The British Journal of Psychiatry (2017)
210, 6774. doi: 10.1192/bjp.bp.115.164020
Cortical thickness in obsessivecompulsive
disorder: multisite mega-analysis of 780 brain
scans from six centres
Jean-Paul Fouche, Stefan du Plessis, Coenie Hattingh, Annerine Roos, Christine Lochner,
Carles Soriano-Mas, Joao R. Sato, Takashi Nakamae, Seiji Nishida, Jun Soo Kwon, Wi Hoon Jung,
David Mataix-Cols, Marcelo Q. Hoexter, Pino Alonso, OCD Brain Imaging Consortium,*
Stella J. de Wit, Dick J. Veltman, Dan J. Stein and Odile A. van den Heuvel
Background
There is accumulating evidence for the role of fronto-striatal
and associated circuits in obsessivecompulsive disorder
(OCD) but limited and conflicting data on alterations in
cortical thickness.
Aims
To investigate alterations in cortical thickness and subcortical
volume in OCD.
Method
In total, 412 patients with OCD and 368 healthy adults
underwent magnetic resonance imaging scans. Between-
group analysis of covariance of cortical thickness and
subcortical volumes was performed and regression analyses
undertaken.
Results
Significantly decreased cortical thickness was found in the
OCD group compared with controls in the superior and
inferior frontal, precentral, posterior cingulate, middle
Obsessivecompulsive disorder (OCD) is characterised by
intrusive thoughts (obsessions) and repetitive behaviours
(compulsions). It is a fairly common mental disorder affecting
13% of the adult population over the course of a lifetime1 and
it is associated with significant personal impairment and socio-
economic burden.2 Current models of OCD are based on animal
laboratory work and human imaging studies, and emphasise the
importance of frontostriatal networks. Meta-analyses of voxel-
based morphometry (VBM) studies have found altered volumes
in frontal and striatal regions, and in a broader range of
structures, including parietal and limbic brain areas.3,4 A recent
VBM mega-analysis on pooled raw magnetic resonance imaging
(MRI) data from our multisite OCD Brain Imaging Consortium
(OBIC), revealed significantly smaller volumes of frontal grey
matter and white matter bilaterally, as well as group6age inter-
actions in frontostriatal and limbic regions.5 Of particular interest
in the meta-analyses and VBM mega-analysis is the finding of
decreased grey matter volume in the dorsomedial prefrontal
cortex,6,7 a region responsible for performance monitoring and
emotional processing, processes which are affected in OCD.8
Although we performed a VBM analysis on this data previously,
other techniques such as surface-based methods can provide
complementary information. Whereas VBM measures grey matter
volume or density, surface-based methods such as FreeSurfer can
calculate morphometric attributes in the native space of the
participant, and allow a determination of cortical thickness.9
*See online supplement DS1 for details of the members of the Consortium.
temporal, inferior parietal and precuneus gyri. There was
also a group6age interaction in the parietal cortex, with
increased thinning with age in the OCD group relative to
controls.
Conclusions
Our findings are partially consistent with earlier work,
suggesting that group differences in grey matter volume and
cortical thickness could relate to the same underlying
pathology of OCD. They partially support a frontostriatal
model of OCD, but also suggest that limbic, temporal and
parietal regions play a role in the pathophysiology of the
disorder. The group6age interaction effects may be the
result of altered neuroplasticity.
Declaration of interest
None.
Copyright and usage
B The Royal College of Psychiatrists 2017.
In addition, segmentation in VBM is suboptimal for some
subcortical areas, such as pallidum and thalamus, because of the
lack of clear greywhite contrast of these structures. FreeSurfer
performs segmentation of whole subcortical structures and
therefore it is not dependent on the contrast difference between
tissue classes.10
Recently, OCD studies have been investigating surface-based
measures such as cortical thickness. Studies have found decreased
thickness in frontostriatal regions such as the orbitofrontal,
inferior and middle frontal cortex, insula and anterior cingulate
cortex.1114 In addition, thinning in parietal and temporal regions
was also evident in some studies.11,13,15 In contrast to these
reports, some studies have reported greater thickness in OCD in
regions of the right inferior frontal cortex, posterior middle
temporal gyrus and right inferior parietal gyrus.16,17 Inconsistent
cortical thickness findings in the literature can perhaps be
attributed to the clinical heterogeneity of the samples. For
example, in many of these studies the patients were already on
medication and/or presented with comorbid depression. In
smaller samples such as these, it is usually difficult to account
for all possible confounders and therefore a mega-analysis is the
ideal method to address these issues. The present study aimed
to address the limitations of previous cortical thickness research
on OCD, by pooling the structural MRI data from 412 patients
with OCD and 368 healthy controls that were collected from six
academic OCD centres across three continents (Asia, Europe
and South America), participating in OBIC.5 This should provide
sufficient sample size to potentially study smaller alterations in
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Fouche et al
cortical thickness in a range of regions, and to examine the effects
of clinical factors such as symptom severity, medication use and
OCD symptom dimensions on cortical thickness and subcortical
volumes, as well as relevant demographic considerations, such as
between-group variance in age-related brain changes. Also,
compared with meta-analyses, mega-analyses ensure the
application of a common protocol, thus excluding the variability
that different computing platforms or preprocessing strategies
can introduce across studies. We hypothesised that consistent with
previous VBM meta-analyses and other OCD cortical thickness
studies, there would be cortical thinning in the frontal regions.
Given the differences in segmentation between VBM and
FreeSurfer, we also expected FreeSurfer to be more sensitive to
volume changes in areas such as the putamen, pallidum and
thalamus.3,4,7Also, because of the variability in grey matter volume
results between paediatric and adult patients with OCD,3,7 we
expected to find group6age interactions in frontostriatal regions.
Additionally, associations of cortical thickness changes with OCD
severity and symptom dimensions were expected as previous
studies have shown that YaleBrown Obsessive-Compulsive Scale
(YBOCS)18 and symptom dimensions correlate with frontal and
parietal thickness in patients with OCD.12,14,15 Finally, given the
significant variability in previous cortical thickness studies,
potentially as a result of comorbid anxiety/depressive disorders
as well as medication use, additional analyses were performed,
excluding patients on medication and with lifetime comorbid
anxiety or depression.
Method
Participants and data processing
Data were obtained from six sites as part of the OBIC. The cohort
has been described in detail previously.5 Participants were
screened for DSM-IV Axis I disorders19 and exclusion criteria were
aged under 18 and above 65, current psychotic disorder, recent
history of a substance use disorder, intellectual disability and
severe organic or neurological pathology. Other psychiatric
comorbidity was allowed if OCD was the primary diagnosis.
The complete sample consisted of 412 patients with OCD (the
OCD group) and 368 healthy controls (control group).
The collected 780 1.5 Tesla T1-weighted MRI scans were
transferred and processed with FreeSurfer V4.5 (http://
surfer.nmr.mgh.harvard.edu) on the Nehalem cluster at the Centre
for High Performance Computing (CHPC), Rosebank, Cape
Town, South Africa. The standard processing pipeline known as
recon-all has been described and validated previously.20 In short,
T1-weighted images were normalised, bias-field corrected and
skull-stripped. Inner and outer cortical surfaces were modelled
as triangular tessellation. Cortical thickness measurements were
obtained by calculating the distance (in mm) between pial and
greywhite matter surfaces at each vertex location.20 These
surfaces were then normalised to the fsaverage template included
with FreeSurfer by using a curvature matching technique, allowing
vertex-wise comparison of cortical thickness across participants.9
In addition, data were smoothed with a Gaussian kernel of
10 mm full-width at half maximum. For subcortical structures,
the brain was segmented into volume-based labels utilising
probabilistic methods. After reconstruction, each individual scan
was visually inspected for large errors in segmentation and
manually corrected if necessary.
Subcortical regions were parcellated in FreeSurfer to obtain
volumes for all the major subcortical regions, namely hippo-
campus, amygdala, putamen, pallidum, caudate, thalamus and
nucleus accumbens for each hemisphere. Total intracranial volume
68
was extracted from FreeSurfer and used for brain size correction
by utilising the proportion method for each of the subcortical
regions.21
Statistical analysis
Vertex-wise analyses were performed on cortical thickness data
with FreeSurfers mri glmfit software. Subcortical mean volumes
were imported into SPSS 20.0. For both the cortical thickness
and subcortical volumes, group effects were investigated by
utilising a general linear model (GLM) with age, gender, scan
sequence and level of education as covariates. In addition, post
hoc analyses were performed to determine whether there was an
interaction of scan sequence with main group effects between
the control and OCD groups (see online supplement DS2 and
online Tables DS13). To investigate the effects of age and group6
age interactions, we used both linear and quadratic models of age
as regressors in the analysis. In addition to the main group
comparison and the group6age interaction, the neural correlates
of clinical variability within the patient group were assessed.
Multiple regression analyses were performed to investigate the
effects of OCD severity and symptom dimensions within the
OCD group. The analysis was also repeated after excluding (a)
patients with OCD on medication, (b) patients with comorbid
anxiety and (c) patients with comorbid depression in turn (see
Results and online supplement DS3 and online Tables DS47).
In addition, within the OCD group the influence of medication
status and the presence of lifetime anxiety disorder(s) or major
depressive disorder on cortical thickness and subcortical volumes
were studied (see online supplements DS47 and online Tables
DS810 for details on these analyses).
Data-sets for these regression analyses were selected based on
the availability of clinical information. Covariates of no interest
included age, gender, sequence and level of education, as well as
total YBOCS18 score as indication of illness severity in the case
of the symptom dimension analysis. All cortical thickness analyses
were corrected with 10 000 Monte-Carlo simulations (P50.05)
using Freesurfers mri_glmfit software. SPSS subcortical analyses
were Bonferroni corrected with an a of P50.0036 for the 14
regions-of-interest (7 regions per hemisphere) when examining
main group effects.
In order to confirm whether group differences were not
confounded by group differences in age, gender, education and
ethnicity, the analysis was repeated in a smaller sample group that
were matched for these attributes (see de Wit et al 5 for further
details on how these groups were matched).
Results
Sample characteristics
The OCD (n = 412) and control (n = 368) groups were matched
on gender, handedness and ethnicity. However, patients were
significantly older (OCD group 32.1 years (s.d. = 9.6); control
group 30.2 years (s.d. 9.3), t = 2.9, P = 0.004) and had a lower level
of education (OCD group 13.7 years (s.d. = 2.8); control group
14.6 years (s.d. = 3.1), t = 74.0, P50.001) than the control group.
The OCD group had a mean YBOCS score of 24.9 (s.d. = 6.2) and
a mean age of clinical onset of 20.1 years (s.d. = 8.7). See de Wit
et al,5 online supplement DS2 and online Table DS11 for further
details on the demographic and clinical characteristics of the total
sample, as well as the age-, gender, education and ethnicity-
matched sample (n = 329 patients with OCD and n = 316 healthy
controls).
 Cortical thickness in obsessivecompulsive disorder

