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.
