Brain changes in bipolar disorders (BD) may represent inherited risk factors or consequences of the illness (brain plasticity). Neuroanatomical changes, which predispose for BD could aid in early diagnosis, whereas the neuronal sequellae of BD could yield biological outcome measures for prevention and treatment.

To separate neuroanatomical changes into those that increase the risk of BD versus those that result from it, we acquired MRI/clinical data from participants at different stages of BD, including: (1) affected and unaffected offspring of bipolar parents (n = 86); (2) participants with substantial illness burden who had had at least 2 years of current Li treatment (n = 37) or were Li naive (n = 19). We also recruited 99 healthy controls matched to the above-mentioned cohorts by age and sex.

Relative to controls, both the affected and unaffected offpring of bipolar probands showed increased right inferior frontal gyrus (rIFG) volume, but comparable hippocampal volumes and prefrontal N-acetyl aspartate (NAA) levels. Larger rIFG volume was associated with an increased risk of conversion to psychiatric disorders within 4 years following the MRI scanning (hazard ratio = 4.5). In contrast, Li naive patients with substantial illness burden had smaller rIFG, hippocampal volumes and prefrontal NAA levels than controls, who were comparable in these indices to the the Li treated subjects with substantial illness burden.

Brain structural changes in BD may not be static, but may instead result from an interplay between illness burden and compensatory processes. This illness related brain plasticity may be modulated by lithium treatment.

The authors have not supplied his declaration of competing interest.