Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings

Abstract

Deficits in the volume of the thalamus have been observed in both individuals with schizophrenia and their nonpsychotic relatives. However, no studies to date have examined the underlying pattern of thalamic shape change in relatives of individuals with schizophrenia. This study examined the volume and shape of the thalamus in schizophrenia subjects, their siblings, and healthy control individuals. T1-weighted magnetic resonance scans were collected in a group of young subjects with schizophrenia (mean age, 23 years) and their nonpsychotic siblings (n ϭ 25 pairs), and control subjects and their siblings (n ϭ 40 pairs). Thalamic surfaces were generated using high-dimensional brain mapping. A canonical weighting function was derived from the contrast between schizophrenia and control subjects and then used to generate a canonical shape score for all subjects. Maps of the estimated surface displacement between groups were also created to visualize the thalamic shape differences between groups. The thalamic canonical scores of the siblings of the schizophrenia probands were intermediate between the probands and healthy control subjects. These siblings also displayed an intermediate degree of the inward surface deformation of the anterior and posterior thalamus that was present between schizophrenia probands and controls. There was no main effect of group status on thalamic volume and no significant correlations of the structural measures with measures of psychopathology or cognitive function. Our results indicate that thalamic shape abnormalities are present in relatively young individuals with schizophrenia and their siblings. Inward deformation of the anterior and posterior regions of the thalamus represents a potential neuroanatomical endophenotype of schizophrenia.

Basal Ganglia Shape Abnormalities in the Unaffected Siblings of Schizophrenia Patients

“…The canonical analysis was designed to score the SCZ-SIB and CON-SIB along the dimension that "maximized" the difference between SCZ and CON. Thus, the canonical weighting coefficients were obtained from the contrast between SCZ and CON (33). A canonical score was obtained for each structure and subject by applying these weighting coefficients to the original dependent variables (i.e.…”

“…From an initial group of 216 potential subjects that fit inclusion criteria (see below), the final group of study subjects were selected from those who had an MR scan of acceptable quality and whose sibling also completed MR scanning. This cohort of subjects was the same as that used in our previous report on the thalamus (33).…”

“…We have previously used large-deformation high-dimensional brain mapping (HDBM-LD) (30,31), to characterize shape deformities of the hippocampus (32) and thalamus (33) in unaffected siblings of schizophrenia subjects. Shape analysis has been shown to be complementary to volumetry in discriminating between normal and neuropsychiatric conditions (34,35).…”

Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis

“…However, at the subcortical level, it was not until the advent of shape analysis techniques (e.g., Patenaude et al 2011) that successfully estimating regional shape variations in subcortical structures with high anatomical precision was possible. This approach has been mainly applied to unveil abnormal subcortical morphology in mental disorders or disease (Coscia et al 2009;Harms et al 2007;Kang et al 2008;McKeown et al 2008;Qiu et al 2008;Xu et al 2008) but recently also to understand the role of subcortical shape in high-order cognition in healthy populations (Burgaleta et al 2013b). …”

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

“…Abnormalities in the medio-dorsal, pulvinar, and centromedian nuclei of the thalamus, all connected to the lateral prefrontal cortex (LPFC), a site of well-documented abnormalities in schizophrenia (Weinberger et al, 2001), have been reported with several methods (eg, Andrews et al, 2006;Byne et al, 2002;Byne et al, 2007;Harms et al, 2007;Hazlett et al, 1999;Kemether et al, 2003;Kessler et al, 2009;Kumari et al, 2010;Lehrer et al, 2005;Popken et al, 2000;Rose et al, 2006, but see, for example, Danos et al, 2005;Dorph-Petersen et al, 2004;Kreczmanski et al, 2007 for negative findings). Some functional MRI (fMRI) studies found abnormalities in the correlation between the activity in the thalamus and the PFC in schizophrenia (eg, Meda et al, 2010;Schlosser et al, 2003;Welsh et al, 2010;Zhou et al, 2007), which may reflect alterations in anatomical connectivity.…”