Transcript Cerebral Glucose Metabolism in Obsessive

Cerebral Glucose Metabolism in
Obsessive-Compulsive Hoarding
Authored by S. Saxena, A.L. Brody, K.M. Maidment,
E.C. Smith, N. Zohrabi, E. Katz, S.K. Baker, and L.R.
Baxter Jr. , 2004.
Presentation by Michael Wu
Introduction
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Obsessive-Compulsive Disorder (OCD):
◦ A mental disorder that covers a wide range of
symptoms, including:
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Aggressive/sexual/religious obsessions;
Symmetrical/organizational obsessions;
Contamination obsessions;
Hoarding/saving/collecting obsessions.
◦ Often treated with SSRIs or cognitive
behavioural therapy, but these treatments
have been met with poor success when
directed towards hoarding.
Introduction
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Compulsive Hoarding:
◦ The accumulation and inability to discard
worthless items.
◦ Also observed in schizophrenia, dementia,
eating disorders, autism, mental retardation,
and also in normal populations.
◦ Most common in OCD patients.
Introduction
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Animal studies suggest that hoarding may be mediated by
the ventromedial striatum, globus pallidus, and
medial dorsal thalamus, which are all structures linked
to human OCD.
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Electrical stimulation and lesioning studies also show that
the anterior cingulate gyrus, hypothalamus,
hippocampus, and the septum play mediation roles of
hoarding in rodents. Drugs also affect hoarding
symptoms.
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In normal subjects, the provocation of hoarding-related
anxiety activates the ventral prefrontal regions and the
left amygdala, but the reason behind this is unknown.
Methods
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A total of 62 subjects were studied:
◦ 45 with OCD (as diagnosed by the DSM-IV), 17
without.
◦ Of the 45 patients, 12 had compulsive-hoarding as the
most prominent symptom of their OCD.
◦ The patients with hoarding symptoms were
significantly older than those without.
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Level of activity defined as the level of glucose
metabolized within a certain brain area.
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No cognitive task was given during the scanning.
Methods
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MRI-based region-of-interest analysis was conducted,
targeting broad areas that were associated with OCD and
compulsive-hoarding from past research.
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The areas were the:
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Dorsolateral prefrontal cortex;
Ventrolateral prefrontal cortex;
Orbitofrontal cortex;
Dorsal anterior cingulate gyrus;
Ventral anterior cingulate gyrus;
Caudate;
Thalamus;
Amygdala;
Hippocampus.
To narrow down smaller areas, another technique called
statistical parametric mapping (SPM) was used.
Methods
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MRI scans were taken first (region-ofinterest analysis), then PET scans were
taken (SPM).
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2 of the patients had invalid PET results,
and were thus excluded from SPM.
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The activity shown on the brain regions
were then superimposed onto the MRI
images, producing the following results.
Methods
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The scans were averaged for each group
(OCD-with-hoarding, OCD-withouthoarding, normal).
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The images were then compared with
each other, identifying areas with
abnormal rates of glucose metabolism as
areas of interest.
Results
Figure 1. Hoarders vs. Control
Figure 2. Hoarders vs. Control
A lower glucose metabolism was
observed in the right posterior
cingulate gyrus and the bilateral
cuneus in hoarding patients.
A higher glucose metabolism was
observed in the left and right
dorsolateral prefrontal cortices.
Results
Figure 3. Non-hoarders vs. Control
A higher glucose metabolism was observed in the bilateral thalamus and the
caudate in non-hoarding patients.
Results
Figure 4. Hoarders vs. Non-hoarders
A lower rate of glucose metabolism
was observed in the anterior cingulate Figure 5. Hoarders vs. Non-hoarders
gyrus in hoarding patients.
A higher glucose metabolism was observed in
a small region in the right sensory motor
cortex in non-hoarding patients.
Discussion
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In all the patients, symptoms of compulsivehoarding may be due to lowered activity in
the cingulate cortex, as shown by altered
activity in the dorsal anterior cingulate
gyrus.
