Summary: | (1) Background: Recently, a series of clinical neuroimaging studies on fibromyalgia (FM) have shown a reduction in cortical volume and abnormally high glutamate (Glu) and glutamate + glutamine (Glx) levels in regions associated with pain modulation. However, it remains unclear whether the volumetric decreases and increased Glu levels in FM are related each other. We hypothesized that higher Glu levels are related to decreases in cortical thickness (CT) and volume in FM patients. (2) Methods: Twelve females with FM and 12 matched healthy controls participated in a session of combined 3.0 Tesla structural magnetic resonance imaging (MRI) and single-voxel MR spectroscopy focused on the thalami and ventrolateral prefrontal cortices (VLPFC). The thickness of the cortical and subcortical gray matter structures and the Glu/Cr and Glx/Cr ratios were estimated. Statistics included an independent <i>t</i>-test and Spearman’s test. (3) Results: The Glu/Cr ratio of the left VLPFC was negatively related to the CT of the left inferior frontal gyrus (pars opercularis (<i>p</i> = 0.01; <i>r</i> = −0.75) and triangularis (<i>p</i> = 0.01; <i>r</i> = −0.70)). Moreover, the Glx/Cr ratio of the left VLPFC was negatively related to the CT of the left middle anterior cingulate gyrus (<i>p</i> = 0.003; <i>r</i> = −0.81). Significantly lower CTs in FM were detected in subparts of the cingulate gyrus on both sides and in the right inferior occipital gyrus (<i>p <</i> 0.001). (4) Conclusions: Our findings are in line with previous observations that high glutamate levels can be related, in a concentration-dependent manner, to the morphological atrophy described in FM patients.
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