BRIEF REPORTS
apie, Universitätskrankenhaus-Eppendorf, Hamburg, Germany;
Cees Slooff, Psychosencluster GGZ N-Drenthe, Kenniscentrum
Schizofrenie, Assen, the Netherlands; Jordi Alonso, Health Services
Research Unit, Institut Municipal d’Investigacio Medica, University
of Barcelona, Barcelona, Spain; Josep Maria Haro, Research and Development Unit, Sant Joan de Déu-SSM, Santt Boi, Barcelona, Spain;
Peter B. Jones and Tim Croudace, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.; Martin Knapp, LSE Health and
Social Care, London School of Economics, and Centre for the Economics of Mental Health, Institute of Psychiatry, London.
References
1. Woerner MG, Alvir JM, Saltz BL, Lieberman JA, Kane JM: Prospective study of tardive dyskinesia in the elderly: rates and
risk factors. Am J Psychiatry 1998; 155:1521–1528
2. Jeste DV, Caligiuri MP, Paulsen JS, Heaton RK, Lacro JP, Harris
MJ, Bailey A, Fell RL, McAdams LA: Risk of tardive dyskinesia in
older patients: a prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry 1995; 52:756–765
3. Saltz BL, Woerner MG, Kane JM, Lieberman JA, Alvir JM, Bergmann KJ, Blank K, Koblenzer J, Kahaner K: Prospective study of
tardive dyskinesia incidence in the elderly. JAMA 1991; 266:
2402–2406
4. Chouinard G, Annable L, Mercier P, Ross-Chouinard A: A five
year follow-up study of tardive dyskinesia. Psychopharmacol
Bull 1986; 22:259–263
5. Oosthuizen PP, Emsley RA, Maritz JS, Turner JA, Keyter N: Incidence of tardive dyskinesia in first-episode psychosis patients
treated with low-dose haloperidol. J Clin Psychiatry 2003; 64:
1075–1080
6. Geddes J, Freemantle N, Harrison P, Bebbington P: Atypical antipsychotics in the treatment of schizophrenia: systematic
overview and meta-regression analysis. BMJ 2000; 321:1371–
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7. Correll CU, Leucht S, Kane JM: Lower risk for tardive dyskinesia
associated with second-generation antipsychotics: a systematic
review of 1-year studies. Am J Psychiatry 2004; 161:414–425
8. Haro JM, Edgell ET, Jones PB, Alonso J, Gavart S, Gregor KJ,
Wright P, Knapp M, Group SS: The European Schizophrenia
Outpatient Health Outcomes (SOHO) study: rationale, methods
and recruitment. Acta Psychiatr Scand 2003; 107:222–232
9. Kane JM, Woerner M, Lieberman J: Tardive dyskinesia: prevalence, incidence, and risk factors. J Clin Psychopharmacol
1988; 8(4 suppl):52S–56S
10. Stata Statistical Software: Release 8.0. College Station, Tex,
Stata Corp, 2002
Brief Report
Visuospatial Processing and the Function of Prefrontal-Parietal
Networks in Autism Spectrum Disorders: A Functional MRI Study
Timothy J. Silk, B.B.N.Sc.
Nicole Rinehart, Ph.D.
John L. Bradshaw, D.Sc.
Bruce Tonge, M.D.
Gary Egan, Ph.D.
Michael W. O’Boyle, Ph.D.
Ross Cunnington, Ph.D.
Objective: Individuals with autism spectrum disorders typically have normal visuospatial abilities but impaired executive
functioning, particularly in abilities related to working memory
and attention. The aim of this study was to elucidate the func-
tioning of frontoparietal networks underlying spatial working
memory processes during mental rotation in persons with autism spectrum disorders.
Method: Seven adolescent males with normal IQ with an autism spectrum disorder and nine age- and IQ-matched male
comparison subjects underwent functional magnetic resonance
imaging scans while performing a mental rotation task.
Results: The autism spectrum disorders group showed less activation in lateral and medial premotor cortex, dorsolateral prefrontal cortex, anterior cingulate gyrus, and caudate nucleus.
Conclusions: The finding of less activation in prefrontal regions but not in parietal regions supports a model of dysfunction of frontostriatal networks in autism spectrum disorders.
