Aberrant structural covariance networks in youth at high familial risk for mood disorder

Current research suggests significant disruptions in functional brain networks in individuals with mood disorder, and in those at familial risk. Studies of structural brain networks provide important insights into synchronized maturational change but have received less attention. We aimed to investigate developmental relationships of large-scale brain networks in mood disorder using structural covariance (SC) analyses.

We conducted SC analysis of baseline structural imaging data from 121 at the time of scanning unaffected high risk (HR) individuals (29 later developed mood disorder after a median time of 4.95 years), and 89 healthy controls (C-well) with no familial risk from the Scottish Bipolar Family Study (age 15-27, 64% female). Voxel-wise analyses of covariance were conducted to compare the associations between each seed region in visual, auditory, motor, speech, semantic, executive-control, salience and default-mode networks and the whole brain signal. SC maps were compared for (a) HR(all) versus C-well individuals, and (b) between those who remained well (HR-well), versus those who subsequently developed mood disorder (HR-MD), and C-well.

There were no significant differences between HR(all) and C-well individuals. On splitting the HR group based on subsequent clinical outcome, the HR-MD group however displayed greater baseline SC in the salience and executive-control network, and HR-well individuals showed less SC in the salience network, compared to C-well, respectively (P < .001).

These findings indicate differences in network-level inter-regional relationships, especially within the salience network, which precede onset of mood disorder in those at familial risk.