407. Altered prefrontal-thalamic neuronal integrity in bipolar I disorder

Abstract

Evidence from structural MRI and PET studies suggests that bipolar I disorder involves localized abnormalities in fronto-subcortical circuits regulating mood. Therefore, N-acetylaspartate (NAA; a neuronal/axonal marker) was measured by proton magnetic resonance spectroscopic imaging (1H MRSI) in the dorsolateral prefrontal cortex (DLFPC), prefrontal white matter, and thalamus bilaterally to determine whether there was evidence for altered neuronal integrity (neuronal loss or dysfunction) in prefrontal-thalamic pathways. Eleven medicated euthymic bipolar I disorder patients (diagnosed by DSM-IV criteria) and 11 normal control subjects underwent MRI and 1H MRSI using a Siemens VISION MRI/MRS system. MRI imaging sequences included T1 weighted scout views along with coronal MP RAGE and axial DSE images. Multi-slice 1H MRSI (TR/TE = 1960/135 ms; 280 × 280 mm2 FOV providing 8 × 8 mm2 in plane resolution) was acquired using 3 parallel slices along the same orientation as the DSE. Using in-house spectroscopic imaging display software, individual MRSI voxels (1.5 ml) were selected for spectral analysis in comparable regions bilaterally in the DLPFC, prefrontal white matter, and thalamus. Tissue enclosed in each MRSI voxel was also analyzed for amounts of gray matter, white matter, hyperintense white matter, and CSF using in-house software (SICORE) in order to obtain tissue volume corrected NAA concentration estimates. Repeated measures ANOVA revealed that compared to the control group, the patients with bipolar I disorder demonstrated: 1) decreased DLPFC NAA bilaterally (p = 0.0004), 2) decreased prefrontal white matter NAA bilaterally (p = 0.0014), 3) increased thalamic NAA bilaterally (p = 0.01), and 4) no significant group or lateralized differences in voxel tissue composition for any of the regions studied. Thus, the NAA alterations in the bipolar group were not due to any differences in voxel tissue heterogeneity between groups. The DLFPC reduction in NAA suggests neuronal loss/dysfunction whereas the observed prefrontal white matter NAA reduction is evidence for compromised axonal integrity that may result in functional disconnection of prefrontal-thalamic pathways. Increased thalamic NAA may represent neuronal hypertrophy, neuronal hyperplasia, or abnormal synaptic/dendritic pruning. The results definitely suggest that neuronal/axonal integrity of DLFPC-thalamic pathways is abnormal in bipolar I disorder.