Bipolar disorder (BD) is characterised by emotional dysregulation; relatives of BD patients have a high rate of affective symptoms, and therefore abnormalities in emotional information processing are likely to be part of the genetic predisposition to BD. Examination of unaffected siblings of patients with BD can contribute to determining features of the BD phenotype which are related to familial predisposition as opposed to disease expression.

To identify the neural correlates of facial affect recognition in BD patients and their unaffected siblings.

Event-related functional magnetic resonance imaging (fMRI) EPI data was collected with a 1.5T scanner. Blood oxygenation level-dependent (BOLD) data was obtained from 41 BD type I patients, 22 of their unaffected siblings and 51 matched healthy controls during recognition of fearful, angry and sad facial expressions. A random effects analysis was implemented using SPM5 (http://www.fil.ion.ucl.ac.uk/spm).

BD patients showed reduced prefrontal cortex (PFC) activation, when compared to controls and siblings, with evidence of differentiation in location and laterality of activation maxima across different facial expressions. Regardless of valence, patients showed reduced extrastriate cortex activation. During angry faces, when compared to controls, siblings showed reduced activation in posterior cingulate gyrus, and during sad faces, enhanced activation in left ventral PFC and right parahippocampal gyrus.

Dorsolateral PFC (BA47) activation may represent a marker for genetic risk for BD. During sad faces, siblings showed greater activation of this region than HC, whilst BD patients showed reduced activation. This is consistent with previous findings implicating this region in BD.