Longitudinal Structural MRI Findings in Individuals at Genetic and Clinical High Risk for Psychosis: A Systematic Review

Abstract

Background: Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. However, longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset.Methods: We conducted a systematic review to determine if brain trajectories differ between (i) those with psychotic experiences (PE), genetic (GHR) or clinical high risk (CHR), compared to healthy volunteers, and (ii) those who transition to psychosis compared to those who do not.Results: Thirty-eight studies measured gray matter and 18 studies measured white matter in 2,473 high risk subjects and 990 healthy volunteers. GHR, CHR, and PE subjects show an accelerated decline in gray matter primarily in temporal, and also frontal, cingulate and parietal cortex. In those who remain symptomatic or transition to psychosis, gray matter loss is more pronounced in these brain regions. White matter volume and fractional anisotropy, which typically increase until early adulthood, did not change or reduced in high risk subjects in the cingulum, thalamic radiation, cerebellum, retrolenticular part of internal capsule, and hippocampal–thalamic tracts. In those who transitioned, white matter volume and fractional anisotropy reduced over time in the inferior and superior fronto-occipital fasciculus, corpus callosum, anterior limb of the internal capsule, superior corona radiate, and calcarine cortex.Conclusion: High risk subjects show deficits in white matter maturation and an accelerated decline in gray matter. Gray matter loss is more pronounced in those who transition to psychosis, but may normalize by early adulthood in remitters.

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis via the ENIGMA Consortium

“…Similarly, lower FA in the PCR and corpus callosum (CC) has also been reported in clinical high-risk populations (39, 41, 42). In addition, differences in white matter of the SFO, PCR, and CC have been associated with the transition to psychosis (43). Similar to other major white matter tracts, FA within the SLF increases significantly during adolescence (44).…”

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity

“…In addition, there are reports of cerebellar abnormalities in idiopathic psychosis (107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118) and pathology in Purkinje cells, the output neurons of the cerebellar cortex, has been documented in schizophrenia (119)(120)(121). Further, altered functional or structural connectivity and morphology of the cerebellum has been identified in CHR groups (49,(122)(123)(124)(125)(126)(127)(128)(129)(130).…”

Multivariate Analysis and Modelling of multiple Brain endOphenotypes: Let’s MAMBO!

“…Much of the existing work in the field, as we previously described, analyzes neuroimaging data cross-sectionally, which does not provide information about changes in the structure and functionality of the brain over time. A better understanding of the longitudinal trajectories of brain endophenotypes would improve our knowledge of the underlying biological characterisation of complex neurological diseases [86] , [87] , [88] . For example, application of mixed-effect models to longitudinal brain imaging data has helped to identify a large number of significant genetic-multiphenotype associations [89] , [90] .…”