title: Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.
abstract: OBJECTIVE
  We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE.
  
  
  METHODS
  MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity.
  
  
  RESULTS
  MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population.
  
  
  CONCLUSIONS
  The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE.
authors.affiliation: Molecular and Cellular Therapeutics Department, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Saud
authors.initials: S
authors.lastname: Alhusaini
authors.forename: Cathy
authors.initials: C
authors.lastname: Scanlon
authors.forename: Lisa
authors.initials: L
authors.lastname: Ronan
authors.forename: Sinead
authors.initials: S
authors.lastname: Maguire
authors.forename: James F
authors.initials: JF
authors.lastname: Meaney
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fagan
authors.forename: Gerard
authors.initials: G
authors.lastname: Boyle
authors.forename: Gabor
authors.initials: G
authors.lastname: Borgulya
authors.forename: Parameswaran M
authors.initials: PM
authors.lastname: Iyer
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Daniel
authors.initials: D
authors.lastname: Costello
authors.forename: Elijah
authors.initials: E
authors.lastname: Chaila
authors.forename: Mary
authors.initials: M
authors.lastname: Fitzsimons
authors.forename: Colin P
authors.initials: CP
authors.lastname: Doherty
authors.forename: Norman
authors.initials: N
authors.lastname: Delanty
authors.forename: Gianpiero L
authors.initials: GL
authors.lastname: Cavalleri
mesh_terms: D000328:Adult; D000679:Amygdala / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000473:pathology*; D004833:Epilepsy, Temporal Lobe / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D040582:Inheritance Patterns; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011699:Putamen / Q000473:pathology*; D035781:Siblings; D013788:Thalamus / Q000473:pathology*