Supplementary Material for: Frontal Cortex Myo-Inositol Is Associated with Sleep and Depression in Adolescents: A Proton Magnetic Resonance Spectroscopy Study

<p><b><i>Aim:</i></b> This study used proton magnetic resonance spectroscopy (<sup>1</sup>H MRS) to evaluate the neurochemistry of the frontal cortex in adolescents with symptoms of sleep and depression. <b><i>Methods:</i></b> Nineteen non-medicated adolescent boys (mean age 16.0 years; 9 clinical cases with depression/sleep symptoms and 10 healthy controls) underwent <sup>1</sup>H MRS at 3 T. MR spectra were acquired from the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex, and frontal white matter. Concentrations of N-acetyl aspartate, total creatine, choline-containing compounds, total glutamine plus glutamate, and myo-inositol (mI) were compared in the 2 subgroups, and correlated with sleep and clinical measures in the total sample. Sleep was assessed with self-report questionnaires and ambulatory polysomnography recordings. <b><i>Results:</i></b> Concentrations of mI were lower in both frontal cortical regions among the depressed adolescents than in controls. No statistically significant differences in other metabolite concentrations were observed between the subgroups. Frontal cortex mI concentrations correlated negatively with depression severity, subjective daytime sleepiness, insomnia symptoms, and the level of anxiety, and correlated positively with total sleep time and overall psychosocial functioning. The correlations between mI in the ACC and total sleep time as well as daytime sleepiness remained statistically significant when depression severity was controlled in the analyses. <b><i>Conclusion:</i></b> Lower frontal cortex mI may indicate a disturbed second messenger system. Frontal cortical mI may thus be linked to the pathophysiology of depression and concomitant sleep symptoms among maturing adolescents. Short sleep and daytime sleepiness may be associated with frontal cortex mI independently from depression.</p>