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Supplemental Text
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Results
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Comorbidities and index traumas
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In addition to the major depression comorbidities discussed in the main
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text, we noted the following current and historical diagnoses. For the PTSD
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group, current diagnoses included panic disorder (3) and bulimia (2). Past
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diagnoses included major depression (2), panic disorder (2), alcohol dependence
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(3), benzodiazepine dependence (1) and marijuana dependence (1). For the
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GAD group, the primary comorbidity was social anxiety disorder (7), social
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anxiety and panic disorder (2), dysthymia (2), social anxiety and obsessive
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compulsive disorder (1), panic disorder (1) and obsessive compulsive disorder
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with bulimia (1). Historical diagnoses included major depression (7), alcohol
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dependence (5) and panic disorder (2).
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Index traumas for the PTSD group included interpersonal violence (6),
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motor vehicle accident (4), combat (3), childhood sexual abuse (2), rape (1) and
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natural disaster (1). No GAD patients who reported criterion A traumas that in
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any way explain their symptomatology were included in the study.
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Effects of potential motion-related confounds in resting-state data
It has recently been recognized that motion during resting-state scans can
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lead to spurious significant results in functional connectivity analyses(Power et
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al., 2012; Van Dijk et al., 2012). To examine whether this may confound some of
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our connectivity differences between groups we carried out two additional
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analyses. First, we looked for an effect of group on the six calculated motion
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parameters, but found no significant differences (F-test p’s>0.26). Second, we
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conducted functional connectivity analyses within a network that we did not
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expect to change across groups, namely from left to right auditory cortex. The
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anatomical distance between these regions is comparable to most of the long-
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range connections between which connectivity has been found to be affected by
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motion confounds in prior work(Power et al., 2012; Van Dijk et al., 2012). As
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predicted, we found no group differences in left-right auditory cortical connectivity
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(p’s>0.09).
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Hippocampal volume analyses
Patients with PTSD have previously been found to have smaller
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hippocampal volumes, mostly with the structure as a whole (Bremner et al.,
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1995; Karl et al., 2006), but evidence exists for a more localized abnormality as
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well (Bonne et al., 2008; Vythilingam et al., 2005). We therefore examined
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whether changes in gray matter volume within the hippocampus, as measured by
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VBM analyses, may contribute to the functional connectivity abnormalities
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observed in our PTSD cohort. VBM analyses indicated that there were no gray
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matter volume difference for the whole hippocampus between patients and
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healthy controls (“common deficit hypothesis”; F1,91=2.35, p>0.13), nor between
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PTSD patients, and either GAD patients or healthy controls (“disorder-specific
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deficit hypothesis”; versus GAD, F1,54=0.64, p>0.43; versus HC, F1,53=0.57,
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p>0.45). Similarly, we found no gray matter volume difference for the posterior
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subdivision specifically (patient versus control: F1,91=0.9, p>0.35; PTSD versus
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GAD, F1,54=0.38, p>0.54; PTSD versus HC, F1,53=0.17, p>0.68). Furthermore, the
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abnormality of posterior hippocampus functional connectivity to pgACC and PCC
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in PTSD patients (compared to the other 2 groups) remained statistically
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significant, even when controlling for subjects’ hippocampal gray matter volume
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(data not shown). Thus, PTSD-specific impairments in posterior hippocampal
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connectivity are not due to volumetric differences, at least not as measured by
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VBM.
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Effects of comorbid depression in the PTSD and GAD cohorts
Anxiety disorders are also highly comorbid with major depression,
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epidemiologically(Kessler et al., 2005a; Kessler et al., 2005b; Kessler et al.,
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1995), as well as in our study sample (12 of 17 PTSD; 23 of 39 GAD patients
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have major depression). We therefore examined whether depression comorbidity
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contributes to the observed connectivity abnormality in posterior hippocampus
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found in PTSD patients. Overall, the average posterior hippocampal connectivity
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with either the PCC or pgACC did not significantly differ as a function of
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depression comorbidity in GAD or PTSD (For PCC: GAD patients, t(37)=1.04,
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p>0.3; PTSD, t(15)=0.026, p>0.98; For pgACC: GAD, t(37)=0.79, p>0.44; PTSD,
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t(15)=0.014, p>0.99). When depression comorbidity was further entered as a
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covariate, all main findings remained as well, such that there was a PTSD-
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specific abnormality in posterior hippocampal connectivity and task-induced
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deactivations.
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Figure Legends
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Supplemental Figure 1. Connectivity “targets” of the hippocampus subdivisions,
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as defined by an independent cohort. Maps of differential connectivity from
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healthy cohort #1, at p<0.05 uncorrected, were used to define a priori
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connectivity “targets” of each subdivision - Targets of the posterior hippocampus
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(red), and targets of the anterior hippocampus (blue). pgACC, pregenual anterior
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cingulate cortex; PCC, posterior cingulate cortex; dACC/pre-SMA, pre-
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supplementary motor area/dosal anterior cingulate cortex.
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Supplemental Figure 2. Voxelwise group difference maps for analyses reported
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for a priori hippocampal network ROIs in the main text, shown here at p<0.05
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(uncorrected) for visualization and completeness. Maps of group differences in
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connectivity for the posterior hippocampus (A) or anterior hippocampus (B).
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Similarly, (C) group differences in task-independent deactivation.
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Supplemental Figure 1.
dACC/PreSMA
Precuneus
PCC
pgACC
(X=0)
Amygdala
Striatum
(Y=-2)
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(Y=6)
Post. Targets
Ant. Targets
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Supplemental Figure 2.
A
GAD > PTSD
B
C
Posterior Hippocampus
Connectivity
Healthy > PTSD
Anterior Hippocampus
Connectivity
Healthy > GAD
Healthy > PTSD
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Task-independent
Deactivation
GAD > PTSD
Healthy > PTSD
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