(Am J Psychiatry 2006; 163:1440–1443)
I
ndividuals with autism spectrum disorders typically
have normal or superior visuospatial abilities (1) but show
dysfunction in working memory (2) as an aspect of executive functioning capability. Functional magnetic resonance
imaging (fMRI) studies of persons with autism spectrum
disorders have shown significant metabolic reduction in
the prefrontal cortex, specifically in divisions of the anterior
cingulate gyrus (3), a region critically involved in executive
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function. Reduced activity has also been observed in the
posterior cingulate (4), which has connections to the lateral
prefrontal cortex and posterior parietal cortex, regions that
aid visuospatial cognition by monitoring sensory events associated with spatial orientation and memory.
Mental rotation is a form of spatial working memory
task that consistently activates superior and inferior parietal regions, underlying spatial attention and visuospatial
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FIGURE 1. Statistical Maps of Between-Groups Random-Effects Analysis for Regions in Which Activation Was Significantly
Greater in the Comparison Group Than in the Autism Spectrum Disorders Group During Performance of a Mental Rotation
Task
z=7
y=14
t value
6.03
2.62
x=2
processing, as well as prefrontal areas, such as the dorsolateral prefrontal cortex and anterior cingulate gyrus, reflecting working memory components (5). The aim of this
study was to examine the functioning of frontoparietal
networks in autism spectrum disorders. We hypothesized
that individuals with autism spectrum disorders would
display impaired activation in the anterior cingulate gyrus
and lateral prefrontal cortices, consistent with known deficits in attentional and executive functions in autism spectrum disorders.
z=58
were screened with the parent form of the Child Behavior Checklist (7) and the Autism Spectrum Screening Questionnaire (8).
Method
The mental rotation task used three-dimensional ShepardMetzler-type block shapes as stimuli (angles of rotation: 45 degrees to 180 degrees), with a target stimulus and four test stimuli
presented concurrently for 10 seconds. Participants were asked to
press one of four buttons on a fiber-optic button console to indicate which of the test stimuli represented the rotated target stimulus. A baseline condition required subjects to indicate which test
stimulus was the closest visual match to a target stimulus with no
rotation involved. A total of 18 rotation stimuli and 18 baseline
stimuli were presented, in alternating blocks of three rotation trials followed by three baseline trials, covering a scanning duration
of 6 minutes 36 seconds.
Seven male adolescents 11–18 years of age (mean=14.7 years,
SD=2.9) who met DSM-IV criteria for autistic disorder or Asperger’s disorder were identified through administration of the
revised Autism Diagnostic Interview (6), a structured parent interview, direct child observations, and reports from teachers and
therapists. All participants were right-handed, and all had a
Wechsler full-scale IQ above 70 (full-scale IQ, mean=114, SD=
16.9; performance IQ, mean=118, SD=16.4). Nine healthy righthanded male comparison subjects with no known medical, neurological, or psychiatric disorders were matched to the autism
spectrum disorders group by age (mean=15.0 years, SD=1.8) and
performance IQ as indicated by the School and College Ability
Tests (Career-Wise, Pty., Ltd., Australia). Comparison subjects
Gradient-echo echo-planar images were acquired on a 3-T GE
Signa MR scanner (TR=3000 ms, TE=40 ms, 128×128 matrix at
1.875×1.875 mm resolution, 22 axial slices, 4.5 mm thick, 0.5 mm
gap). Functional images were realigned, spatially normalized to
Talairach space, and spatially smoothed (8 mm full width at half
maximum) using SPM2 (Wellcome Department of Cognitive Neurology, University College, London). For general linear model
analysis, each rotation trial was modeled as a discrete event, including both temporal and dispersion derivatives. Realignment
parameters were included in the model to account for residual
signal variance related to head motion. Random-effects group
analysis used single-sample t tests to examine activation in the
two groups separately and independent t tests to examine differences between groups. Suprathreshold clusters with a corrected p
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value of <0.05, in which peak voxels had an uncorrected p value of
<0.001, were considered significant.
Results
Mental rotation response times and accuracy did not
differ significantly between the two groups (accuracy: autism spectrum disorders group, 49%, SD=15; comparison
group: 51%, SD=16; response time: autism spectrum disorders group, 5.51 s, SD=1.55; comparison group: 6.48 s,
SD=0.77; Mann-Whitney test, p>0.05). The comparison
group showed significant bilateral activation in the inferior parietal cortex, dorsal premotor cortex, supplementary motor area, and anterior cingulate gyrus. Significant
activation was also observed in the left dorsolateral prefrontal cortex and in the right inferior and medial frontal
gyri, extending into the left caudate head. The autism
spectrum disorders group showed only one significant
cluster in the right parietal cortex, including the inferior
and superior parietal lobule and the supramarginal gyrus.
