NEW RESEARCH

Amygdala and Hippocampus Enlargement

During Adolescence in Autism
Wouter Groen,

M.D., Ph.D.,

Michelle Teluij, M.D., Jan Buitelaar,

Indira Tendolkar, M.D., Ph.D.

M.D., Ph.D.,

Objective: The amygdala and hippocampus are key components of the neural system
mediating emotion perception and regulation and are thought to be involved in the
pathophysiology of autism. Although some studies in children with autism suggest that there
is an enlargement of amygdala and hippocampal volume, findings in adolescence are
sparse. Method: We measured amygdala and hippocampus volume in a homogeneous
group of adolescents with autism (12 through18 years; n 23) and compared them with an
age-, sex-, and IQ-matched control group (n 29) using a validated automated segmentation
procedure in 1.5-T magnetic resonance images. All analyses were adjusted for total brain
volume. Results: Repeated-measures analysis revealed a significant group hemisphere
brain structure interaction (p .038), even when corrected for total brain volume. Post-hoc
analysis showed that the right amygdala and left hippocampus were significantly enlarged (p
.010; p .015) in the autism compared with the control group. There were no significant
correlations between age and amygdala or hippocampus volume. Conclusions: The abnormal enlargement of the amygdala and hippocampus in adolescents with autism adds to
previous findings of enlargement of these structures in children with autism. This may reflect
increased activity of these structures and thereby altered emotion perception and regulation.
Our results could therefore be interpreted in light of developmental adaptation of the autistic
brain to a continuous overflow of emotional learning experiences. J. Am. Acad. Child Adolesc.
Psychiatry, 2010;49(6):552560. Key Words: autism, emotion, amygdala, hippocampus

Autism is a neurodevelopmental disorder characterized by impaired social interaction, language and communication
deficits, and stereotyped repetitive behavior. Despite the great variation in clinical presentation, a
central feature of autism is the impairment in
social and emotional behavior. Persons with autism typically do not exhibit adequate socioemotional reciprocity, have difficulty understanding social-emotional cues, and often display
blunted affect.1 Development of adequate socioemotional behavior depends on the structural
and functional integrity of brain regions mediating emotion perception and regulation.2 Volumetric investigation of these brain regions may
provide important clues that can help to eluci-

This article is the subject of an editorial by Dr. Bradley Peterson on

page 533.
Supplemental material cited in this article is available online.

date which structures contribute to the emotional

impairment in autism.
Converging evidence from studies in human
beings and in animals suggests that emotion
perception and regulation is mediated by a brain
circuit in which the amygdala and hippocampus
are central components.3 The amygdala enables
the instantaneous recognition and evaluation of
emotionally salient stimuli, subsequent production of affective states, and regulation of the
autonomic response.4 Apart from its general role
in memory, the hippocampus is implicated in the
regulation of affective behavior elicited by emotionally salient stimuli. It does so through inhibitory connections with the amygdala and other
structures involved in emotion perception, enabling the production of contextually appropriate affective behavior.4 Thus, structural and functional abnormalities of the amygdala and
hippocampus may result in impaired affective
behavior and emotion regulation, which has indeed been shown in a variety of psychiatric

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TABLE 1

Overview of Studies on Amygdala and Hippocampus Volume in Autism

Study

Group

First Author, Year, Ref.

PD

Dager 20075
Nicolson 20066
Rojas 20067
Nacewicz 20068
Palmen 20069a
Rojas 200410
Schumann 200411
Schumann 200411
Herbert 200312
Bigler 200313
Sparks 200214
Pierce 200115
Saitoh 200116
Haznedar 200017
Howard 200018a
Abell 199919
Aylward 199920
Piven 199821
Saitoh 199522

29
21
24
23
42
15
19
19
17
38
29
7
59
10
10
15
14
35
33

16

AS

11
11

16

Sex

HP

Age

IQ

13
24
23
26
42
17
11
11
15
27
26
8
51
17
10
15
14
36
32

3-4
6-16
7-44
8-25
7-25
19-47
7-12
12-18
7-11
7-31
3-4
20-42
2-49
27b
16-40
28,8b
20,5b
12-29
13,8b

45
45
47
54
81
11
41
41
22
65
56
15
92
30
20
24
28
71
58

13
0
0
0
3
11
0
0
0
0
15
0
18
4
0
6
0
25
7

NR
70
60-133
97c
80
62-140
/70
/70
80
62
NR
73-102
41-135
55-125
NR
NR
106c
52-136
NR

MF
Sex
Age,
Age,
Age,
Age,
Age,
Age
Age
Sex
Age,
Age
Age,
NR
NR
Age,
Age,
Age,
NR
Age

TBVa

HC, VIQ
IQ, educ
sex
sex, IQ
sex

sex
sex

VIQ, sex
sex, IQ
sex, IQ

AM

L1

L2 L1
1
1

1
2d 2d

1e 1
2
2f

L1
2
2

Note: A autistic disorder; AM amygdala volume; AS Aspergers disorder; C controls; educ education; F female; HC head circumference;
HP hippocampus; IQ intelligence quotient; M male; MF matching factors; NR not reported; PD pervasive developmental disorder not
otherwise specified; s shape; TBVa total brain volume adjusted; v volume; VIQ verbal IQ.
a
Autism sample includes people with Aspergers disorder.
b
Mean age.
c
Mean IQ.
d
Combined measurement of the amygdala and hippocampus.
e
Disproportional enlargement of the amygdala in the autistic disorder subgroup.
f
Decreased area dentata (part of the hippocampus).

disorders.23 It is therefore hardly surprising that

structural and functional abnormalities of amygdala and hippocampus have been found in autism.24,25 Yet, it is important to take into account
that volumetric abnormalities of the amygdala
and hippocampus in autism may have a different
impact, as they are linked to developmental
abnormalities rather than to disease-state abnormalities (as has been shown, for example, in
depression).26 Investigating amygdala and hippocampus volume throughout development in
children or adolescents with autism may therefore reveal crucial insights in the neurobiology of
autism.
Several studies have investigated amygdala
volume in autism. As is evident from Table 1,
there is substantial variance with respect to age
ranges, clinical presentation, and methodological
approaches in the volumetric amygdala studies.
Nevertheless, there seems to be convergence
across studies toward enlargement of the amyg-

dala in children with autism and disappearance

of this overgrowth in adults with autism. There is
to date, however, no report of a homogenous
sample of adolescents with autism.
Findings of abnormal amygdala volumes in autism fit microscopic evidence from neuropathology
studies that have demonstrated increased cellpacking density, abnormally small neurons, and a
decreased number of neurons in the amygdala,
indicative of a curtailed maturation process.27 Postmortem studies25 and neuro-imaging studies5 have
additionally demonstrated structural abnormalities
in the hippocampus in autism. The neuropathologic abnormalities observed in the hippocampus
are consistent with those observed in the amygdala.25
Hippocampal volume studies in autism show an
inconsistent pattern. The majority of studies did not
find significant volume differences between the
autism and control group, but the authors mainly
focused on adults or included participants of a
broad age range.3,17,18,21 Nonetheless, there is some

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TABLE 2

Participant characteristics (mean SD)

Age (years)
Sex (m/f)
Full scale IQ
Performance IQ
Verbal IQ
ADI: social deficits
ADI: communication deficits
ADI: repetitive behavior

Autism group (n23)

Controls (n29)

p-value

Statistic (t or 2)

15.15 1.86
20/3
99.52 20.12
99.39 16.64
99.52 21.68
16.30 5.89
20.00 8.09
12.52 4.93

15.65 1.66
23/5
104.93 8.68
105.24 11.56
104.90 9.62
NA
NA
NA

0.31
0.68
0.23
0.14
0.28

1.03
0.17
1.20
1.49
1.11

Note: ADI Autism Diagnostic InterviewRevised; IQ intelligence quotient; NA not applicable.

indication of an enlargement of the hippocampus

in children with autism and a normalized volume
in adults with autism (Table 1). Again, evidence for
volumetric abnormalities of this structure during
adolescence is missing.
The contradictory results from the aforementioned volumetric studies investigating amygdala and hippocampus in autism may be caused
by the heterogeneity of the autism samples included in these studies. As the phenotypic variation probably reflects heterogeneity on the neurobiologic level, it is important to investigate
volumetric differences in homogeneous samples
to provide more insight into the neuropathologic
underpinnings of autism. As many studies found
a volume increase of the amygdala and hippocampus during childhood and normalization
or decrease in adulthood, the aim of the current
study was to evaluate the volume of the amygdala and hippocampus in a homogeneous, welldefined group of adolescents with autism (between 12 and 18 years of age) and a matched
control group.
Most studies used manual tracing procedures,
but differences in the anatomic definitions of the
amygdala and hippocampus impede the comparability of the studies. We used an automated
segmentation procedure, which is shown to be
equal in accuracy to manual tracing methods.28

METHOD
Participants
Two groups participated in the study: 29 typically
developing (TD) adolescents (five girls and 24 boys)
and 23 adolescents with autism (three girls and
20 boys). All participants were between 12 and 18
years of age, right-handed, and Caucasian. Written
informed consent was obtained from all participants

and their parents after complete description of the

study. The study was approved by the local medical
ethical committee.
Matching was performed rigorously; more than 200
TD adolescents from local high schools were assessed
for verbal IQ, performance IQ and full-scale IQ using
a short form of the Wechsler Intelligence Scale for
Children III (WISC-III) including Vocabulary, Similarities, Block Design, and Picture Completion to find
suitable matches. As a result, the autism group was
matched without significant differences in age, sex,
total intelligence quotient (IQ), performance IQ, and
verbal IQ (Table 2). In the autism group, seven
participants had previously used psychotropic medication, of whom four had used risperidone and two
pipamperone.
The participants with autism were recruited
through Karakter Child and Adolescent Psychiatry
University Center in Nijmegen. Diagnostic assignment
followed DSM-IV criteria for autistic disorder. Diagnostic characterization included the Autism Diagnostic
InterviewRevised29 as assessed by a trained clinician
and a series of clinical assessments that included
detailed developmental history, clinical observation,
medical work-up, and cognitive testing. The participants with autism were tested with the full Wechsler
Intelligence Scale for Children III. To screen for the
presence of psychiatric disorders or behavior problems
in the controls, CBCL questionnaires were completed
by the parents/guardians of the control participants,
and TRF questionnaires were completed by a teacher
at school. None of the control participants scored
within the clinical range on any of the CBCL or TRF
problem scales. Exclusion criteria included any medical condition affecting CNS function, neurological disorders, and substance abuse. In particular, none of the
participants had a history of seizure disorder, as this is
known to affect the volumes of interest.30,31

Data Acquisition and Procedure

Neuroimaging data were acquired on a 1.5-T Siemens Sonata MR scanner at the Donders Institute for

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TABLE 3

Summary of Repeated-Measures Analysis of Covariance Results

Effect
Group
Brain structure
Hemisphere
Group brain structure
Group hemisphere
Brain structure hemisphere
Brain structure hemisphere group

df

F ratio

1.49
1.49
1.49
1.49
1.49
1.49
1.49

5.53
32.57
0.28
1.28
1.07
0.13
4.55

.023
.001
.598
.264
.307
.722
.038

Note: Df degrees of freedom.

Brain, Cognition and Behavior. For each subject, a

T1-weighted, whole-brain scan was collected
(MPRAGE; TI 850 ms, TR 2250 ms, TE 3.68 ms, flip
angle 15, field of view [FoV] 256 256 176 mm,
voxel size 1.0 1.0 1.0 mm). The participants were
familiarized with the set-up and normal scanning
procedures before the actual MR acquisition by
means of a 30-minute introductory rehearsal in a
separate replica (dummy) scanner.

MRI Volumetric Analysis

Volumetric analysis of the amygdala and hippocampus was performed with Freesurfer (4.0.5 version), an
automated whole-brain segmentation procedure.28 We
used Freesurfer in the fully automated form. Briefly,
the processing stream comprises removal of the skull
and dura, automated Talaraich transformation, defining the graywhite matter boundary, intensity normalization, and segmentation of subcortical gray matter.
The Freesurfer application enables automatic labeling
of subcortical structures using a probabilistic algorithm. Initially, each image is a rigid body registered to
a probabilistic atlas based on manually labeled images.
Thereafter, the image is morphed to the atlas by a
nonlinear transform, and a Bayesian segmentation
procedure is used. Each voxel in the MRI volume is
automatically assigned to a neuro-anatomical label
based on probabilistic information estimated from a
manually labeled training set. The labeling procedure
is not biased by anatomical variability.32 The segmentation procedure is based on three types of probabilities to disambiguate labels. First, the likelihood that a
given structure occurs at a specific atlas location.
Second, the likelihood of the image intensity given that
tissue class. Third, the probability that a voxel belongs
to a given tissue class based on likelihood of the spatial
configuration of labels. This automated segmentation
and labeling procedure has been shown to be of
accuracy equal to that of manual tracing methods32
and relatively insensitive to changes in acquisition
parameters.28 Examples of amygdala and hippocampal region definitions in 1.5-T MR images can be found
in Figures S1, S2, and S3, available online.

Data Analysis
Statistical analysis was performed with Statistical Program for the Social Sciences (SPSS) Edition 15.0 (SPSS
Inc., Chicago, IL). To investigate the presence of volume
differences between the groups, we performed a group
(autism versus controls) hemisphere (right versus left)
brain structure (amygdala and hippocampus) repeated-measures analysis of covariance, with group as a
between-subjects variable and hemisphere and brain
structure as within-subject variables. In these and subsequent analyses, total brain volume was used as a covariate to control for possible differences in brain volume
between the autism and control group. Post-hoc analyses
of covariance (ANCOVAs) with total brain volume as
covariate were performed to investigate significant effects. To investigate whether the developmental time
course showed a deviant pattern in the autism group, we
calculated Pearsons correlations between age, amygdala,
and hippocampus volume in both participant groups. To
explore whether the brain volumes were associated with
social impairment in autism, we calculated Pearsons
correlations between the social impairment score on the
ADI-R and volumes of the amygdala and hippocampus.

RESULTS
All volumes were distributed normally. Table 3
shows a summary of the results. As expected, the
repeated-measures ANCOVA with TBV as a covariate revealed a significant main effect for brain
structure (F(1,49) 32.57, p .001), reflecting the
larger size of hippocampus when compared with
the amygdala. We also found a significant main
effect of group (autism versus controls; F(1,49)
5.53, p .023) and a significant main effect of
brain structure (amygdala and hippocampus;
F(1,49) 32.57, p .001). Importantly, we found
a significant group hemisphere brain structure interaction (F(1,49) 4.55, p .038), indicating that the group differences of the amygdala
volume and hippocampus volume differed per
hemisphere. Post-hoc ANCOVAs for each hemi-

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sphere showed that the left hippocampus (F(1,49)

6.31, p .015) and the right amygdala (F(1,49)
7.20, p .010) were significantly enlarged in
the autism group (corrected for TBV), whereas
volume differences between groups for left
amygdala (F(1,49) 2.69, p .11) and right
hippocampus (F(1,49) 1.55, p .22) did not
reach significance (TBV corrected). The results
indicate that the enlargement of the left hippocampus and the right amygdala is disproportionate to (i.e., greater than) the enlargement of
the total brain volume in the autism group. It is
noteworthy that the results of the group comparisons were similar without inclusion of TBV as a
covariate.
The volume measurements of the amygdala,
hippocampus, and total brain volume (TBV) are
shown in Figure 1 and Table 4. The volumes of
the amygdala and hippocampus were enlarged
in the autism group. Compared with the control
group, the autism group showed, in the right and
left amygdala, a 7.8% and a 5.8% enlargement
respectively, whereas the left hippocampus demonstrated a 6.25% enlargement and the right
hippocampus a 3.8% enlargement. There were no
significant differences in TBV between the
groups (t 0.825, df 50, p .41).
Age correlated with neither volumes of the
amygdala or hippocampus in the autism group
(left amygdala: r 0.024, right amygdala: r
0.099, left hippocampus: r 0.11, right hippocampus: r 0.172) nor in the control group
(left amygdala: r 0.16, right amygdala: r
0.12, left hippocampus: r 0.07, right hippocampus: r 0.11). Because of the sex specificity in maturation of the amygdala and hippocampus,33 we calculated the age correlations in
male participants separately. However, this did
not reveal a significant correlation between age
and hippocampus or amygdala volume either.
Finally, we did not find significant correlations in
the autism group between social impairment
subscore on the ADI-R and volume of any of the
structures investigated.

DISCUSSION
In the current study, we used an automated
segmentation procedure to investigate amygdala
and hippocampus volumes in a well-defined
sample of high-functioning adolescents with autism (12 through 18 years) and a carefully
matched control group. Although there were no

