Neural Mechanisms of CBT Response in Hoarding Disorder

The purpose of this research is to measure changes in brain activity with functional magnetic resonance imaging (fMRI) before and after cognitive-behavioral therapy for compulsive hoarding. Cognitive-behavioral therapy aims to help people change the thoughts and behaviors that maintain symptoms of hoarding. The investigators intend to enroll approximately 80 people with hoarding disorder and 40 people with no psychiatric disorder, between the ages of 20 and 60, for this study. The investigators believe that after treatment there will be changes in the brain activity of individuals with compulsive hoarding.

The long-term goal of the proposed research is to improve clinical outcomes for Hoarding Disorder (HD), a common and potentially debilitating condition that poses a severe public health burden. The PI has developed and tested a cognitive-behavioral therapy (CBT) that appears moderately effective, although there is clear room for improvement. In the present study, the investigators propose to merge this line of research with the PI's recent NIH-supported neuroimaging research that points to specific functional abnormalities in regions of interest (ROIs) related to cognitive and affective decisionmaking processes. Patients with HD n = 80) will be randomized to CBT or wait list (WL). At pre-treatment, mid-treatment, and post-treatment, patients will undergo functional magnetic resonance imaging (fMRI) during an acquiring and discarding decision-making task that has been used successfully in the investigators' previous work. In addition, patients will complete a number of laboratory tasks designed to assess decision-making capacity and impairment. A group of healthy control (HC) participants (n = 40) will also complete these measures as a normative control group. The primary aim of the proposed study is to determine the extent to which the observed patterns of neural activity in HD change following CBT. Under this aim, the investigators predict that HD patients (vs.HCs) will show greater hemodynamic activity in ROIs associated with cognitive and affective aspects of decision-making. The investigators further predict that HD patients receiving CBT (vs. WL) will show decreased activity in those ROIs, and will no longer differ from HCs following CBT. A secondary aim of the proposed study is to determine the relationship between change in activity in brain regions of interest and hoarding-related symptoms and impairments. The investigators expect, that hemodynamic activity in the target ROIs will correlate with symptoms of HD and with performance on decision-making tasks; and that change in brain activity will correspond to both symptom and mechanism changes over the course of treatment. Finally, an exploratory aim is to explore, using both data-driven and model-constrained approaches, patterns of pre-treatment neural activity that predict response to CBT. The investigators predict that among treated HD patients, pre-treatment activity in the target ROIs will correlate significantly with HD symptom change from pre- to posttreatment. Results of the proposed study are expected to elucidate the neural mechanisms of successful response to CBT treatment for hoarding patients, and to set the stage for further treatment development and possible improvements in outcome for this disorder.

Hoarding Disorder, Clutter, CBT, Cognitive behavior therapy, fMRI, Obsessive compulsive disorder (OCD), Healthy control

This group is matched to the immediate treatment group on age and gender. They do not receive an active treatment and will be used a a healthy comparator group.

The SI-R is a 23-item questionnaire with 3 factor-analytically defined sub-scales for difficulty discarding, excessive clutter and compulsive acquisition

The CGI is a widely used measure of global symptom severity (CGI-S) and symptom improvement after treatment (CGI-I). On the CGI-S the scale ranges from 1 (no symptoms) to 7 (extreme symptoms). On the CGI-I the scale ranges from 1 (very much improved) to 7 (very much worse). The CGI can be used in both a self-report and clinician administered version and this study utilizes both formats.

Inclusion Criteria: Aged 20-65 Hoarding Disorder primary condition Score at least 4 on the CGI Free from all psychotropic medications for at least 4 weeks(5 weeks for fluoxetine) Participant is fluent in English Control over current living environment (i.e. not living in a nursing home or with relatives) Physically able to complete therapy assignments (i.e able to discard etc) Able to complete study measures If female: Using an approved method of contraception Exclusion Criteria: More than 10 sessions of CBT for HD Actively suicidality, previous suicide attempt, current use of self harming behaviors or is at risk for harming others Current or past diagnosis of serious psychological disorder (psychotic disorder, bipolar disorder, substance use disorder or uncontrolled anorexia) Psychiatric hospitalization within the past 12 months History of anoxic or traumatic brain injury Evidence of cognitive dysfunction that would interfere in the ability to provide informed consent or engage in CBT Claustrophobia Pacemaker, aneurysm clip, or other metal in the body that would pose a risk during fMRI? If female: Pregnant or lactating

We will upload de-identified study data to an online database to be shared with colleagues upon request.

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