Limbic and cortical regions as functional biomarkers associated with emotion regulation in bipolar disorder: A meta-analysis of neuroimaging studies

Bipolar disorder (BD) is a psychiatric disorder characterized by episodes of depression and mania, associated with impaired emotion processing. Several functional MRI (fMRI) studies have been used to investigate the structural and functional alteration in BD. Here, we aim to investigate the current fMRI findings of brain activation during emotion-regulation tasks between BD patients and healthy controls (HC).A systematic search through PubMed database for fMRI studies on bipolar patients and HC yielded 685 studies. We performed an activation likelihood estimation (ALE) on 21 studies for emotion regulation in BD patients and HC. Furthermore, we performed subgroup analyses for task performances in response time and accuracy between bipolar patients and HC.The total sample included 21 fMRI studies, comprising 543 BD patients, compared to 565 HC. ALE maps for emotion-related tasks showed hyperactivation in BD patients in the caudate, amygdala, precentral gyrus, middle frontal gyri, and sub-gyrus. Whereas hypoactivation was seen in the inferior frontal gyrus and anterior cingulate gyrus.We could not apply a correction for p-value thresholds, as it needs large number of foci. Second, functional abnormalities were investigated for adult BD patients only, as BD patients have functional differences correlated with age.Our results showed that limbic and cortical regions can represent a potential biomarker for the diagnosis and management of BD, by showing clustered brain regions of abnormal patterns of increased activation between BD patients and HC.