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What is Obsessive-Compulsive Disorder?
Obsessive-compulsive disorder (OCD) is the fourth most
common neurobiological illness with one in forty adults and one in two
hundred children having a lifetime occurrence. OCD is characterized by
recurrent, disturbing thoughts (obsessions) and/or repetitive, ritualistic
behaviors that the individual feels compelled to perform (compulsions).
While individuals with OCD recognize these symptoms as irrational, they
have little control over them.
Typical Obsessions or Compulsions
- Dirt, germs, contamination Excessive handwashing
or bathing
- Fear of acting on aggressive impulses Checking
(for potential hazards)
- Uncomfortable religious or sexual thoughts
Repetitive actions such as touching
- Concern with ordering, arranging, counting.
counting, arranging.
Etiology of OCD
OCD is believed to be a neurobiological illness that
affects specific neural pathways in the brain using the neurotransmitter
serotonin. Currently there is significant research that is trying to pinpoint
the pathways and neurobiological mechanisms involved. One of the research
tool which holds significant promise for characterizing the OCD pathway
is functional magnetic resonance imaging fMRI.
Available Treatment
While impairment caused by OCD ranges from mild to severe,
many people with OCD will require treatment. Two types of treatment have
been demonstrated to be helpful: Cognitive Behavioral Therapy (CBT) and
medication. Selective serotonin reuptake inhibitors (SSRI's) including
fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline
(Zoloft), and clomipramine (Anafranil) have been approved for the treatment
of OCD. In spite of the improvement in medication therapy for people with
OCD, a significant number do not respond to several trials of medication.
Using Functional MRI to Predict
and Assess Treatment Response
Goal of the OCD fMRI Project
This study is designed to add an innovative research
tool, functional magnetic resonance imaging (fMRI), to a clinical trial
involving patients with treatment-refractory OCD. We predict that fMRI
can be successfully used as a new clinical approach: (1) to predict and
follow the response of individuals with OCD to new pharmacological therapies
such as IV clomipramine and (2) to augment our knowledge base concerning
the neurobiology of OCD. To use fMRI to increase our understanding of
the neurobiology of OCD
Imaging Protocol
These subjects will undergo fMRI scanning the day prior
to starting the pharmacological study and then four days after receiving
the loading dose. Each research subject will then again be scanned at
the end of the three month treatment period. While in the scanner, the
subjects will perform cognitive and behavioral tasks that assess key information
processing abilities of individuals with OCD.
Proposed Results
- Baseline brain activation patterns associated
with the first scan will provide critical knowledge about activation
in the frontal-striatal neural circuit thought to be involved in the
etiology of OCD. Detection of varying patterns of frontal- striatal
activation in individuals with OCD will provide information about biological
mechanisms that underlie heterogeneity in this condition.
- The characterization of OCD as a deficit in
a neurobiological pathway will lead to more accurate diagnosis of this
illness as well as a better understanding of the symptoms and associated
neurocognitive deficits.
- Scans obtained after IV clomipramine will demonstrate
differential brain activation patterns, indicating dynamic changes that
occur in OCD-specific neural pathways with treatment. The third set
of fMRI scans will monitor long-term changes in brain activation that
correspond to treatment response.
This proposal will help pioneer a state-of-the-art diagnosis
and treatment design that utilizes an innovative treatment modality for
refractory OCD (using I.V. clomipramine as a loading dose prior to oral
treatment) and advanced neuroimaging technology (high resolution fMRI).
Functional MRI does not expose an individual to ionizing radiation, and
thus has the potential to be used widely as a clinical tool. The combination
of innovative psychopharmacology with neuroimaging technology will result
in a powerful and comprehensive treatment approach for individuals with
OCD and other neuropsychiatric disorders.
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