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.

Hippocampal alterations and functional correlates in adolescents and young adults with congenital heart disease

“…Our findings further suggest that volumetric measures alone may not be sufficient to detect changes in brain structures (M. M. Chakravarty et al, 2015). Shape analyses have the potential to explain structural differences such as bending, flattening or local differences which may provide biologically meaningful information about the development of the hippocampus (M. M. Chakravarty et al, 2015).…”

“…The few studies which have explored the hippocampal integrity in CHD have specifically focused on volumetric measurement and have reported nonspecific volume reduction associated with total intelligence quotient (IQ), working memory, and verbal comprehension Munoz-Lopez et al, 2017;von Rhein et al, 2014). Shape analysis has the potential to further identify structural differences that cannot be captured by gross volume measurement and has been shown to be an index that is sensitive to neurodevelopmental abnormalities (Achterberg et al, 2014;M. Shape analysis has the potential to further identify structural differences that cannot be captured by gross volume measurement and has been shown to be an index that is sensitive to neurodevelopmental abnormalities (Achterberg et al, 2014;M.…”

TSPO expression and brain structure in the psychosis spectrum

“…Hippocampal surface displacement was used as a metric for measuring shape, and was assessed as previously described 49, 50 . Briefly, this is estimated by calculating the dot product between the average nonlinear deformation vector derived from the average atlas-to-subject transformation, and the surface normal.…”

Dynamic endophenotypes and longitudinal trajectories: capturing changing aspects of development in early psychosis

“…29 Longitudinal designs can thus improve statistical power for detecting group differences in neuroanatomical trajectories, allowing for the investigation of novel endo phenotypes. For example, shape metrics are heritable and may have alterations specific to schizophrenia.…”