Is depression modulating brain metabolism in migraine? Insights from proton magnetic resonance spectroscopy of the left dorsolateral prefrontal cortex

Objectives: Migraine commonly co-occurs with major depressive disorder (MDD). The dorsolateral prefrontal cortex (DLPFC) is central to cognitive processing, emotional regulation, and pain modulation. Although chronic migraine and MDD may share neurobiological underpinnings, these remain insufficiently defined. Metabolite profiling in the DLPFC could elucidate shared pathophysiological mechanisms and support biomarker development for precision management. This study aimed to compare brain metabolite levels in patients with migraine with and without depression using proton magnetic resonance spectroscopy (1H-MRS) to explore neuromodulation targets in the left DLPFC. Materials and Methods: Patients with migraine only (Group A; n = 27) and migraine with comorbid depression (Group B; n = 30) were recruited from neurology and psychiatry outpatient services at a tertiary care hospital. Comorbid psychiatric conditions were excluded, and depression severity was assessed using the Inventory of Depressive Symptomatology-Clinician Rated. A single-voxel 1H-MRS scan targeting the left DLPFC was performed using a 3.0 Tesla scanner. Results: Mean metabolite ratios for Group A and B were N-acetyl aspartate (NAA)/total creatine (tCr) (1.79 ± 0.48 vs. 1.79 ± 0.52), choline (Cho)/tCr (0.90 ± 0.40 vs. 0.96 ± 0.28), and myo-inositol (mI)/tCr (0.42 ± 0.26 vs. 0.42 ± 0.30). No significant differences were observed between groups: NAA/tCr (t = 0.22, P = 0.983), Cho/tCr (W = 686, P = 0.121), and mI/tCr (W = 854, P = 0.798). Conclusion: No significant differences in left DLPFC metabolite levels were found between migraine patients with and without comorbid depression. These findings suggest similar neurometabolic profiles in this region within the current sample and methodological limitations. Further studies with larger samples and advanced imaging are needed to clarify the DLPFC’s role in the shared pathophysiology and its potential as a neuromodulation target.