Group comparisons
The cortical thickness in the OCD group compared with healthy
controls was significantly decreased in the superior (left hemi-
sphere z = 5.515, P50.0001; right hemisphere: z = 2.368,
P = 0.0179) and inferior frontal (right hemisphere: z = 3.060,
p = 0.0022), precentral (right hemisphere: z = 3.354, P = 0.0008),
posterior cingulate (left hemisphere: z = 3.288, P = 0.0010), middle
temporal (right hemisphere: z = 3.959, P = 0.0001), inferior parie-
tal (left hemisphere: z = 4.259, P50.0001) and precuneus gyri
(right hemisphere: z = 3.781, P = 0.0002) (see Table 1 and Fig.
1). The OCD group, compared with the control group, also
showed decreased volume of the hippocampus (left hemisphere:
F = 8.630, P = 0.0002; right hemisphere: F = 6.727, P = 0.0007)
(Table 2). After performing a post hoc analysis in the subsample
matched for age, gender, educational level and ethnicity, similar
findings were obtained (see online Tables DS1 and DS2). There
was also no significant sequence by diagnosis interaction for the
group comparisons (online supplement DS2). There were no
regions that showed significantly increased cortical thickness or
subcortical volume in the OCD group when compared with
healthy controls.
Group6interaction effects
There were no significant group6age interaction effects for
cortical thickness, nor were there significant group6age effects
for the subcortical volumes. However, the post hoc matched
sample analysis showed that compared with controls, the OCD
group have significant age-related cortical thinning of the left
inferior parietal gyrus (linear: z = 2.957, P = 0.0031, quadratic:
z = 3.197, P = 0.0014), in addition to quadratic age-related cortical
thinning of the right superior parietal gyrus (z = 2.355, P = 0.0185)
(see online Table DS3).
Association and exclusion of clinical variables
Disease severity
There was an association between increased disease severity
(YBOCS score) and decreased cortical thickness in the bilateral
lateral occipital gyrus (left hemisphere: z = 5.634, P50.0001;
right hemisphere: z = 73.984, P = 0.0001, see online Table DS12).
Comparison between controls and participants
in the OCD group not on psychotropic medication
Unmedicated participants in the OCD group (n = 222) compared
with healthy controls (n = 368) showed decreased cortical
thickness in the left superior frontal (z = 4.222, P50.0001), right
inferior frontal (z = 5.680, P50.0001), right precentral
(z = 3.771, P = 0.0002), right posterior cingulate (z = 5.639,
P50.0001) and bilateral middle temporal (left hemisphere:
z = 6.470, P50.0001; right hemisphere: z = 5.840, P50.0001) gyri
(online Table DS4). ANCOVA analyses of subcortical volumes
revealed no significant differences between the unmedicated
participants in the OCD group and healthy controls.

Table 1 Areas of decreased cortical thickness in the obsessivecompulsive disorder (OCD) group ( n = 412) compared with the
control group ( n = 368) a
Thickness, mm: mean (s.d.)
Local maxima Talaraich coordinates
Grey matter region and hemisphere Control group OCD group z-value P (x, y, z)

Frontal
Superior frontal
Left 3.1093 (0.2089) 3.0545 (0.2258) 75.515 50.0001 78.8, 26.6, 32.7
Right 2.9013 (0.2009) 2.8609 (0.2049) 72.368 0.0179 9.1, 36.1, 26.8
Inferior frontal, right 2.7068 (0.1697) 2.6593 (0.1714) 73.060 0.0022 50.1, 23.8, 16.3
Precentral right 2.6220 (0.1673) 2.5760 (0.1790) 73.354 0.0008 47.6, 5.2, 14.8
Parietal
Inferior parietal, left 2.4988 (0.1637) 2.4504 (0.1639) 74.259 50.0001 737.3, 757.1, 26.2
Posterior cingulate, left 2.5745 (0.1693) 2.5154 (0.1736) 73.288 0.0010 75.9, 714.1, 36.7
Precuneus, right 2.6424 (0.2421) 2.5751 (0.2395) 73.781 0.0002 7.0, 756.0, 17.8
Temporal
Middle temporal, right 2.7882 (0.1645) 2.7292 (0.1651) 73.959 0.0001 57.9, 742.7, 78.5

a. Results are shown at P50.05 corrected for multiple comparisons with Monte-Carlo simulations. Covariates of no interest in this analysis included scan sequence, level of
education, age and gender. No significant increases of cortical thickness in the OCD group compared with healthy controls were observed.

Fig. 1 Grey matter regions exhibiting decreases in cortical thickness for the obsessivecompulsive disorder group compared with the
control group with analysis of covariance.
Results are shown at P50.05 corrected for multiple comparisons with Monte-Carlo simulation. Covariates of no interest included scan sequence, level of education, age and gender.
The colour bar indicates the z-value at each vertex. LH, left hemisphere; RH, right hemisphere.

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Fouche et al

Table 2 Subcortical regional volumes in the obsessivecompulsive disorder group ( n = 412) compared with control group ( n = 368) a
Volume, mm3: mean (s.d.)
Subcortical region and hemisphere Control group OCD group F-value P

Basal ganglia total volume, left+right 38 087.3 (3984.2) 38 014.5 (3986.5) 0.093 0.761
Thalamus
Left 7361.8 (633.2) 7368.8 (642.7) 0.269 0.043
Right 7348.1 (544.9) 7309.4 (553.1) 2.093 0.011
Caudate
Left 3637.3 (371.2) 3662.4 (376.7) 0.418 0.037
Right 3653.4 (387.4) 3666.6 (393.2) 0.031 0.061
Putamen
Left 5841.7 (528.6) 5855.5 (536.5) 0.134 0.051
Right 5569.9 (497.8) 5615.2 (505.2) 0.044 0.060
Pallidum
Left 1740.8 (186.3) 1769.0 (189.1) 2.174 0.010
Right 1609.7 (203.7) 1644.6 (206.7) 3.178 0.005
Hippocampus
Left 4270.1 (361.2) 4205.2 (366.6) 8.630 0.0002**
Right 4357.6 (354.9) 4300.0 (360.2) 6.727 0.0007**
Amygdala
Left 1517.6 (159.1) 1524.3 (161.6) 0.029 0.061
Right 1598.0 (172.9) 1594.2 (175.4) 0.371 0.039
Accumbens-area
Left 597.4 (95.0) 591.4 (96.4) 0.734 0.028
Right 600.6 (91.6) 590.0 (92.9) 1.918 0.012

a. Results of the ANCOVA analysis between groups are shown here. Covariates of no interest in this analysis included scan sequence, level of education, age and gender.
**Results with P50.0036 (P50.05 Bonferroni corrected) were considered significant.

