Potential of pretreatment neural activity in the visual cortex during emotional processing to predict treatment response to scopolamine in major depressive disorder.
BACKGROUND
The need for improved treatment options for patients with major depressive disorder (MDD) is critical. Faster-acting antidepressants and biomarkers that predict clinical response will facilitate treatment. Scopolamine produces rapid antidepressant effects and thus offers the opportunity to characterize potential biomarkers of treatment response within short periods.


OBJECTIVE
To determine if baseline brain activity when processing emotional information can predict treatment response to scopolamine in MDD.


METHODS
A double-blind, placebo-controlled, crossover study together with repeated functional magnetic resonance imaging, acquired as participants performed face-identity and face-emotion working memory tasks.


METHODS
National Institute of Mental Health Division of Intramural Research Programs.


METHODS
Fifteen currently depressed outpatients meeting DSM-IV criteria for recurrent MDD and 21 healthy participants, between 18 and 55 years of age.


METHODS
The magnitude of treatment response to scopolamine (percentage of change in the Montgomery-Asberg Depression Rating Scale score between study end and baseline) was correlated with blood oxygen level-dependent (BOLD) signal associated with each working memory component (encode, maintenance, and test) for both identity and emotion tasks. Treatment response also was correlated with change in BOLD response (scopolamine vs baseline). Baseline activity was compared between healthy and MDD groups.


RESULTS
Baseline BOLD response in the bilateral middle occipital cortex, selectively during the stimulus-processing components of the emotion working memory task (no correlation during the identity task), correlated with treatment response magnitude. Change in BOLD response following scopolamine administration in overlapping areas in the middle occipital cortex while performing the same task conditions also correlated with clinical response. Healthy controls showed higher activity in the same visual regions than patients with MDD during baseline.


CONCLUSIONS
These results implicate cholinergic and visual processing dysfunction in the pathophysiology of MDD and suggest that neural response in the visual cortex, selectively to emotional stimuli, may provide a useful biomarker for identifying patients who will respond favorably to scopolamine.


BACKGROUND
clinicaltrials.gov Identifier: NCT00055575.
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. mfurey@mail.nih.gov
Maura L
ML
Furey
Wayne C
WC
Drevets
Elana M
EM
Hoffman
Erica
E
Frankel
Andrew M
AM
Speer
Carlos A
CA
Zarate
D000328:Adult; D016022:Case-Control Studies; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D004644:Emotions; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D012601:Scopolamine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014793:Visual Cortex / Q000503:physiopathology*
D018680:Cholinergic Antagonists; D012601:Scopolamine