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Background: While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need. Methods: Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence. Results: Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age. Conclusions: We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis. [ABSTRACT FROM AUTHOR]

Disrupted auditory networks play an important role in the pathophysiology of psychosis, with abnormalities already observed in individuals at clinical high-risk for psychosis (CHR). Here, we examine structural and functional connectivity of an auditory network in CHR utilising state-of-the-art electroencephalography and diffusion imaging techniques. Twenty-six CHR subjects and 13 healthy controls (HC) underwent diffusion MRI and electroencephalography while performing an auditory task. We investigated structural connectivity, measured as fractional anisotropy in the Arcuate Fasciculus (AF), Cingulum Bundle, and Superior Longitudinal Fasciculus-II. Gamma-band lagged-phase synchronisation, a functional connectivity measure, was calculated between cortical regions connected by these tracts. CHR subjects showed significantly higher structural connectivity in the right AF than HC (p <.001). Although non-significant, functional connectivity between cortical areas connected by the AF was lower in CHR than HC (p =.078). Structural and functional connectivity were correlated in HC (p =.056) but not in CHR (p =.29). We observe significant differences in structural connectivity of the AF, without a concomitant significant change in functional connectivity in CHR subjects. This may suggest that the CHR state is characterised by a decoupling of structural and functional connectivity, possibly due to abnormal white matter maturation. [ABSTRACT FROM AUTHOR]

It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP). Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed. There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP. Our study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals. [ABSTRACT FROM AUTHOR]

Background Altered gamma-band connectivity has been shown across all stages of schizophrenia (SZ) and for persons at High Risk for Psychosis (HRP). Oscillations in the gamma-band frequency range are suggested to play a crucial role for both local and long-range synchronization within the brain during perceptual and cognitive processes. Structural connectivity in the brain is provided by white matter (WM) tracts connecting these areas. Reduced WM integrity is also a feature of SZ that has often been described. The aim of this study is to investigate the relationship between altered gamma-band connectivity and WM structural connectivity in Clinical High Risk for Psychosis (HRP) patients using Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) to achieve a better understanding of which factors could predict a transition to SZ considering functional and structural connectivity. The identification of those biomarkers would be a further step toward understanding the causes of SZ and could contribute to a more individualized and targeted therapy to achieve a better outcome in patients. Methods The study includes a total of 26 HRP patients, 7 converted to schizophrenia after one year (HRP-C) and 13 healthy controls (HC). High density EEG (64 channels) was recorded during the performance of a cognitively demanding auditory choice reaction task. Source estimation and analysis of the functional gamma-band connectivity was done using eLORETA. We defined Regions of Interest (ROIs) that were known to be generators of the auditory evoked Gamma-Band Response (aeGBR) from a previous combined EEG-fMRI study of this population – the dorsal anterior cingulate cortex (dACC) and the bilateral auditory cortices. MRI data acquisition was done with a 3T Siemens scanner (Trio). We generated whole-brain 2-Tensor-Tractography for all subjects in order to analyze the integrity of the underlying WM fiber bundles implicated in this functional network, namely the Cingulum Bundle (CB), the Medial Longitudinal Fasciculus (MdLF), the Arcuate Fasciculus (AF) and the Extreme Capsule (EC).The primary outcome measure is the fractional anisotropy of the tissue (FAt), which is corrected for free water (FW) in the brain. Results Our preliminary results show a lower aeGBR in HRP-C patients compared to HC with the HRP-NC at an intermediate level. We found longer reaction times for HRP compared to HC. The study is presently on-going. Based on previous work in this sample, we hypothesize that the CB, MdLF, AF and EC of the HRP-C will exhibit decreased FAt and increased FW compared to HC. Discussion The combination of EEG with its high temporal resolution and DTI with its high spatial resolution allows for detailed insight into the possible disturbances in HRP patients compared to HC. Alterations in both modalities have been shown before, however, in this study we aim to link functional connectivity alterations in the previously described networks to their structural correlate to achieve a better insight into their interaction. Taken together, the quantification of those possible biomarkers might help to detect a transition to SZ earlier and thus allow an early intervention. [ABSTRACT FROM AUTHOR]