Comparison between controls and participants in the OCD group
without lifetime comorbid anxiety
Participants in the OCD group without lifetime comorbid anxiety
(n = 190) compared with healthy controls (n = 368) demonstrated
decreased cortical thickness in the right insula (z = 8.205,
P50.0001), right caudal middle frontal (z = 3.530, P = 0.0004), left
paracentral (z = 10.419, P50.0001) and right pericalcarine
(z = 12.531, P50.0001) gyri (online Table DS5). There was also
decreased volume of the bilateral hippocampus (left hemisphere:
F = 7.677, P50.001; right hemisphere: F = 5.057, P = 0.002) in the
OCD group compared with healthy controls (online Table DS7).
Comparison between controls and OCD group
without lifetime comorbid depression
Patients without lifetime comorbid depression (n = 287) compared
with healthy controls (n = 368) showed decreased cortical thickness
in the left superior frontal (z = 4.576, P50.0001), bilateral inferior
frontal (left hemisphere: z = 2.869, P = 0.0041; right hemisphere:
z = 3.516, P50.0004), left rostral middle frontal (z = 2.823,
P = 0.0048), right medial orbitofrontal (z = 3.240, P = 0.0012)
and left lateral occipital (z = 4.115, P50.0001) gyri (online Table
DS6). ANCOVA analyses of subcortical volumes revealed no
significant differences between the OCD group without depression
and healthy controls.
Symptom dimensions
Information on the presence/absence of specific OCD symptom
dimensions was available for 331 patients. The presence of five
symptom dimensions was assessed. These included the
aggressive/checking, contamination/cleaning, symmetry/ordering,
sexual/religious obsessions and hoarding subdimensions. A
dimension was considered as present if the patient has reported
a current or lifetime history of at least one of the symptoms. For
an overview of the results of the correlation analyses on symptom
dimensions, see online supplement DS8 and Table DS12. The
contamination/cleaning dimension was associated with increased
cortical thickness in the left lateral orbitofrontal (z = 5.840,
P50.0001), precentral (z = 4.109, P50.0001) and right frontal gyri
(z = 5.275, P50.0001). The hoarding dimension was associated with
increased cortical thickness in the bilateral inferior frontal gyri (left
hemisphere: z = 4.543, P50.0001; right hemisphere: z = 4.965,
P50.0001), left lateral orbitofrontal (z = 3.062, P = 0.0022), superior
parietal (z = 2.417, P = 0.0156), middle temporal (z = 3.256,
P = 0.0011) and lateral occipital gyri (z = 3.501, P = 0.0005), right
superior frontal (z = 6.088, P50.0001) and medial orbitofrontal
gyri (z = 4.012, P = 0.0001) and cuneus (z = 2.323, P = 0.0202).
The sexual/religious dimension was associated with increased
cortical thickness in the left isthmus cingulate (z = 4.802,
P50.0001), rostral middle frontal (z = 4.383, P50.0001), lateral
occipital (z = 4.035, P = 0.0001), right lateral orbitofrontal
(z = 2.558, P = 0.0105), superior parietal (z = 4.237, P50.0001),
supramarginal gyri (z = 3.183, P = 0.0015) and precuneus
(z = 2.959, P = 0.0031). The symmetry/order dimension was
associated with increased cortical thickness in left insular
(z = 5.263, P50.0001), lingual (z = 3.040, P = 0.0024), precentral
(z = 5.444, P50.0001) and postcentral gyri (z = 3.822,
P = 0.0001), as well as right medial orbitofrontal (z = 3.594,
P = 0.0003) and lateral occipital gyri (z = 3.729, P = 0.0002). It
was also associated with decreased cortical thickness in the right
superior temporal gyrus (z = 73.927, P = 0.0001). The aggression/
checking dimension was associated with increased cortical
thickness in the right lateral occipital gyrus (z = 2.924,
P = 0.0035), as well as lower entorhinal thickness (z = 73.930,
P = 0.0001). There were no significant positive or negative
association with subcortical volumes in the OCD group.
Discussion
Main findings
This FreeSurfer mega-analysis of multisite T1-weighted MRI scans
showed that patients with OCD exhibit decreased cortical

70

thickness in a number of frontoparietal regions. These included
the superior and inferior frontal gyri findings similar to
previous VBM meta-analyses and cortical thickness work. In
addition to other temporoparietal regions such as the precentral,
posterior cingulate, middle temporal, inferior parietal and
precuneus gyri. There was also limbic involvement as evidenced
by decreased hippocampal volume compared with healthy
controls. Another finding was a group6age interaction effect
for left parietal thickness suggesting that there is exaggerated
cortical thinning of the parietal gyri with advancing age and/or
illness duration in patients compared with controls.
The most notable finding in this FreeSurfer study, consistent
with the findings of our VBM mega-analysis,5 is the involvement
of the inferior frontal gyrus/operculum and superior frontal
gyrus/dorsomedial prefrontal cortex in OCD. This is important,
insofar as findings from smaller studies have been contra-
dictory.22,23 This finding in both the mega-analyses suggests that
cortical thinning and grey matter volume could relate to a similar
underlying pathological process responsible for abnormalities in
these regions. This finding was even more pronounced when
excluding patients on medication and with lifetime comorbid
anxiety and depression, indicating that it may be specific to
OCD. Cortical thinning in the inferior frontal gyrus and superior
frontal gyrus is also consistent with the findings of some previous
VBM studies7,22,24 and one cortical thickness study.11 Decreased
cortical thickness of the inferior frontal gyrus and superior frontal
gyrus may be involved in impairments of cognitive and emotional
control in OCD; the inferior frontal gyrus together with the
anterior insula is part of a circuit implicated in behavioural
inhibition and disgust-related responses.8 The inferior frontal
gyrus is also part of a network implicated in working memory
and emotion regulation,8 together with the interconnected
precentral and superior (including dorsomedial) frontal gyri, that
both show decreased cortical thickness in the present study. The
decreased thickness in these regions could also be related to the
abnormal connectivity evident in the default-mode and attention
network of people with OCD. Previous investigations have
demonstrated that there is an increased functional connectivity
between the prefrontal and insula/cingulate regions, suggesting
greater cognitive control, but weaker connectivity between
precentral gyrus and prefrontal cortex (suggesting lower motor
inhibition) in OCD.25 This incongruence between the dorsal and
ventral networks has also been demonstrated in another study
which investigated the structural covariance of cortical thickness
networks in OCD.26
Both our data and previous work suggest at least some
involvement of parietal and temporal regions in OCD,4,7,11
consistent with the suggested involvement of the fronto-parietal
and limbic circuits in the pathophysiology of OCD. The results
also held true after exclusion of patients on medication and with
lifetime comorbid anxiety and/or depression. Evidence from
functional MRI and cognitive testing has demonstrated that
parietal and temporal regions are involved in impairment of
inhibitory control27,28 and executive planning29,30 in OCD,
whereas the hippocampus together with amygdala and anterior
cingulate cortex may comprise affective components of the OCD
fronto-cortical circuit.31 Resting-state studies confirm abnormal
connectivity of frontoparietal networks, with increased connectivity
of motor networks,32 but decreased connectivity in frontotemporal
networks, especially in the posterior cingulate (an important
hub of the default-mode network).33,34
Although previous VBM studies have found greater striatal
volume,4,7 the same findings could not be replicated in this
mega-analysis. A possible reason for the absence of this finding is
as a result of the manner in which Freesurfer segments subcortical
Cortical thickness in obsessivecompulsive disorder
structures. Whereas VBM performs segmentation of the striatum
based on contrast differences between grey and white matter,
Freesurfer segments whole structures based on probabilistic
information from a predefined atlas.35 Therefore, only global
changes in subcortical structure can be inferred from Freesurfer,
rather than local morphology as with a voxel-based method such
as VBM. It is thus possible that these volume increases in the
striatum are not detectable when averaging across the whole
structure. Also, because the MRI scans were 1.5 T, there are
limitations to the signal-to-noise ratio of the data, as well as to
the resolution.36
Findings from the group6age interaction analyses
Group6age interaction analyses show that the inferior and superior
parietal regions demonstrate relatively exaggerated age-related
cortical thinning in the OCD group compared with controls.
Cortical thinning with age is normal,37,38 but this exaggerated
decrease in the parietal lobes of our patient cohort might explain
some characteristics typical of OCD: the parietal lobes are
involved in planning and response inhibition, both processes that
are impaired in OCD and potentially aggravated with age and
disease duration.31 Although we did not find any significant
association of disease severity or disease duration with grey matter
volume5 or thickness, the possibility exists that the more
pronounced thinning in parietal regions in older patients,
compared with older controls, may partly be explained by longer
disease duration. Additionally the association with age was
squared, indicating that rapid parietal cortical thinning occurred
