SUPPLEMENTAL MATERIAL
This document describes two supplementary analyses of the data:
1) A mixed effects ANOVA model comprising a main effect of group, a main effect
of time, and the group x time interaction, with right or left amygdala coupling
separately treated as the dependent variable was fitted at each voxel. Factorial effects
on right or left amygdala coupling were tested by a cluster-level permutation test with
P < 0.005 so that the expected number of false positive clusters was less than one per
map.
The maps of the group x time interaction confirm that the right prefrontal cortex is the
main locus of a group difference in time-related change of left amygdala coupling.
There was no significant group x time effect on coupling of right amygdala. In Fig S1,
we illustrate the compatibility of this result with that previously reported by fitting an
ANOVA model comprising a main effect of group, a main effect of side (right or left
amygdala), and the group x side interaction, with time-related difference in right or
left amygdala coupling as the dependent variable.
Figure S1: Comparison of the results from two different ANOVA models
showing similar changes in functional coupling of the amygdala after
antidepressant treatment.
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Top panel: ANOVA maps shown in the main text (see Figure 2) based on a group x
side ANOVA model that was specified to include a main effect of group (with 2
levels: control and depressed groups), a main effect of side (with 2 levels: left and
right amygdala), and a group x side interaction. The dependent variable is the value of
functional coupling of the amygdala at week 0 subtracted from the value at week 8
(see Methods). These two rows show the anatomical locations of a main effect of
group on time-related change in amygdala coupling. A significantly greater timerelated increase in functional coupling of the left amygdala to these regions (e.g., right
prefrontal and anterior cingulate cortex) was shown in depressed patients treated with
antidepressant medication over the course of 8 weeks.
Bottom panel: ANOVA maps based on a group x time ANOVA model that was
specified to include a main effect of group (with 2 levels: control and depressed
groups), a main effect of time (with 2 levels: week 0 and week 8), and a group by time
interaction. This model was separately fit for left and right amygdale coefficients at
each voxel. There was a significant group x time interaction in the right caudate, right
insula, bilateral middle frontal cortex, right superior frontal gyrus, and midcingulate.
These regions showed increased functional coupling with the left amygdala in
depressed patients after treatment. There was no significant interaction for the right
amygdala.
Results from both models are consistent with the hypothesis that antidepressant
treatment was associated with significantly increased coupling between right frontal
regions and (specifically) left amygdala.
2) Direct between-group comparisons, by independent t-tests, of right or left
amygdala coupling at week 0 and week 8. Loci of significant differences were
identified by means of a cluster-level permutation test identical to the method used in
the ANOVA analysis (see Methods).
Functional coupling of the left amygdala was decreased in depressed patients
compared to matched healthy controls at baseline in hippocampus, contralateral
amygdala, putamen, insula, parahippocampus, inferior, middle and superior temporal
cortices, inferior and middle frontal cortices. Functional coupling of the right
amygdala was decreased in depressed patients compared to healthy controls at
baseline in hippocampus, contralateral amygdala, putamen, insula, parahippocampus,
inferior, middle and superior temporal cortices, inferior and middle frontal cortices,
lingual gyrus, fusiform gyrus and cerebellum. No regions showed greater functional
coupling of the bilateral amygdala in depressed patients compared to healthy controls
at baseline. There was no significant difference between depressed and control groups
in functional coupling of the amygdala after treatment.
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Figure S2: Functional coupling of the right and left amygdala was significantly
decreased (blue voxels) in depressed patients compared to healthy controls
before treatment (week 0). There were no loci of significant between-group
difference in amygdala coupling at week 8, suggesting that antidepressant
treatment normalises functional coupling of the amygdala in patients.
Supplementary information is available at the Neuropsychopharmacology website
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