Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.
Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.
Brody
A L
AL
UCLA Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute and Hospital, Los Angeles, CA 90024, USA. abrody@ucla.edu
Saxena
S
S
Silverman
D H
DH
Alborzian
S
S
Fairbanks
L A
LA
Phelps
M E
ME
Huang
S C
SC
Wu
H M
HM
Maidment
K
K
Baxter
L R
LR
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D011379:Prognosis; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D017374:Paroxetine