at set age intervals, rather than linear progressive thinning as
patients became older. Even in healthy individuals, grey matter
density decline in parietal regions is non-linear, with the majority
of loss occurring between 50 and 70 years of age.37 To further
disentangle the effect of ageing and the effect of disease chronicity
a longitudinal design is needed.
Comparison with findings from other VBM studies
There is some consistency of this study with previous VBM meta-
analyses. Most notably previous VBM studies have also found grey
matter volume decreases in inferior frontal, orbitofrontal and
dorsolateral prefrontal regions.4,22 However in contrast to
previous VBM work, there were no cortical thickness changes in
the anterior cingulate and supramarginal gyri. In addition this
mega-analysis described decreased cortical thickness in regions
such as the middle temporal, inferior parietal, precentral,
precuneus and lateral occipital regions, for which grey matter
volume changes were not evident in previous VBM meta-analyses.3,4
The inconsistencies in findings likely reflect, at least partly, the
differences in the methodologies of the analyses techniques.
Segmentation of structures is performed in fundamentally different
ways across the techniques, i.e., FreeSurfer uses a surface-based
morphometry approach compared with VBMs voxel-wise
registration.39 The inconsistencies might also indicate that for
some brain regions differences in grey matter volume are not
explained by differences in cortical thickness.40 Grey matter
volume differences as found by VBM can result from (a) a change
in cortical thickness in the absence of surface area changes, (b) a
change in surface area in the absence of cortical thickness changes,
or (c) changes in both cortical thickness and cortical surface
area.40 An increase in surface area together with a decrease in
cortical thickness might mask the effect when expressed in grey
matter volume. Conversely, minor increases or decreases in both
surface area and cortical thickness may remain undetected when
analysed separately, but might reach significance when combined
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with grey matter volume. Therefore, findings of cortical thickness
and grey matter volume are complementary and the combined
interpretation of both measures strengthens the conclusions that
can be drawn from this data-set.
Comorbid anxiety and depression
Given that comorbid anxiety and depressive disorders are
frequently observed in OCD,41 we examined whether the lifetime
presence of such disorders would partly explain or influence our
main findings of decreased cortical thickness in patients with
OCD. In the current study prefrontal involvement was most
pronounced in the patients with comorbid anxiety disorders,
whereas ventral frontal structures and the hippocampus were most
affected in those with comorbid major depressive disorder.
Previous work has also shown these regions to be affected in both
anxiety and major depressive disorder, perhaps suggesting a
shared mechanism underlying emotional and cognitive deficits
across disorders.7,42,43 In addition, decreased cortical thickness
of the inferior frontal regions, insula and dorsomedial prefrontal
cortex was found in the OCD group compared with controls when
excluding the confounding effects of comorbid anxiety and
depression in this sample. This suggests that involvement of these
cortical areas is unique to OCD. This is consistent with previous
work,42 together with findings from the OCD VBM mega-analysis.5
Impact of medication
We examined whether psychotropic medication use has a
confounding effect on the changes observed in cortical thickness
or subcortical volume. For the prefrontal, temporal and occipital
regions there was greater cortical thinning in patients with OCD
on medication compared with unmedicated patients. Although
it has been suggested that selective serotonin reuptake inhibitors
might modulate neuroplasticity in brain regions of people with
OCD,44 these findings show little internal consistency. Thus, the
extent to which medication has consistent effects on brain
structure remains open for future study. That being said, after
excluding patients on medication, the main findings in the
inferior and superior frontal, precentral, posterior cingulate and
middle temporal regions still held true, indicating that
irrespective of medication use, these regions are altered in patients
with OCD. Indeed, the findings were somewhat more pronounced
when patients on medications were excluded, emphasising the
power that mega-analyses have to address confounding variables.
The negative association of lateral occipital thickness with the
YBOCS severity score is also a unique finding, together with
the increased cortical thickness of this region in patients with
OCD that were not on medication. Although not part of the
corticostriatal and limbic pathways thought to be affected in
OCD, previous volumetric studies have found decreased grey
matter volume in the occipital lobe of people with OCD.45,46
Findings from the symptom dimensions analysis
In addition, the finding that different symptom dimensions have
distinctive neuroanatomical correlates is consistent with previous
work.7,16 Similar to our present cortical thickness findings,
associations of temporal and occipital regional volumes with the
harm/checking and symmetry/order dimensions have been shown
before,22 as well as positive associations of the sexual/religious
dimension and hoarding dimensions with prefrontal and lateral
orbitofrontal volumes.46 Not all FreeSurfer findings of the
symptom dimension analyses are consistent with previous VBM
analyses,22,47 possibly as a result of clinical heterogeneity of
72
participants and differences in quantification of the dimension
variables for each study. For example, in this study, symptom
dimensions were defined in a binary manner as absent or present
for each participant, whereas the above-mentioned studies have
correlated the dimension scores with grey matter volumes. Our
seemingly incongruent findings of a positive association between
cortical thickness and specific dimensions coupled with decreased
cortical thickness in patients may reflect these methodological
problems in measuring symptom dimensions. In contrast to a
considerably clear image of the general structural brain changes
in OCD, there is arguably a paucity of literature to support a
detailed model of the underlying neuroanatomy of each particular
symptom dimension and therefore replication of these findings is
warranted. Also, because of the limitations of the clinical data-set,
a cluster analysis of symptom dimensions was not possible.48
Conclusions drawn from this analysis about the neurocircuitry
of symptom dimensions must be tentative.
Strengths and limitations
The benefit of a large multisite study such as this is the greater
sample size, which decreases the likelihood of type I and type II
errors. Another benefit is the congruency of preprocessing and
analytical methods in a mega-analysis compared with meta-
analyses. Sample size and other clinical confounders such as
comorbid anxiety/major depressive disorder and medication use
have limited previous investigations of cortical thickness in
OCD. By performing an analysis in this large group, these clinical
confounders can be controlled for more easily.
The present study also has some important limitations. These
include the potential confounders of scan sequence and other site
differences. Therefore, variance in scan sequence was controlled
for in the main and regression analyses. The measurement of
symptom dimension scores was based on the symptom checklist
of the YBOCS and was perhaps suboptimal because of variance
in use of the instrument across the participating centres. Although
the strength of this study is that clinical confounders could be
controlled for with a stepwise regression and participant
exclusion, it is still difficult to fully disentangle the confounding
effects of medication and comorbidity. Future studies should
employ instruments specifically designed and validated for this
purpose. In addition, our group6age findings are weakened by
the cross-sectional design of the study. Future longitudinal studies
of brain imaging in OCD will help shed light on the neuro-
developmental aspects of this disorder. This involves both the
altered neurodevelopment before the onset of the disease and
the disease-related and treatment-related neuroplastic changes
during the course of the disease. Also, we performed this
analysis on 1.5 T brain scans, which do have inherent resolution
limitations compared with 3 T MRI. Further work, using
longitudinal designs, 3 T MRI and incorporating genetic and
environmental variables, will be useful in understanding the
precise mechanisms underlying the structural abnormalities
preceding the onset of the disease and that occur during the course
of the disease.
In summary, this is the largest cortical thickness and subcortical
volume study of OCD to date. The results support the importance of
structural abnormalities in fronto-striatal, fronto-parietal and limbic
circuits in the pathophysiology of OCD. There is notable consistency
of the present FreeSurfer findings with previous VBM meta-
analyses and cortical thickness findings with regard to inferior
frontal gyrus/operculum and superior frontal gyrus/dorsomedial
prefrontal cortex, suggesting that cortical thinning as well as grey
matter volume abnormalities could perhaps relate to a similar
pathological process underlying the disorder.

