The British Journal of Psychiatry

16. doi: 10.1192/bjp.bp.114.154393

Neuroimaging distinction between neurological

and psychiatric disorders
Nicolas A. Crossley, Jessica Scott, Ian Ellison-Wright and Andrea Mechelli
Background
It is unclear to what extent the traditional distinction
between neurological and psychiatric disorders reflects
biological differences.
Aims
To examine neuroimaging evidence for the distinction
between neurological and psychiatric disorders.
Method
We performed an activation likelihood estimation
meta-analysis on voxel-based morphometry studies
reporting decreased grey matter in 14 neurological and
10 psychiatric disorders, and compared the regional
and network-level alterations for these two classes of
disease. In addition, we estimated neuroanatomical
heterogeneity within and between the two classes.
Results
Basal ganglia, insula, sensorimotor and temporal cortex
showed greater impairment in neurological disorders;

The ICD-10,1 arguably the dominant classification system in

use in medicine, makes a distinction between neurological and
psychiatric disorders. This distinction is based on nosological
criteria, such as aetiological or syndromatic similarities, but also
reflects historical2 or social factors.3 It has important implications
for clinical practice, since the remit of services frequently mirror
the boundaries between groups of disorders, which might
determine the type of treatment individual patients receive.4,5
Over the past few years, however, the distinction between
psychiatric and neurological disorders has been called into
question on the basis of the latest scientific data.6 It has been long
known that neurological disorders can present with affective or
psychotic symptoms traditionally thought to be specific to
psychiatric disorders,7,8 and that psychiatric disorders present
motor symptoms more frequently seen in a neurology clinic.9
More recently, brain imaging has provided an in vivo window into
the human brain, and has revealed that both neurological and
psychiatric disorders are associated with neuroanatomical and
neurofunctional alterations.1012 This dynamic and efficient
perspective on regional changes in brain disorders can
complement the histopathological information provided by
neuropathological studies.13 This approach has challenged the
simplistic view of neurological disorders as organic and
psychiatric disorders as functional. In addition to neuroscientific
evidence, genetic studies have also begun to reveal the genetic
underpinnings of neurological and psychiatric disorders. Allelic
variants, copy number variants, epistatic effects and gene
environment interactions appear to play a critical role in both
classes of disorders,1416 suggesting the presence of comparable
aetiological mechanisms. In a recent, thought-provoking article,
White and colleagues6 suggested that the traditional distinction
between disorders of the mind and disorders of the brain is a
fundamental misconception, and called for a radical rethinking

whereas cingulate, medial frontal, superior frontal and

occipital cortex showed greater impairment in psychiatric
disorders. The two classes of disorders affected distinct
functional networks. Similarity within classes was higher than
between classes; furthermore, similarity within class was
higher for neurological than psychiatric disorders.
Conclusions
From a neuroimaging perspective, neurological and
psychiatric disorders represent two distinct classes of
disorders.
Declaration of interest
None.
Copyright and usage
B The Royal College of Psychiatrists 2015. This is an open
access article distributed under the terms of the Creative
Commons Attribution (CC BY) licence.

in which psychiatric disorders should be reclassified as disorders

of the central nervous system. The merging of these two
categories, the authors argued, would be a logical decision given
that both neurological and psychiatric disorders are rooted in
the brain and are associated with a combination of both
sensorimotor and psychological symptoms. However, concerns
have been raised about the actual benefits patients would receive
from the merging of both fields.17,18
We acknowledge that the distinction between the fields of
psychiatry and neurology involves multiple factors, ranging from
social and historical to biological, and that any new classification
should ultimately reflect an improvement in clinical outcomes.
However, it is imperative that this debate is informed by
scientific evidence including the biology underpinning the two
classes of disorders. In this context, we investigated whether
neurological and psychiatric disorders have distinct neuroimaging
correlates that arguably could reflect distinct neuropathologies. In
particular, we examined whether the two classes of disorders
affected different sets of regions, whether these regions were
localised in different functional networks and whether neuroanatomical variability within each class of disorders is smaller
than between classes. Our investigation was based on a metaanalysis of 168 published studies that used structural magnetic
resonance imaging (sMRI) to investigate neuroanatomy in a total
of 4227 patients and 4504 healthy controls.

