The Shape of Things to Come: Brain Structure and Response to Lithium in Bipolar Disorder

Posted on:February 19, 2020
Last Updated: October 9, 2020
Time to read: 3 minutes

This article is based on the presentation by Dr Letizia Squarcina (IRCCS “E. Medea” Scientific Institute, Lecco, Italy) at RCPsych2019.

The Response to Lithium Network [R-LiNK] initiative aims to identify a predictive biomarker for lithium long-term response and tolerance, a personalized approach to treatment, improved monitoring of lithium exposure, and improved patient adherence to therapy. At the moment, there is no biomarker available to identify patients who will respond to lithium, or if lithium is the best therapy for an individual. 

The University of Milan as an R-LINK consortium member is responsible for the MRI work package to investigate the connectivity and neuroplastic changes in patients with bipolar disorder treated with lithium.  

On enrolment, patients undertake an MRI examination and provide a blood sample before the initiation of lithium therapy. After 12 weeks, the MRI examination and blood sample are repeated, and patients are closely monitored during a three-year follow-up with monthly interviews and a self-monitoring device where a smartphone app will store data. 

MRI plays a crucial role in identifying brain signatures for bipolar disorder related to brain structure or metabolism, and in this project, MRI is used to identify a brain biomarker for treatment efficacy in bipolar disorder through detection of changes in brain volume, diffusion in white matter tracts, and metabolite concentrations.  

T1-weighted images in bipolar disorder have consistently found reduced brain volume, enlarged ventricles, decreased volume in the corpus callosum, and reduced cortical thickness and volume, particularly in the frontal, temporal and parietal areas.[Rimol et al. 2010] 

Meta-analyses show that volumes of grey matter, hippocampus and amygdala increased when the proportion of bipolar patients taking lithium increased. [Kempton et al. 2008], [Hallahan et al. 2011], [Sun et al. 2018] The remodeling action of lithium on the hippocampus may be due to dendrite growth, glia cell production, increased neurogenesis, and reduced apoptosis. 

Learn More: Neuroprotective action of Lithium

Imaging studies produce results at a group level, whereas a clinical decision for a patient is taken on an individual basis.

However, despite great interest in MRI, it has had little impact on clinical practice within psychiatry. We know that lithium has a normalizing effect on brain volumes, structures, and connections, and the ability to provide personalized treatment for individuals is of utmost importance.