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The functions of the dorsal anterior
cingulate gyrus include motivation, executive
control, focused attention, emotional
connections to stimuli, emotional selfcontrol, problem solving, error detection,
and selecting responses.
Discussion
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Lower activity levels were found in the
posterior cingulate cortex and
cuneus in hoarders compared to control
samples.
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The posterior cingulate cortex is
responsible for monitoring visual events,
episodic memory, emotional processing,
and spatial orientation.
Discussion
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The anterior and posterior cingulate
gyrus have been linked to low activity,
even after antidepressant treatment.
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This could mean that it is not the
symptoms of hoarding are hard to treat,
but that the activity in the cingulate gyri
actually mediate the responses of the
symptoms to the treatment.
Discussion
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Occipital cortex deficits in hoarders were
consistent with past research.
◦ Past research also found decreased grey
matter density in these regions.
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This is linked to deficits in visuospatial
processing and visual memories, which is
observed in some OCD patients.
◦ Based on this imaging study, these deficits may
be found primarily in hoarding patients.
Conclusion
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The severity of hoarding was found to be negatively
correlated with the activity in the dorsal anterior
cingulate gyrus and posterior cingulate gyrus.
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Summary of brain activity variations:
◦ In hoarders:
 Lower posterior cingulate gyrus and cuneus activity;
 Lower dorsal anterior cingulate gyrus activity compared to nonhoarders;
◦ In non-hoarders:
 Higher thalamus and caudate activity;
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Significantly different neural patterns exist between the three
groups, and the symptom of compulsive-hoarding is believed
to be associated with suppressed activity in the cingulate
cortex.
Strengths and Weaknesses
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Strengths:
◦ Large sample size.
◦ Multiple imaging and analytical parameters (MRI
combined with PET to accurately identify regions of
interest.)
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Weaknesses:
◦ No cognitive task given, cognitive subtraction
between groups only. No individual baseline to
compare to.
◦ Why not fMRI and measure BOLD signal?
◦ Average ages not stated, only that hoarders were
much older than non-hoarders and control samples.
◦ No graphs provided, only brain images.
What Next?
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Research on lesioned OCD patients and the
effects of damage to the dorsal anterior
cingulate gyrus?
◦ One would expect that hoarding would get
worse.
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Study patients that have undergone
cingulotomies?
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Investigate whether hoarding associated with
other mental disorders also follow this
pattern of neural activation?
Future Applications?
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Development of medication that raises
activity in cingulate cortex to treat
compulsive-hoarding? (eg. Amphetamines
directed towards cingulate cortex.)
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New behavioural therapy approaches? (eg.
Psychotherapy directed towards
emotions and behaviour rather than
Exposure and Response Prevention.)
References
Saxena, S., Brody, A.L., Maidment, K.M., Smith,
E.C., Zohrabi, N., Katz, E., Baker, S.K., &
Baxter Jr., L.R. (2004). Cerebral Glucose
Metabolism in Obsessive-Compulsive
hoarding. American Journal of Psychiatry,
161, 1038-1048.
Questions?
Summary
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Objective:
◦ Compulsive hoarding has been observed in OCD patients. PET scans
were conducted to identify metabolic patterns in the brain associated
with hoarding.
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Methods:
◦ Radiolabeled fluorodeoxyglucose PET scans were conducted on 45
adult OCD patients. Control measures were 17 healthy patients.
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Results:
◦ Patients with hoarding had significantly lower glucose metabolism in the
posterior cingulate gyrus and cuneus, while non-hoarding patients
had significantly higher glucose metabolism in the bilateral thalamus
and caudate.
◦ Compared to non-hoarding OCD patients, hoarders had significantly
lower metabolism in the dorsal anterior cingulate gyrus.
◦ The lower the metabolism was in the dorsal anterior cingulate gyrus,
the more severe the hoarding.
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Conclusions:
◦ OCD patients with compulsive hoarding had different cerebral glucose
metabolism patterns than control subjects or non-hoarding subjects.
◦ Obsessive-compulsive hoarding could be considered as a variant of
OCD, where the symptoms are mediated by suppressed activity in the
cingulate cortex.