Neural response to emotional stimuli associated with successful antidepressant treatment and behavioral activation.
BACKGROUND
Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states.


OBJECTIVE
To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task.


METHODS
Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40-60 mg/day) and olanzapine (5-12.5mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week.


RESULTS
There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings.


CONCLUSIONS
Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.
Departments of Pharmaceutical Sciences and Neuroscience, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University Health Network, Toronto, Ontario, Canada. Electronic address: sidney.kennedy@uhn.ca.
Sakina J
SJ
Rizvi
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada.
Tim V
TV
Salomons
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada.
Jakub Z
JZ
Konarski
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Jonathan
J
Downar
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Peter
P
Giacobbe
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Roger S
RS
McIntyre
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Sidney H
SH
Kennedy
D000328:Adult; D000339:Affect; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001526:Behavioral Symptoms; D001569:Benzodiazepines / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D004338:Drug Combinations; D004644:Emotions; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
D000928:Antidepressive Agents; D004338:Drug Combinations; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines
Antidepressant combination; Biomarker; Emotional processing; Major depressive disorder; Response; fMRI