Method
The present meta-analysis was informed by the guidelines
provided by the PRISMA (Preferred Reporting Items for
Systematic reviews and Meta-Analyses) Statement (http://www.
prisma-statement.org/); PRISMA flow diagrams illustrating the

Crossley et al

number of articles identified for each group of disorders, the

number of included and excluded articles, and the reasons for
exclusions, can be found in the online Fig. DS1.

Literature search and selection of studies

In brief, we performed a systematic search for published studies
that had employed sMRI and voxel-based morphometry
(VBM)19 to examine neuroanatomy in patients with a
neurological or psychiatric disorder compared with healthy
controls. The list of neurological and psychiatric disorders was
obtained from chapters V and VI from ICD-10 (2010 version).
A total of 91 electronic searches were performed between 2 and
3 May 2012 using the PubMed database. Each electronic search
comprised the following general structure: (voxel based OR
morphometr* OR VBM) AND (MRI OR magnetic resonance)
AND terms related to disorder as listed in the ICD-10. When a
meta-analysis on a certain neurological or psychiatric disorder
was found, we checked the reference list for any studies that had
not been detected using our search terms. Some disorders had
been examined in only a few VBM studies, whereas others had
been examined in a large number of studies. We sought a
pragmatic compromise between the need to include as many
studies as possible to improve precision of each disorder-specific
meta-analysis, and the requirement to include as many disorders
as possible to obtain a representative sample of each class. This
resulted in the selection of 24 different disorders that had been
investigated in at least seven VBM studies (Table 1, and see online
Fig. DS1 for a flow diagram of study selection). We classified
disorders described in chapter V of the ICD-10 as psychiatric,
and those described in chapter VI as neurological. We
acknowledge that a number of disorders, in particular the
Table 1 List of neurological and psychiatric disorders
examined in the present investigation a
Studies
included/
published, n

Patients/
controls
included, n

Neurological disorders
Amyotrophic lateral sclerosis
Dementia in Alzheimers disease
Dementia in Parkinsons
Developmental dyslexia
Dystonia
Frontotemporal dementia
Hereditary ataxia
Huntingtons disease
Juvenile myoclonic epilepsy
Multiple sclerosis
Parkinsons disease
Progressive supranuclear palsy
Temporal lobe epilepsy left
Temporal lobe epilepsy right

7/8
7/36
7/10
7/8
7/10
7/37
7/15
7/9
7/7
7/11
7/17
7/7
7/14
7/10

114/121
114/122
133/172
109/108
151/160
158/170
97/121
206/165
220/218
335/179
216/197
108/182
232/334
196/246

Psychiatric disorders
Attention-deficit hyperactivity disorder
Anorexia nervosa
Autism
Asperger syndrome
Bipolar affective disorder
Depressive disorder
Obsessivecompulsive disorder
Panic disorder
Post-traumatic stress disorder
Schizophrenia

7/13
7/10
7/12
7/9
7/18
7/24
7/14
7/7
7/14
7/51

245/214
108/130
132/129
135/177
234/270
146/205
236/211
142/133
128/126
332/414

a. For each disorder, we report the number of included and published studies and
the total number of patients and healthy controls in the included studies. See Online
supplement DS1 for details of the included studies.

