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Nakatani E, Nakgawa A, Ohara Y, Goto S, Uozumi N, Iwakiri M,
Yamamoto Y, Motomura K, Iikura Y, Yamagami T.
Effects of behavior
therapy on regional cerebral blood flow in obsessive-compulsive disorder.
Psychiatry
Res. 2003 Oct 30;124(2):113-20.
"Very few functional neuroimaging studies
have been performed on patients with obsessive-compulsive disorder (OCD) undergoing
behavior therapy, even though it is recognized to be an effective treatment for
this disorder. We measured the regional cerebral blood flow (rCBF) using the Xenon
inhalation method in 31 treatment-refractory patients with OCD and the same number
of age-matched normal controls. We also studied changes in rCBF in 22 OCD patients
who had demonstrated a significant improvement after the behavior therapy. The
OCD patients showed a significant bilateral elevation in the rCBF in the basal
ganglia compared with the normal controls. After successful treatment, a significant
decrease was found in the rCBF in the right head of the caudate nucleus that tended
to correlate with clinical improvement." [Abstract]
Benazon NR, Moore GJ, Rosenberg DR.
Neurochemical
analyses in pediatric obsessive-compulsive disorder in patients treated with cognitive-behavioral
therapy.
J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1279-85.
"OBJECTIVE:
To investigate neurochemical changes in the caudate nucleus of pediatric obsessive-compulsive
disorder (OCD) patients before and after cognitive-behavioral therapy (CBT), and
to examine corresponding changes in symptom severity. METHOD: Single-voxel proton
magnetic resonance spectroscopic (1H-MRS) examination of the left caudate was
conducted in 21 treatment-naive children, aged 6 to 16 years, before and after
12 weeks of CBT. Subjects were measured at baseline and posttreatment by the Yale-Brown
Obsessive Compulsive Scale for Children, Hamilton Depression Rating Scale, and
Hamilton Anxiety Rating Scale. RESULTS: No significant changes in caudate neurochemistry
were observed in OCD patients before and after CBT despite unambiguous improvement
in OCD symptoms, depression, and anxiety. CONCLUSIONS: Findings suggest that reduction
in caudate Glx may be specific to SSRI treatment and not due to a more generalized
treatment response or spontaneous improvement of symptoms. Differential sets of
pathophysiologic and treatment response markers may moderate/mediate the effects
of particular treatments on outcome." [Abstract] Kang
DH, Kwon JS, Kim JJ, Youn T, Park HJ, Kim MS, Lee DS, Lee MC.
Brain
glucose metabolic changes associated with neuropsychological improvements after
4 months of treatment in patients with obsessive-compulsive disorder.
Acta
Psychiatr Scand. 2003 Apr;107(4):291-7.
"OBJECTIVE: The study was designed
to elucidate regional brain metabolic changes according to a treatment and their
relationship with neuropsychological performance changes in obsessive-compulsive
disorder (OCD). METHOD: Cerebral glucose metabolic rates were repeatedly measured
before and after treatment in 10 patients with OCD using [18F]-2-fluoro-deoxyglucose
positron emission tomography (PET). They were compared on a voxel-basis, and the
correlations were counted between the regional metabolic changes and the degree
to improvement on the neuropsychological assessments. RESULTS: After treatment,
the patients showed significant (P < 0.005, two-tailed) regional metabolic
changes in multiple brain areas involving frontal-subcortical circuits and parietal-cerebellar
networks. Especially, the metabolic changes of the putamen, the cerebellum, and
the hippocampus were significantly correlated with the improvement of the immediate-
and delayed-recall scores of the Rey-Osterrieth Complex Figure Test (RCFT). CONCLUSION:
These results suggest a possibility that metabolic changes of frontal-subcortical
and parietal-cerebellar circuit changes may underlie cognitive improvements in
patients with OCD." [Abstract] Szeszko
PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, Banerjee SP, Moore GJ,
Rosenberg DR.
Amygdala volume reductions in pediatric patients with
obsessive-compulsive disorder treated with paroxetine: preliminary findings.
Neuropsychopharmacology.
2004 Apr;29(4):826-32.
"The amygdala is believed to be highly relevant
to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent
role in fear conditioning and because it is an important target of the serotonin
reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present
study, we measured in vivo volumetric changes in the amygdala in pediatric patients
with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine
hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic
resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to
and then following treatment. Eleven healthy pediatric comparison subjects also
had baseline and follow-up scans, but none of these subjects received medication.
Patients demonstrated significant asymmetry of the amygdala (L>R) prior to
pharmacologic intervention in contrast to healthy comparison subjects who showed
no asymmetry at the time of their baseline scan. Mixed model analyses using age
and total brain volume as time varying covariates indicated that left amygdala
volume decreased significantly in patients following treatment. The reduction
in left amygdala volume in patients correlated significantly with higher paroxetine
dosage at the time of the follow-up scan and total cumulative paroxetine exposure
between the scans. No significant changes in either right or left amygdala volume
were evident among healthy comparison subjects from the baseline to the follow-up
scan. These preliminary findings suggest that abnormal asymmetry of the amygdala
may play a role in the pathogenesis of OCD and that paroxetine treatment may be
associated with a reduction in amygdala volume." [Abstract] Saxena,
Sanjaya, Brody, Arthur L., Ho, Matthew L., Zohrabi, Narineh, Maidment, Karron
M., Baxter, Lewis R., Jr.
Differential Brain Metabolic Predictors
of Response to Paroxetine in Obsessive-Compulsive Disorder Versus Major Depression
Am
J Psychiatry 2003 160: 522-532
"OBJECTIVE: Serotonin reuptake inhibitor
(SRI) medications are effective in the treatment of both major depressive disorder
and obsessive-compulsive disorder (OCD), but it is unknown whether the neural
substrates of treatment response for the two disorders are the same or different.
The authors sought to identify pretreatment cerebral glucose metabolic markers
of responsiveness to SRI treatment in patients with OCD versus major depressive
disorder and to determine whether the pretreatment patterns associated with improvement
of OCD symptoms were the same as or different from those associated with improvement
of major depressive disorder symptoms. METHOD: [18F]Fluorodeoxyglucose positron
emission tomography was used to measure cerebral glucose metabolism in 27 patients
with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent
OCD and major depressive disorder, who were all then treated with 30–60 mg/day
of paroxetine for 8–12 weeks. Correlations were calculated between pretreatment
regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms,
depressive symptoms, and overall functioning. RESULTS: While improvement of OCD
symptoms was significantly correlated with higher pretreatment glucose metabolism
in the right caudate nucleus (partial r=–0.53), improvement of major depressive
disorder symptoms was significantly correlated with lower pretreatment metabolism
in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher
pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate
gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91). CONCLUSIONS: These findings
suggest that, although both OCD and major depressive disorder respond to SRIs,
the two syndromes have different neurobiological substrates for response. Elevated
activity in the right caudate may be a marker of responsiveness to antiobsessional
treatment, while lower right amygdala activity and higher midline prefrontal activity
may be required for response of depressive symptoms to treatment." [Abstract]
Hansen
ES, Hasselbalch S, Law I, Bolwig TG.
The caudate nucleus in obsessive-compulsive
disorder. Reduced metabolism following treatment with paroxetine: a PET study.
Int
J Neuropsychopharmacol. 2002 Mar;5(1):1-10.
"Several neuroimaging studies
of patients with OCD have pointed to basal ganglia and the frontal cortical regions
being relevant for an understanding of the pathophysiology and therapy of OCD.
In a search for the neural substrate underlying the therapeutic action of paroxetine
in the therapy of OCD we measured regional glucose metabolism in a PET study of
20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose
PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in
20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied
before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor
paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive
Scale (Y-BOCS) was performed before the first and after the second study. The
PET data was analysed regionally using statistical parametric mapping (SPM-96).
A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score.
There was no difference in global cerebral metabolism before and after treatment
whereas a post-treatment reduction in normalized rCMRglc was found in the right
caudate nucleus. This finding also showed a significant positive correlation with
symptom severity. Our results support hypotheses regarding a malfunction of the
cortico-striato-thalamic system in the pathophysiology of OCD and particularly
point to the caudate nucleus playing an important role for the therapeutic action
of paroxetine in the treatment of OCD." [Abstract] Rosenberg
DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ.
Decrease
in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder
patients taking paroxetine.
J Am Acad Child Adolesc Psychiatry.
2000 Sep;39(9):1096-103.
"OBJECTIVE: To measure in vivo neurochemical
changes in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD)
before and after treatment. METHOD: Single-voxel proton magnetic resonance spectroscopic
(1H-MRS) examinations of the left caudate were conducted in 11 psychotropic drug-naive
children, aged 8 to 17 years, with OCD before and after 12 weeks of monotherapy
with the selective serotonin reuptake inhibitor paroxetine (10-60 mg/day) and
11 healthy children aged 8 to 17 years. A different sample of 8 pediatric OCD
patients and 8 healthy children had a 1H-MRS examination of occipital cortex.
RESULTS: Caudate glutamatergic concentrations (Glx) were significantly greater
in treatment-naive OCD patients than in controls but declined significantly after
paroxetine treatment to levels comparable with those of controls. Decrease in
caudate Glx was associated with decrease in OCD symptom severity. Occipital Glx
did not differ between OCD patients and controls. CONCLUSIONS: These preliminary
findings provide new evidence of Glx abnormalities in the caudate nucleus in pediatric
OCD and suggest that paroxetine treatment may be mediated by a serotonergically
modulated reduction in caudate Glx." [Abstract]
Bolton J, Moore GJ, MacMillan S, Stewart CM, Rosenberg
DR.
Case study: caudate glutamatergic changes with paroxetine persist
after medication discontinuation in pediatric OCD.
J Am
Acad Child Adolesc Psychiatry. 2001 Aug;40(8):903-6.
"Proton magnetic
resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities
in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated
with severity of illness and response to acute (12 weeks) treatment with paroxetine.
In this report, OCD symptoms improved markedly in an 8-year-old girl treated for
14 months with the selective serotonin reuptake inhibitor paroxetine (titrated
from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements
and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired
before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after
medication discontinuation. A striking decrease in caudate Glx was observed after
12 weeks of treatment which persisted after medication discontinuation. These
data provide further support for a reversible glutamatergically mediated dysfunction
of the caudate nucleus in OCD that may serve as a pathophysiological and treatment
response marker." [Abstract] Diler
RS, Kibar M, Avci A.
Pharmacotherapy and regional cerebral blood
flow in children with obsessive compulsive disorder.
Yonsei
Med J. 2004 Feb 29;45(1):90-9.
"While regional cerebral blood flow (rCBF)
studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated
areas have been reported, no such published data on children exist. In this study,
we aimed to determine the significance of pre- and post-treatment regional cerebral
blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD)
and compared them with healthy controls. Eighteen drug-free obsessive compulsive
children, aged 11 to 15, without comorbid states except for anxiety disorders--participated
in this study. The control group consisted of 12 children, aged 11 to 15, with
no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized
Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO),
the rCBF was calculated in 15 regions of the control group according to a standard
protocol, while in the study group, it was measured at baseline and after 12 weeks
of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting
pre- and post-treatment CBF values for the control group and study group. The
right and left caudates, right and left dorsolateral prefrontals, and cingulate
had significantly higher rCBF in children with obsessive compulsive disorder than
in the control group. These areas, in addition to the right anteromedial temporal,
showed significant rCBF reduction after treatment with paroxetine. The mean percentage
of change in obsession scores during the treatment correlated significantly with
the baseline and post- treatment rCBF level of the right caudate, post-treatment
left caudate, and baseline left caudate. Our findings on children are consistent
with adult studies and support the theory of a cortical-striatal-thalamic-cortical
loop disturbance in OCD." [Abstract]
Rauch
SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA.
Predictors
of fluvoxamine response in contamination-related obsessive compulsive disorder:
a PET symptom provocation study.
Neuropsychopharmacology.
2002 Nov;27(5):782-91.
"The purpose of this study was to identify neuroimaging
predictors of medication response in contamination-related obsessive compulsive
disorder (OCD). Prior studies of OCD had indicated that glucose metabolic rates
within orbitofrontal cortex (OFC) were inversely correlated with subsequent response
to serotonergic reuptake inhibitors (SRIs) and that glucose metabolic rates within
posterior cingulate cortex (PCC) were positively correlated with subsequent response
to cingulotomy. Nine subjects with contamination-related OCD underwent a 12-week
open trial of treatment with the SRI fluvoxamine. Percent change in Yale-Brown
Obsessive Compulsive Scale score, from pre- to post-treatment, served as the index
of treatment response. Positron emission tomography (PET) measurements of regional
cerebral blood flow (rCBF) were obtained prior to treatment, in the context of
a symptom provocation paradigm. Statistical parametric mapping was used to identify
brain loci where pre-treatment rCBF was significantly correlated with subsequent
treatment response. Consistent with a priori hypotheses, lower rCBF values in
OFC and higher rCBF values in PCC predicted better treatment response. This same
pattern of associations was present regardless of whether the imaging data were
acquired during a provoked or neutral state. These findings are consistent with
prior studies of OCD, indicating that PET indices of brain activity within OFC
are inversely correlated with subsequent response to SRIs. In addition, similar
to findings regarding cingulotomy for OCD, indices of activity within PCC appear
to be positively correlated with response to fluvoxamine as well. Finally, this
pattern is sufficiently robust as to be relatively independent of symptomatic
state at the time of tracer uptake." [Abstract]
Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan
M, Alborzian S, Phelps ME, Baxter LR Jr.
Localized orbitofrontal
and subcortical metabolic changes and predictors of response to paroxetine treatment
in obsessive-compulsive disorder.
Neuropsychopharmacology.
1999 Dec;21(6):683-93.
"Previous positron emission tomography (PET) studies
of patients with obsessive-compulsive disorder (OCD) have found elevated glucose
metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize
with response to treatment. Furthermore, OCD symptom provocation differentially
activates specific subregions of the OFC, which have distinct patterns of connectivity
and serve different functions. Therefore, we sought to determine the role of specific
subregions of the OFC and associated subcortical structures in mediating OCD symptoms,
by determining how glucose metabolism in these structures changed with paroxetine
treatment of OCD patients. We also sought to determine whether pretreatment OFC
metabolism would predict response to paroxetine, as it has for other OCD treatments.
Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before
and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who
responded to paroxetine, glucose metabolism decreased significantly in right anterolateral
OFC and right caudate nucleus. Lower pretreatment metabolism in both left and
right OFC predicted greater improvement in OCD severity with treatment. These
results add to evidence indicating that orbitofrontal-subcortical circuit function
mediates the symptomatic expression of OCD. Specific subregions of the OFC may
be differentially involved in the pathophysiology of OCD and/or its response to
pharmacotherapy." [Abstract] Swedo
SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI,
Rapoport JL, Grady CL.
Cerebral glucose metabolism in childhood-onset
obsessive-compulsive disorder. Revisualization during pharmacotherapy.
Arch
Gen Psychiatry. 1992 Sep;49(9):690-4.
"To investigate the effects of drug
treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated
positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine,
two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy.
As a group, the patients had a significant improvement on all OCD and anxiety
ratings. Positron emission tomography revealed a significant decrease in normalized
orbitofrontal regional cerebral glucose metabolism (relative to global metabolism)
bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism
was directly correlated with two measures of OCD improvement. These results extend
previous positron emission tomographic findings of regional dysfunction in OCD
and suggest involvement of the orbitofrontal regions in the pathophysiology of
OCD." [Abstract] Rubin
RT, Ananth J, Villanueva-Meyer J, Trajmar PG, Mena I.
Regional 133xenon
cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive
disorder before and during treatment.
Biol Psychiatry. 1995
Oct 1;38(7):429-37.
"We previously reported increased regional cerebral
cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients
with obsessive-compulsive disorder(OCD) before treatment compared to matched normal
controls. In the present study, we determined whether or not these changes persisted
during treatment. Single-photon emission computed tomography was used to measure
regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of
99mTc-HMPAO in eight adult male OCD patients before and during treatment with
chlomipramine, and in eight age-matched normal male controls. With 133Xe, there
were no significant differences in rCBF between patients with OCD and their matched
controls, and no significant differences in rCBF in the patients before and during
treatment. Significantly increased HMPAO uptake in the orbital frontal cortex,
posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in
the OCD patients before treatment compared to their matched controls, and there
were significant reductions of HMPAO uptake, into the normal range, in all these
areas in the patients during treatment. Significantly reduced HMPAO uptake in
the caudate nucleus bilaterally occurred in the patients before treatment compared
to their matched controls, and these reductions persisted during treatment. This
study provides additional support for the involvement of both the orbital frontal
cortex and the caudate nuclei in the pathophysiology of OCD." [Abstract]
Saxena S, Brody AL, Ho ML, Alborzian S, Maidment
KM, Zohrabi N, Ho MK, Huang SC, Wu HM, Baxter LR Jr.
Differential
cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder
vs major depression.
Arch Gen Psychiatry. 2002 Mar;59(3):250-61.
"BACKGROUND:
Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder
(MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the
functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders
occurred separately and concurrently by measuring pretreatment to posttreatment
cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS:
We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain
scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before
and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n
= 16) were scanned 10 to 12 weeks apart without treatment. Treatment response
was defined as a more than 25% decline in OCD symptom severity, a more than 50%
decline in MDD severity, and "much improved" clinical global impression.
RESULTS: Although all patient groups received the same paroxetine dose for the
same duration, regional metabolic changes differed significantly among diagnostic
groups. Subjects with OCD alone showed significant metabolic decreases in the
right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral
orbitofrontal cortex, and thalamus that were not seen in any other group. Both
the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left
VLPFC and increases in the right striatum. Treatment response was associated with
a decrease in striatal metabolism in nondepressed OCD patients but with an increase
in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic
responses to SRIs are both disorder-specific and response-specific. They vary
according to the underlying pathophysiology of the patient and the degree of symptomatic
improvement." [Abstract] Hoehn-Saric
R, Schlaepfer TE, Greenberg BD, McLeod DR, Pearlson GD, Wong SH.
Cerebral
blood flow in obsessive-compulsive patients with major depression: effect of treatment
with sertraline or desipramine on treatment responders and non-responders.
Psychiatry
Res. 2001 Nov 30;108(2):89-100.
"We examined the effects of sertraline
and of desipramine on patients with OCD and comorbid major depressive episodes
at study entry. Sixteen patients, 9 receiving sertraline and 7 desipramine, received
HMPAO SPECT scans while free of medication and after 12 weeks of treatment. Patients
on sertraline showed significantly reduced regional cerebral blood flow (rCBF)
in the right prefrontal and temporal regions. Patients on desipramine showed more
diffuse rCBF reductions in frontal and temporal regions, more so in the left side.
In a second analysis, patients who had a symptom reduction on the Yale-Brown Obsessive
Compulsive Scale (YBOCS), irrespective of the type of medication, were retrospectively
classified as 'responders' to treatment. Eleven patients were 'responders' and
5 'non-responders'. Before being medicated, responders differed from non-responders
through higher rCBF in prefrontal regions, mostly on the left, and higher rCBF
in the cingulate and basal ganglia bilaterally. After 12 weeks of treatment, responders
showed a diffuse reduction of rCBF in prefrontal regions while non-responders
showed only a few scattered low-frequency responses. Thus, higher prefrontal and
subcortical activity was associated with better response to drug treatment. In
addition, clinical change, but not the administration of medication as such, was
associated with a decrease of prefrontal rCBF." [Abstract] Saxena
S, Brody AL, Ho ML, Alborzian S, Ho MK, Maidment KM, Huang SC, Wu HM, Au SC, Baxter
LR Jr.
Cerebral metabolism in major depression and obsessive-compulsive
disorder occurring separately and concurrently.
Biol Psychiatry.
2001 Aug 1;50(3):159-70.
"BACKGROUND: The frequent comorbidity of major
depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental
relationship between them. We sought to determine whether MDD and OCD have unique
cerebral metabolic patterns that remain the same when they coexist as when they
occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography
(PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone,
17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated
state. Regional cerebral glucose metabolism was compared between groups. RESULTS:
Left hippocampal metabolism was significantly lower in subjects with MDD alone
and in subjects with concurrent OCD+MDD than in control subjects or subjects with
OCD alone. Hippocampal metabolism was negatively correlated with depression severity
across all subjects. Thalamic metabolism was significantly elevated in OCD alone
and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism
in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS:
Left hippocampal dysfunction was associated with major depressive episodes, regardless
of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and
MDD occurring separately were not seen when the disorders coexisted. Depressive
episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic
abnormalities than in primary MDD patients." [Abstract]
Lucey JV, Costa DC, Busatto G, Pilowsky LS, Marks
IM, Ell PJ, Kerwin RW.
Caudate regional cerebral blood flow in obsessive-compulsive
disorder, panic disorder and healthy controls on single photon emission computerised
tomography.
Psychiatry Res. 1997 Mar 14;74(1):25-33.
"We
compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive
disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls
matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene
amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT).
Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects
and panic disorder patients. When four patients were excluded from each group,
right caudate rCBF remained significantly lower in OCD patients than in panic
disorder patients or healthy subjects. The data suggest functional involvement
of the right caudate nucleus is present in OCD." [Abstract] Kim
JJ, Lee MC, Kim J, Kim IY, Kim SI, Han MH, Chang KH, Kwon JS.
Grey
matter abnormalities in obsessive-compulsive disorder: statistical parametric
mapping of segmented magnetic resonance images.
Br J Psychiatry.
2001 Oct;179:330-4.
"BACKGROUND: Although a number of functional imaging
studies are in agreement in suggesting orbitofrontal and subcortical hyperfunction
in the pathophysiology of obsessive-compulsive disorder (OCD), the structural
findings have been contradictory. AIMS: To investigate grey matter abnormalities
in patients with OCD by employing a novel voxel-based analysis of magnetic resonance
images. METHOD: Statistical parametric mapping was utilised to compare segmented
grey matter images from 25 patients with OCD with those from 25 matched controls.
RESULTS: Increased regional grey matter density was found in multiple cortical
areas, including the left orbitofrontal cortex, and in subcortical areas, including
the thalamus. On the other hand, regions of reduction were confined to posterior
parts of the brain, such as the left cuneus and the left cerebellum. CONCLUSIONS:
Increased grey matter density of frontal-subcortical circuits, consonant with
the hypermetabolic findings from functional imaging studies, seems to exist in
patients with OCD, and cerebellar dysfunction may be involved in the pathophysiology
of OCD." [Abstract] Choi
JS, Kang DH, Kim JJ, Ha TH, Lee JM, Youn T, Kim IY, Kim SI, Kwon JS.
Left
anterior subregion of orbitofrontal cortex volume reduction and impaired organizational
strategies in obsessive-compulsive disorder.
J Psychiatr
Res. 2004 Mar-Apr;38(2):193-9.
"The orbitofrontal cortex (OFC) may be
involved in the clinical and cognitive expressions of obsessive-compulsive disorder
(OCD) and is a heterogenous region with respect to its cytoarchitecture, function
and connectivity. This study was designed to examine the morphological abnormality
of the anterior subregion of OFC and its relationship to clinical symptoms and
cognitive performance in patients with OCD. We divided the OFC into anterior and
posterior subregions using an external landmark and measured the gray matter volumes
of each by three-dimensional magnetic resonance imaging in age- and sex-matched
groups, which consisted of 34 OCD and 34 normal volunteers. Clinical and cognitive
evaluations were completed using Yale-Brown Obsessive Compulsive Scale (YBOCS)
and four sets of neuropsychological tests that assessed executive functions and
visual memory. Volume reduction of the left anterior OFC was observed in patients
with OCD versus normal controls. Also, a significant positive correlation was
found between left anterior OFC gray matter volume and the copy score of the Rey-Osterrieth
Complex Figure Test in patients with OCD. These results suggest that left anterior
subregion volume reduction of the OFC may be related to impaired organizational
strategies in patients with OCD." [Abstract]
Alptekin K, Degirmenci B, Kivircik B, Durak H, Yemez
B, Derebek E, Tunca Z.
Tc-99m HMPAO brain perfusion SPECT in drug-free
obsessive-compulsive patients without depression.
Psychiatry
Res. 2001 Jul 1;107(1):51-6.
"The aim of this study was to confirm prior
results of brain-imaging studies on obsessive-compulsive disorder (OCD) in a sample
of Turkish patients, as a cross-cultural study. Tc-99m HMPAO brain perfusion SPECT
imaging was performed in nine drug-free OCD patients without depression and six
controls. The patients' Hamilton Depression Rating Scale scores were <16. The
severity of obsessive-compulsive symptoms was rated with the Yale-Brown Obsessive-Compulsive
Rating Scale (YBOCS). Quantitative evaluation of regional cerebral blood flow
revealed that right thalamus, left frontotemporal cortex and bilateral orbitofrontal
cortex showed significant hyperperfusion in patients with OCD compared with controls.
YBOCS scores did not show any correlation with hyperperfusion in regional cerebral
blood flow in these areas. Results of this cross-cultural study may support orbitofrontal
and thalamic dysfunction in OCD in a sample of Turkish patients." [Abstract]
Berthier
ML, Kulisevsky JJ, Gironell A, Lopez OL.
Obsessivecompulsive disorder
and traumatic brain injury: behavioral, cognitive, and neuroimaging findings.
Neuropsychiatry
Neuropsychol Behav Neurol. 2001 Jan;14(1):23-31.
"OBJECTIVE: The goal
of this study was to evaluate behavior and cognition in a consecutive series of
patients who developed obsessive-compulsive disorder (OCD) after suffering a traumatic
brain injury (TBI). BACKGROUND: Because OCD is a rare sequelae of TBI, the phenomenology
of obsessions and compulsions, the comorbid psychiatric disorders, the performance
on cognitive tests, and the neural correlates have not been well characterized.
METHODS: Ten adult patients who met DSM-IV diagnostic criteria for OCD after suffering
either mild (6 cases), moderate (2 cases), or severe (2 cases) TBI were studied
using structured psychiatric rating scales (i.e., Yale-Brown Obsessive Compulsive
Scale), cognitive tests, and magnetic resonance imaging (MRI). RESULTS: Global
severity of OCD ranged from moderate to severe, and all patients had multiple
obsessions and compulsions. There was a high frequency of aggressive, contamination,
need for symmetry/exactness, somatic, and sexual obsessions as well as cleaning/washing,
checking, and repeating compulsions. Unusual features such as obsessional slowness
(3 cases) and compulsive exercising (3 cases) were also documented. Comorbid psychiatric
diagnoses were common and included posttraumatic stress disorder, anxiety with
panic attacks, depression, and intermittent explosive disorder. Compared with
10 age-matched normal controls, the OCD group had poor performance on tests of
general intelligence, attention, learning, memory, word-retrieval, and executive
functions; these cognitive deficits were more pervasive among patients displaying
obsessional slowness. All OCD patients with mild TBI had normal MRI scans, whereas
focal contusions in the frontotemporal cortices, subcortical structures (caudate
nucleus), or both were found in OCD patients with moderate and severe TBI. CONCLUSIONS:
Posttraumatic OCD has a relatively specific pattern of symptoms even in patients
with mild TBI and is associated with a variety of other psychiatric disorders,
particularly non-OCD anxiety. The patterns of cognitive deficits and MRI findings
suggest dysfunction of frontal-subcortical circuits." [Abstract] Rauch
SL, Kim H, Makris N, Cosgrove GR, Cassem EH, Savage CR, Price BH, Nierenberg AA,
Shera D, Baer L, Buchbinder B, Caviness VS Jr, Jenike MA, Kennedy DN.
Volume
reduction in the caudate nucleus following stereotactic placement of lesions in
the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging
study.
J Neurosurg. 2000 Dec;93(6):1019-25.
