Gray matter study uncovers two neuroanatomically different OCD subtypes

Obsessive compulsive disorder (OCD) is a mental health disorder associated with persistent, intrusive thoughts (i.e., obsessions), accompanied by repetitive behaviors (i.e., compulsions) aimed at reducing the anxiety arising from obsessions. Past studies have showed that people diagnosed with OCD can present symptoms that vary significantly, as well as distinct brain abnormalities.

A team of researchers at the First Affiliated Hospital of Zhengzhou University recently carried out a study aimed at further exploring the well-documented differences among patients with OCD. Their findings, published in Translational Psychiatry, allowed them to identify two broad OCD subtypes, which are associated with different patterns in gray matter volumes and disease epicenters.

“OCD is a highly heterogeneous disorder, with notable variations among cases in structural brain abnormalities,” wrote Baohong Wen, Keke Fang and their colleagues in their paper. “To address this heterogeneity, our study aimed to delineate OCD subtypes based on individualized gray matter morphological differences.”

The researchers recruited 100 individuals who had just been diagnosed with OCD for the first time and had not yet started treatment, along with 106 healthy individuals who received no psychiatric and medical diagnoses. They then used magnetic resonance imaging (MRI) to collect to collect structural imaging scans of all the participants’ brains.

“Utilizing normative models of gray matter volume, we identified subtypes based on individual morphological abnormalities,” wrote Wen, Fang and their colleagues. “Sensitivity analyses were conducted to validate the reproducibility of clustering outcomes. To gain deeper insights into the connectomic and molecular underpinnings of structural brain abnormalities in the identified subtypes, we investigated their associations with normal brain network architecture and the distribution of neurotransmitter receptors/transporters.”

Essentially, the researchers analyzed the brain scans collected from people diagnosed with OCD, comparing them to those of healthy individuals and then with those of others who were also diagnosed with OCD. This allowed them to identify two distinct OCD subtypes characterized by distinct structural brain abnormalities, which were confirmed by follow-up sensitivity analyses.

“Subtype 1 displayed significantly increased gray matter volume in regions including the frontal gyrus, precuneus, insula, hippocampus, parahippocampal gyrus, amygdala, and temporal gyrus, while subtype 2 exhibited decreased gray matter volume in the frontal gyrus, precuneus, insula, superior parietal gyrus, temporal gyrus, and fusiform gyrus,” wrote the researchers. “When considering all patients collectively, structural brain abnormalities nullified.”

The two OCD subtypes uncovered by Wen, Fang and their colleagues are characterized by distinct patterns in gray matter volumes within specific brain regions. People in subtype 1 presented more gray matter in brain areas supporting decision-making (e.g., the frontal gyrus) and emotional processing (i.e., the amygdala).

In contrast, those in subtype 2 were found to present lower gray matter volumes in areas linked to self-referential thinking (i.e., the precuneus) and cognitive function (i.e., the striatum).

Notably, the newly unveiled subtypes were also found to be associated with different disease epicenters and distinct links to neurotransmitter receptors in the brain. This essentially means that the brain regions and receptors most affected by or implicated in the disorder also differed significantly between the two subtypes.

“Subtype 1 showed disease epicenters in the middle frontal gyrus, while subtype 2 displayed disease epicenters in the striatum, thalamus and hippocampus,” wrote the researchers. “Furthermore, structural brain abnormalities in these subtypes displayed distinct associations with neurotransmitter receptors/transporters.”

The findings of this recent study could help to partially explain the differences between patients diagnosed with OCD that have often been observed in the past. In the future, they could pave the way for additional research focusing on the two newly identified disorder subtypes, which could in turn help to devise personalized therapeutic interventions that could be more effective in treating OCD.

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