dementias, are included in both chapters, and therefore could be

classified either as neurological or psychiatric. For the purpose
of the present investigation, we classified neurodegenerative
disorders as neurological; we then performed confirmatory
analyses to examine how classifying dementias as psychiatric
would have an impact on the results.
From each study we extracted the coordinates for grey matter
decreases detected in patients relative to controls using a statistical
threshold of either P50.05 (whole-brain corrected) or P50.001
(uncorrected). Data were extracted independently by two
researchers (N.A.C., J.S.) and any discrepancies resolved by
consensus. Coordinates reported in Talairach space were
transformed into Montreal Neurological Institute (MNI)
coordinates.20
Meta-analysis
In order to obtain a representative picture of the regions affected
in neurological and psychiatric disorders, respectively, it was
critical that every disorder within its class weighed the same in
the final summary. This was ensured in two ways. First, we
included the same number of studies per disorder (i.e. seven); if
a disorder had been studied in more than seven studies, then
the studies included in our investigation were selected randomly.
However, the average sample size tended to be larger for those
disorders investigated in a greater number of studies (for example
schizophrenia) than those investigated in a smaller number of
studies (for example panic disorder). This means that a random
sample of seven studies for each disorder would still result in
different disorders having more or less influence on the results,
depending on the sample size of the individual studies. To control
for this, we applied a disorder-specific weight to each of the
studies included, so that the sum of the weighted sample sizes
was equal across disorders. We should highlight that, using this
approach, larger studies would still weigh more than smaller
studies within each disorder.
Selected studies from each disorder were meta-analysed
using the activation likelihood estimation (ALE) method as
implemented in GingerALE software (www.brainmap.org/ale),21
using a P-value of 0.05 (false-discovery rate corrected) and a
cluster size threshold of 200 mm3. This method models the peak
structural differences taking into account the between-subject
variance, but also considers empirically informed betweenlaboratory variance. The comparison between the two classes of
disorders was performed using the ALE subtraction analysis;22 this
involves comparing the difference between the two ALE maps
against a null distribution of differences of two similarly sized
groups of studies built from random permutation (5000
iterations). Differences between the two classes of disorders were
identified using P50.05 (false-discovery rate corrected) and a
cluster size threshold of 200 mm3.
Characterisation of network-level brain abnormalities
Any significant abnormalities were characterised by mapping
them onto functional networks obtained from a previous
investigation using independent component analysis (ICA).23
Readers are referred to the original reference for further details
on these networks, which have been made available to the
neuroimaging community as masks by the authors. We also
report the anatomical coordinates of the peak weights for each
network in online Table DS1). By examining the ratio between
number of affected voxels within a specific network and expected
number of affected voxels in that network, we were able to
establish whether the number of abnormal voxels were randomly

Neuroimaging distinction between neurological and psychiatric disorders

distributed across the different networks. To test whether

psychiatric or neurological disorders affected differentially ICAdefined brain networks, we compared the difference between their
ratios to a null model based on permutation tests. We first
randomly permuted the group label (psychiatric or neurological)
of the included disorders, resulting in two new random groups of
psychiatric and neurological disorders. After meta-analysing them
individually, we calculated the difference between their ratio of
affected voxels within each ICA network. This process was
repeated 100 times. Statistical inferences were then obtained by
comparing the observed difference in each ICA network to this
null-model (one-tailed).
Estimating heterogeneity within and between classes
In order to characterise the heterogeneity of the two classes of
disorders, we computed neuroanatomical variability within each
class and between classes. We first meta-analysed each single
disorder and computed a measure of similarity between every pair
of disorders. This measure was based on the Jaccard index, which
is equal to the overlap (intersection) of abnormal voxels
normalised by the union of abnormal voxels (i.e. voxels abnormal
in both disorders). We then compared the similarity within
neurological disorders against that within psychiatric disorders,
as well as the similarity within each class against that between classes.

when dementias were classified as neurological, whereas it was

primarily implicated in psychiatric disorders when dementias were
classified as psychiatric (online Fig. DS2).
We then identified regions showing different alterations in
neurological and psychiatric disorders by directly comparing the
two classes of disorders. As shown in Fig. 2, neurological disorders
affected a number of regions more than psychiatric disorders did,
including the basal ganglia (thalamus, caudate, putamen and
globus pallidus), insula, lateral and medial temporal cortex
(including the hippocampus), and sensorimotor areas. Psychiatric
relative to neurological disorders showed a more restricted range
of abnormalities, located in the medial frontal cortex, anterior
and posterior cingulate, superior frontal gyrus and occipital cortex
(bilateral lingual gyrus and left cuneus).
Network-level brain abnormalities

