Gray Matter Volumetric Abnormalities Associated with the Onset of Psychosis

Abstract

Patients with psychosis display structural brain abnormalities in multiple brain regions. The disorder is characterized by a putative prodromal period called ultra-high-risk (UHR) status, which precedes the onset of full-blown psychotic symptoms. Recent studies on psychosis have focused on this period. Neuroimaging studies of UHR individuals for psychosis have revealed that the structural brain changes observed during the established phases of the disorder are already evident prior to the onset of the illness. Moreover, certain brain regions show extremely dynamic changes during the transition to psychosis. These neurobiological features may be used as prognostic and predictive biomarkers for psychosis. With advances in neuroimaging techniques, neuroimaging studies focusing on gray matter abnormalities provide new insights into the pathophysiology of psychosis, as well as new treatment strategies. Some of these novel approaches involve antioxidants administration, because it is suggested that this treatment may delay the progression of UHR to a full-blown psychosis and prevent progressive structural changes. The present review includes an update on the most recent developments in early intervention strategies for psychosis and potential therapeutic treatments for schizophrenia. First, we provide the basic knowledge of the brain regions associated with structural abnormalities in individuals at UHR. Next, we discuss the feasibility on the use of magnetic resonance imaging (MRI)-biomarkers in clinical practice. Then, we describe potential etiopathological mechanisms underlying structural brain abnormalities in prodromal psychosis. Finally, we discuss the potentials and limitations related to neuroimaging studies in individuals at UHR.

Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia

“…Overall, studies of CHR individuals show brain structural alterations that are neuroanatomically similar to, but less severe than those commonly reported in established schizophrenia 68 . For example, compared to controls, CHR groups have shown both smaller GM volume and cortical thinning in PFC 69–76 , lateral temporal cortex 69, 72, 73, 75–80 (particularly superior temporal gyrus (STG)), and, to a lesser extent, parietal cortex 72, 81 .…”

Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis: Findings From the Longitudinal Youth at Risk Study: Table 1.

“…Only few whole-brain studies have examined brain structural changes in an ARMS sample of comparable size, particularly in Asian populations. 80 We found no evidence of regional GMV, WMV, or CT differences between ARMS and HC, ARMS-T and HC, or ARMS-T and ARMS-NT at baseline. The small number of ARMS transitioning to psychosis and the absence of longitudinal analysis of brain changes over-time are clear limitations, especially in light of recent findings suggesting progressive structural changes in ARMS despite the absence of baseline differences with HC.…”

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis

“…This assumption is based also on studies of subjects at CHR that report similar but more attenuated findings compared to those reported for schizophrenia, including cognitive impairments, [26][27][28] structural, [29][30][31][32] and functional alterations. 33,34 Moreover, characterizing those at the prepsychotic phase of illness, who evince potential prodromal symptoms, is critical for establishing biomarkers that can be used to follow the effects of treatment or to identify subjects who are at higher risk for developing the illness.…”