Between-group random-effects analysis revealed clusters in the frontal lobe that were significantly more active
in the comparison group than the autism spectrum disorders group, including the right inferior and medial frontal
gyri, incorporating the right caudate head as well as the
right dorsal premotor cortex. The most significant was in
the anterior cingulate gyrus (Figure 1).
A number of other regions showed a trend, just below
our significance threshold, toward greater activation in
the comparison group than the autism spectrum disorders group (cluster level uncorrected p<0.05). These included the left dorsolateral prefrontal cortex, right superior parietal lobule, and left premotor cortex. There were
no regions in which the autism spectrum disorders group
exhibited significantly greater activation than the comparison group.
Discussion
In adolescents with autism spectrum disorders, we observed significantly less activation in cortical and subcortical structures in the frontal lobe, including the anterior
cingulate, dorsolateral prefrontal cortex, and caudate nucleus, than in adolescents without such disorders. This
finding suggests a disruption of the network underlying
key aspects of executive function and working memory. It
is also consistent with neuropsychological theories of executive dysfunction in autism spectrum disorders and
supports previous neuroimaging findings.
Impaired activation within the head of the caudate nucleus may have the most significance for autism spectrum
disorders because of its wide distribution of connections to
frontoparietal cortical systems involved in attentional and
cognitive control and visuospatial processing. The caudate
nucleus is critically connected with the dorsolateral prefrontal cortex and premotor cortex in frontostriatal circuits. Reduced activation in these regions is evidence of
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disruption to this frontostriatal network in individuals with
autism spectrum disorders. These results closely parallel
our previous findings (9) of reduced caudate and prefrontal activation in adolescents with attention deficit hyperactivity disorder (ADHD) performing the same mental rotation task.
Regions of the parietal cortex, including the inferior and
superior parietal lobules, showed significant activation in
both the autism spectrum disorders group and the comparison group. These posterior parietal regions, particularly around the intraparietal sulcus, play a key role in
mental rotation (5) and form part of the dorsal visual processing stream that supports perception of spatial properties (10). Structural differences involving the larger parietal volumes that have been reported in autism spectrum
disorders (11) may be expected to result in altered function of the parietal cortex. However, persons with autism
spectrum disorders generally have relatively normal or superior spatial abilities (2). Similarly, our results showed no
significant difference between the autism spectrum disorders group and the comparison group on visuospatial task
performance, and no difference in activation of the posterior parietal cortex (except for a trend toward reduced activation in part of the right superior parietal lobule). This
finding contrasts with what we observed in adolescents
with ADHD, who showed significantly worse task performance and reduced activation in the posterior parietal regions during the mental rotation task (10).
While high-functioning autism and Asperger’s disorder
are commonly grouped together, recent research suggests
that their neurobiological underpinnings may not be
equivalent (12). Nonetheless, studies such as this one provide an essential starting point for understanding the
changes in brain function that accompany autism spectrum disorders. Our findings clearly support a model of
dysfunction of frontostriatal networks in these disorders.
Received May 20, 2005; revision received Sept. 12, 2005; accepted
Oct. 18, 2005. From the Howard Florey Institute, University of Melbourne, Australia. Address correspondence and reprint requests to
Dr. Cunnington, Howard Florey Institute, University of Melbourne,
Victoria 3010, Australia; r.cunnington@hfi.unimelb.edu.au (e-mail).
Supported in part by funding from the Howard Florey Institute and
from Neurosciences Victoria. Dr. Cunnington and Dr. Egan are supported by fellowships 217025 and 217019, respectively, from the
Australian government’s National Health and Medical Research
Council. The authors thank the staff of the Brain Research Institute at
Austin Health, Emma Hornsey, and Todd Little for their assistance
with MRI measurements.
References
1. Caron MJ, Mottron L, Rainville C, Chouinard S: Do high functioning persons with autism present superior spatial abilities?