We first identified those regions consistently affected in

neurological and psychiatric disorders separately. As shown in
Fig. 1, neurological disorders affected a widespread network
comprising the caudate, thalamus, hippocampus, insula, anterior
cingulate and sensorimotor cortex bilaterally (see online Table
DS2 for details); similarly, psychiatric disorders affected a bilateral
network of regions comprising the caudate, hippocampus, insula
and anterior cingulate (online Table DS3). Classifying dementing
illnesses (Alzheimers, frontotemporal and dementia in
Parkinsons Disease) as psychiatric rather than neurological did
not change the overall pattern of results; however, it did result
in noticeable changes throughout the temporal cortex. This area
of the cortex was primarily implicated in neurological disorders

We proceeded by mapping significant abnormalities onto

networks obtained from ICA. Specifically, we explored the
distribution of abnormalities in each class of disorders among
ten well-known networks obtained from ICA from resting
state functional MRI data.23 This additional analysis provided
us with information about which functional networks are
disproportionately targeted by each group of disorder (for
example how many more/less voxels are abnormal in a network
compared with the expected number if the distribution of lesions
were homogeneously spread across different networks). This
revealed that both classes of disorders affected the auditory
temporal network (M7), which includes language areas, and the
frontal executive control network (M8), which includes cingulate
and paracingulate regions, more than expected. By contrast, both
neurological and psychiatric disorders tend to affect the cerebellar
(M5) network less than expected. Figure 3 shows that neurological
disorders appeared to affect the sensorimotor network (M6) and
frontoparietal network (M9) more than psychiatric disorders. By
contrast, psychiatric disorders appeared to affect visual networks
(M1 and M3) and the default mode network (M4) more than
neurological disorders. Permutation tests showed that the two
classes of disorders significantly differed in the visual cortex
(M1) and default-mode network (M4) (P50.01 and P = 0.04,
respectively, one-tailed permutation test). This was mostly driven
by neurology disorders affecting these networks less than was
expected.

(a)

(b)

Results
Neuroanatomy of neurological and psychiatric
disorders

Fig. 1

Areas affected in neurological disorders (a) and psychiatric disorders (b) (P50.05 false-discovery rate corrected).

Crossley et al

Neurological 4 Psychiatric

Psychiatric 4 Neurological

Fig. 2

Differential abnormalities between neurological and psychiatric disorders (P50.05 false-discovery rate corrected).

Heterogeneity within and between classes

We also estimated the neuroanatomical heterogeneity within and
between classes (online Fig. DS3). The degree of similarity within
each class of disorders was higher than the degree of similarity
between classes (P50.015, t-test). In addition, the degree of
similarity was higher for neurological than psychiatric disorders
(P51074, t-test).
M1

Less than expected (log)

More than expected (log)

Visual

M2
Visual

M3
Visual

M4

Discussion
Main findings
The way in which clusters of symptoms are grouped into different
disorders is an important clinical issue, as it determines both
diagnosis and treatment of individual patients. The aim of our
M5

M6

Default mode Cerebellar Sensorimotor

M7
Auditory

M8

M9

M10

Executive

Frontoparietal

Frontoparietal

71

Psychiatric
71

Fig. 3

Neurological

Network fingerprint for neurological (white) and psychiatric (grey) disorders.

This figure illustrates the distribution of neuroimaging abnormalities across networks for psychiatric and neurological disorders respectively. In particular, it shows whether psychiatric
or neurological disorders affect each of our ten networks of interest more or less than expected (based on the total number of affected voxels). Values correspond to the logarithm
of the ratio between observed and expected, with values below zero denoting that abnormalities are less frequent than expected and values above zero denoting that abnormalities
are more frequent than expected. The asterisk indicates a statistically significant difference between the two classes at P50.05 (one-tailed permutation tests).

