Diffusion tensor imaging (DTI) provides anatomical connectivity information by examining the directional organization of white matter microstructure. Anatomical connectivity and its abnormalities may be heritable traits associated with schizophrenia. To further examine this hypothesis, two studies were conducted to compare anatomical connectivity between (a) monozygotic (MZ) twin pairs and random pairings among twins and (b) first-degree relatives of schizophrenia patients and a healthy control group. Analyses focused on frontal regions of the brain following previous findings of anatomical connectivity abnormalities associated with schizophrenia. For Study 1, eighteen MZ twin pairs (11 female pairs, age: M = 25.44, SD = 5.69) were recruited. For Study 2, twenty-two first-degree relatives of schizophrenia patients (14 females, age: M = 48.50, SD = 8.22), and 30 healthy controls (12 females, age: M = 43.83, SD = 11.39) were recruited. Fractional anisotropy (FA), a white matter directional organization metric, was measured with DTI. In Study 1, FA values were more strongly correlated between MZ twin pairs than between randomly generated pairs in genu of corpus callosum, anterior cingulum and forceps minor. In Study 2, relatives of schizophrenia patients showed reduced FA values in medial frontal white matter (p < 0.05, corrected). The present study suggested that anatomical connectivity in medial prefrontal cortex appeared significantly heritable within MZ twin pairs, an important criterion in the development of an endophenotype. In addition, altered medial frontal white matter integrity found in non-affected relatives of schizophrenia patients seems to suggest that reduced white matter integrity in medial frontal regions of the brain might be associated with the genetic liability to schizophrenia.
Keywords: diffusion tensor imaging; endophenotype; fractional anisotropy; medial frontal; monozygotic twin pairs; schizophrenia relatives; white matter.
Structural Brain Connectivity as a Genetic Marker for Schizophrenia.JAMA Psychiatry. 2016 Jan;73(1):11-9. doi: 10.1001/jamapsychiatry.2015.1925. JAMA Psychiatry. 2016. PMID: 26606729
Tract-specific analysis of white matter integrity disruption in schizophrenia.Psychiatry Res. 2012 Feb 28;201(2):136-43. doi: 10.1016/j.pscychresns.2011.07.010. Epub 2012 Mar 6. Psychiatry Res. 2012. PMID: 22398298
Impaired empathic abilities and reduced white matter integrity in schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:117-23. doi: 10.1016/j.pnpbp.2013.09.018. Epub 2013 Oct 5. Prog Neuropsychopharmacol Biol Psychiatry. 2014. PMID: 24099786
Diffusion tensor imaging in first degree relatives of schizophrenia and bipolar disorder patients.Schizophr Res. 2015 Feb;161(2-3):329-39. doi: 10.1016/j.schres.2014.12.008. Epub 2014 Dec 24. Schizophr Res. 2015. PMID: 25542860 Free PMC article. Review.
Diffusion tensor imaging in schizophrenia.Biol Psychiatry. 2005 Dec 15;58(12):921-9. doi: 10.1016/j.biopsych.2005.05.015. Epub 2005 Jul 25. Biol Psychiatry. 2005. PMID: 16043134 Review.
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