Linda M Bonnekoh1,2,3, Stephanie Seidenbecher1, Katrin Knigge1, Anne-Kathrin Hünecke1, Coraline D Metzger1,4, Claus Tempelmann5,6, Martin Kanowski5, Jörn Kaufmann5, Gabriela Meyer-Lotz1, Konstantin Schlaaff1,7, Henrik Dobrowolny1, Leonardo Tozzi1,8, Dorothee M Gescher1,9, Johann Steiner1,7, Clemens Kirschbaum10, Thomas Frodl1,6,9. 1. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany. 2. Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany. 3. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Münster, Münster, Germany. 4. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. 5. Department of Neurology, Otto von Guericke University, Magdeburg, Germany. 6. Center of Behavioral Brain Sciences (CBBS), Otto von Guericke Universität Magdeburg, Magdeburg, Germany. 7. Translational Psychiatry Laboratory, Otto von Guericke University, Magdeburg, Germany. 8. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. 9. Department of Psychiatry and Psychotherapy, University RWTH, Aachen, Germany. 10. Department of Psychology, Dresden University of Technology, Dresden, Germany.
Abstract
OBJECTIVES: Major Depression (MDD) and anxiety disorders are stress-related disorders that share pathophysiological mechanisms. There is evidence for alterations of glutamate-glutamine, N-acetylaspartate (NAA) and GABA in the anterior cingulate cortex (ACC), a stress-sensitive region affected by hypothalamic-pituitary-adrenal axis (HPA). The aim was to investigate metabolic alterations in the ACC and whether hair cortisol, current stress or early life adversity predict them. METHODS: We investigated 22 patients with MDD and comorbid anxiety disorder and 23 healthy controls. Proton magnetic resonance spectroscopy was performed with voxels placed in pregenual (pg) and dorsal (d) ACC in 3 T. Analysis of hair cortisol was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The N-acetylaspartate/Creatin ratio (NAA/Cr) was reduced in patients in both pgACC (p = .040) and dACC (p = .016). A significant interactive effect of diagnosis and cortisol on both pg-NAA/Cr (F = 5.00, p = .033) and d-NAA/Cr (F = 7.86, p = .009) was detected, whereby in controls cortisol was positively correlated with d-NAA/Cr (r = 0.61, p = .004). CONCLUSIONS: Our results suggest a relationship between NAA metabolism in ACC and HPA axis activity as represented by long-term cortisol output.
OBJECTIVES: Major Depression (MDD) and anxiety disorders are stress-related disorders that share pathophysiological mechanisms. There is evidence for alterations of glutamate-glutamine, N-acetylaspartate (NAA) and GABA in the anterior cingulate cortex (ACC), a stress-sensitive region affected by hypothalamic-pituitary-adrenal axis (HPA). The aim was to investigate metabolic alterations in the ACC and whether hair cortisol, current stress or early life adversity predict them. METHODS: We investigated 22 patients with MDD and comorbid anxiety disorder and 23 healthy controls. Proton magnetic resonance spectroscopy was performed with voxels placed in pregenual (pg) and dorsal (d) ACC in 3 T. Analysis of hair cortisol was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The N-acetylaspartate/Creatin ratio (NAA/Cr) was reduced in patients in both pgACC (p = .040) and dACC (p = .016). A significant interactive effect of diagnosis and cortisol on both pg-NAA/Cr (F = 5.00, p = .033) and d-NAA/Cr (F = 7.86, p = .009) was detected, whereby in controls cortisol was positively correlated with d-NAA/Cr (r = 0.61, p = .004). CONCLUSIONS: Our results suggest a relationship between NAA metabolism in ACC and HPA axis activity as represented by long-term cortisol output.