Background This study aims to explore the relationship between psychiatric disorders and the risk of epilepsy using Mendelian randomization (MR) analysis. Methods We collected summary statistics of seven psychiatric traits from recent largest genome‐wide association study (GWAS), including major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and insomnia. Then, MR analysis estimates were performed based on International League Against Epilepsy (ILAE) consortium data ( n case = 15,212 and n control = 29,677), the results of which were subsequently validated in FinnGen consortium ( n case = 6260 and n control = 176,107). Finally, a meta‐analysis was conducted based on the ILAE and FinnGen data. Results We found significant causal effects of MDD and ADHD on epilepsy in the meta‐analysis of the ILAE and FinnGen, with corresponding odds ratios (OR) of 1.20 (95% CI 1.08–1.34, p = .001) and 1.08 (95% CI 1.01–1.16, p = .020) by the inverse‐variance weighted (IVW) method respectively. MDD increases the risk of focal epilepsy while ADHD has a risk effect on generalized epilepsy. No reliable evidence regarding causal effects of other psychiatric traits on epilepsy was identified. Conclusions This study suggests that major depressive disorder and attention deficit hyperactivity disorder may causally increase the risk of epilepsy.
Autism spectrum disorders and epilepsies are heterogeneous human disorders that have miscellaneous etiologies and pathophysiology. There is considerable risk of frequent epilepsy in autism that facilitates amplified morbidity and mortality. Several biological pathways appear to be involved in disease progression, including gene transcription regulation, cellular growth, synaptic channel function, and maintenance of synaptic structure. Here, abnormalities in excitatory/inhibitory (E/I) balance ratio are reviewed along with part of an epileptiform activity that may drive both overconnectivity and genetic disorders where autism spectrum disorders and epilepsy frequently co-occur. The most current ideas concerning common etiological and molecular mechanisms for co-occurrence of both autism spectrum disorders and epilepsy are discussed along with the powerful pharmacological therapies that protect the cognition and behavior of patients. Better understanding is necessary to identify a biological mechanism that might lead to possible treatments for these neurological disorders.
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