"OBJECT:
The goal of this study was to test hypotheses regarding changes in volume in subcortical
structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance
(MR) imaging methods were used to assess volume reductions in subcortical regions
following anterior cingulate lesioning in nine patients. Magnetic resonance imaging
data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected
to segmentation and subcortical parcellation. Significant volume reductions were
predicted and found bilaterally within the caudate nucleus, but not in the amygdala,
thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed
that the volume reduction in the caudate nucleus was principally referrable to
the body, rather than the head. Furthermore, the magnitude of volume reduction
in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS:
Taken together, these findings implicate significant connectivity between a region
of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate
body. This unique data set complements published findings in nonhuman primates,
and advances our knowledge regarding patterns of cortical-subcortical connectivity
involving the ACC in humans. Moreover, these findings indicate changes distant
from the site of anterior cingulotomy lesions that may play a role in the clinical
response to this neurosurgical procedure." [Abstract] Szeszko
PR, Robinson D, Alvir JM, Bilder RM, Lencz T, Ashtari M, Wu H, Bogerts B.
Orbital
frontal and amygdala volume reductions in obsessive-compulsive disorder.
Arch
Gen Psychiatry. 1999 Oct;56(10):913-9.
"BACKGROUND: Functional neuroimaging
studies have implicated the frontal lobes and the hippocampus-amygdala complex
in the pathophysiology of obsessive-compulsive disorder (OCD). These brain regions
have not been well investigated in patients with OCD, however, using magnetic
resonance imaging. METHODS: Volumes of the superior frontal gyrus, anterior cingulate
gyrus, orbital frontal region, hippocampus, and amygdala were computed from contiguous
magnetic resonance images in a sample of 26 patients with OCD and 26 healthy comparison
subjects. RESULTS: Patients with OCD had significantly reduced bilateral orbital
frontal and amygdala volumes compared with healthy comparison subjects and lacked
the normal hemispheric asymmetry of the hippocampus-amygdala complex. Neither
brain structure volumes nor asymmetry indices were significantly correlated with
total illness duration or length of current OCD episode. CONCLUSIONS: Findings
of reduced orbital frontal and amygdala volumes in patients implicate a structural
abnormality of these brain regions in the pathophysiology of OCD. Absence of the
normal hemispheric asymmetry of the hippocampus-amygdala complex in patients is
consistent with an anomalous neurodevelopmental process." [Abstract] Santosh,
Paramala Janardhanan
Current topic: Neuroimaging in child and adolescent
psychiatric disorders
Arch. Dis. Child. 2000 82: 412-419
[Full
Text]
Fitzgerald KD, Moore GJ, Paulson LA,
Stewart CM, Rosenberg DR.
Proton spectroscopic imaging of the thalamus
in treatment-naive pediatric obsessive-compulsive disorder.
Biol
Psychiatry. 2000 Feb 1;47(3):174-82.
"BACKGROUND: Neurobiological abnormalities
in the thalamus, particularly the dorsomedial nucleus of the thalamus, are believed
to be involved in the pathophysiology of obsessive-compulsive disorder. Although
obsessive-compulsive disorder commonly arises in childhood and adolescence, no
prior study has examined the thalamus in pediatric obsessive-compulsive disorder
patients. METHODS: In this study, N-acetyl-aspartate, a putative marker of neuronal
viability, creatine/phosphocreatine, and choline levels were measured in the lateral
and medical subregions of the left and right thalami using a multislice proton
magnetic resonance spectroscopic imaging sequence in 11 treatment-naive, nondepressed
obsessive-compulsive disorder outpatients, 8-15 years old, and 11 case-matched
control subjects. RESULTS: A significant reduction in N-acetyl-aspartate/choline
and N-acetyl-aspartate/(creatine/phosphocreatine + choline) was observed in both
the right and left medial thalami in obsessive-compulsive disorder patients compared
with control subjects. The N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine
+ choline) levels did not differ significantly between case-control pairs in either
the left or the right lateral thalamus. Reduction in N-acetyl-aspartate levels
in the left medial thalamus was inversely correlated with increased obsessive-compulsive
disorder symptom severity. CONCLUSIONS: These findings provide new evidence of
localized functional neurochemical marker abnormalities in the thalamus in pediatric
obsessive-compulsive disorder. Our results must be considered preliminary, however,
given the small sample size." [Abstract] Crespo-Facorro
B, Cabranes JA, Lopez-Ibor Alcocer MI, Paya B, Fernandez Perez C, Encinas M, Ayuso
Mateos JL, Lopez-Ibor JJ Jr.
Regional cerebral blood flow in obsessive-compulsive
patients with and without a chronic tic disorder. A SPECT study.
Eur
Arch Psychiatry Clin Neurosci. 1999;249(3):156-61.
"The main goal of the
present study was to explore whether regional cerebral blood flow (rCBF) differs
between obsessive-compulsive disorder (OCD) patients without chronic motor tic
disorder and those OCD patients with a comorbid chronic tic disorder. Twenty-seven
patients suffering from OCD (DSM-IV criteria), including 7 OCD patients who met
DSM-IV criteria for simple chronic motor dic disorder, and 16 healthy volunteers
were examined at rest using a high resolution SPECT. Seven regions of interest
(ROIs) were manually traced and quantified as a percentage of the mean cerebellar
uptake. Severity of obsessive-compulsive symptoms (OCS), anxiety and depressive
symptoms and presence of motor tics were assessed with the Y-BOCS, HRS-A, HRS-D,
MADRS, and Yale Global Tics Severity Scale, respectively. We found a significant
relative decrease in rCBF in OCD patients without motor tics compared to healthy
volunteers in the right orbitofrontal cortex (OCD without tics = 0.87; healthy
volunteers = 0.94; p = 0.02). No significant differences in rCBF were seen when
OCD patients with and without chronic tics were directly compared. A lower severity
of OCS in OCD patients with chronic tics was found. These results are consistent
with previous functional neuroimaging studies at rest that have widely involved
the orbitofrontal cortex in the pathophysiology of the OCD. However, our results
do not support the idea that OCD patients with chronic tics may constitute a biological
subgroup within the OCD." [Abstract] Bartha
R, Stein MB, Williamson PC, Drost DJ, Neufeld RW, Carr TJ, Canaran G, Densmore
M, Anderson G, Siddiqui AR.
A short echo 1H spectroscopy and volumetric
MRI study of the corpus striatum in patients with obsessive-compulsive disorder
and comparison subjects.
Am J Psychiatry. 1998 Nov;155(11):1584-91.
"OBJECTIVE:
It is likely that the corpus striatum is involved in obsessive-compulsive disorder
(OCD). Prior studies have inconsistently found alterations in caudate volumes
in patients with OCD. This study was undertaken in the hope that N-acetylaspartate
and volumetric measures together would elucidate the presence and nature of corpus
striatum volumetric abnormalities in OCD. METHOD: Thirteen patients meeting the
DSM-IV criteria for OCD, who had been medication free for a minimum of 6 weeks,
and 13 psychiatrically normal matched comparison subjects participated in the
study. Short echo 1H magnetic resonance spectroscopy (1H-MRS) was used to measure
levels of N-acetylaspartate and several other cerebral metabolites from a 4.5-cm3
volume in the left corpus striatum of all 26 subjects. Metabolite levels were
estimated by fitting the time domain spectroscopy data with a noninteractive computer
program. Volumes of the left and right head of the caudate nucleus in each subject
were determined by semiautomatic segmentation of the volumetric images. RESULTS:
N-Acetylaspartate levels from the left corpus striatum were significantly lower
in the patients with OCD than in the comparison subjects. There were no differences
in either left or right caudate volume between the two groups. CONCLUSIONS: Despite
the lack of differences in caudate volumes between the OCD patients and the comparison
subjects, the lower level of N-acetylaspartate in the left corpus striatum of
the patients suggests reduced neuronal density in this region. Inconsistent volumetric
findings among prior studies may reflect a poorer sensitivity of magnetic resonance
imaging morphometry for detecting neuronal loss compared with 1H-MRS measurement
of N-acetylaspartate." [Abstract]
Rauch
SL, Savage CR, Alpert NM, Dougherty D, Kendrick A, Curran T, Brown HD, Manzo P,
Fischman AJ, Jenike MA.
Probing striatal function in obsessive-compulsive
disorder: a PET study of implicit sequence learning.
J
Neuropsychiatry Clin Neurosci. 1997 Fall;9(4):568-73.
"Positron emission
tomography was employed to contrast the brain activation pattern in patients with
obsessive-compulsive disorder (OCD) to that of matched control subjects while
they performed an implicit learning task. Although patients and control subjects
evidenced comparable learning, imaging data from control subjects indicated bilateral
inferior striatal activation, whereas OCD patients did not activate right or left
inferior striatum and instead showed bilateral medial temporal activation. The
findings further implicate corticostriatal dysfunction in obsessive-compulsive
disorder. Furthermore, when OCD patients are confronted with stimuli that call
for recruitment of corticostriatal systems, they instead appear to access brain
regions normally associated with explicit (conscious) information processing."
[Abstract] Lucey
JV, Burness CE, Costa DC, Gacinovic S, Pilowsky LS, Ell PJ, Marks IM, Kerwin RW.
Wisconsin
Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive
disorder (OCD).
Br J Med Psychol. 1997 Dec;70 ( Pt 4):403-11.
"We
compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive
disorder (OCD) patients and 19 individually matched healthy controls. Measures
of intelligence and mood were taken into account for all participants. Within
the patient group, factors such as duration and severity of symptoms (as assessed
using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored
the relationship between OCD WCST errors and regional cerebral blood flow (rCBF)
on brain dedicated, high resolution, single photon emission tomography (SPET).
We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate
rCBF, and regional values were quantified as ratios of cerebellar blood flow.
WCST results confirmed OCD patients were significantly impared when compared with
age- and sex-matched healthy volunteers. Patients made significantly more trials,
more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive'
subtotal significantly correlated with many WCST errors. Furthermore OCD WCST
null-sorts correlated significantly with SPET OCD left inferior frontal cortical
rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The
implications of these findings are discussed in the context of other studies which
examine functional imaging and neuropsychology in OCD." [Abstract] Breiter
HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN, Kendrick AD, Davis
TL, Jiang A, Cohen MS, Stern CE, Belliveau JW, Baer L, O'Sullivan RL, Savage CR,
Jenike MA, Rosen BR.
Functional magnetic resonance imaging of symptom
provocation in obsessive-compulsive disorder.
Arch Gen Psychiatry.
1996 Jul;53(7):595-606.
"BACKGROUND: The new technique of functional magnetic
resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive
disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and
5 normal subjects were studied via functional magnetic resonance imaging during
control and provoked conditions. Data analysis entailed parametric and nonparametric
statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3))
showed activation for 70% or more of patients with obsessive-compulsive disorder
in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate,
and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects
exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic
resonance imaging were consistent with past studies of obsessive-compulsive disorder
that used other functional neuroimaging modalities. However, paralimbic and limbic
activations were more prominent in the present study." [Abstract]
Aylward EH, Harris GJ, Hoehn-Saric R, Barta PE,
Machlin SR, Pearlson GD.
Normal caudate nucleus in obsessive-compulsive
disorder assessed by quantitative neuroimaging.
Arch Gen
Psychiatry. 1996 Jul;53(7):577-84.
"BACKGROUND: Prior neuroimaging studies
have not consistently demonstrated a structural or functional abnormality of the
caudate nucleus in patients with obsessive-compulsive disorder (OCD). However,
there is theoretical support for some associated dysfunction of the caudate nucleus.
METHODS: We examined volumes of the caudate nucleus and putamen with magnetic
resonance imaging in 24 patients with adult-onset OCD and 21 control subjects,
group-matched on age, race, education, and sex. Patients were relatively free
from tics. To evaluate function (metabolism or blood flow) of the caudate nucleus,
we performed a quantitative review, including a meta-analysis, of normalized data
from functional neuroimaging studies that compared patients who had OCD with normal
control subjects. RESULTS: All structural basal ganglia measures failed to exhibit
differences between patients with OCD and matched normal control subjects. Patients
did not demonstrate evidence of ventricular enlargement. Quantitative meta-analysis
of the functional neuroimaging literature did not demonstrate a consistent abnormality
of the caudate nucleus. CONCLUSIONS: We did not observe evidence of a structural
abnormality of the caudate nucleus in patients with OCD. Prior reports of a structural
aberration of the caudate nucleus were mixed. We also did not find strong support
for relative caudate metabolic or perfusion dysfunction in the literature, although
increased function in the frontal cerebral cortex was identified. The heterogeneous
nature of this disorder may account for inconsistencies between studies. For example,
ventricular enlargement or reduced caudate volume or blood flow might be evident
in patients with soft neurological signs (eg, tics), while patients in the current
study were relatively free from tics. Although theories of OCD suggest a dysfunction
of the caudate nucleus, the structural and functional neuroimaging literature
has not consistently verified this." [Abstract] Rubin
RT, Villanueva-Meyer J, Ananth J, Trajmar PG, Mena I.
Regional xenon
133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated
patients with obsessive-compulsive disorder and matched normal control subjects.
Determination by high-resolution single-photon emission computed tomography.
Arch
Gen Psychiatry. 1992 Sep;49(9):695-702.
"We measured regional cerebral
blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional
cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO)
by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive
disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe
method, there were no significant differences in cortical or basal ganglia blood
flow between the patients with OCD and their matched controls. In the patients,
there was a positive relationship between rCBF and the severity of both obsessive
and compulsive symptoms (average r = .48). These rCBF findings were consistent
with those of earlier reports of increased rCBF in patients with OCD who were
undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP
administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain
barrier and is converted to a hydrophilic form that is trapped in the brain. The
amount that is trapped is determined primarily by blood flow, but also by membrane
permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic
form. Compared with their matched controls, the patients with OCD had significantly
increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in
the left posterofrontal cortex, and in the orbital frontal cortex bilaterally.
Possible explanations include (1) increased rCBF that was not detected with 133Xe,
(2) increased permeability of the blood-brain barrier and/or cell membranes, and
(3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO
in these regions." [Abstract] Robinson
D, Wu H, Munne RA, Ashtari M, Alvir JM, Lerner G, Koreen A, Cole K, Bogerts B.
Reduced
caudate nucleus volume in obsessive-compulsive disorder.
Arch
Gen Psychiatry. 1995 May;52(5):393-8.