Neuroimaging distinction between neurological and psychiatric disorders

investigation was to contribute in this discussion by examining

whether disorders currently classified as neurological and
psychiatric have distinct neuroimaging correlates. We found that
both types of disorders were associated with widespread
alterations in cortical and subcortical areas (Fig. 1). In a previous
study using a similar approach, we showed that this similarity is
driven by the network organisation of the brain.24 This
observation challenges the traditional distinction between
disorders of the mind and disorders of the brain, and provides
fresh support for a new conceptual framework in which both
neurological and psychiatric disease are considered disorders of
the nervous system.6 Although there were many similar brain
regions affected across types of disorders, our meta-analytic
techniques also showed differences between the two groups of
disorders. The basal ganglia, insula, lateral and medial temporal
cortex, and sensorimotor areas showed greater impairment in
neurological disorders; whereas the medial frontal cortex, anterior
and posterior cingulate, superior frontal gyrus and occipital cortex
(bilateral lingual gyrus and left cuneus) showed greater
impairment in psychiatric disorders. These structural differences
between the two classes of disorders affected distinct functional
networks, with the effect of neurological disorders evident in the
sensorimotor and frontoparietal networks and the effect of
psychiatric disorders evident in the visual and default mode
networks. Although many of these structural differences are
consistent with our existing knowledge of neurological and
psychiatric disorders, the greater effect of psychiatric than
neurological disorders in visual areas might be surprising to some
readers. Closer inspection of the data indicated that this difference
was mostly driven by neurological disorders affecting these areas
less than was expected based on the total number of significant
voxels (Fig. 3). By contrast, abnormalities in occipital areas have
often been detected in studies of post-traumatic stress disorder25
or schizophrenia.26
Disorders within each class, either neurological or psychiatric,
were more similar to each other in terms of neuroanatomical
alterations than disorders belonging to different classes. In
addition, psychiatric disorders were more dissimilar than
neurological disorders, speaking of a more heterogeneous class.
Taken collectively, these results provide some neuroimaging evidence
for the existing distinction between neurological and psychiatric
disorders as separate classes of disease. Although such neuroimaging
evidence does not necessarily mean that the existing distinction is
useful from a clinical perspective, it may inform the current debate
on whether the current system should be reconsidered.6
The observation of neuroimaging differences between
neurological and psychiatric disorders was based on group-level
statistical inferences; this raises the question of whether it might
be possible to use multivariate statistical learning techniques to
identify individual disorders as neurological or psychiatric. We
performed an exploratory analysis using a multivariate statistical
learning technique known as support vector machine;27 this,
however, did not yield any significant findings, suggesting that
group-level differences do not necessarily allow accurate inferences
at the level of the individual disorder. This might be as a result of the
high degree of neuroanatomical heterogeneity within each class or,
alternatively, a suboptimal methodological approach. In particular,
we attempted to classify individual disorders by modelling neuroanatomical abnormalities as spheres centred on the peak coordinates
reported by the individual studies, without taking the heterogeneous
spatial extent of these abnormalities into account.

neurological or psychiatric disorders that had been examined in

more than seven VBM studies may not have resulted in a
representative random sample of each group of disorders. We tried
to overcome this limitation by including as many disorders as
possible in order to increase the level of representativeness within
each class. Similarly, we included disorders with seven or more
VBM studies. As previously described, we selected this number
based on a compromise between trying to maximise the number
of different disorders included, and the precision of the neuroimaging estimate of each disorders. Second, the ALE meta-analysis
is based on the frequency with which an effect has been found
with a selected statistical threshold, but does not consider
variability in the effect size across studies.29 Third, we compared
the two classes of disorders in terms of grey matter volume only.
Ideally, any biologically informed classification of disease should
be based on multiple domains including, for example, both brain
structure and function, and should use multiple approaches such
as neuroimaging, genetics and pharmacology. Finally, we did not
consider the effects of age and gender in the different disorders.
However, we note that the original VBM studies typically used
patient and control groups that were balanced according to age
and gender; this means that our results are unlikely to be a
result of these confounding variables.
In conclusion, we have shown some divergent neuroimaging
findings in neurological and psychiatric disorders; this suggests
that neurological and psychiatric disorders represent two distinct
classes of disorders from a neuroimaging perspective.
Nicolas A. Crossley, MRCPsych, PhD, Jessica Scott, Department of Psychosis
Studies, Institute of Psychiatry, Psychology and Neurosciences, Kings College London,
London; Ian Ellison-Wright, MRCPsych, Avon and Wiltshire Mental Health
Partnership NHS Trust, Salisbury; Andrea Mechelli, PhD, Department of Psychosis
Studies, Institute of Psychiatry, Psychology and Neurosciences, Kings College London,
London, UK
Correspondence: Andrea Mechelli, Department of Psychosis Studies, Institute
of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK.
Email: a.mechelli@kcl.ac.uk
First received 8 Nov 2013, final revision 16 Oct 2014, accepted 19 Oct 2014

