individuals showed a greater decrease over time than those who did not convert to BD. Effect sizes were 0.97 for those without an episode and 0.24 for those with an episode.

This study was likely limited by the small sample size of individuals who experienced a manic or hypomanic episode and formally converted to BD.

The study authors concluded, “Persons with a first-degree relative with bipolar disorder often inquire about their own future risk of the disorder. Epidemiological studies show an overall odds ratio in the range of approximately 7–14, with the incidence peaking in the third decade of life. Prediction algorithms combining phenotypic, neurobiological, and genetic information are urgently needed to better stratify individual risk prediction, identifying those who might benefit from early intervention rather than the present ‘watch and wait’ approach.”

Disclosure: One author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Roberts G, Perry A, Ridgway K, et al. Longitudinal changes in structural connectivity in young people at high genetic risk for bipolar disorder. Am J Psychiatry. 2022;appiajp21010047. doi:10.1176/appi.ajp.2101004