Peripheral and Central Metabolites Affecting Depression, Anxiety, Suicidal Ideation, and Anger in Complex Regional Pain Syndrome Patients Using a Magnetic Resonance Spectroscopy: A Pilot Study

Abstract

Objective This study investigated peripheral and central metabolites affecting depression, anxiety, suicidal ideation, and anger in complex regional pain syndrome (CRPS) patients. Methods Metabolite levels were determined in the right and left thalamus and insula, in 12 CRPS patients using magnetic resonance spectroscopy (MRS). Results There were positive correlations between valine (Val)/tNAA (N-acetylaspartate+N-acetylaspartylglutamate) and the anxiety, and a negative correlation between glutamine (Gln)/NAA and the depression. There were positive correlations between alanine (Ala)/Gln and the depression and suicidal ideation, between glutamate (Glu)/Gln and the depression and suicidal ideation, between N-acetylaspartylglutamate (NAAG)/Gln and the depression. There was a positive correlation between Ala/NAAG and the trait anger and a negative correlation between creatine (Cr)/N-acetylaspartate (NAA) and the trait anger. There was a negative correlation between Cr/Glx (Glu+Gln) and the trait anger. High hemoglobin and alkaline phosphatase were associated with low pain levels, but CO2 and chloride showed positive correlations with pain levels in CRPS patients. Peripheral glucose, CO2 and chloride were associated with depression, anxiety, anger and suicidal ideation. Conclusion The specific central and peripheral metabolites were associated with psychological disorders including depression, anxiety, suicidal ideation and anger in CRPS patients, showing pathological interactions between a painful body and mind.

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

“…Furthermore, using functional imaging, in vivo clinical data provides direct evidence of altered glutamate concentrations in emotional dysregulation. Most studies reported elevated glutamate levels across different brain regions in subjects with anxiety disorders [ 22 , 23 , 24 , 25 , 26 ], while one study found positive correlations between glutamate levels and anxiety symptoms [ 27 ]. However, others reported lower glutamate concentrations in the anterior cingulate cortex (ACC) in participants with anxiety disorders [ 28 ], and a negative correlation between glutamate concentrations in ACC and the anxiety symptoms [ 29 ].…”

Scores of peripheral neuropathic pain predicting long-term mortality in patients with type 2 diabetes: A retrospective cohort study

“…Alterations in the function and structure of the brain were observed in patients with DPN. N-acetyl aspartate was decreased in the thalamus of patients with DPNP (46), and reduced inhibition of central nervous system might be associated with psychological comorbidities (47)(48)(49). A decrease in serum brain-derived neurotrophic factor (BDNF), a neurotrophin family member, is associated with peripheral neuropathy in patients with type 2 diabetes (50).…”

Metabolomic Biomarkers in Anxiety Disorders

“…Central and peripheral metabolites in patients with complex regional pain syndrome were analyzed for their association with psychological disorders, including anxiety [ 85 ]. Specific associations were observed, which might show pathological interactions between a painful body and increases in anxiety in this population.…”

“…As lower NAA levels have been observed in patients with complex regional pain syndrome before, neuronal cell death may affect anxiety symptoms in this population [ 86 , 87 ]. In addition, peripheral CO 2 was positively associated with anxiety, which might be explained by an increase in sensory pain levels due to increased partial CO 2 pressure causing a synergistic boost of neuropsychiatric symptoms, such as anxiety [ 85 ].…”