"BACKGROUND: Current hypotheses
about the neuroanatomical structures involved in obsessive-compulsive disorder
(OCD) suggest abnormalities in cortical-striatal-thalamic-cortical circuits. This
study examined selected brain regions within or adjacent to these circuits. METHODS:
Magnetic resonance imaging scans from 26 patients with OCD and 26 healthy controls
were analyzed to determine the volumes of the following structures: prefrontal
cortex (cortex anterior to the genu of the corpus callosum), caudate nucleus,
lateral and third ventricles, and whole brain. RESULTS: Patients with OCD had
significantly smaller caudate nucleus volumes than controls (F[1,48] = 9.4, P
= .004) but did not differ in prefrontal cortex size or in volumes of the lateral
or third ventricles. Structural volumes were not significantly correlated with
the duration or severity of OCD symptoms. CONCLUSION: Our findings provide additional
evidence for pathological involvement of the caudate in OCD." [Abstract] Scarone
S, Colombo C, Livian S, Abbruzzese M, Ronchi P, Locatelli M, Scotti G, Smeraldi
E.
Increased right caudate nucleus size in obsessive-compulsive disorder:
detection with magnetic resonance imaging.
Psychiatry Res.
1992 Aug;45(2):115-21.
"Magnetic resonance images were used to measure
the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive
disorder and 16 normal control subjects. The obsessive-compulsive patients showed
a significant increase in the volume of the right side of the head of the caudate
nucleus compared with that of control subjects. This finding was not correlated
with demographic, psychopathological, or clinical characteristics." [Abstract] Calabrese
G, Colombo C, Bonfanti A, Scotti G, Scarone S.
Caudate nucleus abnormalities
in obsessive-compulsive disorder: measurements of MRI signal intensity.
Psychiatry
Res. 1993 Jun;50(2):89-92.
"A previous magnetic resonance imaging (MRI)
study from our group reported increased size of the right caudate nucleus in obsessive-compulsive
patients compared with control subjects. To test the hypothesis of a structural
abnormality underlying such volume alteration, MRI signal intensity (SI), as an
index of T1 relaxation values, was measured in the caudate nucleus of the same
sampling data. Results showed higher SI values in the left caudate nucleus compared
with the right in the patient group, whereas no asymmetry was found in the control
group." [Abstract] Perani
D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S, Bellodi L, Smeraldi E,
Fazio F.
[18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic
correlation study after treatment.
Br J Psychiatry. 1995
Feb;166(2):244-50.
"BACKGROUND. We used [18F]FDG and PET in patients with
obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement
before and after treatment with serotonin-specific reuptake inhibitors. METHOD.
In 11 untreated, drug-free adults, regional cerebral metabolic rate for glucose
(rCMRglu) was compared with that of 15 age-matched normal controls. RESULTS. rCMRglu
values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen
complex. After treatment a significant improvement in obsessive-compulsive symptoms
on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral
decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical
and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P
< 0.01). CONCLUSIONS. These findings indicate that OCD is associated with functional
hyperactivity of a selected neuronal network and that treatment to reduce symptoms
may have a selective neuromodulatory effect on cingulate cortex." [Abstract]
Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC,
Savage CR, Fischman AJ.
Regional cerebral blood flow measured during
symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon
dioxide and positron emission tomography.
Arch Gen Psychiatry.
1994 Jan;51(1):62-70.
"BACKGROUND: The study was designed to determine
the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The
short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for
repeated positron emission tomographic determinations of regional cerebral blood
flow on each of eight patients with OCD during a resting and a provoked (symptomatic)
state. RESULTS: Individually tailored provocative stimuli were successful in provoking
OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report
on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically
significant increase in relative regional cerebral blood flow during the OCD symptomatic
state vs the resting state in right caudate nucleus (P < .006), left anterior
cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008);
increases in the left thalamus approached but did not reach statistical significance
(P = .07). CONCLUSIONS: These findings are consistent with results of previous
functional neuroimaging studies and contemporary neurocircuitry models of OCD.
The data further implicate orbitofrontal cortex, caudate nucleus, and anterior
cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms."
[Abstract] Baxter
LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE.
Local
cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison
with rates in unipolar depression and in normal controls.
Arch
Gen Psychiatry. 1987 Mar;44(3):211-8.
"We studied 14 patients with obsessive-compulsive
disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method,
looking for abnormalities in local cerebral metabolic rates for glucose in brain
structures that have been hypothesized to function abnormally in OCD. These patients
were compared with 14 normal controls and 14 patients with unipolar depression.
The patients with unipolar depression and OCD did not differ in levels of anxiety,
tension, or depression. In OCD, metabolic rates were significantly increased in
the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent
on all statistical comparisons with both controls and unipolar depression. The
right orbital gyrus showed at least a trend to an increased metabolic rate in
all comparisons. The metabolic rate in the left orbital gyrus, relative to that
in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly
elevated compared to controls and subjects with unipolar depression, and stayed
high even with successful drug treatment. Though it was in the normal range in
the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere
metabolic ratio increased uniformly and significantly bilaterally. This ratio
did not increase in patients who did not respond to treatment. Thus, OCD showed
cerebral glucose metabolic patterns that differed from controls in both the symptomatic
and recovered states." [Abstract] Amo
C, Quesney LF, Ortiz T, Maestu F, Fernandez A, Lopez-Ibor MI, Lopez-Ibor JJ.
Limbic
paroxysmal magnetoencephalographic activity in 12 obsessive-compulsive disorder
patients: a new diagnostic finding.
J Clin Psychiatry. 2004
Feb;65(2):156-62.
"BACKGROUND: We describe frontotemporal paroxysmal rhythmic
activity recorded by magnetoencephalography (MEG) in patients with obsessive-compulsive
disorder (OCD). METHOD: Twelve patients with OCD (per ICD-10 and DSM-IV criteria),
aged 18 to 65 years, were assessed using MEG. Patients' classification according
to the Yale Brown OCD Scale was as follows: severe = 8, moderate = 3, and mild
= 1. MEG findings were compared with those of 12 age- and sex-matched healthy
subjects (control group) with no previous history of psychiatric or neurologic
disorders. All study participants underwent neurologic and basic medical examinations,
including magnetic resonance imaging, electrocardiograms (EEGs), and electrooculograms.
The study was conducted between January 2001 and January 2002. RESULTS: Two types
of MEG activity were observed in patients with OCD: (1) frontotemporal paroxysmal
rhythmic activity with low-amplitude spikes (< 1 picoTesla) in 92% (11/12)
of patients and (2) intermittent isolated spikes and sharp waves in all patients
(12/12). The OCD group had paroxysmal rhythmic MEG activity in the cingulate cortex
(12/12), insula (10/12), hippocampus (9/12), temporal superior gyrus and angular
and supramarginal gyri (9/12), precentral and post-central gyri (8/12), orbitofrontal
cortex (5/12), and parietal lobes (5/12). MEG recordings were normal in the control
group, and EEG findings were normal in both the OCD and control groups. CONCLUSIONS:
Frontotemporal paroxysmal rhythmic activity with a preferential limbic distribution
is a sensitive MEG finding in patients with OCD. Although the pathophysiology
of this abnormality remains unknown, a corticostriatal network dysfunction was
hypothesized." [Abstract]
Kwon JS, Shin YW, Kim CW, Kim YI, Youn T, Han MH,
Chang KH, Kim JJ.
Similarity and disparity of obsessive-compulsive
disorder and schizophrenia in MR volumetric abnormalities of the hippocampus-amygdala
complex.
J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):962-4.
"OBJECTIVES:
Given that obsessive-compulsive disorder (OCD) and schizophrenia may share clinical
symptoms as well as functional brain abnormalities, this study was designed to
clarify common and different morphological abnormalities in OCD and schizophrenia.
METHODS: Volumes of the hippocampus, the amygdala, and the thalamus were measured
in three age and sex matched groups of 22 patients with OCD, 22 patients with
schizophrenia, and 22 normal subjects using three dimensional magnetic resonance
imaging. Volume tracing was performed manually on serial coronal slices with the
references of sagittal or axial planes using internal landmarks. RESULTS: Hippocampal
volume was bilaterally reduced in both OCD and schizophrenic patients versus the
normal controls. Left amygdala volume was significantly enlarged in patients with
OCD but not in patients with schizophrenia versus the normal controls. The thalamus
did not show any volumetric group differences. CONCLUSIONS: Non-specific hippocampal
reduction in both the OCD and schizophrenic groups is likely to link to a clinical
overlap between the two illnesses, whereas the left amygdala enlargement observed
only in the OCD patients seems to be suggestive of a unique role for the amygdala
in the pathophysiology of OCD." [Abstract]
Gamazo-Garran P, Soutullo CA, Ortuno F.
Obsessive-compulsive
disorder secondary to brain dysgerminoma in an adolescent boy: a positron emission
tomography case report.
J Child Adolesc Psychopharmacol.
2002 Fall;12(3):259-63.
"The neuroanatomical model involved in the pathophysiology
of obsessive-compulsive disorder (OCD) postulates a hyperactivation of orbitofrontal,
limbic, and basal ganglia circuits. We report a case of OCD secondary to brain
dysgerminoma affecting this circuit in an adolescent who responded to citalopram.
The patient is a 16-year-old-boy with a midline germinal tumor (dysgerminoma)
affecting the caudate nuclei; left lenticular, right internal capsule's genu;
and bilateral involvement of the interventricular septum close to the interventricular
foramina. He had OCD symptoms and elevated tumor markers when he had a tumor relapse,
and fluorodeoxyglucose positron emission tomography showed caudate nuclei involvement.
He responded to citalopram that had to be titrated gradually to 80 mg/day."
[Abstract]
Mac Master FP, Keshavan MS, Dick EL, Rosenberg DR.
Corpus
callosal signal intensity in treatment-naive pediatric obsessive compulsive disorders.
Prog
Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):601-12.
"1. Obsessive
compulsive disorder (OCD) is increasingly recognized as a severe, highly prevalent
and chronically disabling disorder, emerging during childhood in as many as 80%
of cases. The authors previously found significant abnormalities in the region
of the corpus callosum (CC) connecting ventral prefrontal cortex and striatum
in pediatric OCD patients compared to controls that correlated significantly with
OCD symptom severity. We speculated that this abnormality might reflect aberrant
myelinization in OCD patients. 2. In order to better characterize the abnormality,
the authors examined CC signal intensity (SI), believed to be a reliable index
of myelinization of the CC. Lower numbers would indicate a greater concentration
of white matter, while higher numbers indicate higher concentrations of gray matter.
We compared the SI from midsagittal magnetic resonance images of 21 treatment-naive
OCD patients, 7.2-17.7 years, and 21 case-matched healthy controls to examine
regional CC signal intensity of the anterior, middle and posterior genu, body,
isthmus, and the anterior, middle and the posterior splenii. 3. Mean total genu
SI for the patient group (.993 + .006) was significantly less than the total genu
SI of controls (.994 + .006) at F(1,37) = 4.73; p = .036. This abnormality in
SI was localized to the CC region connecting ventral PFC and striatum, the anterior
genu for the OCD group (.991 + .007) which was also less than control (.995 +
.007) at F(1,37) = 5.47; p = .025., with no abnormality observed in middle or
posterior genu regions. Genu SI was also inversely correlated with OCD symptom
severity (r = -.55, p = .013) but not illness duration. Genu SI also correlated
positively with genu area (r = .52, p = .020) in OCD patients but not controls.
4. Developmental abnormalities in genu size may arise from abnormalities in myelination
in early onset OCD patients. The increased genu myelination observed in OCD patients
may alter signal transduction and function of VPFC-striatal association circuits."
[Abstract] Rosenberg
DR, Keshavan MS, Dick EL, Bagwell WW, MacMaster FP, Birmaher B.
Corpus
callosal morphology in treatment-naive pediatric obsessive compulsive disorder.
Prog
Neuropsychopharmacol Biol Psychiatry. 1997 Nov;21(8):1269-83.
"1. Abnormalities
in association circuits have been described in Obsessive Compulsive Disorder (OCD)
and may reflect neurodevelopmental abnormalities. Primary and association cortices
are topographically mapped in the corpus callosum (CC). The authors hypothesized
alterations in CC subdivisions that connect association, but not primary cortices
in pediatric OCD. The authors predicted that normal age-related increases in CC
area would be absent in OCD. 2. The authors compared the midsagittal magnetic
resonance images of 21 psychotropic-naive, nondepressed OCD patients, 7.2-17.7
years, and 21 case-matched healthy controls. Total CC area as well as that of
the anterior, middle and posterior genu, anterior and posterior bodies, isthmus,
and the anterior, middle and the posterior splenii were measured. 3. All of the
CC regions except the isthmus were significantly larger in OCD patients than in
controls. CC area correlated significantly with OCD symptom severity but not illness
duration. The age-related increase in CC size seen in normal subjects was absent
in OCD patients. 4. These findings support theories of abnormal association cortex
development in OCD but also suggest possible abnormalities of other primary cortical
regions as well." [Abstract] Farchione
TR, Lorch E, Rosenberg DR.
Hypoplasia of the corpus callosum and
obsessive-compulsive symptoms.
J Child Neurol. 2002 Jul;17(7):535-7.
"Abnormalities
in the corpus callosum, which connects the cerebral hemispheres, have been implicated
in the pathogenesis of obsessive-compulsive disorder. This is a report of two
cases of obsessive-compulsive disorder associated with hypoplasia of the corpus
callosum. These data provide further support for corpus callosum-mediated dysfunction
in obsessive-compulsive disorder." [Abstract]
| Denys
D, van der Wee N, Janssen J, De Geus F, Westenberg HG.
Low level
of dopaminergic D2 receptor binding in obsessive-compulsive disorder.
Biol
Psychiatry. 2004 May 15;55(10):1041-5.
