publication of the American College of Neuropsychopharmacology." href="AL_get(this,%20'jour',%20'Neuropsychopharmacology.');">Neuropsychopharmacology.
2010 Mar 10. [Epub ahead of print]
Cingulate Desynchronization and Functional Connectivity with the
Amygdala During a Working Memory Task Predict Rapid Antidepressant
Response to Ketamine.
Experimental Therapeutics, Mood and
Anxiety Disorders Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD, USA.
Pregenual anterior cingulate
cortex (pgACC) hyperactivity differentiates treatment responders from
non-responders to various pharmacological antidepressant interventions,
including ketamine, an N-methyl-D-aspartate receptor antagonist.
Evidence of pgACC hyperactivition during non-emotional working memory
tasks in patients with major depressive disorder (MDD) highlights the
importance of this region for processing both emotionally salient and
cognitive stimuli. However, it is unclear whether pgACC activity might
serve as a potential biomarker of antidepressant response during working
memory tasks as well, in line with previous research with emotionally
arousing tasks. This study tested the hypothesis that during the N-back
task, a widely used working memory paradigm, low pretreatment pgACC
activity, as well as coherence between the pgACC and the amygdala, would
be correlated with the clinical improvement after ketamine.
Magnetoencephalography (MEG) recordings were obtained from 15 drug-free
patients with MDD during working memory performance 1 to 3 days before
receiving a single ketamine infusion. Functional activation patterns
were analyzed using advanced MEG source analysis. Source coherence
analyses were conducted to quantify the degree of long-range functional
connectivity between the pgACC and the amygdala. Patients who showed the
least engagement of the pgACC in response to increased working memory
load showed the greatest symptomatic improvement within 4 h of ketamine
administration (r=0.82, p=0.0002, false discovery rate (FDR) <0.05).
Pretreatment functional connectivity between the pgACC and the left
amygdala was negatively correlated with antidepressant symptom change
(r=-0.73, p=0.0021, FDR <0.05).These data implicate the pgACC and its
putative interaction with the amygdala in predicting antidepressant
response to ketamine in a working memory task
.Neuropsychopharmacology advance online publication, 10 March