Evaluation of depression risk in LGI1 mutation carriers.
OBJECTIVE
Depression is the most common comorbid condition in epilepsy. The cause of this comorbidity is unknown, and could involve psychosocial consequences of epilepsy, treatment side effects, seizure manifestations, or common neurobiologic mechanisms. One hypothesis of particular interest is a shared genetic susceptibility to epilepsy and depression. We tested this hypothesis by studying depressive symptoms in families with an identified genetic form of epilepsy: autosomal dominant partial epilepsy with auditory features caused by mutations in the leucine-rich, glioma inactivated 1 gene (LGI1).


METHODS
A standardized depression screen was administered to 94 individuals from 11 families with mutations in LGI1, including 38 mutation carriers with epilepsy (AC), 11 clinically unaffected mutation carriers (UC), and 45 noncarriers (NC).


RESULTS
Current depressive symptom scores were significantly higher in AC than in NC, an association that remained after excluding depressive symptoms that appeared likely to be caused by antiepileptic medication use. However, scores did not differ between UC and NC.


CONCLUSIONS
Although LGI1 mutation carriers who were clinically affected with epilepsy had increased depressive symptoms, mutation carriers without epilepsy did not. These findings suggest that the increase in depressive symptoms in affected individuals from these families is related to epilepsy or its treatment rather than to LGI1 mutations per se.
Heiman
Gary A
GA
Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
Kamberakis
Kay
K
Gill
Richard
R
Kalachikov
Sergey
S
Pedley
Timothy A
TA
Hauser
W Allen
WA
Ottman
Ruth
R
D000328:Adult; D017668:Age of Onset; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006304:Health Status; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins