How Does Brain Gene Expression Differ in People with OCD?

What you need to know

• Researchers examined gene activity in brain regions linked to OCD in people with and without the disorder
• They found differences in the activity of many genes, especially those involved in communication between brain cells
• The findings provide new insights into how OCD may develop and could lead to better treatments in the future

Understanding OCD and the brain

Obsessive-compulsive disorder (OCD) is a mental health condition that affects 1-3% of people worldwide. It involves unwanted, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions) that a person feels driven to perform. For example, someone might have obsessive thoughts about germs and feel compelled to wash their hands excessively.

While the exact causes of OCD are not fully understood, research suggests that both genetic and environmental factors play a role. Brain imaging studies have found that certain regions of the brain function differently in people with OCD compared to those without the disorder. Specifically, areas called the orbitofrontal cortex (OFC) and striatum show increased activity in OCD.

The OFC is part of the frontal lobe and is involved in decision-making and regulating emotions. The striatum is a structure deep in the brain that plays a role in reward, motivation, and habitual behaviors. These two regions communicate with each other through connections called synapses, where brain cells exchange chemical signals.

Examining gene activity in the brain

To better understand what might be happening in the brains of people with OCD at the molecular level, researchers conducted a study examining gene expression in post-mortem brain tissue. Gene expression refers to which genes are active and producing proteins in cells at a given time.

The study looked at tissue samples from the OFC and two parts of the striatum (the caudate nucleus and nucleus accumbens) in 7 people who had OCD and 8 people without the disorder. The researchers used a technique called RNA sequencing to measure the activity levels of thousands of genes in these brain samples.

Key findings

When comparing the gene expression patterns between the OCD and non-OCD groups across all brain regions examined, the researchers found 904 genes that showed different activity levels. Many of these differences were concentrated in the striatum, particularly the caudate nucleus and nucleus accumbens.

Importantly, the genes with altered expression were not random. Many were involved in synaptic signaling - the process by which brain cells communicate with each other. In general, genes related to synapses showed lower expression in the OCD group compared to the non-OCD group.

The researchers also estimated the proportions of different cell types in the tissue samples based on gene expression patterns. They found that the OCD samples appeared to have:

• Lower proportions of medium spiny neurons - the main type of neuron in the striatum
• Higher proportions of astrocytes - star-shaped support cells in the brain
• Higher proportions of vascular cells - cells that make up blood vessels

What do these findings mean?

This study provides several important insights into the biology of OCD:

1. It supports the idea that communication between brain cells may be altered in OCD, particularly in the striatum. The lower expression of synapse-related genes could mean that signaling between neurons is reduced or less efficient in some way.

2. The changes in cell type proportions suggest there may be structural differences in the brain tissue of people with OCD. Having fewer medium spiny neurons could affect how the striatum functions and communicates with other brain regions.

3. The increased proportion of astrocytes and vascular cells is interesting, as these cell types are involved in supporting and nourishing neurons. This could potentially be related to the increased brain activity seen in OCD in imaging studies.

It’s important to note that this study can’t tell us whether these changes in gene expression cause OCD or are a result of having the disorder. However, the findings align well with other research on OCD, including brain imaging studies and genetic studies in humans, as well as animal models of compulsive behavior.

Potential implications for treatment

Understanding the molecular changes associated with OCD could lead to new treatment approaches. Current treatments for OCD include psychotherapy (particularly cognitive-behavioral therapy) and medications that affect brain chemicals like serotonin. However, many people with OCD don’t respond fully to these treatments.

The findings from this study suggest that medications targeting synaptic function, particularly in the striatum, might be worth exploring for OCD. Additionally, the changes in astrocyte and vascular cell proportions raise questions about whether targeting these support cells could be beneficial.

It’s also possible that measuring gene expression patterns or looking at the proportions of different cell types could someday help diagnose OCD or predict which treatments might work best for an individual.

Limitations and future directions

While this study provides valuable new information, it’s important to consider its limitations:

• The sample size was small, with only 15 total subjects. Larger studies are needed to confirm and expand on these findings.

• Post-mortem brain studies can’t capture dynamic changes in gene expression that might occur during OCD symptoms.

• The study can’t determine whether the observed changes in gene expression cause OCD or result from having the disorder.

Future research could address these limitations by:

• Examining gene expression in larger groups of people with and without OCD

• Using animal models to test whether altering the expression of specific genes leads to OCD-like behaviors

• Studying how gene expression might change in response to successful OCD treatment

• Investigating whether similar gene expression patterns are seen in other psychiatric disorders that involve compulsive behaviors

Conclusions

• This study found differences in gene expression patterns in brain regions linked to OCD, particularly genes involved in communication between brain cells.

• The findings support the idea that altered signaling in the striatum may play a role in OCD and suggest potential new directions for treatment.

• Further research is needed to understand how these molecular changes relate to OCD symptoms and to develop new therapies targeting these pathways.

By shedding light on the molecular changes occurring in the brains of people with OCD, this research brings us one step closer to understanding this complex disorder and developing more effective treatments.