A longitudinal functional magnetic resonance imaging study of verbal working memory in depression after antidepressant therapy.
BACKGROUND
Impairments in the neural circuitry of verbal working memory are evident in depression. Factors of task demand and depressive state might have significant effects on its functional neuroanatomy.


METHODS
Two groups underwent functional magnetic resonance imaging while performing a verbal working memory task of varying cognitive load (n-back). The patient group comprised 20 medication-free individuals in an acute episode of unipolar major depression and the control group comprised 20 healthy individuals. Scans were acquired at weeks 0 (baseline), 2, and 8. Patients received treatment with fluoxetine after the baseline scan. Cerebral activations were measured for mean overall activation as well as the linear and quadratic load-response activity with increasing task demand (1-, 2-, 3-back).


RESULTS
There were no significant differences in performance accuracy between groups. However, a main effect of group was observed in the load-response activity in frontal and posterior cortical regions within the verbal working memory network in which patients showed a greater load-response relative to control subjects. Group by time effects were revealed in the load-response activity in the caudate and thalamus. As a marker of treatment response, a lower linear load-response at baseline in the dorsal anterior cingulate, left middle frontal, and lateral temporal cortices was associated with an improved clinical outcome.


CONCLUSIONS
Maintenance of performance accuracy in patients was accompanied by a significant increase in the load-response activity in frontal and posterior cortical regions within the verbal working memory network. These data also provide further support for resilience of activity in the anterior cingulate as a predictor of treatment response in depression.
Walsh
Nicholas D
ND
Institute of Psychiatry, King's College London, De Crespigny Park, 103 Denmark Hill, London, UK.
Williams
Steven C R
SC
Brammer
Michael J
MJ
Bullmore
Edward T
ET
Kim
Jieun
J
Suckling
John
J
Mitterschiffthaler
Martina T
MT
Cleare
Anthony J
AJ
Pich
Emilio Merlo
EM
Mehta
Mitul A
MA
Fu
Cynthia H Y
CH
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002421:Caudate Nucleus / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology*; D017352:Echo-Planar Imaging; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D013788:Thalamus / Q000473:pathology; D014705:Verbal Behavior
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine