Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: a longitudinal study

Abstract

There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization.

Keywords: childhood onset schizophrenia; shape analysis; striatal morphology; striatum; unaffected siblings.

Figure 1

Striatal volumes over the developmental trajectory for COS, COSSIBs, and NV. Note that all three groups start with the same absolute volumes at the beginning of the developmental trajectory, but the COS group volume through the course of maturation. Shaded areas indicate 95% confidence intervals.

Figure 2

Shape differences estimated as significant outward or inward displacements along the surface representation. In all image orientations are given for anterior, posterior, left, and right as A, P, L, and R, respectively. All outwards displacements are shown in hot colors (red) and all inward displacements are represented in cool colors (blue). Significant outward displacement in overlapping regions for both (A) the COS and (B) COSSIBs (relative to NVs) were observed in the ventral medial portion of the striatum. Striata are oriented such that the view is ventral and the posterior portion of the striata are exiting the page. A shape difference in the COS subjects relative to the NVs was also observed in (C) the body of the caudate. Significant inward displacements were also estimated along the entire ventral anterior portion of the striatum in both (D) the COS and (E) COSSIBs.

Figure 3

(A) Age‐centered analysis for outward facing displacement along the surface. In the COS group, outward facing displacements are seen all along the ventral‐medial‐posterior aspect of the head of the striatum. This shape difference relative to the NV group is most severe until about age 18 and then begins to dissipate. The COSSIBs demonstrate a similar shape difference relative to NVs, but normalize in the early 20 s. (B) Age‐centered analysis for inward facing displacement along the surface. In the COS group, outward facing displacements are seen all along the ventral‐medial‐anterior aspect of the head the striatum. This shape difference relative to the NV group is most severe until about age 18 and then begins to dissipate. The COSSIBs demonstrate a similar shape difference that normalizes toward age 18.