differences in total brain volume between both

groups, we found a statistically significant enlargement of the right amygdala and left hippocampus even when correcting for total brain
size. Although we did not find significant evidence for enlargement in both hemispheres (possibly because of the small sample size), visual
inspection of the volume scatter plots suggested
that the left amygdala and right hippocampus
were also enlarged in the patient group.
Our finding of an enlarged right amygdala
and left hippocampus in autism supports earlier
studies albeit of different age ranges.7,10,11,14,18,19
Previously, enlargement of the amygdala and
hippocampus has been found in 3- to 4-year-old
toddlers with autism.14 A study later in childhood also provides evidence for persistence of an
enlarged amygdala in 8- to 12-year-olds and
enlarged hippocampus in 8- to 18-year-old children and adolescents with autism, although the
authors did not find a significant enlargement of
the amygdala in older children and adolescents
(12 to 18 years).11 The negative finding in this age
range may be caused by insufficient statistical
power, considering the sample size (n 11), as
visual inspection of the figures provided in that
publication suggest that participants between 12
and 18 years seem to have a larger right amygdala in both the low-functioning as well as the
Aspergers group compared with controls. Furthermore, some authors have observed enlarged
amygdala18,19 and hippocampus volumes7,10 in
adults with autism and mixed samples of children and adults. However, these results have to
be interpreted with caution, because no correction for total brain volume was performed in two
of these studies.18,19
Contrary to our findings, a number of studies observed decreased amygdala and hippocampus volumes or reported negative findings. Several factors may account for this
discrepancy. First, most studies focused on
adults with autism or included a broader age
range, which hampered the detection of developmental changes in volume.8-10,15-17,20,21
Second, several studies investigated small
samples and samples with a heterogenic populations, including mentally retarded individuals
with autism or participants with Aspergers disorder and PDD-NOS.5,8,9,15,17,18,22 Third, several
studies did not tightly match the control
groups.5,13,15,17 Fourth, the anatomical borders
for manual segmentation of the amygdala and

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Volumes of right and left amygdala and hippocampus. Note: ASD subjects with autism spectrum
disorder; TD typically developing participants. *Significantly different from controls at p .05.

FIGURE 1

hippocampus showed a considerable variation

across studies, impeding the comparability of the
results. Finally, at least one paper16 included
patients with autism in which a major proportion

had epilepsy. Epilepsy is known to reduce the

volume of the amygdala31 and hippocampus.30
This may explain the smaller hippocampi in the
autism group reported by Saitoh et al.16

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TABLE 4

Mean Volumetric Data (mm3 SD)

Autism patients (n 23)

Total brain volume

Right amygdala
Left amygdala
Right hippocampus
Left hippocampus

1683259 210873.4
1756.22 199.78*
1685.35 202.49
4724.91 408.00
4875.26 448.16*

Controls (n 29)
1637902 185139.9
1629.10 143.86
1593.45 157.63
4553.31 406.63
4588.38 366.58

*Significantly different from controls at p .05.

In line with another study,9 we did not find a

correlation in the autism or the control group
between age and amygdala or hippocampus volume. This is probably due to the considerable
interindividual variation in brain morphology
that impedes the identification of developmental
changes, and to the narrow age range of the
participants.
Taken together, the data suggest that during
childhood there is a developmental abnormality
in amygdala and hippocampus volume in autism
that persists into adolescence. Thus, the question
arises how this enlargement can be interpreted.
One might speculate that increased use may lead
to an increase in volume, as has been shown for
various brain structures including amygdala in
animal studies34 and the hippocampus35 in human studies. The enlargement of the amygdala
and hippocampus may then reflect an adaptive
effect in response to increased activity throughout childhood and adolescence in autism. Indeed, a significant correlation has been found
between enlarged amygdala volumes and increased anxiety as well as increased social impairments in autism, suggesting that amygdala enlargement may be a predictor of the degree of social
and emotional deficits in autism.36
As the hippocampus has an important regulatory effect on amygdala activity via a dense
network of reciprocal connections, it is plausible
that the hippocampus enlarges in response to
heightened amygdala activity. Although it remains to be elucidated in autism, affective and
cognitive symptoms of stress-related disorders
can, in principle, be attributed to such an interactive effect of both the amygdala and hippocampus.37,38 Given the interaction between amygdala
and hippocampus during emotional memory
processes, our data suggest that the enlargement
of these structures during adolescence in autism
may lead to a broader unselected encoding of
various emotional aspects, thereby changing

