Cerebral Glucose Metabolism in Obsessive Compulsive Hoarding (PowerPoint) by MikeJenny


									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
 Obsessive-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.
 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.
•   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

•   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.
   A total of 62 subjects were studied:
    ◦ 45 with OCD (as diagnosed by the DSM-IV), 17
    ◦ 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.
   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.
 MRI 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.

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

Figure 1. Hoarders vs. Control      Figure 2. Hoarders vs. Control

A lower glucose metabolism was      A higher glucose metabolism was
observed in the right posterior     observed in the left and right
cingulate gyrus and the bilateral   dorsolateral prefrontal cortices.
cuneus in hoarding patients.

Figure 3. Non-hoarders vs. Control

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

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.
   In 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

   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.
              levels were found in the
 Lower activity
 posterior cingulate cortex and
 cuneus in hoarders compared to control

 The posterior cingulate cortex is
 responsible for monitoring visual events,
 episodic memory, emotional processing,
 and spatial orientation.
 The anterior and posterior cingulate
 gyrus have been linked to low activity,
 even after antidepressant treatment.

 Thiscould 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.
          cortex deficits in hoarders were
 Occipital
 consistent with past research.
 ◦ Past research also found decreased grey
   matter density in these regions.

     is linked to deficits in visuospatial
 This
 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.
   The 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-

    ◦ 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
Strengths and Weaknesses
   Strengths:
    ◦ Large sample size.
    ◦ Multiple imaging and analytical parameters (MRI
      combined with PET to accurately identify regions of

   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?
   Research on lesioned OCD patients and the
    effects of damage to the dorsal anterior
    cingulate gyrus?
    ◦ One would expect that hoarding would get

   Study patients that have undergone

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

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