"BACKGROUND: Despite growing evidence
for involvement of the dopaminergic system in obsessive-compulsive disorder (OCD),
the functional anatomy of the dopaminergic system in the basal ganglia has been
investigated sparsely. METHODS: Dopamine D(2) receptor binding was assessed in
10 medication-free OCD patients and 10 healthy control subjects, matched for age,
gender, and handedness. The binding potential was measured with single photon
emission computerized tomography (SPECT) and infusion of the D(2) receptor radiotracer
[(123)I] iodobenzamide. With magnetic resonance imaging as reference, regions
of interest (caudate and putamen) were delineated for each hemisphere and coregistered
with the corresponding SPECT scans. RESULTS: Dopamine D(2) receptor binding in
the left caudate nucleus was significantly lower in the patients with OCD than
in healthy control subjects [F(1,18) = 7.0, p =.016]. In addition, an interhemispheric
difference was observed in the patient sample. Both the D(2) receptor binding
potential (df = 9, p =.012), and the volume (df = 9, p =.029) of the left caudate
nucleus were statistically significantly reduced relative to the right caudate
nucleus. CONCLUSIONS: This study provides in vivo evidence for abnormalities in
the binding potential of the dopamine D(2) receptor, which suggest the direct
involvement of the dopaminergic system in the pathophysiology of OCD." [Abstract] Kim
CH, Koo MS, Cheon KA, Ryu YH, Lee JD, Lee HS.
Dopamine transporter
density of basal ganglia assessed with [123I]IPT SPET in obsessive-compulsive
disorder.
Eur J Nucl Med Mol Imaging. 2003 Dec;30(12):1637-43.
Epub 2003 Sep 25.
"It has been suggested that dopamine, as well as serotonin,
is associated with the pathophysiology of obsessive-compulsive disorder (OCD).
Thus, many studies have been performed on brain regions associated with dopamine
in patients with OCD. In the present study, we investigated the DAT density of
the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)
tropane ([123I]IPT) single-photon emission tomography (SPET) and evaluated the
activity of the presynaptic dopamine function in patients with OCD. Fifteen patients
with OCD and 19 normal control adults were included in the study. We performed
brain SPET 2 h after the intravenous administration of [123I]IPT and carried out
both quantitative and qualitative analyses using the obtained SPET data, which
were reconstructed for the assessment of the specific/non-specific dopamine transporter
(DAT) binding ratio in the basal ganglia. We then investigated the correlation
between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive
Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia.
Compared with normal control adults, patients with OCD showed a significantly
increased specific/non-specific DAT binding ratio in the right basal ganglia and
a tendency towards an increased specific/non-specific DAT binding ratio in the
left basal ganglia. No significant correlation was found between the total scores
on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia.
These findings suggest that the dopaminergic neurotransmitter system of the basal
ganglia in patients with OCD could be involved in the pathophysiology of OCD."
[Abstract] Pogarell
O, Hamann C, Popperl G, Juckel G, Chouker M, Zaudig M, Riedel M, Moller HJ, Hegerl
U, Tatsch K.
Elevated brain serotonin transporter availability in
patients with obsessive-compulsive disorder.
Biol Psychiatry.
2003 Dec 15;54(12):1406-13.
"BACKGROUND: A central serotonergic dysfunction
is considered to be involved in the pathophysiology of obsessive-compulsive disorder
(OCD). The aim of this study was to investigate the serotonin transporter availability
in patients with OCD as an in vivo marker of the central serotonergic system.
METHODS: Nine unmedicated (7 drug-naive) patients with OCD and 10 healthy control
subjects were included and received single photon emission computed tomography
(SPECT) 20.75 +/- 1.51 hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
([(123)I]beta-CIT). As a measure of brain serotonin transporter availability,
a ratio of specific-to-nonspecific [(123)I]beta-CIT binding for the midbrain-pons
(V(3)" = [midbrain/pons-occipital]/occipital) was used. RESULTS: Mean specific-to-nonspecific
ratios showed a 25% higher midbrain-pons [(123)I]beta-CIT binding in the patients
as compared with healthy controls (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The
difference remained significant after adjustment for clinical variables and controlling
for age and gender. Stratification of the patients according to onset of the disorder
revealed significant differences between controls and patients with early (childhood,
adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides
evidence of a serotonergic dysfunction in patients with OCD and suggests a serotonergic
component in the pathophysiology of the disorder." [Abstract]
Simpson HB, Lombardo I, Slifstein M, Huang HY, Hwang
DR, Abi-Dargham A, Liebowitz MR, Laruelle M.
Serotonin transporters
in obsessive-compulsive disorder: a positron emission tomography study with [(11)C]McN
5652.
Biol Psychiatry. 2003 Dec 15;54(12):1414-21.
"BACKGROUND:
Serotonergic abnormalities have been hypothesized to contribute to obsessive-compulsive
disorder (OCD). This study examined whether brain serotonin transporter (SERT)
availability is altered in OCD using positron emission tomography (PET) and the
SERT PET radiotracer [(11)C]McN 5652. METHODS: Eleven OCD subjects, free of psychiatric
medications and comorbid depression, and 11 matched healthy control subjects underwent
PET scans following injection of [(11)C]McN 5652 and magnetic resonance imaging
(MRI) scans. Total distribution volumes (V(T)) were derived by kinetic analysis
(one tissue compartment model) using the arterial input function. Two measures
of SERT availability were computed: binding potential (BP) and specific to nonspecific
partition coefficient (V(3)"). Groups were compared using region of interest
(ROI) analysis and voxelwise analysis of spatially normalized parametric maps;
ROIs were selected based on their relatively high SERT density and included subcortical
(dorsal caudate, dorsal putamen, ventral striatum, midbrain, thalamus) and limbic
(hippocampus, amygdala, anterior cingulate cortex) regions. RESULTS: No significant
group differences were observed in [(11)C]McN 5652 BP or V(3)" in the ROIs.
No significant group differences were detected in the voxelwise analysis of BP
or V(3)" maps. CONCLUSIONS: OCD without comorbid depression, may not be associated
with major changes in SERT availability in subcortical and limbic regions."
[Abstract] Lacerda
AL, Dalgalarrondo P, Caetano D, Haas GL, Camargo EE, Keshavan MS.
Neuropsychological
performance and regional cerebral blood flow in obsessive-compulsive disorder.
Prog
Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):657-65.
"Convergent
findings from neuropsychological and neuroimaging studies have suggested that
neural dysfunction in frontal-subcortical circuits may play a central role in
the pathophysiology of obsessive-compulsive disorder (OCD). To further examine
the relationship between these two sets of findings we investigated both neuropsychological
functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen
unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls
matched for age, gender, handedness, and education were assessed on neuropsychological
tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy
and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test
(WCST). rCBF was studied with 99 mTc-hexamethyl-propyleneamine-oxime (HMPAO) single
photon emission computed tomography (SPECT). Patients performed more poorly than
controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearman's
correlations indicated that severity of OCD correlated inversely with performance
on the RCF (copy and recall scores) and positively with rCBF in the right thalamus.
Positive correlations were observed between nonperseverative errors (WCST) and
rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated
negatively with rCBF in the right thalamus. These findings are consistent with
most previously published studies and suggest neural dysfunctions in the frontal-subcortical
circuits probably more pronounced in the right hemisphere. They also extend the
existing research, showing associations between deficits in cortical-subcortical
circuitry and performance on neuropsychological tests of controlled attention
and visuospatial functions." [Abstract] Kwon
JS, Kim JJ, Lee DW, Lee JS, Lee DS, Kim MS, Lyoo IK, Cho MJ, Lee MC.
Neural
correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive
disorder.
Psychiatry Res. 2003 Jan 20;122(1):37-47.
"Although
results from neuropsychological and neuroimaging studies have postulated the involvement
of the frontal lobe and the subcortical brain regions in the pathophysiology of
obsessive-compulsive disorder (OCD), neuroimaging studies have provided little
evidence that cognitive abnormalities in patients with OCD are related to dysfunctions
in these areas. This study was designed to determine whether the clinical features
and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction.
Fourteen patients with OCD and 14 case-matched normal subjects completed clinical
and cognitive evaluation, including four sets of neuropsychological tests that
assessed the executive functions and visual memory. Cerebral glucose metabolic
rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose.
Behavioral and PET data were analyzed using statistical parametric mapping for
group differences and behavioral-metabolic correlates. The right orbitofrontal
cortex showed increased metabolic activity and the left parieto-occipital junction
showed decreased metabolic activity in patients. Metabolism in the right hippocampus,
the left putamen and the right parietal region was associated with the severity
of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological
test scores in the prefrontal cortex and the putamen occurred only in the patient
group. These results suggest that patients with OCD have distinct features of
brain metabolic activities for performing cognitive tasks as well as presenting
obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits
might mediate not only symptomatic expression but also cognitive expression in
patients with OCD." [Abstract]
Ursu
S, Stenger VA, Shear MK, Jones MR, Carter CS.
Overactive action monitoring
in obsessive-compulsive disorder: evidence from functional magnetic resonance
imaging.
Psychol Sci. 2003 Jul;14(4):347-53.
"The
anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder
(OCD) has been found to be hyperactive at rest, during symptom provocation, and
after commission of errors in cognitive tasks. This hyperactivity might reflect
an abnormality in conflict detection, a hypothesized basic mechanism for the action-monitoring
function of the ACC. This hypothesis was tested using functional magnetic resonance
imaging, by scanning 11 OCD patients and 13 matched control subjects while they
performed a version of the continuous-performance task with four trial types that
induced graded levels of response conflict. Although a behavioral index of conflict
(i.e., accuracy) was similar for patients and control subjects, the ACC activation
was increased in patients during high-conflict trials. The error-related activity
in the same brain region was also higher in patients, consistent with previous
electrophysiological findings. Both conflict- and error-related activity showed
trends for positive correlations with severity of OCD symptoms, but not with anxiety.
These findings suggest that as part of an overactive action-monitoring system,
the ACC is more directly involved in the pathophysiology of OCD than previously
thought." [Abstract] van
der Wee NJ, Ramsey NF, Jansma JM, Denys DA, van Megen HJ, Westenberg HM, Kahn
RS.
Spatial working memory deficits in obsessive compulsive disorder
are associated with excessive engagement of the medial frontal cortex.
Neuroimage.
2003 Dec;20(4):2271-80.
"Recent studies have shown that obsessive compulsive
disorder (OCD) is associated with a specific deficit in spatial working memory,
especially when task difficulty (i.e., working memory load) is high. It is not
clear whether this deficit is associated with dysfunction of the brain system
that subserves spatial working memory, or whether it is associated with a more
generalized effect on executive functions. In contrast to studies in healthy volunteers
and schizophrenia, spatial working memory in OCD has not been investigated before
using functional neuroimaging techniques. We conducted a functional MRI study
in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-,
and handedness pairwise-matched healthy controls in order to assess performance
on a parametric spatial n-back task as well as the underlying neuronal substrate
and its dynamics. Patients with OCD performed poorly at the highest level of task
difficulty and engaged the same set of brain regions as the matched healthy controls.
In this set, the effect of difficulty on magnitude of brain activity was the same
in patients and in controls except for a region covering the anterior cingulate
cortex. In this region activity was significantly elevated in patients with OCD
at all levels of the parametric task. These findings do not provide evidence for
a deficit of the spatial working memory system proper, but suggest that the abnormal
performance pattern may be secondary to another aspect of executive dysfunctioning
in OCD." [Abstract]
van Veen V, Carter CS.
The anterior
cingulate as a conflict monitor: fMRI and ERP studies.
Physiol
Behav. 2002 Dec;77(4-5):477-82.
"We propose that the anterior cingulate
cortex (ACC) contributes to cognition by detecting the presence of conflict during
information processing, and to alert systems involved in top-down control to resolve
this conflict. Here, we review several functional magnetic resonance imaging (fMRI)
and event-related potential (ERP) studies that have used simple response interference
tasks, and propose that ACC activity is activated prior to the response during
correct conflict trials and reflected in the frontocentral N2, and immediately
following error trials and reflected in the error-related negativity (ERN). Furthermore,
we suggest that certain disturbances in cognition and behavior in common mental
disorders such as schizophrenia and obsessive-compulsive disorder (OCD) can be
understood as resulting from alteration in performance monitoring functions associated
with this region of the brain." [Abstract] Saxena
S, Brody AL, Maidment KM, Smith EC, Zohrabi N, Katz E, Baker SK, Baxter LR Jr.
Cerebral
glucose metabolism in obsessive-compulsive hoarding.
Am
J Psychiatry. 2004 Jun;161(6):1038-48.
"OBJECTIVE: Compulsive hoarding
and saving symptoms, found in many patients with obsessive-compulsive disorder
(OCD), are part of a discrete clinical syndrome that includes indecisiveness,
disorganization, perfectionism, procrastination, and avoidance and has been associated
with poor response to medications and cognitive behavior therapy. The authors
sought to identify cerebral metabolic patterns specifically associated with the
compulsive hoarding syndrome using positron emission tomography (PET). METHOD:
[(18)F]Fluorodeoxyglucose PET scans were obtained for 45 adult subjects who met
DSM-IV criteria for OCD (12 of whom had compulsive hoarding as their most prominent
OCD symptom factor) and 17 normal comparison subjects. All subjects had been free
of psychotropic medication for at least 4 weeks. Regional cerebral glucose metabolism
was compared between the groups. RESULTS: In relation to the comparison subjects,
the patients with compulsive hoarding syndrome had significantly lower glucose
metabolism in the posterior cingulate gyrus and cuneus, whereas the nonhoarding
OCD patients had significantly higher glucose metabolism in the bilateral thalamus
and caudate. In relation to nonhoarding OCD patients, compulsive hoarders had
significantly lower metabolism in the dorsal anterior cingulate gyrus. Across
all OCD patients, hoarding severity was negatively correlated with glucose metabolism
in the dorsal anterior cingulate gyrus. CONCLUSIONS: OCD patients with the compulsive
hoarding syndrome had a different pattern of cerebral glucose metabolism than
nonhoarding OCD patients and comparison subjects. Obsessive-compulsive hoarding
may be a neurobiologically distinct subgroup or variant of OCD whose symptoms
and poor response to anti-obsessional treatment are mediated by lower activity
in the cingulate cortex." [Abstract] Mataix-Cols
D, Wooderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML.
Distinct
neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive
disorder.
Arch Gen Psychiatry. 2004 Jun;61(6):564-76.
