BDNF and COMT Alleles Associated With Psychiatric Symptoms in Refractory Epilepsy

A study has found evidence for a genetic basis of psychiatric comorbidities in refractory epilepsy.

A retrospective, cross-sectional study has found that both BDNF and COMT may be associated with the pathophysiology of psychiatric comorbidities in patients with epilepsy. Findings from this study were published in Epilepsy Behavior.

A total of 148 adult patients with refractory epilepsy from the Cleveland Clinic Epilepsy Center were administered self-reported assessments of mood, anxiety, and/or personality/psychopathology.

Only patients who completed these assessments and have genotyping results for APOE, BDNF, or COMT were included in the final analysis. The researchers investigated whether the presence of APOE4, BDNF Val66Met, or COMT Val158Met were associated with increases in psychiatric symptomatology.

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Carriers of BDNF Met (rs6265) reported greater depression symptoms on the self-reported Personality Assessment Inventory compared with patients without a Met allele (P =.004).

In addition, carriers of COMT Val (rs4680) reported greater symptoms related to schizophrenia (P =.007), antisocial features (P =.04), and alcohol (P =.03) vs those who did not carry COMT Val. A greater proportion of carriers of the BDNF Met allele had higher Personality Assessment Inventory Depression scores vs those without BDNF Met (P =.046).

A higher proportion of carriers of COMT Val also had increased Personality Assessment Inventory scores related to anxiety vs individuals without COMT Val (P =.036).

Limitations of the study include its retrospective nature, as well as the reliance on self-reported measures for identification of participants’ symptoms.

“Our study provides preliminary evidence for a genetic contribution to psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population,” the researchers concluded.


Doherty C, Hogue O, Floden DP, et al. BDNF and COMT, but not APOE, alleles are associated with psychiatric symptoms in refractory epilepsy. Epilepsy Behav. 2019;94:131-136.