Compulsivity in gambling disorder and obsessive-compulsive disorder: a functional magnetic resonance imaging (fMRI) study

In recent years there is an increasing interest in psychiatry to investigate
behavioral dimensions that cross traditional diagnostic boundaries. Current
DSM-categories of mental disorders are based on a broad set of heterogeneous
symptoms that overlap between different disorders. This heterogeneity of
symptoms within disorders as well as respective overlap of symptoms between
disorders hinders investigation into biological factors of psychiatric
disorders. Examining behavioral dimensions with a closer correlation to brain
processes is thought to be a more promising avenue. The U.S. National Institute
of Mental Health Strategic Plan supports this change in research approach and
has developed the Research Domain Criteria (RDoC) project that promotes
investigation into these dimensions and aims to provide a new framework for
psychiatric disorders based on neurocognitive research instead of clinical
observations.

Compulsivity is such a behavioral dimension that is associated with several
psychiatric disorders including substance use disorders, pathological gambling
disorder, obsessive-compulsive disorder and eating disorders. Patients
suffering from these disorders compulsively engage in behavior that leads to
serious life impairments and suffering.
These compulsive behaviors may differ in many aspects between disorders but
they have in common that they are experienced as *out of control* and seem
driven by an internal urge that goes beyond simple explanations. This common
phenomenology across different disorders has led to the hypothesis of shared
mechanisms connecting these different compulsive behaviors. Understanding these
mechanisms may have promising implications for treatment and prevention: new
interventions may target these behaviors and their associated brain circuits
directly and across disorders.

Two psychiatric disorders with compulsive behaviors at the core of their
pathology are obsessive-compulsive disorder (OCD) and gambling disorder (GD).
Compulsions in OCD are the prototypical compulsive behaviors; they are fixed
behavioral patterns or mental acts (e.g., counting, washing or checking). These
compulsions are typically performed to regain a sense of control or order but
paradoxically spiral out of control to such an extent that they cause severe
suffering and debilitation. Gambling on the other hand typically starts out as
exciting or pleasurable behavior. However, over time patients can find it
increasingly difficult to stop and gambling can turn compulsive where the loss
of control and dire consequences on their lives overshadow the pleasurable
aspects. Because these compulsive behaviors are so differently in content and
developmental trajectory they are specifically suitable to investigate overlap
and differences in compulsive behaviors across psychiatric disorders.

Investigating and comparing two disorders (i.e., OCD and GD) with
phenomenological different types of compulsive behaviors central to their
pathology can elucidate common mechanisms of compulsivity in psychiatry - core
features- as well as specific aspects resulting in a diverse display of
compulsive behaviors across disorders. In the present study we will investigate
behavioral and neural mechanisms contributing to these behaviors. We will
explore different aspects that have been related to compulsivity in previous
studies: affect and habit formation, confidence and (negative) outcome
anticipation. With fMRI imaging we will investigate the neurobiological
correlates of these compulsive behaviors in both GD and OCD. Results from OCD
and GD patients will be compared to healthy controls (HC) to assess disorder
specific abnormalities.

Behavioural and neurobiological outcome measures will be used to test
similarities and differences in compulsive behaviours in OCD and GD. We will
measure 3 important aspects that have been associated with compulsive
behaviour. 1) We will investigate the respective roles of affect and
habituation in compulsive behaviour by a previous used task that habituates
avoidance responses in subjects. This makes it possible to measure the tendency
of OCD and GD patients to habituate to *affective states-avoidance response*
contingencies and compare this to HC. 2) distortion of judgment and choice, as
seen in compulsive behaviors, are suggested to arise from abnormal confidence
coding in the ventral medial prefrontal cortex (VMPFC). Here we will use a fMRI
paradigm to investigate abnormalities in confidence coding in OCD and GD
patients in comparison to healthy controls.3) We will examine the role of
negative outcome anticipation in compulsive behaviour and brain responses in
all three groups (OCD, GD and HC) with the use of an in-house developed fMRI
paradigm. Additionally we can investigate whether negative outcome anticipation
affects compulsive behaviour differently between groups

The risk associated with participation can be considered negligible and the
burden can be considered minimal. Total participation time is approximately 4
hours, including a fMRI scan of 1 hour. In addition, structured diagnostic
interviews for psychiatric disorders and clinical and personality
questionnaires will be administered.