"CONTEXT:
Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous
functional neuroimaging studies grouped together patients with mixed symptoms,
thus potentially reducing the power and obscuring the findings of such studies.
OBJECTIVE: To investigate the neural correlates of washing, checking, and hoarding
symptom dimensions in OCD. DESIGN: Symptom provocation paradigm, functional magnetic
resonance imaging, block design, and nonparametric brain mapping analyses. SETTING:
University hospital. PARTICIPANTS: Sixteen patients with OCD (11 inpatients, 5
outpatients) with mixed symptoms and 17 healthy volunteers of both sexes.Intervention
All subjects participated in 4 functional magnetic resonance imaging experiments.
They were scanned while viewing alternating blocks of emotional (washing-related,
checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral
pictures, and imagining scenarios related to the content of each picture type.Main
Outcome Measure Blood oxygenation level-dependent response. RESULTS: Both patients
and control subjects experienced increased subjective anxiety during symptom provocation
(patients significantly more so) and activated neural regions previously linked
to OCD. Analyses of covariance, controlling for depression, showed a distinct
pattern of activation associated with each symptom dimension. Patients demonstrated
significantly greater activation than controls in bilateral ventromedial prefrontal
regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus,
and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal
cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated).
These results were further supported by correlation analyses within patients,
which showed highly specific positive associations between subjective anxiety,
questionnaire scores, and neural response in each experiment. There were no consistently
significant differences between patients with (n = 9) and without (n = 7) comorbid
diagnoses. CONCLUSIONS: The findings suggest that different obsessive-compulsive
symptom dimensions are mediated by relatively distinct components of frontostriatothalamic
circuits implicated in cognitive and emotion processing. Obsessive-compulsive
disorder may be best conceptualized as a spectrum of multiple, potentially overlapping
syndromes rather than a unitary nosologic entity." [Abstract] Mataix-Cols
D, Cullen S, Lange K, Zelaya F, Andrew C, Amaro E, Brammer MJ, Williams SC, Speckens
A, Phillips ML.
Neural correlates of anxiety associated with obsessive-compulsive
symptom dimensions in normal volunteers.
Biol Psychiatry.
2003 Mar 15;53(6):482-93.
"BACKGROUND: The neural correlates of anxiety
associated with obsessive-compulsive symptomlike provocation in normal volunteers
are unknown. METHODS: Ten healthy volunteers participated in four functional magnetic
resonance experiments. Subjects were scanned while viewing alternating blocks
of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant
pictures) and neutral pictures, and imagining scenarios related to the content
of each picture type. Nonparametric brain mapping analyses were used. RESULTS:
In response to the provocative pictures in all experiments, increases in subjective
anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal,
and visual regions were demonstrated. Anxiety related to different symptom dimensions
was associated with different patterns of activation: provocation of washing-relevant
anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant
anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant
anxiety predominantly activated ventral prefrontal regions and the left amygdala.
CONCLUSIONS: Our findings support a dimensional model of obsessive-compulsive
disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety
in response to symptom-related material in normal subjects are similar to those
identified in OCD patients during symptom provocation, and 2) anxiety associated
with different symptom dimensions is associated with differential patterns of
activation of these neural systems. Further investigation of the neural basis
of OCD symptom dimensions is required." [Abstract]
Phillips ML, Marks IM, Senior C, Lythgoe D, O'Dwyer
AM, Meehan O, Williams SC, Brammer MJ, Bullmore ET, McGuire PK.
A
differential neural response in obsessive-compulsive disorder patients with washing
compared with checking symptoms to disgust.
Psychol Med.
2000 Sep;30(5):1037-50.
"BACKGROUND: Patients with obsessive-compulsive
disorder (OCD) have symptoms that predominantly concern washing (washers) or checking
(checkers), or both. Functional neuroimaging has been used to identify the neural
correlates of the urge to ritualize but has not distinguished between washing
and checking symptoms in OCD. We used functional magnetic resonance imaging to
compare the neural response to emotive pictures in washers and checkers. METHODS:
In one of two 5-minute experiments, washers (N = 7), checkers (N = 7) and age-matched
normal controls (N = 14) were scanned while viewing alternating blocks of normally
disgusting (rated as disgusting by all subjects) and neutral pictures. In the
other experiment, all patients and a normal subgroup (N = 8) viewed alternating
blocks of washer-relevant (rated as more disgusting by washers than normal controls
or checkers) and neutral pictures. RESULTS: In all subjects, normally disgusting
pictures activated visual regions implicated in perception of aversive stimuli
and the insula, important in disgust perception. Only in washers were similar
regions activated by washer-relevant pictures. In checkers, these pictures activated
fronto-striatal regions associated with the urge to ritualize in OCD. Normal controls
were more similar in neural response to checkers than washers to these pictures.
Both normal controls and checkers had frontal regions activated significantly
more by washer-relevant than normally disgusting pictures, and had these regions
activated significantly more than washers by washer-relevant pictures. CONCLUSIONS:
We demonstrate a differential neural response to washer-relevant disgust in washers
and checkers: only washers demonstrate a neural response to washer-relevant disgust
associated with emotion perception rather than attention to non-emotive visual
detail." [Abstract] Shapira
NA, Liu Y, He AG, Bradley MM, Lessig MC, James GA, Stein DJ, Lang PJ, Goodman
WK.
Brain activation by disgust-inducing pictures in obsessive-compulsive
disorder.
Biol Psychiatry. 2003 Oct 1;54(7):751-6.
"BACKGROUND:
There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive
disorder (OCD). METHODS: Eight OCD subjects with contamination preoccupations
and eight gender- and age-matched healthy volunteers viewed pictures from the
International Affective Picture System during functional magnetic resonance imaging
scans. RESULTS: A different distribution of brain activations was found during
disgust-inducing visual stimulation in several areas, most notably the insula,
compared with neutral stimulation in both OCD subjects and healthy volunteers.
Furthermore, whereas activation during the threat-inducing task in OCD subjects
showed a pattern similar to that in healthy volunteers, the pattern of activation
during the disgust-inducing task was significantly different, including greater
increases in the right insula, parahippocampal region, and inferior frontal sites.
CONCLUSIONS: This pilot study supports the relevance of disgust in the neurocircuitry
of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD
individuals with high disgust ratings, non-contamination-preoccupied OCD individuals,
and individuals with other anxiety disorders are needed." [Abstract] Lacerda
AL, Dalgalarrondo P, Caetano D, Camargo EE, Etchebehere EC, Soares JC.
Elevated
thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder:
a SPECT study.
Psychiatry Res. 2003 Jun 30;123(2):125-34.
"Functional
neuroimaging studies have pointed to a possible role of cerebral circuits involving
the prefrontal and anterior cingulate cortices, the striatum, and thalamus in
the pathophysiology of obsessive-compulsive disorder (OCD). Regional cerebral
blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects
matched for age, gender, handedness and level of education was measured with [99m-Tc]
HMPAO single photon emission computed tomography. Analysis of covariance identified
four regions of interest with significantly higher rCBF: the right superior and
inferior frontal cortex and the right and left thalamus. Positive correlations
between symptom severity measured by Clinical Global Impression scores and rCBF
were found in the right and left inferior frontal lobes and in the right basal
ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus,
and duration of illness correlated positively with rCBF in the right and left
superior frontal lobes and with the right thalamus. The findings of this SPECT
study conducted in Brazil are in agreement with prior studies and provide additional
support for the involvement of prefrontal-subcortical circuits in the pathophysiology
of OCD. Furthermore, the study suggests that similar brain mechanisms appear to
be involved cross-culturally." [Abstract] Rosenberg
DR, Amponsah A, Sullivan A, MacMillan S, Moore GJ.
Increased medial
thalamic choline in pediatric obsessive-compulsive disorder as detected by quantitative
in vivo spectroscopic imaging.
J Child Neurol. 2001 Sep;16(9):636-41.
"The
thalamus has been implicated in the pathophysiology of obsessive-compulsive disorder.
Using a multislice spectroscopic imaging sequence, we reported reductions in right
and left medial thalamic N-acetylaspartate/cytosolic choline + creatine/phosphocreatine
and N-acetylaspartate/cytosolic choline levels in 11 pediatric patients with obsessive-compulsive
disorder, 8 to 15 years, versus 11 case-matched healthy controls. These changes
may reflect a change in N-acetylaspartate, cytosolic choline, or creatine concentrations.
Therefore, using a validated phantom replacement methodology, we obtained absolute
measures (mmol/L) of N-acetylaspartate, a putative marker of neuronal viability,
cytosolic choline, and creatine in these subjects. A significant increase in cytosolic
choline was observed in right and left medial but not lateral thalami in patients
with obsessive-compulsive disorder versus controls. N-acetylaspartate and creatine
did not differ significantly between case-control pairs in the medial or lateral
thalamus. These findings provide new evidence of cytosolic choline abnormalities
in the thalamus in pediatric obsessive-compulsive disorder." [Abstract] Smith
EA, Russell A, Lorch E, Banerjee SP, Rose M, Ivey J, Bhandari R, Moore GJ, Rosenberg
DR.
Increased medial thalamic choline found in pediatric patients
with obsessive-compulsive disorder versus major depression or healthy control
subjects: a magnetic resonance spectroscopy study.
Biol
Psychiatry. 2003 Dec 15;54(12):1399-405.
"BACKGROUND: Neurobiologic abnormalities
in medial thalamus have been implicated in the pathogenesis of obsessive-compulsive
disorder (OCD). We previously used multislice proton magnetic resonance spectroscopic
imaging (1-H MRSI) to identify localized functional neurochemical marker alterations
in choline (Cho) in medial but not lateral thalamus in treatment-naive pediatric
patients with OCD compared with matched control subjects. Altered brain Cho levels
have also been implicated in the pathogenesis of mood disorders. METHODS: We used
1-H MRSI to study absolute Cho concentrations in 18 psychotropic-naive pediatric
patients with major depressive disorder (MDD) not suffering from OCD, 9-17 years
of age, 18 case-matched healthy control subjects, and 27 nondepressed, psychotropic-naive
pediatric patients with OCD, 7-16 years of age. RESULTS: Significantly increased
left and right medial thalamic Cho concentrations were observed in OCD patients
compared with both healthy control subjects and patients with MDD. Medial thalamic
Cho concentrations did not differ significantly between patients with MDD and
control subjects. CONCLUSIONS: These results suggest that localized functional
neurochemical marker alterations in medial thalamic Cho differentiate patients
with OCD from healthy control subjects and patients with MDD. Although these results
must be considered preliminary, further study of the diagnostic specificity of
Cho as a relevant biomarker in OCD is clearly warranted." [Abstract] Busatto
GF, Buchpiguel CA, Zamignani DR, Garrido GE, Glabus MF, Rosario-Campos MC, Castro
CC, Maia A, Rocha ET, McGuire PK, Miguel EC.
Regional cerebral blood
flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory
SPECT study.
J Am Acad Child Adolesc Psychiatry. 2001 Mar;40(3):347-54.
"OBJECTIVE:
Recent epidemiological and clinical data suggest that obsessive-compulsive disorder
(OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms.
The regional cerebral blood flow (rCBF) single photon emission computed tomography
(SPECT) technique was used to investigate whether the pathophysiology of OCD differs
between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured
in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects
and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical
parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the
right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal
cortex relative to late-onset subjects (p < .0005, uncorrected for multiple
comparisons). Relative to controls, early-onset cases had decreased left anterior
cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum,
whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased
rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive
symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF
differences in frontal-subcortical circuits between early-onset and late-onset
OCD subjects were found, both in location and direction of changes. These results
provide preliminary evidence that brain mechanisms in OCD may differ depending
on the age at which symptoms are first expressed." [Abstract] Adler
CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM.
fMRI
of neuronal activation with symptom provocation in unmedicated patients with obsessive
compulsive disorder.
J Psychiatr Res. 2000 Jul-Oct;34(4-5):317-24.
"BACKGROUND:
Previous studies suggest that a neural circuit involving over-activation of cortical,
paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but
results may have been limited by medication use in those studies. To address this,
we examined the effects of symptom induction on fMRI neural activation in medication-free
patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually
tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of
OCD symptoms were performed prior to each scan and after exposure to stimuli.
Images were analyzed as composite data sets and individually. RESULTS: Stimulus
presentation was associated with significant increases in OCD self-ratings. Significant
activation was demonstrated in several regions of the frontal cortex (orbitofrontal,
superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral
temporal cortex; and the right anterior cingulate. Right superior frontal activation
inversely correlated with baseline compulsion symptomatology and left orbitofrontal
cortical activation was inversely associated with changes in OCD self-ratings
following provocative stimuli. CONCLUSIONS: These results in unmedicated patients
are consistent with those from previous studies with medicated patients and suggest
that OCD symptomatology is mediated by multiple brain regions including the anterior
cingulate as well as frontal and temporal brain regions." [Abstract] Gilbert
AR, Moore GJ, Keshavan MS, Paulson LA, Narula V, Mac Master FP, Stewart CM, Rosenberg
DR.
Decrease in thalamic volumes of pediatric patients with obsessive-compulsive
disorder who are taking paroxetine.
Arch Gen Psychiatry.
2000 May;57(5):449-56.
"BACKGROUND: Thalamic dysfunction has been implicated
in obsessive-compulsive disorder (OCD). While OCD frequently has its onset during
childhood, to our knowledge, no prior study has measured neuroanatomical changes
in the thalamus of patients with OCD near the onset of illness, and before and
after treatment. METHODS: Volumetric magnetic resonance imaging studies were conducted
in 21 psychotropic drug-naive children, aged 8 to 17 years, with OCD and 21 case-matched
healthy comparison subjects. Magnetic resonance imaging studies were also conducted
in 10 of the 21 patients with OCD after 12 weeks of monotherapy with the selective
serotonin reuptake inhibitor, paroxetine hydrochloride. RESULTS: Thalamic volumes
were significantly greater in treatment-naive patients with OCD than in controls
but declined significantly after paroxetine monotherapy to levels comparable with
those of controls. Decrease in thalamic volume in patients with OCD was associated
with reduction in OCD symptom severity. CONCLUSIONS: Our findings provide new
evidence of thalamic abnormalities in pediatric OCD and further suggest that paroxetine
treatment may be paralleled by a reduction in thalamic volume. These reductions
may, however, not be specific to paroxetine treatment and could be due to a more
general treatment response, and/or spontaneous improvement in symptoms. Our findings
are preliminary given the small sample size and our inability to measure discrete
thalamic nuclei." [Abstract]
Rosenberg DR, Benazon NR, Gilbert A, Sullivan A,
Moore GJ.
Thalamic volume in pediatric obsessive-compulsive disorder
patients before and after cognitive behavioral therapy.
Biol
Psychiatry. 2000 Aug 15;48(4):294-300.
"BACKGROUND: Neurobiologic abnormalities
in the thalamus have been implicated in the pathophysiology of obsessive-compulsive
disorder. We recently reported increased thalamic volume in treatment-naive pediatric
obsessive-compulsive disorder patients versus case-matched healthy comparison
subjects that decreased to levels comparable to control subjects after effective
paroxetine therapy. To our knowledge, no prior study has measured neuroanatomic
changes in the thalamus of obsessive-compulsive disorder patients near illness
onset before and after cognitive behavioral therapy. METHODS: Volumetric magnetic
resonance imaging studies were conducted in 11 psychotropic drug-naive 8-17-year-old
children with obsessive-compulsive disorder before and after 12 weeks of effective
cognitive behavioral therapy monotherapy (> or =30% reduction in obsessive-compulsive
disorder symptom severity). RESULTS: No significant change in thalamic volume
was observed in obsessive-compulsive disorder patients before and after cognitive
behavioral therapy. CONCLUSIONS: Our findings suggest that reduction in thalamic
volume after paroxetine therapy may be specific to paroxetine treatment and not
the result of a general treatment response or spontaneous improvement. These results
are preliminary in view of the small sample studied." [Abstract] Schwartz
JM, Stoessel PW, Baxter LR Jr, Martin KM, Phelps ME.
Systematic changes
in cerebral glucose metabolic rate after successful behavior modification treatment
of obsessive-compulsive disorder.
Arch Gen Psychiatry. 1996
Feb;53(2):109-13.
"BACKGROUND: We sought to determine in a new patient
sample whether symptomatic improvement in obsessive-compulsive disorder treated
with behavior modification is accompanied by significant changes in glucose metabolic
rates in the caudate nucleus, measured with positron emission tomography, as seen
in a previous study. Second, by combining samples from this and the previous study,
we also examined whether there were pathologic correlational relationships among
brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained
before behavioral treatment of obsessive-compulsive disorder, but that decreased
significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive
disorder were studied with positron emission tomography before and after 10 weeks
of structured exposure and response prevention behavioral and cognitive treatment.
Results were analyzed both alone and combined with those from nine similar subjects
from the previous study. RESULTS: Behavior therapy responders had significant
(P < .05) bilateral decreases in caudate glucose metabolic rates that were
greater than those seen in poor responders to treatment. Before treatment, there
were significant correlations of brain activity between the orbital gyri and the
head of the caudate nucleus and the orbital gyri and the thalamus on the right.
These correlations decreased significantly after effective treatment. CONCLUSIONS:
These results replicate and extend previous findings of changes in caudate nucleus
function with behavior therapy for obsessive-compulsive disorder. A prefrontal
cortico-striato-thalamic brain system is implicated in mediation of symptoms of
obsessive-compulsive disorder." [Abstract]
Busatto GF, Zamignani DR, Buchpiguel CA, Garrido
GE, Glabus MF, Rocha ET, Maia AF, Rosario-Campos MC, Campi Castro C, Furuie SS,
Gutierrez MA, McGuire PK, Miguel EC.
A voxel-based investigation
of regional cerebral blood flow abnormalities in obsessive-compulsive disorder
using single photon emission computed tomography (SPECT).
Psychiatry
Res. 2000 Jul 10;99(1):15-27.
"Several functional imaging studies have
reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum
and thalamus in obsessive-compulsive disorder (OCD). These studies have often
been limited by small patient samples and image analysis methods that rely on
region-of-interest (ROI) approaches. We have assessed resting regional cerebral
blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy
control subjects using the voxel-based Statistical Parametric Mapping method for
data analysis. We found a significantly reduced ECD uptake in OCD patients relative
to the control subjects in the right lateral orbitofrontal cortex, and in the
left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for
multiple comparisons). There were significant positive correlations in the OCD
group between the ECD uptake in the left lateral orbitofrontal cortex and ratings
for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right
medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms.
There were also unpredicted significant ECD uptake increases in the cerebellum
in OCD patients, as well as a negative correlation between posterior cingulate
ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These
results implicate specific subregions of the orbitofrontal and anterior cingulate
cortices in the pathophysiology of OCD, as well as suggesting the involvement
of other areas not usually included in ROI-based imaging studies. With the incorporation
of voxel-based methods and the use of large patient samples, rCBF-SPECT studies
may continue to provide valuable information about the functional anatomy of OCD."
[Abstract] Ohara
K, Isoda H, Suzuki Y, Takehara Y, Ochiai M, Takeda H, Igarashi Y, Ohara K.
Proton
magnetic resonance spectroscopy of lenticular nuclei in obsessive-compulsive disorder.
Psychiatry
Res. 1999 Dec 20;92(2-3):83-91.
"Our results suggest the normal viability
of neuronal cells, as indicated by the quantification of NAA, Cr and Cho in the
lenticular nuclei of patients with OCD." [Abstract] Giedd
JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE.
MRI assessment
of children with obsessive-compulsive disorder or tics associated with streptococcal
infection.
Am J Psychiatry. 2000 Feb;157(2):281-3.
"OBJECTIVE:
The authors assessed selective basal ganglia involvement in a subgroup of children
with obsessive-compulsive disorder (OCD) and/or tics believed to be associated
with streptococcal infection. METHOD: Using computer-assisted morphometric techniques,
they analyzed the cerebral magnetic resonance images of 34 children with presumed
streptococcus-associated OCD and/or tics and 82 healthy comparison children who
were matched for age and sex. RESULTS: The average sizes of the caudate, putamen,
and globus pallidus, but not of the thalamus or total cerebrum, were significantly
greater in the group of children with streptococcus-associated OCD and/or tics
than in the healthy children. The differences were similar to those found previously
for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS:
These results support the hypothesis that there is a distinct subgroup of subjects
with OCD and/or tics who have enlarged basal ganglia. These findings are consistent
with the hypothesis of an autoimmune response to streptococcal infection."
[Abstract] Stein
DJ, Van Heerden B, Wessels CJ, Van Kradenburg J, Warwick J, Wasserman HJ.
Single
photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan
challenge in obsessive-compulsive disorder: investigating the functional role
of the serotonin auto-receptor.
Prog Neuropsychopharmacol
Biol Psychiatry. 1999 Aug;23(6):1079-99.
"1. Symptoms of obsessive-compulsive
disorder (OCD) may be acutely exacerbated by administration of certain serotonin
agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar,
1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor
plays an important role in this disorder (El Mansari et al, 1995). 2. In order
to investigate the functional role of the serotonin auto-receptor in OCD, the
authors undertook single photon emission computed tomography in OCD patients after
administration of sumatriptan and placebo. The authors hypothesized that, as in
the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995),
exacerbation of OCD symptoms would be accompanied by increased cortical metabolism
and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal
circuit. They also expected, that as in the case of mCPP challenge (Hollander
et al, 1993), exacerbation of OCD symptoms would be associated with a relatively
poor response to subsequent treatment with serotonin specific reuptake inhibitors.
3. Sumatriptan (100 mg orally) and placebo were administered on separate days
to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized
double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO
and underwent single photon emission computed tomography (SPECT) of the brain.
Activity in regions of interest was calculated, and compared using repeated measures
analysis of variance. Patients were subsequently treated with a serotonin specific
reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous,
with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease
in symptoms. On sumatriptan challenge, there was a significant association between
symptom exacerbation and decreased activity in frontal areas. There was an association
between decreased activity in an inferior frontal area with worse response to
treatment, and also patients with symptom exacerbation after sumatriptan had poorer
response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan
in OCD is consistent with previous studies demonstrating conflicting and heterogenous
behavioral responses to serotonergic challenges (Hollander et al, 1992), and with
underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized
that increased frontal activity in some patients with OCD is itself a compensatory
mechanism. In patients with such compensatory hyperactivity, administration of
a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation
of OCD symptoms. These patients may also be less likely to respond to treatment
with a SSRI. 7. Further work combining pharmacological challenge paradigms and
functional imaging techniques in OCD may be helpful in elucidating the neurobiology
of this complex disorder." [Abstract] Lucey
JV, Costa DC, Blanes T, Busatto GF, Pilowsky LS, Takei N, Marks IM, Ell PJ, Kerwin
RW.
Regional cerebral blood flow in obsessive-compulsive disordered
patients at rest. Differential correlates with obsessive-compulsive and anxious-avoidant
dimensions.
Br J Psychiatry. 1995 Nov;167(5):629-34.
"BACKGROUND.
We tested whether cortical and subcortical regional cerebral blood flow (rCBF)
differs between patients with obsessive-compulsive disorder (OCD) and healthy
controls. We then explored the relationship between rCBF and OCD mental state.
METHOD. Thirty out-patients from the Maudsley Hospital with OCD as defined in
DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single
photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions
of interest and compared with rCBF data in 30 healthy people matched for age,
sex and handedness. Symptom ratings were obtained using standard measures on the
scanning day. Principal components factor analysis identified two distinct clinical
dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These were correlated
with patients' rCBF measurements, using Spearman's rank correlation coefficient,
and multiple regression coefficients calculated. RESULTS. We found significant
reductions in rCBF measurements of OCD patients compared with resting, healthy
controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior
frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal
cortex, right caudate nucleus and right thalamus. Regional differences were not
secondary to generalised reduction in patients' brain perfusion. Reduced blood
flow to the right inferior frontal cortex correlated significantly with illness
severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset,
sex, handedness, depression or medication status. OC clinical dimension, concerning
obsessions, compulsions and low mood, was significantly negatively correlated
with left inferior frontal, medial frontal and right parietal rCBF. AA dimension,
concerning anxiety and avoidance, was significantly positively associated with
left and right superior frontal, right inferior frontal, medial frontal cortical,
and right and left caudate and thalamic rCBF. CONCLUSIONS. rCBF differs significantly
between resting OCD patients and healthy controls, and separate clinical dimensions
are associated with functionally distinct rCBF patterns." [Abstract]
Brody
AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr.
FDG-PET
predictors of response to behavioral therapy and pharmacotherapy in obsessive
compulsive disorder.
Psychiatry Res. 1998 Nov 9;84(1):1-6.
"In
subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism
in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has
been associated with a better response to clomipramine. We sought to determine
pre-treatment metabolic predictors of response to behavioral therapy (BT) vs.
pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron
emission tomography scans of the brain were obtained in subjects with OCD before
treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied
to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate
by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the
larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere)
alone was selected as predicting treatment response in the BT-treated group (F
= 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism
and treatment response revealed that higher normalized metabolism in this region
was associated with greater improvement in the BT-treated group (tau = 0.35, P
= 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group.
These results suggest that subjects with differing patterns of metabolism preferentially
respond to BT vs. medication." [Abstract] Pujol
J, Soriano-Mas C, Alonso P, Cardoner N, Menchon JM, Deus J, Vallejo J.
Mapping
structural brain alterations in obsessive-compulsive disorder.
Arch
Gen Psychiatry. 2004 Jul;61(7):720-30.
"BACKGROUND: Recent technical developments
have made it feasible to comprehensively assess brain anatomy in psychiatric populations.
OBJECTIVE: To describe the structural brain alterations detected in the magnetic
resonance images of a large series of patients with obsessive-compulsive disorder
(OCD) using imaging procedures that allow the evaluation of volume changes throughout
the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary
hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72
age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences
were obtained in all participants. A statistical parametric mapping approach was
used to delineate possible anatomical alterations in the entire brain. To preserve
volumetric information, voxel values were modulated by the Jacobian determinants
(volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES:
Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced
gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex,
and the left insulo-opercular region. A relative increase in gray matter volume
was observed bilaterally in the ventral part of the putamen and in the anterior
cerebellum. All these brain alterations were abnormally correlated in patients
with OCD, and age statistically significantly contributed to the relative enlargement
observed in the striatal areas. Disease severity, the nature of symptoms, and
comorbidities were not related to the changes described. Nevertheless, patients
with prominent aggressive obsessions and checking compulsions showed reduced amygdala
volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features
depicted by this voxelwise approach is consistent with data from functional studies.
The reported anatomical maps identified the specific parts of the frontostriatal
system that were altered in patients with OCD and detected changes in anatomically
connected distant regions. These data further define the structural brain alterations
in OCD and may contribute to constraining the prevailing biological models of
this psychiatric process." [Abstract] Szeszko
PR, MacMillan S, McMeniman M, Chen S, Baribault K, Lim KO, Ivey J, Rose M, Banerjee
SP, Bhandari R, Moore GJ, Rosenberg DR.
Brain structural abnormalities
in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder.
Am
J Psychiatry. 2004 Jun;161(6):1049-56.
"OBJECTIVE: The authors investigated
structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical
loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD:
Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white
matter volumes of the anterior cingulate gyrus and superior frontal gyrus were
computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic
drug-naive pediatric patients with OCD (seven male patients and 16 female patients)
and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS:
Patients had smaller globus pallidus volumes than healthy volunteers, but the
two groups did not differ in volumes of the caudate nucleus, putamen, or frontal
white matter regions. Compared to healthy volunteers, patients had more total
gray matter in the anterior cingulate gyrus but not the superior frontal gyrus.
Total anterior cingulate gyrus volume correlated significantly and positively
with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS:
These findings provide evidence of smaller globus pallidus volume in patients
with OCD without the potentially confounding effects of prior psychotropic drug
exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific
to the gray matter in OCD, at least at the gross anatomic level, and are consistent
with findings of functional neuroimaging studies that have reported anterior cingulate
hypermetabolism in the disorder." [Abstract] Jenike
MA, Breiter HC, Baer L, Kennedy DN, Savage CR, Olivares MJ, O'Sullivan RL, Shera
DM, Rauch SL, Keuthen N, Rosen BR, Caviness VS, Filipek PA.
Cerebral
structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric
magnetic resonance imaging study.
Arch Gen Psychiatry. 1996
Jul;53(7):625-32.
"BACKGROUND: A previous pilot study of only posterior
brain regions found lower white-matter volume in patients with obsessive-compulsive
disorder than in normal control subjects. We used new cohorts of patients and
matched normal control subjects to study whole-brain volume differences between
these groups with magnetic resonance imaging-based morphometry. METHODS: Ten female
patients with obsessive-compulsive disorder and 10 female control subjects, matched
for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance
imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized
and segmented by means of well-characterized semiautomated intensity contour mapping
and differential intensity contour algorithms. Brain structures investigated included
the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus
pallidus, hippocampus amygdala, third and fourth ventricles, corpus callosum,
operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions,
including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum,
with adjacent white matter were also measured. Volumes found different between
groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth
Complex Figure Test measures. RESULTS: Confirming results of our earlier pilot
study and expanding the findings to the whole brain, patients with obsessive-compulsive
disorder had significantly less total white matter but, in addition, significantly
greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder
and nonverbal immediate memory correlated with opercular volume. CONCLUSIONS:
Replication of volumetric white-matter differences suggests a widely distributed
structural brain abnormality in obsessive-compulsive disorder. Whereas determining
the etiogenesis may require research at a microscopic level, understanding its
functional significance can be further explored via functional neuroimaging and
neuropsychological studies." [Abstract]
Cottraux J, Gerard D, Cinotti L, Froment JC, Deiber
MP, Le Bars D, Galy G, Millet P, Labbe C, Lavenne F, Bouvard M, Mauguiere F.
A
controlled positron emission tomography study of obsessive and neutral auditory
stimulation in obsessive-compulsive disorder with checking rituals.
Psychiatry
Res. 1996 Mar 29;60(2-3):101-12.
"Ten nondepressed patients with obsessive-compulsive
disorder (OCD) who were characterized by predominant checking rituals were compared
with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral
blood flow levels (rCBF) were measured with positron emission tomography (H2 15O)
across four conditions: rest, auditory stimulation with idiosyncratic normal or
abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest.
Order of neutral and obsessive stimulation was randomized. Higher subjective responses
to obsessive than to neutral stimulation were found in both groups; subjective
response was higher in OCD patients when obsessive stimulation was presented first.
A four-way analysis of variance (group x stimulation order x hemisphere x condition
[neutral or obsessive stimulation]) was performed on stimulation minus rest normalized
rCBF values. Control subjects had significantly higher rCBF in the thalamus and
putamen. A trend toward higher rCBF in OCD patients was found in the superior
temporal regions. When neutral stimulation was presented first, rCBF was significantly
higher in the caudate region of control subjects. Obsessive stimulation was associated
with higher rCBF than neutral stimulation in orbitofrontal regions in both groups
of subjects. Under obsessive stimulation, superior temporal and orbitofrontal
activities were correlated in OCD patients but not in control subjects. Our study
suggests specific abnormalities of information processing in the basal ganglia
and temporal structures of compulsive checkers." [Abstract] Rosenberg
DR, Keshavan MS, O'Hearn KM, Dick EL, Bagwell WW, Seymour AB, Montrose DM, Pierri
JN, Birmaher B.
Frontostriatal measurement in treatment-naive children
with obsessive-compulsive disorder.
Arch Gen Psychiatry.
1997 Sep;54(9):824-30.
"BACKGROUND: Abnormalities in frontostriatal circuits
have been implicated in obsessive-compulsive disorder (OCD). Although OCD commonly
emerges during childhood or adolescence, few studies have examined frontostriatal
anatomy in psychotropic-naive children with OCD near the onset of illness to determine
the possible role of atypical developmental processes in this disorder. METHODS:
Magnetic resonance imaging scans from 19 children with OCD who had not been exposed
to psychotropic drugs, aged 7 to 18 years, and 19 case-matched healthy control
subjects were analyzed to determine the volumes of the following structures: prefrontal
cortex, striatum (caudate and putamen), lateral and third ventricles, and intracranial
volume. RESULTS: Patients with OCD had significantly smaller striatal volumes
and significantly larger third ventricle volumes than controls, but did not differ
in prefrontal cortical, lateral ventricular, or intracranial volumes. Striatal
volumes were inversely correlated with OCD symptom severity but not illness duration.
CONCLUSIONS: Our findings provide new evidence of abnormalities of the striatum
in pediatric OCD. These results are preliminary, given the small sample size."
[Abstract]
Russell A, Cortese B, Lorch E, Ivey J, Banerjee SP,
Moore GJ, Rosenberg DR.
Localized functional neurochemical marker
abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive
disorder.
J Child Adolesc Psychopharmacol. 2003;13 Suppl
1:S31-8.
"BACKGROUND: Neurobiological abnormalities in the prefrontal
cortex have been implicated in the pathogenesis of obsessive-compulsive disorder
(OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge,
no prior study has examined prefrontal cortex neurochemistry in pediatric patients
with OCD. METHODS: A multislice spectroscopic imaging sequence with validated
phantom replacement methodology was used to measure N-acetyl-aspartate (NAA),
a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine
(Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naive
OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects.
RESULTS: A significant increase (21% higher) in NAA was observed in left but not
right DLPFC in OCD patients versus control subjects. No significant differences
in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS:
These results provide new evidence of localized functional neurochemical marker
alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent
neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning
of neural brain elements in DLPFC." [Abstract] Edmonstone
Y, Austin MP, Prentice N, Dougall N, Freeman CP, Ebmeier KP, Goodwin GM.
Uptake
of 99mTc-exametazime shown by single photon emission computerized tomography in
obsessive-compulsive disorder compared with major depression and normal controls.
Acta
Psychiatr Scand. 1994 Oct;90(4):298-303.
"Twelve patients with obsessive-compulsive
disorder (OCD) were investigated at rest using single photon emission computerized
tomography with 99mTc-exametazime. The uptake of 99mTc-exametazime was expressed
relative to calcarine/occipital cortex. Patients were matched for drug treatment
with 12 patients with a major depressive episode and the patient groups were compared
with a control group. Significant bilateral decreases in tracer uptake were confined
to basal ganglia in the OCD group. There was a paradoxical positive correlation
between anxiety ratings and tracer uptake to basal ganglia in the OCD group. The
findings confirm that the functional topography of OCD implicates altered function
in the basal ganglia." [Abstract] Adams
BL, Warneke LB, McEwan AJ, Fraser BA.
Single photon emission computerized
tomography in obsessive compulsive disorder: a preliminary study.
J
Psychiatry Neurosci. 1993 May;18(3):109-12.
"Patterns of cerebral perfusion
in patients with obsessive compulsive disorder were evaluated using single photon
emission computerized tomography. Eleven patients, who satisfied the DSM-III-R
criteria and Research Diagnostic Criteria for the disorder, were evaluated using
the distribution of 99m-Tc-HMPAO as a radiotracer. The Yale-Brown Obsessive Compulsive
Scale was administered to each patient to assess the severity of their symptoms.
The images obtained were evaluated qualitatively and semi-quantitatively by a
physician in nuclear medicine who was blind to the patients' diagnoses. Eight
of the 11 patients demonstrated asymmetric perfusion of the basal ganglia; the
left side showed impaired perfusion in six patients." [Abstract] Machlin
SR, Harris GJ, Pearlson GD, Hoehn-Saric R, Jeffery P, Camargo EE.
Elevated
medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study.
Am
J Psychiatry. 1991 Sep;148(9):1240-2.
"Regional cerebral blood flow was
measured with single photon emission computed tomography in 10 obsessive-compulsive
patients and eight comparison subjects. The patients had a significantly higher
ratio of medial-frontal to whole cortex blood flow; this was unrelated to symptom
severity but was correlated negatively with anxiety. No differences in orbital-frontal
blood flow were found." [Abstract] Kellner
CH, Jolley RR, Holgate RC, Austin L, Lydiard RB, Laraia M, Ballenger JC.
Brain
MRI in obsessive-compulsive disorder.
Psychiatry Res. 1991
Jan;36(1):45-9.
"Magnetic resonance imaging (MRI) brain scans were performed
on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements
of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal
horn ratio, and area of the corpus callosum did not differ between the two groups.
These limited data do not support the presence of a consistent gross brain structural
abnormality in obsessive-compulsive disorder. Further studies using other anatomic
measurements and other brain structural imaging techniques are warranted."
[Abstract]
Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy
DL, Cohen RM.
Local cerebral glucose metabolic rates in obsessive-compulsive
disorder. Patients treated with clomipramine.
Arch Gen Psychiatry.
1990 Sep;47(9):840-8.
"In a recent study, we reported abnormal local cerebral
glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive
disorder. Eight patients with obsessive-compulsive disorder scanned previously
were scanned again during treatment with the tricyclic antidepressant clomipramine
hydrochloride. Comparisons of local cerebral glucose metabolic rates for both
groups showed a relative decrease in regions of the orbital frontal cortex and
the left caudate, and an increase in other areas of the basal ganglia, including
the right anterior putamen. When comparing patients who responded well to clomipramine
with those who were either poor or partial responders, we found significant decreases
only in the left caudate of patients who responded well to the drug. The present
study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms
is associated with a return of regional brain metabolism to a more normal level
in regions of the orbital frontal cortex and the caudate nucleus." [Abstract]
Martinot
JL, Allilaire JF, Mazoyer BM, Hantouche E, Huret JD, Legaut-Demare F, Deslauriers
AG, Hardy P, Pappata S, Baron JC, et al.
Obsessive-compulsive disorder:
a clinical, neuropsychological and positron emission tomography study.
Acta
Psychiatr Scand. 1990 Sep;82(3):233-42.
"The authors compared 16 nondepressed
obsessive-compulsive patients (OCS) with 8 normal controls (NC) of similar age
for resting-state regional cerebral glucose metabolic rates (rCMRglu) using positron
emission tomography with the fluorodeoxyglucose method. OCS were rated for clinical
data, and a neuropsychological battery was administered to 14 patients on the
day of the scan. Absolute rCMRglu for whole cortex, and normalized prefrontal
lateral cortex metabolic rates, were both significantly lower in OCS than in NC.
No significant difference between treated (n = 10) and drug-free (n = 6) OCS was
found for those variables. OCS were significantly impaired in the neuropsychological
tasks assessing memory and attention. The rCMRglu for prefrontal lateral cortex
were negatively correlated to Stroop-test subscores. This "frontal-oriented"
task assessed the ability of OCS to inhibit immediate but inappropriate responses.
These results suggest, in OCS, a modification of the general activating systems
of cortical function and a relationship between the lateral prefrontal rCMRglu
decrease and a selective attention deficit." [Abstract]
Garber
HJ, Ananth JV, Chiu LC, Griswold VJ, Oldendorf WH.
Nuclear magnetic
resonance study of obsessive-compulsive disorder.
Am J Psychiatry.
1989 Aug;146(8):1001-5.
"Magnetic resonance imaging (MRI) of the brains
of 32 patients who met the DSM-III criteria for obsessive-compulsive disorder
and of 14 normal subjects frequently revealed abnormalities, but none was specific
to obsessive-compulsive disorder. Spin-lattice relaxation time (T1) for right
frontal white matter was prolonged in the patients compared to the control subjects,
and the patients had greater right-minus-left T1 differences for frontal white
matter. Right-minus-left T1 differences in the orbital frontal cortex were strongly
correlated with symptom severity in the unmedicated patients and in the patients
with family histories of obsessive-compulsive disorder." [Abstract]
Swedo SE, Schapiro MB, Grady CL, Cheslow DL, Leonard
HL, Kumar A, Friedland R, Rapoport SI, Rapoport JL.
Cerebral glucose
metabolism in childhood-onset obsessive-compulsive disorder.
Arch
Gen Psychiatry. 1989 Jun;46(6):518-23.
"The cerebral metabolic rate for
glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder
(OCD) and in age- and sex-matched controls using positron emission tomography
and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory
and visual stimulation. The group with OCD showed an increased glucose metabolism
in the left orbital frontal, right sensorimotor, and bilateral prefrontal and
anterior cingulate regions as compared with controls. Ratios of regional activity
to mean cortical gray matter metabolism were increased for the right prefrontal
and left anterior cingulate regions in the group with OCD as a whole. Correlations
between glucose metabolism and clinical assessment measures showed a significant
relationship between metabolic activity and both state and trait measurements
of OCD and anxiety as well as the response to clomipramine hydrochloride therapy.
These results are consistent with the suggestion that OCD may result from a functional
disturbance in the frontal-limbic-basal ganglia system." [Abstract]
Nordahl TE, Benkelfat C, Semple WE, Gross M, King
AC, Cohen RM.
Cerebral glucose metabolic rates in obsessive compulsive
disorder.
Neuropsychopharmacology. 1989 Mar;2(1):23-8.
"Brain
metabolism was measured with positron emission tomography and [18F] 2-fluoro-2-deoxyglucose
in normal subjects and in patients with obsessive compulsive disorder (OCD) while
they performed a continuous auditory discrimination task designed to evaluate
the functional localization of sustained attention. Data on 8 nondepressed patients
with OCD were compared with 30 normal volunteers. We observed significantly higher
normalized regional metabolism both in the right orbital frontal cortex (p = 0.002,
two-tailed t test) and in the left anterior orbital frontal cortex (p = 0.017,
one-tailed t test) and in patients with OCD as compared to normal controls. We
observed no normalized glucose metabolic differences in basal ganglia structures
in patients with OCD as compared to our normal controls. There were no statistical
differences in global glucose metabolic values between the OCD and the control
group. Our findings are consistent with the findings of Baxter et al. (Arch Gen
Psychiatry 44:211-218, 1987). Regions in the parietal cortex also appear to show
differences in this preliminary study." [Abstract] |