Jean-Paul Fouche, MSc, Department of Psychiatry and Mental Health, University
of Cape Town, Cape Town, South Africa; Stefan du Plessis, MD, Department of
Psychiatry, University of Stellenbosch, Cape Town, South Africa; Coenie Hattingh,
MSc, Department of Psychiatry and Mental Health, University of Cape Town, Cape
Town, South Africa; Annerine Roos, PhD, MRC Unit on Anxiety & Stress Disorders,
Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa;
Christine Lochner, PhD, MRC Unit on Anxiety & Stress Disorders, Department
of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Carles
Soriano-Mas, PhD, Department of Psychiatry, Bellvitge University Hospital-IDIBELL,
Barcelona, Spain, Carlos III Health Institute, Centro de Investigacion Biomedica en
Red de Salud Mental (CIBERSAM), Spain, and Department of Psychobiology and
Methodology in Health Sciences, Universitat Autonoma de Barcelona, Spain;
Joao R. Sato, PhD, Center of Mathematics, Computation and Cognition, Universidade
Federal do ABC, Santo Andre, Brazil and Laboratorio Interdisciplinar de Neurociencias
Clnicas, Department of Psychiatry, Universidade Federal de Sao Paulo, Sao Paulo,
Brazil; Takashi Nakamae, MD, PhD, Department of Psychiatry, Graduate School of
Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Seiji
Nishida, MD, PhD, Department of Psychiatry, Graduate School of Medical Science,
Kyoto Prefectural University of Medicine, Kyoto, Japan; Jun Soo Kwon, MD, PhD,
Department of Psychiatry, Seoul National University College of Medicine, Seoul,
Republic of Korea and Institute of Human Behavioral Medicine, SNU-MRC, Seoul,
Republic of Korea and Department of Brain and Cognitive Sciences, College of Natural
Sciences, Seoul National University, Seoul, Republic of Korea; Wi Hoon Jung, PhD,
Department of Psychiatry, Seoul National University College of Medicine, Seoul,
Republic of Korea; David Mataix-Cols, PhD, Department of Clinical Neuroscience,
Karolinska Institute, Stockholm, Sweden; Marcelo Q. Hoexter, MD, PhD, Laboratorio
Interdisciplinar de Neurociencias Clnicas, Department of Psychiatry, Universidade
Federal de Sao Paulo, Sao Paulo, Brazil and Department & Institute of Psychiatry,
University of Sao Paulo Medical School, Sao Paulo, Brazil; Pino Alonso, MD, PhD,
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain and
Carlos III Health Institute, Centro de Investigacion Biomedica en Red de Salud Mental
(CIBERSAM), Spain, and Department of Clinical Sciences, Faculty of Medicine,
University of Barcelona, Spain; Stella J. de Wit, MD, Department of Psychiatry,
VU University Medical Centre, Amsterdam, The Netherlands; Dick J. Veltman, MD,
PhD, Department of Psychiatry, VU University Medical Centre, Amsterdam, The
Netherlands; Dan J. Stein, MD, PhD, Department of Psychiatry and Mental Health,
University of Cape Town, Cape Town, South Africa and MRC Unit on Anxiety & Stress
Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South
Africa; Odile A. van den Heuvel, MD, PhD, Department of Psychiatry, VU University
Medical Centre, Amsterdam, The Netherlands, Department of Anatomy &
Neurosciences, VU University Medical Center, Amsterdam, The Netherlands
Correspondence: Jean-Paul Fouche, Department of Psychiatry and Mental
Health, University of Cape Town, Faculty of Health Sciences, Anzio Road,
Observatory, 7935, South Africa. Email: FCHJEA002@myuct.ac.za
First received 24 Mar 2015, final revision 18 Aug 2015, accepted 27 Sep 2015
Funding
Supported by the Dutch Organization for Scientific Research (NWO) (grants 912-02-050,
907-00-012, 940-37- 018 and 916.86.038); the Carlos III Health Institute (PI09/01331,
PI10/01753, PI10/01003, CP10/00604, PI13/01958 and CIBER-CB06/03/0034); the Agency
for Administration of University and Research (AGAUR, Barcelona; 2009SGR1554); a Miguel
Servet contract from the Carlos III Health Institute (CP10/00604) to C.S.-M.; Ministry of
Education, Culture, Sports, Science, and Technology (Japan) Grants-in-Aid for Young
Scientists to J.N. (member of the OCD Brain Imaging Consortium, 23591724) and to
T.N. (24791223); Wellcome Trust project grant 064846; a grant from the Foundation
for the Support of Research in the State of Sao Paulo (FAPESP) to E.C.M. (member of
the OCD Brain Imaging Consortium, 2011/21357-9); a FAPESP scholarship to M.Q.H.
(2005/ 04206-6); and a National Research Foundation of Korea grant funded by the Korean
government (Ministry of Education, Science, and Technology, 2012-0005150).
Acknowledgements
We would like to thank the CSIR Centre for High Performance Computing at Rosebank,
Cape Town, South Africa for providing the supercomputing facilities to perform FreeSurfer
image processing and analysis. We would also like to thank all the authors who contributed
to this study as well as the members of the OCD Brain Imaging Consortium.
References
1 Fontenelle LF, Mendlowicz MV, Versiani M. The descriptive epidemiology of
obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry
2006; 30: 32737.
2 Hollander E, Stein DJ, Fineberg NA, Marteau F, Legault M. Quality of life
outcomes in patients with obsessive-compulsive disorder: relationship to
treatment response and symptom relapse. J Clin Psychiatry 2010; 71:
78492.
3 Rotge J-Y, Guehl D, Dilharreguy B, Tignol J, Bioulac B, Allard M, et al.
Meta-analysis of brain volume changes in obsessive-compulsive disorder.
Biol Psychiatry 2009; 65: 7583.
Cortical thickness in obsessivecompulsive disorder
4 Rotge J-Y, Langbour N, Guehl D, Bioulac B, Jaafari N, Allard M, et al. Gray
matter alterations in obsessive-compulsive disorder: an anatomic likelihood
estimation meta-analysis. Neuropsychopharmacology 2010; 35: 68691.
5 de Wit SJ, Alonso P, Schweren L, Mataix-Cols D, Lochner C, Menchon JM,
et al. Multicenter voxel-based morphometry mega-analysis of structural brain
scans in obsessive-compulsive disorder. Am J Psychiatry 2014; 171: 3409.
6 Radua J, Mataix-Cols D. Voxel-wise meta-analysis of grey matter changes in
obsessivecompulsive disorder. Br J Psychiatry 2009; 195: 393402.
7 Radua J, van den Heuvel OA, Surguladze S, Mataix-Cols D. Meta-analytical
comparison of voxel-based morphometry studies in obsessive-compulsive
disorder vs other anxiety disorders. Arch Gen Psychiatry 2010; 67: 70111.
8 Tops M, Boksem MAS. A potential role of the inferior frontal gyrus and
anterior insula in cognitive control, brain rhythms, and event-related
potentials. Front Psychol 2011; 2: 330.
9 Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I.
Segmentation and surface reconstruction. Neuroimage 1999; 9: 17994.
10 Wonderlick JS, Ziegler DA, Hosseini-Varnamkhasti P, Locascio JJ, Bakkour A,
van der Kouwe A, et al. Reliability of MRI-derived cortical and subcortical
morphometric measures: effects of pulse sequence, voxel geometry, and
parallel imaging. Neuroimage 2009; 44: 132433.
11 Shin Y-W, Yoo SY, Lee JK, Ha TH, Lee KJ, Lee JM, et al. Cortical thinning in
obsessive compulsive disorder. Hum Brain Mapp 2007; 28: 112835.
12 Kuhn S, Kaufmann C, Simon D, Endrass T, Gallinat J, Kathmann N. Reduced
thickness of anterior cingulate cortex in obsessive-compulsive disorder.
Cortex 2013; 49: 217885.
13 Venkatasubramanian G, Zutshi A, Jindal S, Srikanth SG, Kovoor JME, Kumar
JK, et al. Comprehensive evaluation of cortical structure abnormalities in
drug-nave, adult patients with obsessive-compulsive disorder: a surface-
based morphometry study. J Psychiatr Res 2012; 46: 11618.
14 Fullana MA, Cardoner N, Alonso P, Subira M, Lopez-Sola C, Pujol J, et al.
Brain regions related to fear extinction in obsessive-compulsive disorder and
its relation to exposure therapy outcome: a morphometric study. Psychol
Med 2014; 44: 84556.
15 Nakamae T, Narumoto J, Sakai Y, Nishida S, Yamada K, Kubota M, et al.
Reduced cortical thickness in non-medicated patients with obsessive-
compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37:
905.
16 Narayan VM, Narr KL, Phillips OR, Thompson PM, Toga AW, Szeszko PR.
Greater regional cortical gray matter thickness in obsessive-compulsive
disorder. Neuroreport 2008; 19: 15515.
17 Fan Q, Palaniyappan L, Tan L, Wang J, Wang X, Li C, et al. Surface anatomical
profile of the cerebral cortex in obsessive-compulsive disorder: a study of
cortical thickness, folding and surface area. Psychol Med 2013; 43: 108191.
18 Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL,
et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and
reliability. Arch Gen Psychiatry 1989; 46: 100611.
19 American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorder (4th edn) (DSMIV). APA, 1994.
20 Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex
from magnetic resonance images. Proc Natl Acad Sci USA 2000; 97:
110505.
21 Mathalon DH, Sullivan EV, Rawles JM, Pfefferbaum A. Correction for head
size in brain-imaging measurements. Psychiatry Res 1993; 50: 12139.
22 van den Heuvel OA, Remijnse PL, Mataix-Cols D, Vrenken H, Groenewegen
HJ, Uylings HBM, et al. The major symptom dimensions of obsessive-
compulsive disorder are mediated by partially distinct neural systems. Brain
2009; 132: 85368.
23 Pujol J, Soriano-Mas C, Alonso P, Cardoner N, Menchon JM, Deus J, et al.
Mapping structural brain alterations in obsessive-compulsive disorder. Arch
Gen Psychiatry 2004; 61: 72030.
24 Yoo SY, Roh M-S, Choi J-S, Kang D-H, Ha TH, Lee JM, et al. Voxel-based
morphometry study of gray matter abnormalities in obsessive-compulsive
disorder. J Korean Med Sci 2008; 23: 2430.
25 Li P, Li S, Dong Z, Luo J, Han H, Xiong H, et al. Altered resting state functional
connectivity patterns of the anterior prefrontal cortex in obsessive-
compulsive disorder. Neuroreport 2012; 23: 6816.
26 Kim S-G, Jung WH, Kim SN, Jang JH, Kwon JS. Disparity between dorsal and
ventral networks in patients with obsessive-compulsive disorder: evidence
revealed by graph theoretical analysis based on cortical thickness from MRI.
Front Hum Neurosci 2013; 7: 302.
27 Bannon S, Gonsalvez CJ, Croft RJ, Boyce PM. Executive functions in
obsessive-compulsive disorder: state or trait deficits? Aust NZ J Psychiatry
2006; 40: 10318.
73
Fouche et al
28 Penades R, Catalan R, Rubia K, Andres S, Salamero M, Gasto C. Impaired
response inhibition in obsessive compulsive disorder. Eur Psychiatry 2007;
22: 40410.
29 van den Heuvel OA, Veltman DJ, Groenewegen HJ, Cath DC, van Balkom
AJLM, van Hartskamp J, et al. Frontal-striatal dysfunction during planning in
obsessive-compulsive disorder. Arch Gen Psychiatry 2005; 62: 3019.
30 Chamberlain SR, Fineberg NA, Blackwell AD, Clark L, Robbins TW,
Sahakian BJ. A neuropsychological comparison of obsessive-compulsive
disorder and trichotillomania. Neuropsychologia 2007; 45: 65462.
31 Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET.
Integrating evidence from neuroimaging and neuropsychological studies of
obsessive-compulsive disorder: the orbitofronto-striatal model revisited.
Neurosci Biobehav Rev 2008; 32: 52549.
32 Stern ER, Fitzgerald KD, Welsh RC, Abelson JL, Taylor SF. Resting-state
functional connectivity between fronto-parietal and default mode networks
in obsessive-compulsive disorder. PLoS One 2012; 7: e36356.
33 Zhang T, Wang J, Yang Y, Wu Q, Li B, Chen L, et al. Abnormal small-world
architecture of top-down control networks in obsessive-compulsive disorder.
J Psychiatry Neurosci 2011; 36: 2331.
34 Meunier D, Ersche KD, Craig KJ, Fornito A, Merlo-Pich E, Fineberg NA, et al.
Brain functional connectivity in stimulant drug dependence and obsessive-
compulsive disorder. Neuroimage 2012; 59: 14618.
35 Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole
brain segmentation: automated labeling of neuroanatomical structures in the
human brain. Neuron 2002; 33: 34155.
36 Zhou Y, Zambelli J, Heredia G. SU-E-I-70: Comparison of brain volume
quantification with NeuroQuant & FreeSurfer. Med Phys 2015; 42: 3258.
37 Sowell ER, Thompson PM, Toga AW. Mapping changes in the human cortex
throughout the span of life. Neuroscientist 2004; 10: 37292.
38 Grieve SM, Clark CR, Williams LM, Peduto AJ, Gordon E. Preservation of
limbic and paralimbic structures in aging. Hum Brain Mapp 2005; 25:
391401.
39 Clarkson MJ, Cardoso MJ, Ridgway GR, Modat M, Leung KK, Rohrer JD, et al.
A comparison of voxel and surface based cortical thickness estimation
methods. Neuroimage 2011; 57: 85665.
74
40 Palaniyappan L, Liddle PF. Differential effects of surface area, gyrification and
cortical thickness on voxel based morphometric deficits in schizophrenia.
Neuroimage 2012; 60: 6939.
41 Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-
compulsive disorder in the National Comorbidity Survey Replication. Mol
Psychiatry 2010; 15: 5363.
42 van Tol M-J, van Der Wee NJA, van den Heuvel OA, Nielen MMA,
Demenescu LR, Aleman A, et al. Regional brain volume in depression and
anxiety disorders. Arch Gen Psychiatry 2010; 67: 100211.
43 Cardoner N, Soriano-Mas C, Pujol J, Alonso P, Harrison BJ, Deus J, et al. Brain
structural correlates of depressive comorbidity in obsessive-compulsive
disorder. Neuroimage 2007; 38: 41321.
44 Hoexter MQ, de Souza Duran FL, DAlcante CC, Dougherty DD, Shavitt RG,
Lopes AC, et al. Gray matter volumes in obsessive-compulsive disorder
before and after fluoxetine or cognitive-behavior therapy: a randomized
clinical trial. Neuropsychopharmacology 2012; 37: 73445.
45 Togao O, Yoshiura T, Nakao T, Nabeyama M, Sanematsu H, Nakagawa A,
et al. Regional gray and white matter volume abnormalities in obsessive-
compulsive disorder: a voxel-based morphometry study. Psychiatry Res
2010; 184: 2937.
46 Kim J-J, Lee MC, Kim J, Kim IY, Kim SI, Han MH, et al. Grey matter
abnormalities in obsessivecompulsive disorder: statistical parametric
mapping of segmented magnetic resonance images. Br J Psychiatry 2001;
179: 3304.
47 Alvarenga PG, do Rosario MC, Batistuzzo MC, Diniz JB, Shavitt RG, Duran FLS,
et al. Obsessive-compulsive symptom dimensions correlate to specific
gray matter volumes in treatment-nave patients. J Psychiatr Res 2012; 46:
163542.
48 Lochner C, Hemmings SMJ, Kinnear CJ, Nel D, Hemmings SMJ, Seedat S, et al.
Cluster analysis of obsessive-compulsive symptomatology: identifying
obsessive-compulsive disorder subtypes. Isr J Psychiatry Relat Sci 2008; 45:
16476.
 Data supplement to Fouche et al. Cortical thickness in obsessive-compulsive disorder: a
multisite mega-analysis of 780 brain scans from 6 centres. Br J Psychiatry doi:
10.1192/bjp.bp.115.164020

