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.
Highlights
Schizophrenia is posited to be a neurodevelopmental disorder, in which genetic and environmental factors interplay (1)
Defined as ultra high risk or individuals meeting an at risk mental state, are referred to as
Only 5 studies examined whether brain development differs in those who transition to psychosis and those who do not (Table 4), and all found greater reductions in white matter volume or Fractional anisotropy (FA) in the former group, principally in the corpus callosum (3 studies) and in white matter regions near the superior fronto-occipital fasciculus (SFOF) (2 studies)
Summary
Schizophrenia is posited to be a neurodevelopmental disorder, in which genetic and environmental factors interplay (1). A better understanding of the neurobiological changes that occur prior to the onset of disorder could identify new treatment targets to prevent transition to schizophrenia. With this aim, numerous studies have reported cross-sectional differences in brain structure. Longitudinal MRI in High-Risk Psychosis predict who will transition (3). A large multisite study found less parahippocampal gray matter volume in those who later developed psychosis (13). Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. Longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset
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