A Multi-Dimensional and Integrative Approach to Examining the High-Risk and Ultra-High-Risk Stages of Bipolar Disorder

Abstract

BackgroundValidating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies.MethodsWe followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8–28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes.FindingsCompared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual–spatial, and general function were impaired in the UHR offspring but not in the HR offspring.InterpretationThe abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.

Obesity and frontal‐striatal brain structures in offspring of individuals with bipolar disorder: Results from the global mood and brain science initiative

“…Lower cerebellar volumes have been previously reported . We previously found decreased GM volumes in the right cerebellum in asymptomatic offspring compared to controls using another neuroimaging analytical method (ie voxel‐based morphometry) with a smaller sample size, but not in symptomatic offspring vs controls . Conversely, functional and neurochemical abnormalities have also been documented in at‐risk populations .…”

“…A detailed description of the assessment procedures for the REI‐PBD study is available elsewhere . Briefly, REI‐PBD participants underwent in‐depth and systematic assessments and were prospectively followed up.…”

Aberrant brain structural–functional connectivity coupling in euthymic bipolar disorder

“…The current study forms part of the ongoing Recognition and Early Intervention on Prodromal BDs project, initiated by the Global Mood and Brain Science Initiative (Lin et al, 2015;Lin et al, 2017;Mansur et al, 2018;McIntyre et al, 2017). This study was approved by the Institutional Review Board of the Guangzhou Brain Hospital.…”

BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative

“…The analysis herein was conducted using data from the Recognition and Early Intervention on Prodromal Bipolar Disorders (REI‐PBD) study by the Guangzhou Brain Hospital research team and the Global Mood and Brain Science Initiative. The primary aims of the REI‐PBD were to validate the early stages preceding full‐blown BD and to assess the effectiveness of aerobic exercise as an early intervention in individuals with ultra‐high‐risk for BD without current or past diagnosis of BD (ClinicalTrials.gov Identifier: NCT01863628).…”

“…Participants underwent in‐depth and systematic assessments and were prospectively followed up . The Schedule for Affective disorders and Schizophrenia for school‐aged Children‐Present and Lifetime version (K‐SADS‐PL) or the SCID‐I/P (for participants older than 18 years) was utilized to screen for psychiatric disorders.…”