No evidence for structural brain changes in young adolescents at ultra high risk for psychosis

https://doi.org/10.1016/j.schres.2009.04.013Get rights and content

Abstract

Objective

The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing of these changes has not been established. We investigated structural brain changes in a sample of young adolescents (12–18 years) at ultra high-risk for psychosis (UHR).

Methods

Structural MRI data from young UHR subjects (n = 54) and typically developing, matched controls (n = 54) were acquired with a 1.5 Tesla scanner and compared.

Results

None of the measures differed between UHR subjects and controls.

Conclusions

Our results do not support the presence of gross neuroanatomical changes in young UHR subjects. This suggests that early changes are too subtle to detect with conventional imaging techniques. Therefore, changes observed in older cohorts may only onset later developmentally or occur secondary to prodromal symptoms.

Introduction

A growing body of evidence suggests early neurodevelopmental brain changes preceding psychosis that are thought to progress into adolescence and adulthood (Rapoport et al., 2005). Recently, neuroimaging studies have focused on genetic and clinical high-risk cohorts to define the nature of these changes and to identify which of these may mark vulnerability for psychosis (Cannon, 2005). Subjects of clinical high-risk cohorts are commonly referred to as being at “ultra high-risk” (UHR), at “prodromal high-risk” or having an “at risk mental state” (ARMS) for psychosis. Several research groups have reported premorbid structural and functional brain changes in these cohorts. However, the timing of these changes is not established (for reviews see Pantelis et al., 2005, Wood et al., 2008): It is unclear whether they are truly premorbid or rather associated with prodromal symptoms.

A large volumetric MRI study in a UHR population aged 20 years reported smaller whole brain volume for subjects at UHR for psychosis compared to controls (Velakoulis et al., 2006), while several voxelbased morphometry (VBM) studies have shown changes in both gray (GM; Borgwardt et al., 2007, Borgwardt et al., 2008, Meisenzahl et al., 2008, Pantelis et al., 2003) and white matter (WM; Walterfang et al., 2008, Witthaus et al., 2008) clusters in young adults (20–25 years) at UHR, predominantly in (pre-)frontal and temporal lobe areas. Interestingly, longitudinal reports suggest a differential development of changes in brain structure for individuals who convert to psychosis compared to those who do not (Pantelis et al., 2003, Walterfang et al., 2008). Reports to date of brain changes in subjects at UHR have focused on the age range of 20–25 years, when psychosis typically first occurs (Kessler et al., 2007). However, on average the earliest prodromal signs occur 4.8 years before onset (Hafner and Maurer, 2006). If neurobiological changes precede psychotic breakdown, these should be present in the at-risk period irrespective of the age at which psychotic breakdown occurs. To test whether this is indeed the case, we investigated brain structure volumes in a well-defined sample of young adolescents at UHR for psychosis (aged 12–18 years). We hypothesized that the UHR group would have smaller total brain volume and less GM and WM density in (pre-) frontal and medial temporal lobe areas.

Section snippets

Subjects

Fifty-four adolescents (52 Caucasian, 2 Asian) meeting at least 1 of 4 criteria for UHR were referred by general practitioners or other psychiatric clinics and included in this study. A further 54 matched typically developing adolescents (52 Caucasian, 1 Asian, 1 Hispanic) were included. There was also a subgroup of nineteen (35%) UHR patients that met criteria for pervasive developmental disorder – not otherwise specified (PDD-NOS; American Psychiatric Association, 1994). While these subjects

Sociodemographic and clinical parameters

Subjects were matched for age, gender, handedness, height and parental education (Table 2). Controls had significantly higher Total IQ (TIQ) scores than the UHR group (t =  2.56, df = 106, p < .012). Clinical parameters differed between both groups (p < .001), with the UHR-group reporting more symptoms and lower GAF-scores (Table 2). Fifty-one of 54 UHR subjects completed the eighteen months follow-up period at which transition to psychosis was determined. Two subjects had dropped out, as they felt

Discussion

The aim of the current study was to investigate whether structural brain changes are present in young adolescents at clinical high risk for psychosis. In our young UHR sample of adolescents aged 12–18 years, we find no evidence for gross or regional brain changes. Furthermore, we find no correlations between brain volumes and clinical symptoms.

These results suggest that the brain changes reported in older UHR populations (Borgwardt et al., 2007, Borgwardt et al., 2008, Meisenzahl et al., 2008,

Role of funding source

This work was funded by a grant from ZonMw – the Netherlands organisation for health research and development. ZonMW had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Contributors

Drs. Durston, van Engeland, Schothorst, and Mr. Ziermans conceived the idea and methodology of this study. Drs. Durston, Lahuis, Schothorst, Sprong and Mr. Ziermans were involved in subject recruitment. Drs. Lahuis, Schothorst, Sprong, van Engeland and Mr. Ziermans were involved in clinical and diagnostic assessments. Mr. Ziermans processed MRI images and wrote the manuscript. Dr. Durston and Mr. Ziermans conducted the statistical analyses. Drs. van Haren and Schnack and Ms. Nederveen provided

Conflict of interest

The authors have no competing financial interests to declare in relation to the current work.

Acknowledgements

The authors would like to thank Anneke J. Schouten and Petra W. Klaassen who assisted with collecting the data for our analysis.

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