Funding
A.M. is funded by a research grant from the Medical Research Council (grant ID 99859).
N.C. is funded by a Wellcome Trust Clinical Research Training Fellowship (WT093907).
The data used in this study were subsequently used in a collaborative project with the
BrainMap database (supported by NIH/NIMH R01 MH074457) where they are now available.
The sources of funding had no role in study design, data collection, analysis, interpretation,
writing the report, or in the decision to submit the article for publication.

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Limitations
The present investigation has several limitations. First, our results
might suffer from a selection bias.28 In particular, the inclusion of

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Crossley et al. Neuroimaging distinction between neurological and psychiatric

disorders. Br J Psychiatry
doi: 10.1192/bjp.bp.114.154393
Online supplement DS1
Details of included studies (references)

ADHD (1-7)
Alzheimers disease (8-14)
Anorexia Nervosa (15-21)
Asperger (22-28)
Bipolar Affective Disorder (29-35)
Dementia in Parkinsons Disease / Lewy Body (36-42)
Dyslexia (43-49)
Dystonia (50-56)
Frontotemporal Dementia (57-63)
Ataxia (64-70)
Huntingtons (71-77)
Juvenile Myoclonic Epilepsy (78-84)
Amyotrophic lateral sclerosis (85-91)
Multiple sclerosis (92-98)
OCD (99-105)
Panic disorder (106-112)
Parkinson (41, 113-118)
Progressive Supranuclear Palsy (118-124)
PTSD (125-131)
Major depressive disorder (132-138)
Schizophrenia (139-145)
Temporal Lobe Epilepsy
- Left (146-152)
- Right (146, 149, 151-154)

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Table DS1 Peak voxels within each ICA network.

ICA Network

M1
M2

Visual
Visual

M4

Default Mode

M5
M6

Cerebellar
Sensori-motor

M7

Auditory

M3

Visual

M8

Executive

M9

Fronto-parietal

M10

Fronto-parietal

MNI coordinates
y

-6
-10
-8
46
-46
-28
30
2
-44
2
54
-4
44
-38
0
-62
60
0
-28
30
4
12
-6
56
52
6
-48
-42
-32
-62
-4

-74
-104
-14
-66
-76
-70
-48
-58
-60
56
-62
-50
-16
-26
-12
-24
0
36
54
52
-18
-76
-78
-50
12
32
-52
50
-68
-54
24

8
-4
4
-10
-4
-20
-18
30
24
-4
28
-34
48
56
50
14
-2
22
14
14
8
34
34
46
42
40
50
-2
48
-8
42

Table DS2 Abnormalities consistently found across neurological disorders.

Cluster
1

Volume
(mm3)
142496

4240

3
4

3640
2672

2504

6
7
8
9
11

1864
1336
1168
1120
1016

12
13

848
808

MNI
coordinates
x
y
z
10
4
8
0
-16 10
-28 -38 -2
-10 10
8
-30 -16 -18
42 -10 8
28
-6 -18
50 12 24
52 -10 38
12 -32 2
2
2 -12
-40
6
4
-48 10 24
38 -24 -14
-54 -14 44
56 -20 46
-46 10 48
-24
0
10
24
4
8
54 -16 -8
-58 -4
4
-48 16 -18
-40 -14 -32
0
38 24
-2
46 24
4
48 14
-4
30 16
-46 -30 46
-32 -20 60
-32 -34 62
-40 -64 -12
58
4
20
52
8
0
8
-28
-28

