Alterations in brain structures underlying language function in young adults at high familial risk for schizophrenia.
BACKGROUND
Neuroanatomical and cognitive alterations typical of schizophrenia (SZ) patients are observed to a lesser extent in their adolescent and adult first-degree relatives, likely reflecting neurodevelopmental abnormalities associated with genetic risk for the illness. The anatomical pathways for language are hypothesized to be abnormal and to underlie the positive symptoms of schizophrenia. Examining non-psychotic relatives at high familial risk (FHR) for schizophrenia may clarify if these deficits represent trait markers associated with genetic vulnerability, rather than specific markers resulting from the pathological process underlying schizophrenia.


METHODS
T1 MRI scans from a 3T Siemens scanner of young adult FHR subjects (N=46) and controls with no family history of illness (i.e. at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. We explored volumetric and lateralization alterations in regions associated with language processing. An extensive neuropsychological battery of language measures was administered.


RESULTS
No significant differences were observed between groups on any language measures. Controlling intracranial volume, significantly smaller left pars triangularis (PT) (p<0.01) and right pars orbitalis (PO) (p<0.01) volumes and reversal of the L>R pars orbitalis (p<0.001) lateralization were observed in FHR subjects. In addition, the L pars triangularis and R pars orbitalis correlated with performance on tests of linguistic function in the FHR group.


CONCLUSIONS
Reduced volume and reversed structural asymmetry in language-related regions hypothesized to be altered in SZ are also found in first degree relatives at FHR, despite normal language performance. To clarify if these findings are endophenotypes for Sz, future studies would need to be performed of ill and well family members no longer within the age range of risk for illness to show these deficits segregate with schizophrenia within families. Moreover, measures of complex language need to be studied to determine if FHR individuals manifest impairments in some aspects of language function.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Alan N
AN
Francis
Larry J
LJ
Seidman
Gul A
GA
Jabbar
Raquelle
R
Mesholam-Gately
Heidi W
HW
Thermenos
Richard
R
Juelich
Ashley C
AC
Proal
Martha
M
Shenton
Marek
M
Kubicki
Ian
I
Mathew
Matcheri
M
Keshavan
Lynn E
LE
Delisi
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005192:Family Health; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007806:Language Disorders / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult