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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 mor |