-52
-10
-72
-64
-24
-32
-24
-88
44

Label
R Caudate
L Thalamus
L Hippocampus
L Caudate
L Parahippocampus
R Insula
R Parahippocampus
R Inferior frontal gyrus
R Precentral gyrus
R Thalamus
L Anterior cingulate
L Insula
L Inferior frontal gyrus
R Hippocampus
L Postcentral gyrus
R Postcentral gyrus
L Middle frontal gyrus
L Putamen
R Putamen
R Superior temporal gyrus
L Precentral gyrus
L Superior temporal gyrus
L fusiform
Left cingulate
L medial frontal gyrus
R medial frontal gyrus
L anterior cingulate
L inferior parietal lobe
L Precentral gyrus
L inferior parietal lobe
L fusiform
Right inferior temporal
-10 gyrus
30 R Cingulate gyrus
24 R Cuneus
40 R Parietal lobe
54 R paracentral gyrus
52 L precuneus gyrus
44 R cingulate gyrus
20 L middle occipital gyrus
18 L Middle frontal gyrus

14
15
16
17
18
19

720
640
616
600
592
568

20
21
22
23
24
25
26
27
28
29
30
31

560
552
536
488
456
424
392
336
288
272
272
264

-54
-60
-24
26
-42
30
32
46
12
-4
62
8
54
28
32
18
-48
-64
6

-52
-52
-76
-4
54
-86
-90
-58
-50
8
-42
-6
26
52
32
34
-32
-34
10

34
6
40
50
-10
30
20
52
24
34
12
58
14
20
40
32
2
14
56

L parietal gyrus
L middle temporal gyrus
L precuneus gyrus
R middle frontal gyrus
L Inferior frontal gyrus
R cuneus
R middle occipital gyrus
R superior parietal gyrus
R posterior cingulate gyrus
L cingulate gyrus
R superior temporal gyrus
R medial frontal gyrus
R Inferior frontal gyrus
R superior frontal gyrus
R middle frontal gyrus
R medial frontal gyrus
L Superior temporal gyrus
L Superior temporal gyrus
R medial frontal gyrus

Table DS3 Abnormalities consistently found across psychiatric disorders.

Cluster
1

Volume
(mm3)
14576

10104

7056

4504

4456

3752

3712

2952

2840

10
11
12
13

2464
2032
1936
1680

MNI
Coordinates
x
y
z
8
14
0
-20
-6 -22
-2
8
-2
-18
4
12
-34
-30
-16
-36
4
-6
-2
10
6
16
2
54
16
36
34
44
44

-26
-12
2
-14
18
48
48
60
48
64
38
6
26
20
40
-76
-78

-28
-18
-10
-38
12
-8
26
26
-2
-2
44
6
-18
4
-16
8
-12

56
-22
-12
-12
-12

-64
-20
-28
-66
-50

-2
70
60
20
2

-16
2
-10

-40
-82
-88

6
8
12

18
34
-56
-46
-36
-4
38
32

-6
-6
2
8
22
16
46
-22

-24
-26
-4
-10
-2
26
16
-16

Label
R Caudate
L amygdala
L caudate head
L putamen
L parahippocampal
gyrus
L hippocampus
L globus pallidum
L uncus
R caudate
L anterior cingulate
L medial frontal gyrus
R superior frontal gyrus
R anterior cingulate
R medial frontal gyrus
L superior frontal gyrus
R precentral gyrus
R inferior frontal gyrus
R insula
R middle frontal gyrus
R middle occipital gyrus
R fusiform gyrus
R inferior temporal
gyrus
L precentral gyrus
L paracentral gyrus
L posterior cingulate
L lingual gyrus
L parahippocampal
gyrus
L lingual gyrus
L cuneus
R parahippocampal
gyrus
R amygdala
L superior frontal gyrus
L insula
L insula
L cingulate gyrus
R middle frontal gyrus
R hippocampus

