How Do Genes Affect Contamination Symptoms and Treatment Response in OCD?

What you need to know

• A genetic variant in the SAPAP3 gene was associated with contamination/washing symptoms in obsessive-compulsive disorder (OCD)
• This same genetic variant predicted poorer response to standard medication treatments for OCD
• The findings suggest contamination-related OCD may have a distinct biological basis linked to the SAPAP3 gene

Background on OCD and genetics

Obsessive-compulsive disorder (OCD) is a mental health condition that affects about 2% of the population worldwide. People with OCD experience unwanted, intrusive thoughts (obsessions) and feel compelled to perform repetitive behaviors or mental acts (compulsions) to relieve anxiety.

OCD tends to run in families, suggesting genetic factors play a role. However, identifying specific genes involved has been challenging. This study focused on a gene called SAPAP3, which has been linked to compulsive grooming behaviors in mice. The researchers wanted to see if variations in this gene relate to particular OCD symptoms or treatment outcomes in humans.

How the study was conducted

The study included 200 people diagnosed with OCD who were receiving treatment at a specialty clinic in India. Participants completed detailed assessments of their OCD symptoms, other mental health conditions, and family history. Their response to medication treatment was tracked over time.

The researchers looked at a specific variation in the SAPAP3 gene - a change from an “A” to a “G” at a particular location. They compared people who had at least one copy of the “G” version to those who had two copies of the “A” version.

Key findings on OCD symptoms

The main finding was that people with the “G” version of SAPAP3 were more likely to have contamination obsessions and washing compulsions. Specifically:

• 81% of those with the “G” version had contamination obsessions, compared to 59% of those without it
• 79% of those with the “G” version had washing compulsions, compared to 57% of those without it

When the researchers looked at overall symptom patterns, they found the “G” version was significantly associated with higher scores on a contamination/washing symptom dimension.

This suggests the SAPAP3 gene may play a particular role in contamination-related OCD symptoms. Interestingly, animal studies have found that mice lacking the SAPAP3 gene show excessive grooming behaviors. The human findings align with this, indicating SAPAP3 may be involved in cleaning and grooming across species.

Impact on treatment response

The study also looked at how people responded to standard OCD medications called serotonin reuptake inhibitors (SRIs). They found that people with the “G” version of SAPAP3 were more likely to have poor response to these medications:

• 52% of those with the “G” version were classified as SRI resistant, compared to 35% of those without it
• Those with the “G” version had failed an average of 1.8 adequate medication trials, compared to 1.2 trials for those without it

This suggests the SAPAP3 gene may affect not just symptom type, but also how well standard treatments work. The researchers found an interesting interaction - among people with the “G” version, those with more severe contamination symptoms were especially likely to have poor medication response.

What this means for understanding OCD

These findings add to growing evidence that OCD is not one uniform condition, but may have distinct subtypes with different biological bases. Contamination-related OCD in particular may be linked to variations in the SAPAP3 gene and associated brain circuits.

SAPAP3 is involved in glutamate signaling in the brain, particularly in a region called the striatum. Disruptions to this signaling may contribute to compulsive behaviors. The association with treatment response suggests medications targeting the serotonin system may be less effective when glutamate signaling is affected in this way.

Implications for treatment

While more research is needed, these findings could eventually help guide more personalized treatment approaches for OCD. For example:

• Genetic testing for SAPAP3 variants might help predict who is more likely to respond to standard SRI medications
• People with the high-risk genetic variant may benefit from starting with a combination of medication and psychotherapy, rather than medication alone
• New medications that target the glutamate system might be especially helpful for those with contamination symptoms and the high-risk genetic variant

However, it’s important to note that many factors influence OCD symptoms and treatment response beyond just this one gene. The SAPAP3 variant likely interacts with other genetic and environmental factors in complex ways.

Limitations and future directions

Some key limitations of this study include:

• It was conducted in one clinic in India, so findings may not generalize to all populations
• The sample size was relatively small for a genetic study
• Treatment response was assessed naturalistically rather than in a controlled trial

Larger studies across diverse populations are needed to confirm and expand on these findings. Future research could also look at how SAPAP3 interacts with other genes, and examine its effects on brain structure and function using neuroimaging.

Conclusions

• A variation in the SAPAP3 gene was associated with contamination/washing symptoms in OCD
• This same genetic variant predicted poorer response to standard SRI medications
• The findings suggest contamination-related OCD may have a distinct biological basis involving glutamate signaling
• With further research, genetic testing could potentially help guide more personalized treatment approaches for OCD in the future

While more work is needed, this study adds to our understanding of the complex genetic factors that contribute to OCD. It highlights how examining specific symptom dimensions, rather than just OCD as a whole, may help uncover the biological mechanisms involved. This line of research offers hope for developing more targeted and effective treatments for this challenging disorder.