Reinforcement Learning and Obsessive-compulsive Disorder: Exploring the Role of the Orbitofrontal Cortex

Status: Recruiting
Location: See location...
Study Type: Observational
SUMMARY

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition affecting 1-3% of the population. Typically, symptoms start in adolescence or early adulthood, are time-consuming, and have a significant impact on quality of life. However, first-line approved treatments, based on a combination of pharmacotherapy and psychotherapy, are ineffective in at least 50% of cases. Since the pathophysiology of OCD remains largely unknown, it is expected that a better understanding of the biological mechanisms of OCD would contribute to improved strategies for treatment of the disorder. Current neurobiological models for OCD highlight the role of corticostriatal dysfunction and hyperactivity of the orbitofrontal cortex (OFC), a part of the prefrontal cortex. Indeed, the lateral OFC plays a crucial role in controlling transitions between automatic, repetitive stimulus-response driven behaviors, and behaviors that reflect the acquisition, by the agent, of a predictive model of the consequences of each action. Previous studies have suggested that the ability to operate this transition is compromised in OCD and may be objectively measured using specifically designed Reinforcement Learning (RL) tasks. Furthermore, growing evidence has suggested that OCD may be associated with systemic immune dysfunction, as has been shown in other common neuropsychiatric conditions, such as depressive disorders. Indeed, there is evidence to support OCD-like symptoms occurring acutely in children after streptococcal infection. These findings have raised the hypothesis that vulnerable individuals exposed to pro-inflammatory early-life environmental risk factors, such as infections and childhood adversity, may suffer neuroinflammatory-induced dysfunction in corticostriatal pathways, increasing the risk of OCD psychopathology. In this case-control study, the investigators propose an integrative approach to address how structural, functional, and metabolic brain changes involving the corticostriatal circuit correlate with performance in an RL task, as well as with peripheral blood markers of immune dysfunction and associated environmental risk factors such as infection and childhood trauma. Furthermore, since neuromodulation of the prefrontal cortex, using repetitive transcranial magnetic stimulation (rTMS), has recently received FDA clearance for adjunctive treatment in patients with OCD, these associations will be further explored in patients treated with this method. Indeed, in patients with OCD enrolled in the study upon referral to the rTMS Programme for OCD at the Champalimaud Clinical Centre, a follow-up visit will be conducted after the end of treatment (30 sessions of excitatory rTMS over the medial prefrontal cortex). In this subgroup of participants with longitudinal assessment, we will measure change in study parameters and the associations between such change and the clinical effects of treatment, as well as prediction of treatment effects according to baseline assessments.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 65
Healthy Volunteers: t
View:

• Exclusively for the OCD group: established diagnosis of Obsessive-Compulsive Disorder according to DSM-5 criteria;

• Exclusively for the control group: does not meet DSM criteria for any of the psychiatric diagnoses screened by the Mini International Neuropsychiatric Interview;

• Age between 18 and 65 years-old;

• Fluent Portuguese or English speaker.

Locations
Other Locations
Portugal
Champalimaud Foundation
RECRUITING
Lisbon
Contact Information
Primary
Sofia Marques
sofia.marques@research.fchampalimaud.org
00351 210480048
Time Frame
Start Date: 2019-10-01
Estimated Completion Date: 2026-12-31
Participants
Target number of participants: 230
Treatments
Obsessive-compulsive disorder group
Obsessive-compulsive disorder group: Adult patients (18 to 65 years-old) with obsessive-compulsive (OCD) disorder will be recruited both at Champalimaud Clinical Center and collaborating clinical centers, namely Centro Hospitalar Psiquiátrico de Lisboa, Centro Hospitalar de Lisboa Ocidental and Hospital Garcia de Orta.
Healthy subjects group
Control subjects group: Adult individuals (18 to 65 years-old) age- and sex-mateched without past or current diagnosis of major neuropsychiatric disorders, including OCD.
Sponsors
Leads: Fundacao Champalimaud

This content was sourced from clinicaltrials.gov