Online Supplement DS1

OCD Brain Imaging Consortium:
Geraldo F. Busatto MD, PhD, Department & Institute of Psychiatry, University of Sao Paulo Medical
School, Sao Paulo, Brazil; Narcs Cardoner MD, PhD, Department of Psychiatry, Bellvitge University
Hospital- IDIBELL, Barcelona, Spain and Carlos III Health Institute, Centro de Investigacin Biomdica
en Red de Salud Mental (CIBERSAM), Spain; Danielle C. Cath MD, PhD, Altrecht Academic Anxiety
Center, Utrecht, The Netherlands; Damiaan Denys MD, PhD, Department of Psychiatry, Academic
Medical Center, Amsterdam, The Netherlands; Kenji Fukui MD, PhD, Department of Psychiatry,
Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Joon
Hwan Jang MD, PhD, Department of Psychiatry, Seoul National University College of Medicine, Seoul,
Republic of Korea; Sung Nyun Kim MD, Department of Psychiatry, Seoul National University College of
Medicine, Seoul, Republic of Korea; Jos M. Menchn MD, PhD, Department of Psychiatry, Bellvitge
University Hospital-IDIBELL, Barcelona, Spain and Carlos III Health Institute, Centro de Investigacin
Biomdica en Red de Salud Mental (CIBERSAM), Spain; Euripides C. Miguel MD, PhD, Department &
Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil; Jin Narumoto MD,
PhD, Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of
Medicine, Kyoto, Japan; Mary L. Phillips MD, PhD, Department of Psychiatry, Western Psychiatric
Institute and Clinic, University of Pittsburg School of Medicine, Pittsburgh, USA; Jesus Pujol MD, PhD,
MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain; Centro Investigacin Biomdica en
Red de Salud Mental, CIBERSAM G21, Barcelona, Spain; Peter L. Remijnse MD, PhD, Department of
Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands; Yuki Sakai
MD, PhD, Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University
of Medicine, Kyoto, Japan; Lizanne Schweren MSc, Department of Psychiatry, VU University Medical
Centre, Amsterdam, The Netherlands; Na Young Shin MA, Department of Psychiatry, Seoul National
University College of Medicine, Seoul, Republic of Korea; Kei Yamada MD, PhD, Department of
Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

DS2 Post-hoc analysis of cortical thickness between healthy controls and OCD patients in a
matched sample group
To ensure that demographic variables such as age and education were not confounders in the
original dataset, a post-hoc analysis was performed on participants closely matched on
demographics (n=645). Participants were excluded based on frequency spectra of age and
educational level per site (See De Wit et al. 2014). This resulted in a sample group of controls
(n=316) and patients (n=329) that were matched on age, sex, educational level, handedness
and ethnicity overall and per site (See online Tables DS13 for results).

Post-hoc analysis of the effects of scan sequence on group-interaction findings.

To determine that results were not affected by specific scan sequences from each site an
ANCOVA was performed to investigate the interaction of scan sequence with group
comparisons of cortical thickness and subcortical volumes. The ANOVA were comprised of 9
levels (one for each scan sequence) and 2 levels for diagnosis as between-subjects factors.
Age, gender and level of education were added as covariates of no interest in the model. For
cortical thickness there were no sequence by diagnosis interactions at p < 0.05 corrected for
multiple comparisons with Monte-Carlo permutation testing. For subcortical structures, no
sequence by diagnosis interaction was evident at p < 0.0036 (p < 0.05 Bonferroni corrected).
 Table DS1 Areas of decreased cortical thickness in the matched sample of OCD patients
(n=329) compared to healthy controls (n=316)
Grey matter region Hemisp Mean thickness (mm) Local p- Talaraich
here maxima Z- val coordinates
value ue
FRONTAL HC (SD) OCD (SD)

Inferior frontal Right 2.630 2.583 -3.461 0.00 50.6 23.5

(0.152) (0.160) 05 16.3
Superior frontal Left 3.098 3.045 -5.371 < -8.8 26.6
(0.203) (0.230) 0.00 32.7
Right 2.818 2.780 -2.807 0.00 8.0 56.8
(0.201) (0.209) 50 22.3
PARIETAL

Inferior parietal Left 2.421 2.370 -3.367 0.00 -41.5 -63.5

(0.181) (0.175) 08 26.5
TEMPORAL

Middle temporal Right 2.755 2.699 -3.659 0.00 57.9 -42.4

(0.165) (0.167) 03 -8.2
Results are shown at p < 0.05 corrected for multiple comparisons with Monte-Carlo
simulations. Covariates of no interest in this analysis included scan sequence, level of
education, age and sex. No significant increases of cortical thickness in OCD patients
compared with healthy controls were observed.

Table DS2 Subcortical regional volumes in the matched sample of OCD patients (n=329)
compared to healthy controls (n=316)
Subcortical Hemisphere F-value p-value
region
Hippocampus Left 7.554 0.0004

Right 5.641 0.0013

Results of the ANOVA analysis between groups are shown here. Results are shown at p <
0.0036 (p < 0.05 Bonferroni corrected). Covariates of no interest in this analysis included scan
sequence, level of education, age and sex

Table DS3 Group-by-age interaction effects for cortical thickness, in matched sample of OCD
patients (n=329) and healthy controls (n=316)
Grey Hemis Surface Local p-value Talaraich coordinates
matter phere area maxima
region (mm2) Z-value
Relative cortical thinning with aging in OCD patients vs. controls
Linear
Inferior Left 953.72 2.957 0.0031 -38.3 -67.1 36.5
parietal
Non-
linear
Inferior Left 1723.93 3.197 0.0014 -38.2 -63.7 45.6
parietal
Superior Right 1027.55 2.355 0.0185 14.3 -79.1 37.0
parietal
Results are shown at p < 0.05 corrected for multiple comparisons with Monte-Carlo
simulations. Covariates of no interest in this analysis included scan sequence, level of
education, age and sex.
DS3 Comparison of OCD patients with healthy controls after excluding patients on medication,
and with lifetime co-morbid anxiety and major depressive disorder

In order to investigate the comparison of OCD patients with healthy controls in the absence of
confounding variables such as medication use and co-morbid anxiety and depression, a
secondary analysis comparing cortical thickness and subcortical volumes between groups was
conducted where 1) patients on medication, 2) patients with lifetime co-morbid anxiety, 3)
patients with lifetime co-morbid depression were excluded in turn. Cortical thickness was
compared with a GLM ANCOVA model in Freesurfers glm_fit and subcortical volumes were
analysed in SPSS 20.0 with the same model. Age, sex, level of education and scan sequence
was included as covariates of no interest. The results of these analyses are presented in Tables
DS4-7. There were no significant differences in subcortical volumes between controls and
OCD patients when excluding patients with lifetime co-morbid anxiety disorder, as well as
patients on medication.

