Article

Neuroimaging Findings in the At-Risk Mental State: A Review of Recent Literature.

Professor of Adolescent Brain Development and Mental Health, School of Psychology, University of Birmingham, Edgbaston, England
Canadian journal of psychiatry. Revue canadienne de psychiatrie (Impact Factor: 2.41). 01/2013; 58(1):13-18.
Source: PubMed

ABSTRACT The at-risk mental state (ARMS) has been the subject of much interest during the past 15 years. A great deal of effort has been expended to identify neuroimaging markers that can inform our understanding of the risk state and to help predict who will transition to frank psychotic illness. Recently, there has been an explosion of neuroimaging literature from people with an ARMS, which has meant that reviews and meta-analyses lack currency. Here we review papers published in the past 2 years, and contrast their findings with previous reports. While it is clear that people in the ARMS do show brain alterations when compared with healthy control subjects, there is an overall lack of consistency as to which of these alterations predict the development of psychosis. This problem arises because of variations in methodology (in patient recruitment, region of interest, method of analysis, and functional task employed), but there has also been too little effort put into replicating previous research. Nonetheless, there are areas of promise, notably that activation of the stress system and increased striatal dopamine synthesis seem to mark out patients in the ARMS most at risk for later transition. Future studies should focus on these areas, and on network-level analysis, incorporating graph theoretical approaches and intrinsic connectivity networks.

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    • "(2014), http://dx.doi.org/10.1016/j.schres.2014.10.041 high-risk subjects: while some have provided overviews on studies in genetic high-risk relatives (Palaniyappan et al., 2012), others have included studies with a broader spectrum of the high-risk paradigm, including individuals at risk for psychosis not only through affected relatives , but also through either psychometric or subclinical symptom profiles (Chan et al., 2011; Wood et al., 2013). There has been little research into the biological diversity of subgroups of people within at-risk mental state for the psychosis spectrum, i.e. testing the hypothesis that distinct brain structural changes characterize subgroups of at-risk populations depending on their risk profile. "
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    ABSTRACT: While schizophrenia and bipolar disorder have been assumed to share phenotypic and genotypic features, there is also evidence for overlapping brain structural correlates, although it is unclear whether these relate to shared psychotic features. In this study, we used voxel-based morphometry (VBM8) in 34 schizophrenia patients, 17 euthymic bipolar I disorder patients (with a history of psychotic symptoms), and 34 healthy controls. Our results indicate that compared to healthy controls schizophrenia patients show grey matter deficits (p<0.05, FDR corrected) in medial and right dorsolateral prefrontal, as well as bilaterally in ventrolateral prefrontal and insular cortical areas, thalamus (bilaterally), left superior temporal cortex, and minor medial parietal and parietooccipital areas. Comparing schizophrenia vs. bipolar I patients (p<0.05, FDR corrected) yielded a similar pattern, however, there was an additional significant reduction in schizophrenia patients in the (posterior) hippocampus bilaterally, left dorsolateral prefrontal cortex, and left cerebellum. Compared to healthy controls, the deficits in bipolar I patients only reached significance at p<0.001 (uncorr.) for a minor parietal cluster, but not for prefrontal areas. Our results suggest that the more extensive prefrontal, thalamic, and hippocampal deficits that might set apart schizophrenia and bipolar disorder might not be related to mere appearance of psychotic symptoms at some stage of the disorders. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 04/2015; 165(2-3). DOI:10.1016/j.schres.2015.04.007 · 4.43 Impact Factor
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    • "(2014), http://dx.doi.org/10.1016/j.schres.2014.10.041 high-risk subjects: while some have provided overviews on studies in genetic high-risk relatives (Palaniyappan et al., 2012), others have included studies with a broader spectrum of the high-risk paradigm, including individuals at risk for psychosis not only through affected relatives , but also through either psychometric or subclinical symptom profiles (Chan et al., 2011; Wood et al., 2013). There has been little research into the biological diversity of subgroups of people within at-risk mental state for the psychosis spectrum, i.e. testing the hypothesis that distinct brain structural changes characterize subgroups of at-risk populations depending on their risk profile. "
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    ABSTRACT: Early intervention research in schizophrenia has suggested that brain structural alterations might be present in subjects at high risk of developing psychosis. The heterogeneity of regional effects of these changes, which is established in schizophrenia, however, has not been explored in prodromal or high-risk populations. We used high-resolution MRI and voxel-based morphometry (VBM8) to analyze grey matter differences in 43 ultra high-risk subjects for psychosis (meeting ARMS criteria, identified through CAARMS interviews), 24 antipsychotic-naïve first-episode schizophrenia patients and 49 healthy controls (groups matched for age and gender). Compared to healthy controls, resp., first-episode schizophrenia patients had reduced regional grey matter in left prefrontal, insula, right parietal and left temporal cortices, while the high-risk group showed reductions in right middle temporal and left anterior frontal cortices. When dividing the ultra-high-risk group in those with a genetic risk vs. those with attenuated psychotic symptoms, the former showed left anterior frontal, right caudate, as well as a smaller right hippocampus, and amygdala reduction, while the latter subgroup showed right middle temporal cortical reductions (each compared to healthy controls). Our findings in a clinical psychosis high-risk cohort demonstrate variability of brain structural changes according to subgroup and background of elevated risk, suggesting frontal and possibly also hippocampal/amygdala changes in individuals with genetic susceptibility. Heterogeneity of structural brain changes (as seen in schizophrenia) appears evident even at high-risk stage, prior to potential onset of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.10.041 · 4.43 Impact Factor
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    • "Cognitive deficits, a core feature of schizophrenia, are more prevalent in UHR individuals compared to healthy controls and are associated with a higher risk of transition to psychotic disorders (Bora et al., 2014). Neuroimaging studies have identified that people who are UHR for psychosis show some brain alterations in comparison to healthy controls, but there is a lack of consistent findings as to which of these alterations is associated with transition to psychosis (Wood et al., 2013). "
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    ABSTRACT: Objective: Despite social environmental factors such as deprivation, urbanicity, migration and adversity being established risk factors for psychotic disorders, there is a paucity of knowledge on the influence of social environ-mental risk factors in the UHR population. Firstly, we aimed to investigate the association between social depri-vation and risk of transition and secondly, we aimed to investigate the association between migration status and the risk of transition. Method: UHR individuals at the Personal Assessment and Crisis Evaluation (PACE) service in Melbourne were in-cluded. Social deprivation as assessed according to postal code area of residence was obtained from census data and Cox regression analysis was used to calculate hazard ratios. Results: A total of 219 UHR individuals were included and over the median follow-up time of 4.8 years, 32 indi-viduals (14.6%) were known to have transitioned to a psychotic disorder. 8.8% of UHR individuals were first gen-eration migrants and 41.9% were second generation migrants. The level of social deprivation was not associated with the risk of transition (p = 0.83). Similarly, first or second generation migrants did not have an increased risk of transition to psychosis (p = 0.84). Conclusions: Despite being established risk factors for psychotic disorders, social deprivation and migrant status have not been found to increase the risk of transition in a UHR population.
    Schizophrenia Research 11/2014; 161(2-3). DOI:10.1016/j.schres.2014.10.050 · 4.43 Impact Factor
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