Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use

Abstract

BACKGROUND: Bipolar disorder (BD) is a highly heritable psychiatric disorder characterized by episodes of manic and depressed mood states and associated with cortical brain abnormalities. Although the course of BD is often progressive, longitudinal brain imaging studies are scarce. It remains unknown whether brain abnormalities are static traits of BD or result from pathological changes over time. Moreover, the genetic effect on implicated brain regions remains unknown. METHODS: Patients with BD and healthy control (HC) subjects underwent structural magnetic resonance imaging at baseline (123 patients, 83 HC subjects) and after 6 years (90 patients, 61 HC subjects). Cortical thickness maps were generated using FreeSurfer. Using linear mixed effects models, we compared longitudinal changes in cortical thickness between patients with BD and HC subjects across the whole brain. We related our findings to genetic risk for BD and tested for effects of demographic and clinical variables. RESULTS: Patients showed abnormal cortical thinning of temporal cortices and thickness increases in visual/somatosensory brain areas. Thickness increases were related to genetic risk and lithium use. Patients who experienced hypomanic or manic episodes between time points showed abnormal thinning in inferior frontal cortices. Cortical changes did not differ between diagnostic BD subtypes I and II. CONCLUSIONS: In the largest longitudinal BD study to date, we detected abnormal cortical changes with high anatomical resolution. We delineated regional effects of clinical symptoms, genetic factors, and medication that may explain progressive brain changes in BD. Our study yields important insights into disease mechanisms and suggests that neuroprogression plays a role in BD.

Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal cortex

“…Cortical thickness is a widely used measure of cortical in tegrity in controls and in pathological conditions, [39][40][41][42] includ ing bipolar disorder. [5][6][7]43,44 For this reason, and because the largest crosssectional study on bipolar disorder to date spe cifically found abnormalities in cortical thickness but not sur face area, 5 we used cortical thickness as the primary structural measure in the present study. Given that cortical volume is a function of cortical thickness and surface area -2 phenotyp ically and genetically distinct measures 45,46 -we performed separate analyses on cortical surface area and cortical volume for completeness.…”

Sex Differences in Lifespan Trajectories and Variability of Human Sulcal and Gyral Morphology

“…Reduced cortical thickness and progressive thinning has been consistently found in schizophrenia and they seem to be associated with worsening of clinical symptoms and prognosis (20,51). It remains to be elucidated whether biological mechanisms underpinning differing trajectories of cortical thickness development in healthy females and males may also underlie some of the sex differences in the epidemiology and clinical presentation of psychotic and other mental disorders (52,53).…”

Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders

“…Few studies have focused on the effects of atypical antipsychotic on age-related cortical structural changes. Previous studies found greater age-related loss of cortical structures in SZ and BD patients than in HC but were unable to comprehensively examine the influence of antipsychotics (Cropley et al, 2017;Abe et al, 2020). Most studies indicate the absence of antipsychotic effects in the age-related trajectory of cortical measures (Cropley et al, 2017;Altamura et al, 2018), while some show the presence of antipsychotic effects (van Haren et al, 2011).…”