Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies

Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies


J Psychiatry Neurosci 2012;37(3):170-84

Paolo Fusar-Poli, MD, PhD; Oliver Howes, PhD; Andreas Bechdolf, PhD; Stefan Borgwardt, PhD

Fusar-Poli, Howes, Borgwardt — Institute of Psychiatry, Department of Psychosis Studies, King’s College London, London, United Kingdom; Bechdolf — ORYGEN Youth Health Melbourne, Victoria, Australia


Background: Although early interventions in individuals with bipolar disorder may reduce the associated personal and economic burden, the neurobiologic markers of enhanced risk are unknown.
Methods: Neuroimaging studies involving individuals at enhanced genetic risk for bipolar disorder (HR) were included in a systematic review. We then performed a region of interest (ROI) analysis and a whole-brain meta-analysis combined with a formal effect-sizes meta-analysis in a subset of studies.
Results: There were 37 studies included in our systematic review. The overall sample for the systematic review included 1258 controls and 996 HR individuals. No significant differences were detected between HR individuals and controls in the selected ROIs: striatum, amygdala, hippocampus, pituitary and frontal lobe. The HR group showed increased grey matter volume compared with patients with established bipolar disorder. The HR individuals showed increased neural response in the left superior frontal gyrus, medial frontal gyrus and left insula compared with controls, independent from the functional magnetic resonance imaging task used. There were no publication biases. Sensitivity analysis confirmed the robustness of these results.
Limitations: As the included studies were cross-sectional, it remains to be determined whether the observed neurofunctional and structural alterations represent risk factors that can be clinically used in preventive interventions for prodromal bipolar disorder.
Conclusion: Accumulating structural and functional imaging evidence supports the existence of neurobiologic trait abnormalities in individuals at genetic risk for bipolar disorder at various scales of investigation.

Submitted June 30, 2011; Revised Sept. 26, Oct. 11, 2011; Accepted Oct. 13, 2011.

Competing interests: None declared for P. Fusar-Poli, O. Howes and S. Borgwardt. A. Bechdolf declares having received speaker fees from Bristol Meyers Squibb, Lilly and Wyeth.

Contributors: P. Fusar-Poli designed the study, acquired the data and wrote the article. All authors analyzed the data, reviewed the article and approved its publication.

DOI: 10.1503/jpn.110061

Correspondence to: P. Fusar-Poli, Department of Psychosis Studies, Institute of Psychiatry, De Crespigny Park 16, SE58AF London, United Kingdom;