The Biology of Aggressive Behavior in Bipolar Disorder: A Systematic Review

Aggressive behavior (AB) represents a public health concern often associated with severe psychiatric disorders. Although most psychiatric patients are not aggressive, untreated psychiatric illness, including bipolar disorder (BD), may associate with an increased risk of AB. Accurate predictive models of AB are still lacking and it is crucial to delineate AB biomarkers state of the art in BD. We performed a systematic review according to PRISMA guidelines to identify biological correlates of AB in BD. Final results included 20 studies: 10 involving genetic and 10 other biological AB biomarkers (total sample size N = 5,181). Our results pointed to a serotoninergic hypoactivation in violent suicidal BD patients. Similarly, BD violent suicide attempters had a blunted hypothalamic-pituitary-adrenal (HPA) activity. Violent behavior in BD was associated with a chronic inflammatory state. While the role of lipids as biomarkers for AB remains equivocal, uric acid appears as a potential biomarker for hetero-AB in BD. Available data can be useful in the fulfill of specific biomarkers of AB in BD, ultimately leading to the development of accurate predictive models.