Association between dorsolateral prefrontal N-acetyl aspartate and depression in chronic back pain: an in vivo proton magnetic resonance spectroscopy study

Most studies of pain, including chronic pain, agree that depression and pain are interrelated, although the neurobiology of this relationship remains unknown. Neuroimaging studies suggest a specific role of the prefrontal brain regions in the mechanisms of mood disorders and chronic pain. The present study examines the interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left dorsolateral prefrontal cortex [DLPFC], orbitofrontal cortex, cingulate and thalamus), depression (as measured by the Beck Depression Inventory), and pain (as measured by short form of the McGill Pain Questionnaire) in 10 chronic back pain (CBP) patients with depression, and compared to the relationship between regional brain NAA levels and depression in 10 normal subjects (sex and age-matched). Reduction of NAA levels was demonstrated in the right DLPFC of CBP patients with depression, as compared to the normal controls (p < 0.02, two-tailed t-test). The depression levels in CBP patients were highly correlated with NAA levels in the right DLPFC (r = -0.99, p < 0.0001), and were unrelated to the other studied regional NAA in both groups, including the right DLPFC in normal subjects (p < 10(-6); comparing the difference between r values in the right DLPFC between the two groups). The pain levels in CBP patients were also associated with the right DLPFC (r = -0.62, p < 0.05), although these relationships were much weaker as compared to depression-NAA correlations (p < 0.0001; comparing the difference between r values). The interrelationships between NAA across brain regions were examined using correlation analysis, which detected different connectivity patterns between CBP patients with depression and normal subjects. These findings provide evidence for a stronger association of prefrontal NAA to depression than to pain in CBP, which may reflect the common neurobiological substrate underlying these conditions in CBP patients. Spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the depression and pain measures might be used for segregation of their circuitries in the chronic pain brain.