title: The effect of antidepressant treatment on N-acetyl aspartate levels of medial frontal cortex in drug-free depressed patients.
abstract: The medial frontal cortex has been shown to modulate emotional behavior and stress responses, suggesting that the dysfunction of this region may be involved in the pathogenesis of depressive symptoms. The present study was performed to determine whether there was any effect of antidepressant treatment on the metabolite levels in the left medial frontal cortex as measured by proton magnetic resonance spectroscopy in depressed patients. Twenty patients diagnosed as having major depressive disorder according to DSM-IV and 18 healthy volunteer subjects were included in the study. Twelve of patients had their first episode and were drug-naïve. Other depressed patients were drug-free for at least 4 weeks. The severity of depression was assessed by HAM-D and Clinical Global Impression Scale-Severity (CGI-S). Single voxel, 8 cm(3), 1H MR spectra of left medial frontal cortex was acquired both before and following antidepressant treatment. The concentrations and ratios of N-acetyl aspartate (NAA), Creatine+Phosphocreatine (Cr+PCr) and Choline (Cho) were measured. Pretreatment NAA/Cr values of patients were lower than those of healthy controls, but this difference did not reach to statistically significant levels (t=1.83, df=36, p=0.07). However, antidepressant treatment had significant effect on NAA/Cr ratios (groupxtreatment interaction: F=9.93 df=1,36, p=0.03). After the treatment, NAA/Cr values of patients increased significantly compared to pretreatment values (t=3.32, df=19, p=0.004). No significant difference was observed between the post-treatment NAA/Cr values of patients and those of controls (t=1.64, df=36, p=0.19). Correlation analysis detected negative correlation between pretreatment CGI-S scores and NAA/Cr ratios (r=-0.51, p=0.02). This preliminary result suggests that there might be a possible defect in the neuronal integrity in the left medial frontal cortex (mainly left anterior cingulate cortex) of depressed patients. Antidepressant treatment with its neurotrophic effects might play a positive role in restoring the neuronal integrity. Further studies are needed to support these initial findings.
authors.affiliation: Department of Psychiatry Affective Disorders Unit, Ege University, School of Medicine, 35100 Izmir, Turkey. ali.saffet.gonul@med.ege.edu.tr
authors.forename: Ali Saffet
authors.initials: AS
authors.lastname: Gonul
authors.forename: Omer
authors.initials: O
authors.lastname: Kitis
authors.forename: Erol
authors.initials: E
authors.lastname: Ozan
authors.forename: Fisun
authors.initials: F
authors.lastname: Akdeniz
authors.forename: Cagdas
authors.initials: C
authors.lastname: Eker
authors.forename: Ozlem Donat
authors.initials: OD
authors.lastname: Eker
authors.forename: Simavi
authors.initials: S
authors.lastname: Vahip
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male
chemical_list: D000928:Antidepressive Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline