Lithium Affects Cortical and Subcortical Volume in Bipolar Depressed Patients

• Gray and white matter volumetric increases can be seen after only six weeks of lithium monotherapy • Such improvements can be seen in younger, less severe patients and a low serum lithium concentration • Despite clinical shifts towards second-generation antipsychotics as first line mood stabilizers, expanding the use of lithium into demographics represented in this study may have underappreciated benefits in long-term neuronal preservation Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients’ lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics.