Among patients with epilepsy, psychiatric comorbidities occur frequently; however, the underlying mechanisms that contribute to this correlation are complex, multifactorial, and remain primarily unknown.

In a recent publication in the Journal of Affective Disorders, researchers conducted a bidirectional two-sample Mendelian randomization (MR) study to assess the causal correlation between epilepsy and seven common psychiatric comorbidities.

The authors noted that to their knowledge, this is the first MR study to systematically evaluate bidirectional genetic causal relationships between epilepsy and seven psychiatric comorbidities.

In this study, researchers evaluated various psychiatric comorbidities, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, anorexia nervosa, major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder (OCD).

Statistics regarding epilepsy were gathered from the International League Against Epilepsy, and those regarding psychiatric comorbidities were found in the Psychiatric Genomics Consortium.

Utilizing genome-wide association studies, researchers gathered and assessed information from single-nucleotide polymorphisms associated with epilepsy, which included 29,677 controls and 15,212 cases, and seven psychiatric comorbidities, which included 485,436 controls and 269,495 cases. The researchers employed inverse variance weighting to estimate causal significance, and sensitivity analyses included the weighted median, MR-Egger, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO).

The results revealed that forward and reverse genetic correlations were observed for the examined psychiatric disorders. The authors wrote, “Notably, ADHD was significantly associated with an increased risk of generalized epilepsy (odds ratio [OR], 1.09;95 % confidence interval [CI], 1.01-1.18; P = .013). However, MR-PRESSO detected the existence of pleiotropy (P = .001). Additionally, focal epilepsy was significantly associated with a higher risk of OCD (OR, 1.44; 95 % CI, 1.08-1.92; P = .013), and all sensitivity tests yielded favorably nonsignificant results.”

The authors concluded that this study uncovered significant genetic causality between focal epilepsy and OCD and links between ADHD and generalized epilepsy. The authors also noted that no casual significance was uncovered with the remaining psychiatric comorbidities that were investigated in this study.

Lastly, the authors concluded, “Notably, the significant existence of pleiotropy was detected by MR-Egger, indicating the inherent limitations of MR analysis in the current study. Therefore, the absence of significance should be interpreted with caution. Although further studies are necessary to expand upon these findings, the results of this study offer valuable insights into the bidirectional association between epilepsy and various psychiatric comorbidities.”

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