Abstract
Myo-inositol, a second messenger glucose isomer and glial marker, is potentiated by melatonin. In addition to common abnormalities in melatonin regulation, depressive disorders have been associated with reduced myo-inositol in frontal structures. This study examined associations between myo-inositol in the anterior cingulate cortex and the timing of evening melatonin release. Forty young persons with unipolar depression were recruited from specialized mental health services (20.3 ± 3.8 years old). Healthy controls were recruited from the community (21.7 ± 2.6 years old). The timing of dim light melatonin onset (DLMO) was estimated using salivary melatonin sampling. Myo-inositol concentrations (MI/CrPCr ratio) in the anterior cingulate cortex were obtained using proton magnetic resonance spectroscopy. After controlling for age, sex, and CrPCr concentration the depression group had significantly lower MI/CrPCr ratios than healthy controls [F(4, 75) = 11.4, p = 0.001]. In the depression group, later DLMO correlated with lower MI/CrPCr ratio (r = −0.48, p = 0.014). These findings suggest that neurochemical changes in the frontal cortex are associated with circadian disruptions in young persons with depression.
Highlights
While disruptions in circadian rhythms have long been proposed to play a role in mood disorders, little is known about how they relate to the neurobiology of depression
The present findings suggest that some neurochemichal alterations in young people with depression may be associated with circadian disruptions and sleep difficulties
Decreased levels of myo-inositol in the anterior cingulate cortex (ACC), a cortical region highly involved in emotional regulation, were found to correlate with later dim light melatonin onset (DLMO) and more severe “insomnia” symptoms on the Hamilton Rating Scale for Depression (HRSD)
Summary
While disruptions in circadian rhythms have long been proposed to play a role in mood disorders, little is known about how they relate to the neurobiology of depression. Depression is often accompanied by reduced myo-inositol in the anterior cingulate cortex (ACC) and neighboring prefrontal regions, a phenomenon thought to reflect glial loss or dysfunctions (Coupland et al, 2005). Myo-inositol production and glial cell survival are both actively promoted by melatonin, a hormone closely involved in circadian rhythms (Popova and Dubocovich, 1995; Borlongan et al, 2000). Myo-inositol production may be affected by the circadian disruptions commonly occurring in depression. Since inositol trisphosphate receptors are involved in circadian entrainment (Hamada et al, 1999), depression-related changes in myo-inositol could possibly affect melatonin rhythms.
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