Table DS4 Comparison of cortical thickness between OCD patients (N=222) and healthy
controls (N=368) after exclusion of patients on medication
Grey matter Hemis Local p-value Talairach
region phere maxima coordinates
Z- value
HC > OCD
Superior Left 4.222 < 0.0001 -9.7 4.4
Inferior Right 5.680 < 0.0001 51.7 23.0
Precentral Right 3.771 0.0002 27.0 -18.0
Posterior Right 5.639 < 0.0001 6.1 -12.2
Middle Left 6.470 < 0.0001 -57.6 -42.1 -
Right 5.840 < 0.0001 59.5 -45.3 -
Results are shown at p< 0.05 corrected for multiple comparisons with Monte Carlo
simulations. Covariates of no interest include age, sex, scan sequence and level of education.

Table DS5 Comparison of cortical thickness between OCD patients (N=190) and healthy
controls (N=368) after exclusion of patients with lifetime co-morbid anxiety disorder
Grey matter Hemis Local p- Talaraich
region phere maxima value coordinates
Z- value
HC > OCD
Insula Right 8.205 < 34.4 -16.5
Caudal middle Right 3.530 0.000 36.7 4.1
Paracentral Left 10.419 < -6.5 -21.1
Pericalcarine Right 12.531 < 12.3 -86.3 4.5
Results are shown at p < 0.05 corrected for multiple comparisons with Monte Carlo
simulations. Covariates of no interest include age, sex, scan sequence and level of education.

Table DS6 Comparison of cortical thickness between OCD patients (N=287) and healthy
controls (N=368) after exclusion of patients with lifetime co-morbid major depressive disorder
Grey matter Hemis Local p- Talaraich
region phere maxima value coordinates
Z- value
HC > OCD
Superior frontal Left 4.576 < -8.5 26.1
Inferior frontal Left 2.869 0.004 -32.1 29.1 3.8
Right 3.516 0.000 49.1 25.0
Rostral middle Left 2.823 0.004 -31.2 46.7 6.3
Medial Right 3.240 0.001 8.3 51.6 -
Lateral occipital Left 4.115 < -15.5 -90.2
Results are shown at p < 0.05 corrected for multiple comparisons with Monte Carlo
simulations. Covariates of no interest include age, sex, scan sequence and level of education.
Table DS7 Comparison of subcortical volumes between OCD patients and healthy controls
after exclusion of patients with lifetime co-morbid anxiety disorder
Subcortical Hemisphere F-value p-value
HC > OCD
Hippocampus Left 7.677 < 0.001
Right 5.057 0.002
Results of the ANOVA analysis between groups are shown here. Results are shown at p
<0.0036 (p < 0.05 Bonferroni corrected). Covariates of no interest in this analysis included
scan sequence, level of education, age and sex

DS4 Post-hoc hierarchical multiple linear regression analysis on medication status

The mean cortical thickness and subcortical volume of regions that showed significant
differences within OCD patients based on medication use were extracted from Freesurfer for
analysis in SPSS 20.0. The cortical regions included the left lateral orbitofrontal, insula,
superior temporal, inferior temporal, bilateral lateral occipital and right superior frontal and
middle temporal gyri. Subcortical regions included bilateral caudate, putamen, hippocampus,
amygdala and accumbens, as well as left pallidum. Stepwise multiple linear regression
analyses were then performed on each region by stepwise entering scan sequence, age, sex,
education, YBOCS total score and medication status (present = 1, absent = 0) into the model.

The following regions remained significant for medication status: left lateral occipital (model
R-square change=0.065; F-change=24.645; beta 95% confidence interval=-0.256; t=-4.964;
p<0.001), left lateral orbitofrontal (model R-square change=0.048; F- change=27.576; beta
95% confidence interval=-0.225; t=-5.251; p<0.001), left superior temporal (model R-
square change=0.014; F-change=6.050; beta 95% confidence interval=- 0.118; t=-2.460;
p=0.014), right lateral occipital (model R-square change=0.074; F- change=28.264; beta
95% confidence interval=-0.273; t=-5.316; p<0.001), right superior frontal (model R-
square change=0.010; F-change=5.582; beta 95% confidence interval=- 0.101; t=-2.363;
p=0.19) and right middle temporal (model R-square change=0.018; F- change=7.318; beta
95% confidence interval=0.137; t=2.705; p=0.007).

The following regions did not remain significant after stepwise regression and controlling for
demographic and clinical variability: left insula and left inferior temporal gyri.
 Table DS8 Effect of medication use on cortical thickness in OCD patients.
Medication use in patients (med+ n=176; med- n=222)
Grey Hemis Mean thickness Local p-value Talairach coordinates
matter phere maxim
region a Z-
value
- med + med
(SD) (SD)
- med > + Lateral Left 2.015 1.875 20.020 < 0.0001 -9.7 -98.7 7.6
med occipital (0.213) (0.164)
Lateral 2.573 2.430 10.267 < 0.0001 -26.6 32.2 -9.1
orbitofront (0.190) (0.185)
al
Insulaa 2.580 2.439 6.477 < 0.0001 -28.6 16.3 8.0
(0.192) (0.197)
Superior 3.073 2.953 3.264 0.0011 -46.6 -2.3 -14.9
temporal (0.202) (0.236)
Lateral Right 1.899 1.861 19.136 < 0.0001 11.3 -97.0 12.8
occipital (0.167) (0.157)
Superior 2.658 2.506 7.036 < 0.0001 15.5 44.2 4.6
frontal (0.214) (0.222)
Middle 2.857 2.803 3.092 0.0020 61.8 -36.0 -3.6
temporal (0.177) (0.185)
+ med > - Inferior Left 2.442 2.506 -4.424 < 0.0001 -42.0 -60.2 -1.4
med temporala (0.189) (0.173)
Results are shown at p < 0.05 corrected for multiple comparisons with Monte-Carlo simulations. Covariates of no interest in this analysis included
scan sequence, level of education, age and sex. Abbreviations: - med: not on medication at time of scan; + med: on medication at time of scan.
a
Indicates results that are not significant after stepwise regression controlling for demographic and clinical variability
DS5 Co-morbid anxiety analysis

There was information on co-morbid anxiety presence/absence in 273 OCD patients. These
included panic disorder, social phobia, specific phobia, post-traumatic stress disorder, general
anxiety disorder and anxiety disorders not otherwise specified. Lifetime diagnosis of co-
morbid anxiety was available in 83 OCD patients and in 75 of these patients it was currently
present as well. Because there was a large overlap of lifetime and current anxiety co-
morbidity, only the lifetime (n=75) diagnoses were considered for analysis. Cortical thickness
(in FreeSurfer) and subcortical volumes (in SPSS 20.0) were compared between OCD patients
with (n=83) and without (n=190) a lifetime diagnosis of anxiety. Age, sex, educational level
and scan sequence were included as covariates of no interest (See Table DS9 for results).

DS6 Co-morbid major depressive disorder (MDD) analysis

There was information on MDD presence/absence in 388 OCD patients. Patients with lifetime
MDD (n=101) were compared with OCD patients without MDD (n=287) on measures of
cortical thickness and subcortical volumes. Age, sex, educational level and scan sequence
were included as covariates of no interest (See Table DS9 and DS10 for results).
 Table DS9 The effect of co-morbid anxiety and depression on cortical thickness within OCD
patients
Grey matter Hemi Mean thickness Local p-value Talairach
region spher maxima coordinates
e Z-value
Lifetime co-morbid anxiety disorder (anx+ n=83; anx- n=190)

anx- anx+ (SD)

(SD)
anx- > anx+

a Left 2.567 2.445 (0.187) 6.399 < 0.0001 -28.7 19.1 10.1
Insula
(0.236)
Rostral middle Left 2.408 2.305 (0.167) 5.639 < 0.0001 -25.3 33.4 24.4
frontal (0.200)
Paracentral Left 2.505 2.394 (0.151) 6.383 < 0.0001 -4.0 -30.2 68.2
(0.184)
Pericalcarine Left 2.070 1.972 (0.126) 5.065 < 0.0001 -9.2 -88.0 8.4
(0.140)
Inferior Left 2.392 2.313 (0.144) 2.983 0.0029 -32.3 -76.2 26.2
a (0.193)
parietal
Paracentral Right 2.362 2.253 (0.135) 6.453 < 0.0001 5.4 -23.6 71.1
(0.159)
Insula Right 2.846 2.732 (0.186) 4.770 < 0.0001 34.9 -15.0 18.6
(0.216)
anx+ > anx-

Entorhinal Right 3.075 3.222 (0.163) -6.061 < 0.0001 28.8 1.3 -36.7
(0.180)
Lifetime co-morbid major depression (dep+: n=101; dep-: n=287)

dep- dep+ (SD)

(SD)
dep+ > dep-

Inferior frontal Left 2.474 2.506 (0.240) 5.750 < 0.0001 -32.4 26.8 8.7
(0.205)
Superior Left 2.585 2.607 (0.322) 3.982 0.0001 -14.1 43.0 10.9
a (0.312)
frontal
Lateral Left 2.383 2.417 (0.207) 4.197 < 0.0001 -33.6 35.0 -8.3
orbitofrontal (0.190)
dep- > dep+

Entorhinal Right 3.196 3.047 (0.157) -4.204 < 0.0001 29.1 0.3 -36.0
(0.154)
Middle Left 2.868 2.756 (0.224) -4.619 < 0.0001 -51.9 -60.5 -0.3
temporal (0.201)
Results are shown at p < 0.05 corrected for multiple comparisons with Monte Carlo
simulations. Covariates of no interest include age, sex, scan sequence and level of education.
a
Indicates results that are not significant after stepwise regression controlling for demographic
and clinical variability
Table DS10 The effect of co-morbid depression on subcortical volumes within OCD patients
Subcortical Hemisphere F-value p-value
region
Lifetime co-morbid major depression (dep+ n=101; dep- n=287)
dep- > dep+
Hippocampusa Left 4.877 0.002
Results of the ANOVA analysis between groups are shown here. Results are shown at p < 0.0036 (p < 0.05
Bonferroni corrected). Covariates of no interest in this analysis included scan sequence, level of education, age and
sex
a
Indicates results that are not significant after stepwise regression controlling for demographic
and clinical variability

DS7 Post-hoc hierarchical multiple linear regression analysis on co-morbid anxiety and major

depression

The mean cortical thickness and subcortical volume of regions that showed significant difference between patients
with co-morbid anxiety and/or MDD and patients without co-morbidity was extracted from FreeSurfer for analysis
in SPSS 20.0. Stepwise multiple linear regression analyses were performed on these regions by entering scan
sequence, age, sex, education, YBOCS total score and lifetime/current co-morbid anxiety disorder or
lifetime/current co-morbid MDD (present =1, absent = 0) into the model.

