Abstract
RationaleAnorexia nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. There are no established pharmacological treatments and the neurobiology of the condition is poorly understood. Previous studies using magnetic resonance spectroscopy (MRS) have shown that AN may be associated with reductions in indices of brain glutamate; however, at conventional field strengths (≤3 T), it is difficult to separate glutamate from its precursor and metabolite, glutamine.ObjectivesThe objective of the present study was to use high field (7 T) MRS to measure concentrations of glutamate, in three separate brain voxels, in women with AN.MethodsWe studied 13 female participants with AN and 12 healthy female controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen. Neurometabolites were calculated using the unsuppressed water signal as a reference and corrected for individual cerebrospinal fluid concentration in the voxel.ResultsWe found that participants with AN had significantly lower concentrations of glutamate in all three voxels (mean reduction 8%, p = 0.002) but glutamine levels were not altered. Concentrations of N-acetylaspartate, creatine, GABA and glutathione were also unchanged. However, inositol was lower in AN participants in anterior cingulate (p = 0.022) and occipital cortex (p = 0.002).ConclusionsWomen with AN apparently have widespread reductions in brain glutamate. Further work will be needed to assess if this change has pathophysiological relevance or whether it is a consequence of the many physical changes produced in AN by food restriction.
Highlights
Anorexia nervosa (AN) is a serious mental illness with a high morbidity and mortality
Inositol was lower in AN participants in anterior cingulate (p = 0.022) and occipital cortex (p = 0.002)
Four magnetic resonance spectroscopy (MRS) spectra were excluded due to their quality, leaving 11 AN participants and 10 controls who had valid glutamate and glutamine data for all three brain regions The repeated measures analysis of variance (ANOVA) for glutamate showed a main effect of diagnosis (F = 13.7; df = 1.19; p = 0.002) but no interaction with region (F = 0.053; df = 2.19; p = 0.95) indicating a reduction of glutamate in AN participants in all three voxels (Fig. 2)
Summary
Anorexia nervosa (AN) is a serious mental illness with a high morbidity and mortality. Glutamate is the main excitatory neurotransmitter in brain and is implicated in a number of psychiatric disorders relevant to AN, including depression and obsessive compulsive disorder (Yüksel and Öngür 2010; Naaijen et al 2015). It is Psychopharmacology (2017) 234:421–426 possible to measure glutamate concentrations in the brain noninvasively with magnetic resonance spectroscopy (MRS) but at conventional field strengths, there is difficulty distinguishing glutamate from its precursor and metabolite, glutamine. The availability of MRS at 7 Tesla (7 T) permits clear separation of glutamate and glutamine resonances as well as a more precise quantification of neurometabolites (Tkáč et al 2009)
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