Biological correlates of agitation in severe mental disorders

Abstract

Agitation is a state of restlessness and excessive psychomotor activity accompanied by anxiety, irritability, and impaired impulse control. Despite that agitation is a particularly challenging clinical feature, therapeutic options are limited, and its biological correlates are largely unknown. The aim of the thesis was to identify biological correlates of agitation in severe mental disorders, focusing on feasibly accessible blood-sampling based markers with putative links to agitation. In a cross-sectional sample of patients with bipolar or schizophrenia spectrum disorder, linear and logistic regressions were applied to test associations between agitation and systemic biological markers (i.e., circulating immune markers and cholesterol). Additionally, associations between impulsivity and psychopharmacotherapy were examined. The main findings include an association between agitation and circulating interleukin-18 binding protein, whereas the other investigated immune markers and circulating cholesterol did not show any significant associations with agitation. Furthermore, lithium treatment was associated with lower impulsivity, whereas antidepressant treatment was associated with higher impulsivity. These core findings add to the growing but complex evidence-base of immune system disturbances in severe mental disorders and somewhat challenge the previous indications of links between systemic cholesterol and agitation. Specifically, the findings indicate interleukin-18 binding protein as a part of the biological correlate of agitation, which warrants future clinical studies to address the source and regulation of this immune signal related to agitation. However, the paucity of associations to circulating markers of immune activation suggest that other factors contribute to agitation. Additionally, the cross-sectional associations between psychopharmacotherapy and impulsivity warrant further studies to replicate the findings and determine causal directionality.