emotional learning experiences. Note that a parallel enlargement of both hippocampus and
amygdala throughout childhood and adolescence in autism is more long lasting than, for
example, the state-related volumetric abnormalities during a first depressive episode, in which
only amygdala enlargement has been found.26
Our findings in individuals with autism, combined with previous work, suggest that there is a
volume increase of the amygdala and hippocampus in childhood that persists into adolescence. Yet,
as individuals with autism pass from adolescence
into adulthood, their amygdala and hippocampus
volumes seem to normalize, suggesting that there is
a relative loss of volume. We hypothesize that a
process of chronic stress in autism, possibly caused
by a hyperexcitory amygdala, may lead to initial
hypertrophy of the amygdala and hippocampus
and to damaging effects in later life. Daily life, with
its social demands and constantly changing situations, causes severe stress in children with autism.
A number of studies reported significant correlations between enlarged amygdala volumes and
increased anxiety in autism.36,39 Animal models
have demonstrated that stress initially evokes hypertrophy of the amygdala neuron.34 Yet, chronic
dysregulation of the stress response (also referred
to as allostatic overload) may lead to amygdala and
hippocampal volume decreases in later life. This
has been supported by studies on recurrent major
depression, a disorder that is associated with
chronic stress, in which volume decreases of the
amygdala and hippocampus have been shown late
in the disease process.40,41 Animal studies have
demonstrated that chronic repeated stress evokes
excitotoxic changes in the hippocampus, resulting
in degeneration.42 To conclude, a model of hyperactivity-induced structural changes is compatible
with the majority of previous findings on amygdala
and hippocampus volume in autism, as initial
enlargement in childhood and subsequent decline
of amygdala and hippocampal volume may result

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in either normalized or decreased volumes in

adulthood.
Future combined functional and structural
neuroimaging studies should investigate to what
extent the parallel enlargement of the amygdala
and hippocampus reflects the developmental adaptation of the autistic brain to a continuous
overflow of emotional learning experiences. This
could explain hallmark deficits in autism such as
avoidance of eye contact and social withdrawal,
social fear, high anxiety levels, agitated behavior
in response to sudden changes, and overarousal
in response to particular sensory stimuli. Likewise, further research is needed to establish
whether these abnormalities of the amygdala and
hippocampus are caused by a primary disregulation within these limbic structures or by deficient top-down regulation from the prefrontal
areas of the brain.
There are a few limitations to consider when
interpreting the results of the current study. First,
because our autism sample was restricted to
high-functioning adolescents with autism, our
findings are not representative of the whole autism population. Second, compared with the results from manual tracing methods, the volume
estimates in our study yielded greater hippocampal volumes, as has recently been addressed by
Morey et al.43 This seems to be the case for other
automated segmentation procedures as well. It
has also been shown, however, that manual
segmentation and automated segmentation in
Freesurfer are equally sensitive for detecting
group volume differences. Thus, as the greater
volume estimate is present in the autism group as
well as in the control group, the finding of group
differences are valid. Third, the cross sectional
design limits the inferences that we can make
regarding an abnormal developmental pattern of
the amygdala and hippocampus in adolescents
with autism. As interindividual variation in brain
morphology is probably many times larger than

developmental changes within an individual,44

longitudinal studies are necessary to confirm the
proposed abnormal developmental trajectory of
the amygdala and hippocampus. Establishment
of brain behavior relationships through concomitant functional and structural resonance imaging
will provide promising opportunities to elucidate the neurobiologic underpinnings of this
heterogenic disorder.5-17,20-22
In conclusion, we report an enlargement of
the amygdala and hippocampus in a welldefined sample of high-functioning adolescents
aged 12 through 18 years with autism. Our
findings support a chronically increased activity of these brain structures in early development, evoking initial overgrowth of the amygdala and hippocampus in childhood that
extends into adolescence. Future studies
should focus on the relationship between the
activity and volume of the amygdala and hippocampus over time in subjects with autism
and matched controls. &
Accepted January 6, 2010.
Drs. Groen, Teluij, Buitelaar, and Tendolkar are with the Donders
Institute for Brain Cognition and Behavior, Centre for Cognitive
Neuroimaging, and with Radboud University Nijmegen Medical
Centre, Nijmegen. Drs. Groen and Buitelaar are with Karakter, Child
and Adolescent Psychiatry University Center.
The authors would like to thank Dr. Mark Rijpkema for his invaluable
advice.
Disclosure: Dr. Buitelaar has served as a consultant and on the
advisory board for Shire, Janssen Cilag, Eli Lilly, Pfizer, Organon,
UCB, Servier, and Otsuka. He has served on the speakers bureau for
Janssen Cilag and Eli Lilly. He has received research support from
Shire. Drs. Groen, Teluij, and Tendolkar report no biomedical financial
interests or potential conflicts of interest.
Correspondence to Dr. Wouter B. Groen: Department of Psychiatry,
Radboud University Nijmegen Medical Centre, Reinier Postlaan 10,
PO-Box 9101, 6500 HB Nijmegen, The Netherlands; e-mail: w.
groen@psy.umcn.nl
0890-8567/$36.00/2010 American Academy of Child and
Adolescent Psychiatry
DOI: 10.1016/j.jaac.2009.12.023

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