Neuropsychologia 2004; 42:467–481
2. Russell J: Autism as an Executive Disorder. Oxford, UK, Oxford
University Press, 1997
3. Ohnishi T, Matsuda H, Hashimoto T, Kunihiro T, Nishikawa M,
Uema T, Sasaki M: Abnormal regional cerebral blood flow in
childhood autism. Brain 2000; 123:1838–1844
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4. Luna B, Minshew NJ, Garver KE, Lazar NA, Thulborn KR, Eddy
WF, Sweeney JA: Neocortical system abnormalities in autism:
an fMRI study of spatial working memory. Neurology 2002; 59:
834–840
5. Cohen MS, Kosslyn SM, Breiter HC, DiGirolamo GJ, Thomas WL,
Anderson AK, Bookheimer SY, Rosen BR, Belliveau JW: Changes
in cortical activity during mental rotation: a mapping study using functional MRI. Brain 1996; 119:89–100
6. Lord C, Rutter M, Le Couteur A: Autism Diagnostic Interview—
Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994; 24:659–685
7. Achenbach TM: Manual for the Child Behavior Checklist/4-18
and 1991 Profile. Burlington, University of Vermont, Department of Psychiatry, 1991
8. Ehlers S, Gillberg C, Wing L: A screening questionnaire for Asperger syndrome and other high-functioning autism spectrum
disorders in school age children. J Autism Dev Disord 1999; 29:
129–141
9. Silk T, Vance A, Rinehart N, Egan G, O’Boyle M, Bradshaw JL,
Cunnington R: Fronto-parietal activation in attention-deficit
hyperactivity disorder, combined type: functional magnetic
resonance imaging study. Br J Psychiatry 2005; 187:282–283
10. Sakata H, Taira M, Kusunoki M, Murata A, Tanaka Y: The TINS
lecture: The parietal association cortex in depth perception
and visual control of hand action. Trends Neurosci 1997; 20:
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11. Piven J, Arndt S, Bailey J, Andreasen N: Regional brain enlargement in autism: a magnetic resonance imaging study. J Am
Acad Child Psychiatry 1996; 35:530–536
12. Rinehart NJ, Bradshaw JL, Brereton AV, Tonge BJ: A clinical and
neurobehavioural review of high-functioning autism and Asperger’s disorder. Aust N Z J Psychiatry 2002; 36:762–770
Brief Report
A Preventive Intervention for Pregnant Women on Public
Assistance at Risk for Postpartum Depression
Caron Zlotnick, Ph.D.
Ivan W. Miller, Ph.D.
Teri Pearlstein, M.D.
Margaret Howard, Ph.D.
Patrick Sweeney, M.D., Ph.D.
Objective: Promising results were obtained in an earlier pilot
study of a preventive intervention based on the principles of interpersonal psychotherapy to reduce the risk of postpartum
major depressive disorder. In this study, the authors examined
whether the intervention would reduce the risk of postpartum
major depressive disorder in a larger sample of pregnant
women.
Method: Ninety-nine pregnant women on public assistance
who were assessed to be at risk for postpartum depression were
randomly assigned to receive standard antenatal care plus the
intervention or standard antenatal care only. Diagnostic interviews were administered 3 months after delivery to assess for
major depressive disorder.
Results: Within 3 months after delivery, eight (20%) of the
women in the standard antenatal care condition had developed postpartum major depressive disorder, compared with
two (4%) in the intervention condition.
Conclusions: This study provides further evidence for the efficacy of a brief intervention to reduce the occurrence of major
depressive disorder among financially disadvantaged women
during a postpartum period of 3 months.
(Am J Psychiatry 2006; 163:1443–1445)
P
ostpartum major depressive disorder is a common illness with a high degree of morbidity, especially among
low-income women (1). Several experts on this disorder
have advocated for preventive interventions beginning in
pregnancy (2, 3). In an earlier pilot study (4), we found that
an intervention based primarily on the principles of interpersonal therapy appeared to be successful in preventing
the occurrence of postpartum depression within 3 months
after delivery among pregnant women on public assistance with at least one risk factor for postpartum depression. To date, ours is the only study on interventions aiming to reduce postpartum depression in at-risk pregnant
women that has reported empirical support for an interAm J Psychiatry 163:8, August 2006
vention. The lack of effect in other intervention studies is
difficult to interpret because of methodological limitations, such as high attrition rate, lack of a standardized intervention, and an insufficiently high risk of postpartum
depression among study subjects (5).
The primary aim of this study was to examine whether
participation in a program based primarily on interpersonal therapy could reduce the risk of postpartum depression during the first 3 months after delivery in a larger
sample of pregnant women who were on public assistance
and were at risk for postpartum depression. The ROSE
Program (Reach Out, Stand strong, Essentials for new
mothers) was designed to help mothers-to-be in an ethniajp.psychiatryonline.org
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