For the co-morbid anxiety disorder analysis, the following regions remained significant after controlling for
demographic and clinical variability: left paracentral (model R-square change=0.045; F-change=14.481; beta
95% confidence interval=0.212; t=3.805; p<0.001), left pericalcarine (model R-square change=0.041; F-
change=15.633; beta 95% confidence interval=0.202; t=3.954; p<0.001), left rostral middle frontal (model R-
square change=0.053; F-change=18.393; beta 95% confidence interval=0.230; t=4.289; p<0.001), right
entorhinal (model R-square change=0.086; F-change=24.199; beta 95% confidence interval=-0.293; t=-4.919;
p<0.001), right insula (model R-square change=0.027; F- change=9.221; beta 95% confidence interval=0.165;
t=3.037; p<0.003) and right paracentral (model R-square change=0.064; F-change=20.348; beta 95%
confidence interval=0.253; t=4.511; p<0.001).

The following regions did not remain significant after stepwise regression and controlling for demographic and
clinical variability: left insula and the left inferior parietal regions.

For the lifetime diagnosis of MDD, the following regions remained significant after controlling for demographic
and clinical variability: left lateral orbitofrontal (model R- square change=0.015; F-change=7.890; beta 95%
confidence interval=0.128; t=2.809;
p=0.005), left middle temporal (model R-square change=0.030; F-change=11.640; beta 95% confidence
interval=-0.178; t=-3.412; p=0.001), left inferior frontal (model R-square change=0.016; F-change=8.345; beta
95% confidence interval=0.132; t=2.889; p=0.004), t=3.926; p<0.001) and right entorhinal (model R-square
change=0.064; F-change=23.656; beta 95% confidence interval=-0.253; t=-4.864; p<0.001).

The left hippocampus and superior frontal regions did not remain significant after stepwise regression and
controlling for demographic and clinical variability.
 Table DS11 Demographic and clinical characteristics of the healthy controls (N=368) and OCD patient (N=412)
group (as shown in de Wit et al. 2014)
Characteristic OCD patients Healthy controls Statistics
Mean SD Mean SD t P
Age (years) 32.1 9.6 30.2 9.3 2.9 0.004
Education level 13.7 2.8 14.6 3.1 -4.0 <0.001
YBOCS score 24.9 6.2
Age at onset of 20.1 8.7
clinical symptoms
N % N % 2 P
Male 202 49.0 195 53.0 1.2 0.28
Right-handed 354 85.9 330 89.7 1.0 0.65
Ethnicity 2.7 0.26
Caucasian 195 47.3 192 52.2
Asian 171 41.5 146 39.7
Other 6 1.5 11 3.0
Medication use at 176 42.7 0 0.0 210.1 < 0.001
time of scan
Current 149 36.2 0 0.0 210.1 < 0.001
Lifetime 213 51.7 7 1.9 253.7 < 0.001
Prepubertal OCD 51 13.0
OCD symptom
dimensions
Aggression/checki 236 57.2
Contamination/cle 202 49.0
Symmetry/orderin 168 40.8
Sexual/religious 130 31.6
Hoarding 87 21.1

DS8 Association of OCD symptom dimensions with cortical thickness and subcortical volume

There was information on lifetime presence/absence of OCD symptom dimensions for n=331 patients. The five
dimensions were checking/aggression, contamination/cleaning, sexual/religious, hoarding and symmetry/ordering.
Cortical thickness and subcortical volume were included in a general linear model with the five dimensions to
investigate associations between the variables. Age, education, sex, scan sequence and total YBOCS score were
included as covariates of no interest in the model. 1 for a positive association and -1 for a negative association with
thickness/volume indicated the absence/presence of each dimension (See Table DS12 for results).

Table DS12 Effect of symptom severity and symptom dimensions on cortical thickness in OCD patients
Grey matter region Hemisphere Surface area Local maxima p-value Talaraich
2 Z-value coordinates
size(mm )
- correlation Lateral occipital Left 1610.63 -5.634 < 0.0001 -13.9 -98.6 8.0
YBOCS
Lateral occipital Right 2354.92 -3.984 0.0001 11.7 -96.9 13.7

OCD symptom dimensions (n=331)

+ correlation Lateral orbitofrontal Left 2053.93 5.840 < 0.0001 -12.6 49.5 -17.2
contam/clean
Precentral 1319.85 4.109 < 0.0001 -54.0 3.6 2.6

Frontal pole Right 1169.64 5.275 < 0.0001 8.3 62.0 -6.1

+ correlation Inferior frontal Left 10600.78 4.543 < 0.0001 -32.0 20.8 10.4
hoarding
Lateral occipital 1653.60 3.501 0.0005 -15.9 -94.7 -7.6

Middle temporal 1550.72 3.256 0.0011 -42.9 -60.0 7.2

Lateral orbitofrontal 1052.22 3.062 0.0022 -15.5 17.1 -18.9

Superior parietal 992.99 2.417 0.0156 -17.9 -75.2 33.8

Superior frontal Right 2280.36 6.088 < 0.0001 14.4 38.6 8.8
 Inferior frontal 1799.27 4.965 < 0.0001 37.4 12.5 20.1

Medial orbitofrontal 1792.09 4.012 < 0.0001 8.4 50.9 -12.0

Cuneus 921.23 2.323 0.0202 5.7 -84.7 19.3

+ correlation Isthmus cingulate Left 2054.23 4.802 < 0.0001 -10.1 -51.0 9.8
sex/religious
Rostral middle frontal 6694.23 4.383 < 0.0001 -25.8 27.7 29.8

Lateral occipital 3106.46 4.035 < 0.0001 -22.1 -92.4 -8.9

Superior parietal Right 2827.72 4.237 < 0.0001 19.2 -75.9 35.1

Supramarginal 1287.03 3.183 0.0015 53.3 -29.4 42.8

Precuneus 902.64 2.959 0.0031 8.9 -38.6 41.1

Lateral orbitofrontal 1078.97 2.558 0.0105 27.2 27.1 -12.0

+ correlation Precentral Left 8299.76 5.444 < 0.0001 -28.3 -8.6 44.0
sym/order
Insula 931.44 5.263 < 0.0001 -34.2 -14.5 17.2

Postcentral 832.66 3.822 0.0001 -14.7 -31.1 57.8

Lingual 1557.63 3.040 0.0024 -7.1 -91.0 -3.4

Lateral occipital Right 2959.27 3.729 0.0002 18.4 -95.6 14.7

Medial orbitofrontal 2250.68 3.594 0.0003 10.4 54.5 -6.9

- correlation Superior temporal Right 1825.34 -3.927 0.0001 44.6 -1.2 -17.9
sym/order
+ correlation Lateral occipital Right 1415.53 2.924 0.0035 32.7 -80.6 17.0
check/aggr
- correlation Entorhinal Right 2098.43 -3.930 0.0001 24.8-5.4 -27.0
check/aggr
Results are shown at p < 0.05 corrected for multiple comparisons with Monte-Carlo simulations. Covariates of no
interest in this analysis included scan sequence, level of education, age, sex and YBOCS severity (for the symptom
dimension analysis).
Abbreviations: contam/clean: contamination/cleaning; sym/order: symmetry/order; check/aggr: checking/aggression
a
Indicates results that are not significant after stepwise regression controlling for demographic
and clinical variability
Cortical thickness in obsessivecompulsive disorder: multisite
mega-analysis of 780 brain scans from six centres
Jean-Paul Fouche, Stefan du Plessis, Coenie Hattingh, Annerine Roos, Christine Lochner, Carles
Soriano-Mas, Joao R. Sato, Takashi Nakamae, Seiji Nishida, Jun Soo Kwon, Wi Hoon Jung, David
Mataix-Cols, Marcelo Q. Hoexter, Pino Alonso, OCD Brain Imaging Consortium, Stella J. de Wit, Dick J.
Veltman, Dan J. Stein and Odile A. van den Heuvel
BJP 2017, 210:67-74.
Access the most recent version at DOI: 10.1192/bjp.bp.115.164020

Supplementary Supplementary material can be found at:

Material http://bjp.rcpsych.org/content/suppl/2016/05/09/bjp.bp.115.164020.DC1

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