Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease |
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| Affiliation: | 1. Service de Psychiatrie, CHU de Bicêtre, HUPS, APHP, France;2. Inserm UMR-S 1180 – Cardiovascular pathways and Physiopathology, LabEx LERMIT - DHU TORINO - Institut Paris-Saclay d''Innovation Thérapeutique, France;3. Faculté de Pharmacie, Université Paris-Sud, France;4. INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, France;5. CHU Rangueil, Toulouse, France;6. Dispositif Territorial de Recherche et de Formation (DTRF) Paris-Sud, France;7. INSERM U1178, Team "Depression and antidepressants", CESP, Univ. Paris-Sud, 94275, Le Kremlin Bicêtre, France;1. Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran;2. Neuroscience Research Centre, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran;3. Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran |
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| Abstract: | Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression and aggression scores resulted in depressed/nondepressed (AD + D/AD − D) and aggressive/nonaggressive (AD + Agr/AD − Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E), and respective metabolites were determined using reversed-phase high-performance liquid chromatography. Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD + D compared with AD − D. In AD + Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA to 5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in the hippocampus were significantly decreased compared with AD − Agr. These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD. |
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| Keywords: | Alzheimer's disease Dementia Neuropsychiatric symptoms (NPS) Depression Aggression Neurochemistry Biogenic amines and metabolites Brain tissue |
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