How Do Compulsive Behaviors and Sensory Processing Issues Relate in OCD Mouse Models?

What you need to know

• Mice lacking the Sapap3 gene show OCD-like compulsive grooming behaviors and deficits in sensory processing
• More severe compulsive grooming was linked to worse sensory processing in these mice
• Mice with more severe symptoms had lower levels of dopamine receptors in a brain region called the nucleus accumbens
• Compulsive grooming developed before sensory processing issues appeared in these mice

Background on OCD and sensory processing

Obsessive-compulsive disorder (OCD) is a condition where people experience intrusive, unwanted thoughts (obsessions) and feel compelled to perform repetitive behaviors (compulsions). About 1-3% of people have OCD. In addition to the core symptoms, many people with OCD also have difficulties with sensory processing - the way the brain filters and organizes sensory information from the environment.

One way researchers measure sensory processing in both humans and animals is through a test called prepulse inhibition (PPI). This test measures how well the brain can filter out unnecessary information and avoid being overloaded by sensory input. Some studies have found that people with OCD show reduced PPI, suggesting they may have trouble filtering sensory information. However, it’s unclear exactly how sensory processing issues relate to OCD symptoms.

To better understand the links between compulsive behaviors, sensory processing, and brain changes in OCD, researchers often use animal models. One commonly used model is mice that lack a gene called Sapap3. These mice show excessive grooming behaviors similar to human compulsions.

Key findings on compulsive behavior and sensory processing

In this study, the researchers examined both compulsive grooming behaviors and sensory processing (measured by PPI) in Sapap3 knockout mice. They found:

• Sapap3 knockout mice showed more compulsive grooming than normal mice, as expected
• There was a lot of variation in grooming severity among the knockout mice
• Knockout mice with more severe compulsive grooming also tended to have worse sensory processing (lower PPI scores)
• Sensory processing deficits were only seen in the subset of knockout mice with the most severe compulsive behaviors

These results suggest that compulsive behaviors and sensory processing difficulties may be closely linked in OCD. However, not all mice with compulsive behaviors had sensory issues, similar to how not all people with OCD have sensory sensitivities.

Brain changes associated with symptoms

The researchers also examined the brains of the mice, focusing on a region called the nucleus accumbens. This area is part of the brain’s reward system and has been implicated in OCD. They found:

• Knockout mice had lower levels of dopamine receptors (both D1 and D2/D3 types) in the nucleus accumbens
• Lower dopamine receptor levels were associated with more severe compulsive grooming
• Lower dopamine receptor levels were also linked to worse sensory processing

These findings suggest that changes in dopamine signaling in the nucleus accumbens may contribute to both the compulsive behaviors and sensory processing difficulties seen in OCD. Dopamine is a neurotransmitter involved in motivation, reward, and motor control.

Time course of symptom development

To understand how symptoms progress over time, the researchers observed mice from 2 to 8 months of age. They found:

• Compulsive grooming in knockout mice became apparent around 4 months of age
• Grooming severity gradually increased over time
• Sensory processing deficits weren’t detectable until 7 months of age
• Sensory issues only appeared in mice that had already developed severe compulsive grooming

This suggests that in this OCD model, compulsive behaviors develop first, followed later by sensory processing difficulties. The sensory issues may be a consequence of long-term compulsive behavior rather than a direct cause.

Conclusions

• Compulsive behaviors and sensory processing deficits appear to be linked in this OCD mouse model
• Changes in dopamine signaling in the nucleus accumbens may contribute to both types of symptoms
• Compulsive behaviors develop before sensory processing issues in these mice
• There is significant variation in symptom severity, even among genetically identical mice

These findings help clarify the relationship between different symptoms in OCD and point to brain changes that may underlie them. However, it’s important to note that while animal models are useful tools, they don’t perfectly replicate human disorders. More research is needed to determine if similar patterns occur in humans with OCD.

Understanding these connections could potentially lead to new treatment approaches. For example, therapies that improve sensory processing might help reduce compulsive behaviors in some patients. Additionally, treatments targeting dopamine signaling in specific brain regions may be worth exploring further.