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OCD

This large population-based study in Sweden investigated the potential link between severe infections and obsessive-compulsive disorder (OCD) through a familial co-aggregation approach. By analyzing data from over 4.9 million individuals born between 1960 and 2008, researchers explored the risk of OCD among relatives of those with severe infections, spanning varying degrees of genetic relatedness. The study found that the risk of OCD increased with closer genetic ties, with monozygotic twins showing the highest correlation. A dose-response relationship between the number of infections and the odds of OCD was also identified. These findings remained robust even after adjusting for comorbid autoimmune disorders and infections in relatives. The results suggest that genetic factors play a significant role in the observed association, pointing to shared genetic susceptibilities between infections and OCD. This supports the idea that genetic pleiotropy—where the same genes influence multiple traits—may contribute to both infection susceptibility and OCD risk. The study highlights the importance of considering both genetic and environmental factors in understanding OCD development.

Biria, M., Banca, P., Healy, M.P. et al. Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls. Nat Commun 14, 3324 (2023). https://doi.org/10.1038/s41467-023-38695-z

A Cambridge neuroimaging study found that compulsive behavior is associated with glutamate–GABA imbalance, particularly elevated glutamate, across both individuals with OCD and healthy controls. Using ultra–high field MRS, the authors show that compulsivity maps to excitatory–inhibitory imbalance in brain regions involved in habit formation and control. These findings support a mechanism-based view of compulsive symptoms, while underscoring the need for caution when targeting glutamatergic systems clinically due to their broader downstream effects. The findings are particularly relevant given increasing clinical interest in glutamate-modulating medications, which are sometimes used off-label in OCD and neuroimmune conditions. At the same time, the study reinforces the need for caution: altering glutamatergic systems can have complex downstream effects, especially in conditions where dopamine and immune signaling may also be involved. This work strengthens the rationale for mechanism-focused research while underscoring why individualized, carefully monitored treatment remains essential.

Raposo-Lima, C., Pereira, I.M., Marques, F. et al. Elevated levels of neutrophil gelatinase-associated lipocalin among OCD patients: an exploratory study. BMC Psychiatry 21, 272 (2021). DOI: 10.1186/s12888-021-03289-w

“Although PANDAS might be of relevance for only a minor proportion of OCD cases, this immune/inflammation hypothesis may be significant given the prevalence of OCS among patients with autoimmune diseases [9]…. In conclusion, we herein report differences in NGAL levels among OCD patients compared to healthy controls. We offer additional evidence to the immune dysregulation hypothesis of OCD by reporting elevated levels of NGAL among OCD patients versus healthy controls, with higher differences being found among women”