14

1504

12
4
-2
-2

42
38
42
36

-30
-26
-32
-34

15
16

1368
1288

-44
42

-68
-52

10
-20

17
18

1208
1064

19
20

1016
976

64
2
4
-46
28

-4
-6
-14
4
-96

0
8
10
34
-4

20

-92

-4

976

-66

-20

22
23
24
25

944
840
824
808

-64
-46
42
-58
48

-32
38
28
22
-18

10
-16
36
14
12

26
27
28
29
30
31
32

800
728
712
704
624
528
528

-24
12
50
40
10
-22
-18

-58
-26
36
-14
28
-2
54

-2
44
-14
-38
50
-46
24

33
34

504
504

58
-8

-38
2

-14
54

35

488

54

-20

36

480

37
38
39
40

456
424
384
376

30
32
-52
-22
-4
30

46
56
24
68
74
2

41
42

352
352

-20
-16

-52
-52
-32
4
-30
4
102
42

21

R inferior frontal gyrus

R medial frontal gyrus
L orbital gyrus
L rectal gyrus
L middle temporal
gyrus
R fusiform gyrus
R superior temporal
gyrus
L thalamus
R thalamus
L precentral gyrus
R lingual gyrus
R inferior occipital
gyrus
L superior temporal
gyrus
L superior temporal
gyrus
L middle frontal gyrus
R precentral gyrus
L inferior frontal gyrus
R insula
L parahippocampal
gyrus
R cingulate gyrus
R middle frontal gyrus
R uncus
R superior frontal gyrus
L uncus
L superior frontal gyrus
R middle temporal
gyrus
L medial frontal gyrus
R superior temporal
gyrus
R superior parietal
lobule
R precuneus
L inferior parietal gyrus
L superior frontal gyrus
L paracentral lobule
R putamen

14 L middle occipital gyrus

16 L medial frontal gyrus

43
44

344
344

-10
24
16

12
46
40

45
46
47
48

280
272
264
256

49
50

232
208

50
-32
-34
-16
-10
2
-8

14
34
-92
-54
-58
-12
-94

-22 L medial frontal gyrus

18 R medial frontal gyrus
16 R anterior cingulate
R superior temporal
-34 gyrus
32 L middle frontal gyrus
-8 L inferior occipital gyrus
36 L cingulate gyrus
32 L precuneus
56 L medial frontal gyrus
-2 L inferior frontal gyrus

Figure DS1. Flow diagram of study selection.

A. Neurological Disorders

Abbreviations : ALS= Am yotrophic laterals cleros is ; ALZH= Alzheim ers ; DEM PARK = Dem entia inPark ins ons ;
DYSL= Dys lexia; DYST= Dys tonia; FTD= Frontotem poraldem entia; ATAX= Ataxia;
HU NT= Hu nting tons dis eas e; J M E= J u venile m yoclonic epileps y; M S= M u ltiple s cleros is ;
PARK = Park ins ons ; PSP= Prog res s ive s u pranu clear pals y; TLEl= Tem porallobe epileps y, left;
TLEr= Tem porallobe epileps y, rig ht.

B. Psychiatric Disorders

Abbreviations : ADHD= Attentiondeficit hyperactivity dis order; ANOREX= Anorexia nervos a;

ASPERG = As perg er s yndrom e; BPAD= Bipolar affective dis order;
DEPR= M ajor depres s ive dis order; OCD= Obs es s ive com pu ls ive dis order;
PANIC= Panic dis order; PTSD= Pos t-trau m atic s tres s dis order; SCZ= Schizophrenia.

Figure DS2 Effect of classifying dementias (Alzheimer's, Dementia in

Parkinson's, Frontotemporal) as neurological or psychiatric disorders. Note that
differences between the two statistical analyses are mostly limited to temporal
lobe regions; these regions tend to be primarily implicated in the class of
disorders that includes the dementias.

Figure DS3 Heatmap of similarity between disorders. Note that neurological

disorders were significantly more similar than psychiatric disorders (P<0.015).

Neuroimaging distinction between neurological and psychiatric

disorders

Nicolas A. Crossley, Jessica Scott, Ian Ellison-Wright and Andrea Mechelli

BJP published online June 4, 2015 Access the most recent version at DOI: 10.1192/bjp.bp.114.154393

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