Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Abstract

Objectives We aimed to compare concentrations of N-acetyl aspartate, myo-inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at-risk offspring prior to the onset of mania. Methods A total of 22 children and adolescents aged 9–17 years with a familial risk for bipolar I or II disorder [at-risk offspring with non-bipolar I disorder mood symptoms (AR)], and 25 healthy controls (HC) were examined using proton magnetic resonance spectroscopy at 3T to study metabolite concentrations in an 8-cc voxel in the cerebellar vermis. Results Decreased myo-inositol and choline concentrations in the vermis were seen in the AR group compared to HC (p < 0.01). Conclusions Decreased cellular metabolism and interference with second messenger pathways may be present in the cerebellar vermis in youth at risk for BD as evident by decreased myo-inositol and choline concentrations in this region. These results may be limited by a cross-sectional design, co-occurring diagnoses, and medication exposure. Longitudinal studies are necessary to determine whether early neurochemical changes can predict the development of mania. Improved methods for identifying children with certain neurochemical vulnerabilities may inform preventive and early intervention strategies prior to the onset of mania.

Prospective neurochemical characterization of child offspring of parents with bipolar disorder

“…Thus, metabolite ratios could be influenced by changes in Cr over time, affecting the results. However, we did not find statistically significant group differences in creatine either at baseline or follow-up assessments, or in our previous studies (Singh et al, 2010; Singh et al, 2011). As MRS technology evolves, our understanding of neurochemical substrates of bipolar illness will further refine to be able to draw more definitive conclusions regarding specific neurometabolite markers.…”

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

“…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 . Interestingly, a study found that increased cerebellar volume was a marker of resilience, as it has been noted to be greater in healthy relatives of individuals with BD when compared to individuals with BD, symptomatic BD probands, and HCs .…”

Posterior cerebellar vermal deficits in bipolar disorder

“…Likewise, several neuroimaging studies, using region-of-interest based measurements, have specifically evaluated cerebellar volumes in BD patients although the issues on the regional specificity of cerebellar volume abnormalities have not yet been resolved (DelBello et al, 1999; Brambilla et al, 2001; Mills et al, 2005; Monkul et al, 2008; Womer et al, 2009; Baldacara et al, 2011). Furthermore, neurochemical aberrations as evidenced by decreased myo-insoitol and choline concentrations have been reported in the cerebellar vermis of the high-risk youth for BD (Singh et al, 2011). A recent voxel-based morphometry (VBM) finding that temporal lobe volume reduction in BD patients is correlated with decreased cerebellar gray matter volume (Moorhead et al, 2007) may also corroborate a potential interconnective involvement of these brain areas in the pathophysiology of BD.…”