Brain morphologic changes in early stages of psychosis: Implications for clinical application and early intervention

Abstract

To date, a large number of magnetic resonance imaging (MRI) studies have been conducted in schizophrenia, which generally demonstrate gray matter reduction, predominantly in the frontal and temporo-limbic regions, as well as gross brain abnormalities (e.g., a deviated sulcogyral pattern). Although the causes as well as timing and course of these findings remain elusive, these morphologic changes (especially gross brain abnormalities and medial temporal lobe atrophy) are likely present at illness onset, possibly reflecting early neurodevelopmental abnormalities. In addition, longitudinal MRI studies suggest that patients with schizophrenia and related psychoses also have progressive gray matter reduction during the transition period from prodrome to overt psychosis, as well as initial periods after psychosis onset, while such changes may become almost stable in the chronic stage. These active brain changes during the early phases seem to be relevant to the development of clinical symptoms in a region-specific manner (e.g., superior temporal gyrus atrophy and positive psychotic symptoms), but may be at least partly ameliorated by antipsychotic medication. Recently, increasing evidence from MRI findings in individuals at risk for developing psychosis has suggested that those who subsequently develop psychosis have baseline brain changes, which could be at least partly predictive of later transition into psychosis. In this article, we selectively review previous MRI findings during the course of psychosis and also refer to the possible clinical applicability of these neuroimaging research findings, especially in the diagnosis of schizophrenia and early intervention for psychosis.

Pituitary Volume and Socio-Cognitive Functions in Individuals at Risk of Psychosis and Patients With Schizophrenia

“…Our pituitary findings are generally in line with previous MRI studies in clinical high-risk subjects; the individuals who later develop psychosis may exhibit pituitary expansion prior to psychosis onset ( 10 , 40 ), but those without psychosis onset also have similar pituitary changes ( 10 , 11 ). Although some high-risk studies did not replicate these findings ( 7 , 47 ), probably due to small sample sizes and/or differences in various influencing factors as described below, pituitary expansion reported in psychosis is thought to reflect HPA hyperactivity and a subsequent increase in the size and number of corticotrophs, whereas chronic HPA activation could cause pituitary atrophy by reducing the function of the cells producing other pituitary hormones ( 15 , 48 ). Thus, the pituitary volume in the course of psychosis likely reflects state-related HPA axis dysregulation, which is associated with illness stages and symptom severity ( 15 ), antipsychotic medication ( 2 , 49 ), demographic characteristics [e.g., age, gender ( 50 , 51 )], and other mediating factors.…”

“…Neuroendocrine studies in schizophrenia ( 1 , 2 ) and clinical high-risk subjects for developing psychosis [i.e., at-risk mental state; ARMS ( 3 , 4 )] ( 5 – 7 ) have reported hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response by governing the release of steroids (e.g., cortisol) and also regulates a number of physiological and neurobehavioral processes (e.g., immunity, fertility, anxiety, and cognitive functioning) ( 8 , 9 ), implying the role of hormonal dysregulation during the course of psychosis. Previous magnetic resonance imaging (MRI) studies in schizophrenia and related psychoses have generally reported enlarged volume of the pituitary gland, an integral part of the HPA axis, prior to psychosis onset ( 10 , 11 ), along with ongoing expansion early in the course of schizophrenia ( 12 , 13 ), which was associated with the emergence of psychosis and the early course of clinical symptoms ( 14 , 15 ). However, some discrepant findings, such as an even smaller pituitary volume in antipsychotic-naïve schizophrenia patients with recent onset ( 16 ) or normal pituitary volume both in patients with first-episode schizophrenia and individuals with ARMS ( 7 ), have also been reported.…”

What neuroscience has already done for us

“…5 It seems increasingly likely that there are differences in volume even before the at-risk mental state, although this remains difficult to prove definitively. [6][7][8] Recently developed scientific techniques such as the use of induced pluripotent stem cells to create a 'cortex in a dish' (aka brain organoids) have allowed tantalising insights into why these imaging abnormalities may emerge. Using cells from individuals with schizophrenia (some with a range of predisposing genetic abnormalities) multiple studies have shown abnormalities such as impaired cellular differentiation and synapse formation.…”

“…2 The prevalence of informal caring in the underage population was estimated as a minimum of 2-4% in Western countries. 6 Dearden and Becker reported that most young carers cared for parents, particularly mothers, although some provided support for grandparents, siblings or other relatives.…”

Unraveling Diagnostic Biomarkers of Schizophrenia Through Structure-Revealing Fusion of Multi-Modal Neuroimaging Data

“…With the advances in technology, vast amounts of neuroimaging data has been generated; however, data mining or signal processing methods so far have limited success in terms of finding reliable diagnostic imaging biomarkers for many psychiatric disorders [4,8]. One of the reasons for this limited success has been the fact that data fusion is a particularly challenging task when the goal is to extract reproducible and interpretable patterns.…”