Cerebral Glucose Cerebral Glucose Metabolism in Obsessive-Metabolism in Obsessive-

Compulsive HoardingCompulsive 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

IntroductionIntroductionObsessive-Compulsive Disorder

(OCD):◦A mental disorder that covers a wide

range of symptoms, including: 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.

IntroductionIntroductionCompulsive 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.

IntroductionIntroduction• 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.

• 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.

• 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.

MethodsMethodsA 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.

Level of activity defined as the level of glucose metabolized within a certain brain area.

No cognitive task was given during the scanning.

MethodsMethods MRI-based region-of-interest analysis was

conducted, targeting broad areas that were associated with OCD and compulsive-hoarding from past research.

The areas were the:◦ 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.

MethodsMethodsMRI scans were taken first (region-of-

interest analysis), then PET scans were taken (SPM).

2 of the patients had invalid PET results, and were thus excluded from SPM.

The activity shown on the brain regions were then superimposed onto the MRI images, producing the following results.

MethodsMethodsThe scans were averaged for

each group (OCD-with-hoarding, OCD-without-hoarding, normal).

The images were then compared with each other, identifying areas with abnormal rates of glucose metabolism as areas of interest.

ResultsResults

Figure 2. Hoarders vs. Control

A higher glucose metabolism was observed in the left and right dorsolateral prefrontal cortices.

Figure 1. Hoarders vs. Control

A lower glucose metabolism was observed in the right posterior cingulate gyrus and the bilateral cuneus in hoarding patients.

ResultsResults

Figure 3. Non-hoarders vs. Control

A higher glucose metabolism was observed in the bilateral thalamus and the caudate in non-hoarding patients.

ResultsResults

Figure 5. Hoarders vs. Non-hoarders

A higher glucose metabolism was observed in a small region in the right sensory motor cortex in non-hoarding patients.

Figure 4. Hoarders vs. Non-hoarders

A lower rate of glucose metabolism was observed in the anterior cingulate gyrus in hoarding patients.

DiscussionDiscussionIn all the patients, symptoms of

compulsive-hoarding may be due to lowered activity in the cingulate cortex, as shown by altered activity in the dorsal anterior cingulate gyrus.

The functions of the dorsal anterior cingulate gyrus include motivation, executive control, focused attention, emotional connections to stimuli, emotional self-control, problem solving, error detection, and selecting responses.

DiscussionDiscussionLower activity levels were found in

the posterior cingulate cortex and cuneus in hoarders compared to control samples.

The posterior cingulate cortex is responsible for monitoring visual events, episodic memory, emotional processing, and spatial orientation.

DiscussionDiscussionThe anterior and posterior

cingulate gyrus have been linked to low activity, even after antidepressant treatment.

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.

DiscussionDiscussionOccipital cortex deficits in hoarders

were consistent with past research.◦Past research also found decreased grey

matter density in these regions.

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.

ConclusionConclusionThe severity of hoarding was found to be

negatively correlated with the activity in the dorsal anterior cingulate gyrus and posterior cingulate gyrus.

Summary of brain activity variations:◦ In hoarders:

Lower posterior cingulate gyrus and cuneus activity; Lower dorsal anterior cingulate gyrus activity compared to

non-hoarders;

◦ In non-hoarders: Higher thalamus and caudate activity;

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 Strengths and WeaknessesWeaknessesStrengths:

◦ Large sample size.◦ Multiple imaging and analytical parameters

(MRI combined with PET to accurately identify regions of interest.)

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?What Next?Research on lesioned OCD patients

and the effects of damage to the dorsal anterior cingulate gyrus?◦One would expect that hoarding would

get worse.

Study patients that have undergone cingulotomies?

Investigate whether hoarding associated with other mental disorders also follow this pattern of neural activation?

Future Applications?Future Applications?Development of medication that

raises activity in cingulate cortex to treat compulsive-hoarding? (eg. Amphetamines directed towards cingulate cortex.)

New behavioural therapy approaches? (eg. Psychotherapy directed towards emotions and behaviour rather than Exposure and Response Prevention.)

ReferencesReferences

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?

SummarySummary Objective:

◦ Compulsive hoarding has been observed in OCD patients. PET scans were conducted to identify metabolic patterns in the brain associated with hoarding.

Methods:◦ Radiolabeled fluorodeoxyglucose PET scans were conducted

on 45 adult OCD patients. Control measures were 17 healthy patients.

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.

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.