How Are Obsessive-Compulsive Disorder, Related Symptoms, and Insulin Signaling Genetically Connected?

What you need to know

• This study found shared genetic factors between obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms (OCS) in the general population, and insulin signaling.
• Specific OCS factors like “guilty taboo thoughts” and “symmetry/counting/ordering” showed genetic overlap with diagnosed OCD.
• There was also genetic overlap between OCD/OCS and insulin-related traits like type 2 diabetes, suggesting a biological connection.
• These findings provide new insights into the genetic basis of OCD and related symptoms, as well as potential connections to metabolic factors.

Understanding OCD and Related Symptoms

Obsessive-compulsive disorder (OCD) is a mental health condition characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions). While OCD affects about 2-3% of the population, milder obsessive-compulsive symptoms (OCS) are much more common, occurring in up to 20-30% of people.

Previous research has shown that both OCD and OCS tend to run in families, suggesting they have a genetic component. However, identifying the specific genes involved has been challenging, as many genetic variants likely contribute small effects.

This study aimed to explore the genetic connections between diagnosed OCD, OCS in the general population, and insulin signaling pathways in the body. The researchers were particularly interested in insulin because previous work had suggested a link between insulin-related genes and OCD.

Examining Genetic Overlap

The researchers used data from several large studies:

1. A genome-wide association study (GWAS) of diagnosed OCD including 2,688 patients and 7,037 controls
2. A study of OCS in 650 children and adolescents from the Philadelphia Neurodevelopmental Cohort
3. A validation sample of 5,047 youth from the Spit for Science project

They looked at whether genetic risk scores for OCD could predict OCS in the general population samples. They also examined genetic overlap between OCD/OCS and insulin-related traits like type 2 diabetes.

Key Findings

The study revealed several important findings:

Shared genetics between OCD and OCS

There was significant genetic overlap between diagnosed OCD and certain OCS factors in the general population:

• “Guilty taboo thoughts” in the Philadelphia cohort
• “Symmetry/counting/ordering” and “contamination/cleaning” symptoms in the Spit for Science sample

This suggests that some of the same genetic factors that increase risk for OCD also contribute to milder related symptoms in the broader population.

Connection to insulin signaling

The researchers found genetic overlap between OCD/OCS and insulin-related traits:

• Type 2 diabetes showed genetic sharing with the OCS factor “aggressive taboo thoughts”
• Blood levels of fasting insulin and glucose after an oral glucose test showed genetic overlap with diagnosed OCD

Additionally, a set of genes related to insulin signaling in the brain was associated with symmetry/counting/ordering symptoms.

Implications of the findings

These results provide evidence that OCD, OCS in the general population, and insulin-related biological pathways share some common genetic factors. This suggests there may be shared underlying mechanisms contributing to both psychiatric symptoms and metabolic traits.

The connection to insulin signaling is particularly intriguing. Insulin plays important roles in the brain beyond just regulating metabolism - it’s also involved in signaling pathways that affect learning, memory, and synaptic plasticity (the ability of brain connections to change). Disruptions to these pathways could potentially contribute to OCD symptoms.

Limitations and Future Directions

While these findings are exciting, there are some important limitations to keep in mind:

• The sample sizes were relatively small, limiting the ability to identify specific genetic variants
• The questions used to assess OCS differed somewhat between the two population samples
• The amount of overlap in genetic factors, while statistically significant, was fairly small

Larger studies will be needed to confirm and expand on these results. Future research should also examine the biological mechanisms by which insulin-related genes might influence OCD and related symptoms.

Conclusions

• This study provides evidence for shared genetic factors between OCD, milder OCS in the general population, and insulin signaling pathways.
• The findings suggest that some of the same genetic variants may increase risk for both clinical OCD and related subclinical traits.
• There appears to be a biological connection between OCD/OCS and metabolic factors related to insulin, though the exact mechanisms require further study.
• This work opens up new avenues for understanding the biology of OCD and related symptoms, potentially leading to novel treatment approaches in the future.

The overlap between psychiatric and metabolic factors highlighted by this research underscores the complex connections between brain and body. Continuing to unravel these relationships may lead to important insights for both mental and physical health.