Hajek T, Cullis J, Blagdon R, Propper L, Duffy A, Kopecek M, Novak T, Höschl C, Alda M. Increased right inferior frontal gyrus gray matter in 2 cohorts of unaffected and affected offspring of bipolar parents – replication design, high-risk study. 9th international conference on bipolar disorder, Pittsburg, June 9-11, 2011

17. 1. 2011

Introduction: Bipolar disorders (BD) have a strong genetic underpinning and typical age of onset in adolescence/early adulthood. Studies of offspring of bipolar parents transitioning through the at-risk age (high-risk design) are thus ideal to identify biological vulnerability markers for BD.

Methods: High-risk participants (aged 15-30 years) were recruited from families affected with BD in Halifax for the initial and in Prague for the replication study. They included 50 unaffected (30 in Halifax, 20 in Prague) 35 affected (20 in Halifax , 15 in Prague) offspring at genetic risk for BD, matched by age and sex with 49 controls (31 in Halifax, 18 in Prague) without a personal or family history of psychiatric disorders. Structural imaging data from 1.5T magnets were analyzed using optimized voxel based morphometry in SPM8. Using a replication design, we performed exploratory contrasts in the Halifax group to generate hypotheses, which we then tested for replications in the Prague cohort.

Results: Among the clusters of differences between the groups in the Halifax sample, only increases in the right inferior frontal gyrus (rIFG), Brodmann are 47, which were present in both the affected and unaffected subjects relative to controls were replicated in both the affected and unaffected subjects relative to controls in the Prague cohort (replication corrected p<0.001). The clusters of increased IFG relative to controls directly overlapped between the unaffected and affected subjects in each center.

Discussion: The replication of increased rIFG in both the affected and unaffected subjects in both cohorts is intriguing. Increased rIFG in both the affected and unaffected subjects suggests this to be a marker of vulnerability for BD. The increased GM volume may indicate a compensatory upregulation of neurotrophic mechanisms or a pre-apoptotic oedema.

Key Words: Bipolar disorders, offspring, endophenotypes, MRI, right inferior frontal gyrus