Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

Schmidt, André; Lenz, Claudia; Smieskova, Renata; Harrisberger, Fabienne; Walter, Anna; Riecher-Rössler, Anita; Simon, Andor E.; Lang, Undine E.; McGuire, Philip; Fusar‐Poli, Paolo; Borgwardt, Stefan

doi:10.1159/000442605

Cited by 31 publications

(31 citation statements)

References 48 publications

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“…One possible explanation of these findings is that the association is not present in the early stages of the disease. This is also reflected by the fact that white matter volume alterations are known to be present in schizophrenia and bipolar disorder patients and also the first-episode state [11,13,[38][39][40] and less pronounced in ARMS [41]. Therefore, it might be speculated that white matter volume alterations occur only later in the development of the disorder, and are not detectable in this pooled patient cohort.…”

Section: Discussionmentioning

confidence: 89%

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Harrisberger

Smieskova

Egli

et al. 2018

Cell Physiol Biochem

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Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T₁-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 – 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 – 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.

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Section: Discussionmentioning

confidence: 89%

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Harrisberger

Smieskova

Egli

et al. 2018

Cell Physiol Biochem

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“…DTI studies of ARMS subjects have found reduced FA in frontal regions, the anterior limb of the internal capsule, the posterior cingulate and the angular gyrus (Hoptman et al 2008; Karlsgodt et al 2009; Peters et al 2009; von Hohenberg et al 2014). Increased FA has also been reported in the ACC and the right middle and superior frontal gyri (Hoptman et al 2008) as well as in the superior longitudinal fasciculus (Schmidt et al 2015). Although these inconsistent findings may reflect true heterogeneity in ARMS patients, they may also be attributed to the small sample sizes used in the aforementioned studies.…”

Section: Introductionmentioning

confidence: 88%

Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study

Wang

Hong

et al. 2016

Psychol. Med.

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BackgroundSalience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.MethodWe examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.ResultsARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.ConclusionsOur findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.

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“…Unfortunately, there are few and inconsistent findings regarding diffusivity indices as a complement to FA [ 66 , 73 , 74 ]. Similarly, few studies have investigated the association of white matter changes in CHR with later transition to psychosis, and their findings are heterogeneous.…”

Section: Structural Neuroimagingmentioning

confidence: 99%

Structural and functional imaging markers for susceptibility to psychosis

Andreou

Borgwardt

2020

Mol Psychiatry

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The introduction of clinical criteria for the operationalization of psychosis high risk provided a basis for early detection and treatment of vulnerable individuals. However, about two-thirds of people meeting clinical high-risk (CHR) criteria will never develop a psychotic disorder. In the effort to increase prognostic precision, structural and functional neuroimaging have received growing attention as a potentially useful resource in the prediction of psychotic transition in CHR patients. The present review summarizes current research on neuroimaging biomarkers in the CHR state, with a particular focus on their prognostic utility and limitations. Large, multimodal/multicenter studies are warranted to address issues important for clinical applicability such as generalizability and replicability, standardization of clinical definitions and neuroimaging methods, and consideration of contextual factors (e.g., age, comorbidity).

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Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

Cited by 31 publications

References 48 publications

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study

Structural and functional imaging markers for susceptibility to psychosis

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