title: Ventromedial prefrontal spectroscopic abnormalities over the course of depression: a comparison among first episode, remitted recurrent and chronic patients.
abstract: Structural and neuropathological alterations in the ventromedial prefrontal cortex (vmPFC) described in depression (MDD) might become even more pronounced over the course of illness. Measurement of brain metabolites by means of Magnetic Resonance spectroscopy (MRS) can indirectly deliver information about glial and neuronal integrity or potential cellular loss. The aim of this study was to investigate whether Glutamate (Glu), Choline (Cho) and total N-acetylaspartate (total-NAA) levels in the vmPFC differed among MDD patients in distinct stages of illness and healthy controls. We hypothesized that high-past illness-burden would represent more metabolite abnormalities independently of mood state. A 3-Tesla MR facility was used to measure these metabolites in vmPFC of 45 depressive patients (10 first-episode-MDD, 16 remitted-recurrent-MDD and 19 chronic-MDD) and 15 healthy controls. Multivariate and correlation analyses were carried out to explore the influence of duration of illness, age at onset and mood-state. Levels of Glu were significantly decreased in remitted-recurrent and chronic patients compared with both first-episode and controls (up to 28% mean reduction; p < 0.001, Cohen's d = 2.88) and were negatively correlated with illness duration (r = -0.56; p < 0.001). Cho levels showed an opposite pattern: highest values were detected in chronic patients, correlating positively with duration of illness (r = 0.32; p = 0.03). Total-NAA levels were significantly lowered in remitted-recurrent and chronic patients, which were associated with an earlier age at onset (r = 0.50; p = 0.001). Our data suggest that abnormalities in Glu, Cho and total-NAA levels are consistently related to the course of MDD, supporting the hypothesis that cellular changes would take place in vmPFC over time.
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica, Sant Antoni M(a) Claret, 167, 08025 Barcelona, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Portella
authors.forename: Javier
authors.initials: J
authors.lastname: de Diego-Adeliño
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gómez-Ansón
authors.forename: René
authors.initials: R
authors.lastname: Morgan-Ferrando
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vives
authors.forename: Dolors
authors.initials: D
authors.lastname: Puigdemont
authors.forename: Rosario
authors.initials: R
authors.lastname: Pérez-Egea
authors.forename: Jordi
authors.initials: J
authors.lastname: Ruscalleda
authors.lastname: Enric Álvarez
authors.forename: Víctor
authors.initials: V
authors.lastname: Pérez
mesh_terms: D000328:Adult; D017668:Age of Onset; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D002794:Choline