Pre-attentive and Attentive Auditory Event-related Potentials in Children With Attention-Deficit Hyperactivity Disorder and Autism.

Abnormalities in auditory processing are believed to play a major role in autism and attention-deficit hyperactivity disorder (ADHD). Both conditions often co-occur in children, causing difficulties in deciding the most promising intervention. Event-related potentials (ERPs) have been investigated and are showing promise to act as potential biomarkers for both conditions. This study investigated mismatch negativity (MMN) using a passive listening task and P3b in an active auditory go/no-go discrimination task. Recordings were available from 103 children (24 females): 35 with ADHD, 27 autistic, 15 autistic children with co-occurring ADHD, and 26 neurotypical (NT) children. The age range considered was between 4 and 17 years, but varied between groups. The results revealed increases in the MMN and P3b amplitudes with age. Older children with ADHD exhibited smaller P3b amplitudes, while younger autistic children showed reduced MMN amplitudes in response to phoneme changes compared to their NT counterparts. Notably, children diagnosed with autism and ADHD did not follow this pattern; instead, they exhibited more similarities to NT children. The reduced amplitudes of phonetically elicited MMN in children with autism and reduced P3b in children with ADHD suggest that the two respective ERPs can act as potential biomarkers for each condition. However, optimisation and standardisation of the testing protocol, as well as longitudinal studies are required in order to translate these findings into clinical practice.

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Fronto-temporal cortical grey matter thickness and surface area in the at-risk mental state and recent-onset schizophrenia: a magnetic resonance imaging study.

BACKGROUND: Studies to date examining cortical thickness and surface area in young individuals At Risk Mental State (ARMS) of developing psychosis have revealed inconsistent findings, either reporting increased, decreased or no differences compared to mentally healthy individuals. The inconsistencies may be attributed to small sample sizes, varying age ranges, different ARMS identification criteria, lack of control for recreational substance use and antipsychotic pharmacotherapy, as well as different methods for deriving morphological brain measures. METHODS: A surfaced-based approach was employed to calculate fronto-temporal cortical grey matter thickness and surface area derived from magnetic resonance imaging (MRI) data collected from 44 young antipsychotic-naïve ARMS individuals, 19 young people with recent onset schizophrenia, and 36 age-matched healthy volunteers. We conducted group comparisons of the morphological measures and explored their association with symptom severity, global and socio-occupational function levels, and the degree of alcohol and cannabis use in the ARMS group. RESULTS: Grey matter thickness and surface areas in ARMS individuals did not significantly differ from their age-matched healthy counterparts. However, reduced left-frontal grey matter thickness was correlated with greater symptom severity and lower function levels; the latter being also correlated with smaller left-frontal surface areas. ARMS individuals with more severe symptoms showed greater similarities to the recent onset schizophrenia group. The morphological measures in ARMS did not correlate with the lifetime level of alcohol or cannabis use. CONCLUSIONS: Our findings suggest that a decline in function levels and worsening mental state are associated with morphological changes in the left frontal cortex in ARMS but to a lesser extent than those seen in recent onset schizophrenia. Alcohol and cannabis use did not confound these findings. However, the cross-sectional nature of our study limits our ability to draw conclusions about the potential progressive nature of these morphological changes in ARMS.

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

E-technology social support programs for autistic children: Can they work?

Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals. One such difficulty is recognizing basic and complex facial expressions. Research has previously found that there are many evidence-based support programs available for building non-verbal communication skills. These programs are frequently administered with a therapist or in a group setting, making them inflexible in nature. Programs hosted on e-technology are becoming increasingly popular, with many parents supportive of them. Applications (apps) that are hosted on technology such as iPads or mobile phones allow users to engage in building skills in real-time social settings and own what they are learning. These technologies are frequently used by autistic children, with apps typically focusing on identifying facial features. Yet at this current time, there are mixed reviews of how to design such programs and what their theoretical backing is, with many studies using a mix of observation and psychological assessments as outcome measures. Eye-tracking and electroencephalography are established methodologies that measure neural processing and gaze behaviors while viewing faces. To better support the field moving forward, objective measures such as these are a way to measure outcomes of apps that are designed for helping children on the spectrum build skills in understanding facial expressions.

Youth mental health competencies in regional general practice.

OBJECTIVE: General practitioners (GPs) are key health professionals for referrals to mental health specialists. Youth mental health issues are particularly challenging, requiring a competent assessment and understanding of appropriate referral pathways. We surveyed local GPs about their understanding of youth mental health problems and needs to competently look after young patients. METHODS: GPs working in the Hunter region were contacted via email, fax and post over a 6-month period in 2019. RESULTS: Seventy-five GPs participated. They reported 577 of 1698 (34%) of young people seen 2 weeks prior to being surveyed presented with a mental health problem. Predominantly, referrals were to private practice psychologists and Headspace. Almost a third (31%) reported having limited understanding of 'at-risk mental state' and are 'not always comfortable' when facing a young person with a mental health problem. Nearly all (95%) expressed interest in attending specialised training. GPs identified treatment costs, scarce access to psychiatrists and limited patient engagement as the main obstacles to help young people. CONCLUSIONS: Effective treatment of a mental health problem relies on early identification. GPs are seeing young people on a regular basis but don't feel well equipped for this task and are keen to up-skill, which needs to be addressed by targeted training.

Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA.

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium.

OBJECTIVE: Schizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants. METHODS: The meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition. RESULTS: Meta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44). CONCLUSIONS: This study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Effect of Immune Activation during Early Gestation or Late Gestation on Inhibitory Markers in Adult Male Rats.

People with schizophrenia exhibit deficits in inhibitory neurons and cognition. The timing of maternal immune activation (MIA) may present distinct schizophrenia-like phenotypes in progeny. We investigated whether early gestation [gestational day (GD) 10] or late gestation (GD19) MIA, via viral mimetic polyI:C, produces deficits in inhibitory neuron indices (GAD1, PVALB, SST, SSTR2 mRNAs) within cortical, striatal, and hippocampal subregions of male adult rat offspring. In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing.

Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses.

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called "major psychosis", including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called "polytranscript risk scoring" that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses.

Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort.

OBJECTIVES: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. METHODS: We performed a case-control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. RESULTS: The strongest finding (p = 2.01 × 10-6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10-6). CONCLUSION: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

Impact of rurality and substance use on young people at ultra high risk for psychosis.

BACKGROUND: Longitudinal research into early intervention for youth at ultra high risk (UHR) for psychosis demonstrates beneficial outcomes including increased treatment compliance and greater participation in education and the workforce. Despite known barriers for rural youth accessing mental health services, research comparing urban and rural UHR youth is lacking. The study included an examination of the impact of substance use on functioning of UHR youth. METHODS: Youth aged 12 to 25 years were recruited from the urban area of Newcastle or the rural area of Orange, New South Wales, Australia, and identified as UHR by the Comprehensive Assessment of At Risk Mental States. Rural and urban youth were compared on clinical profiles, social and occupational functioning and substance use. RESULTS: The rural youth showed different help-seeking behaviours and had greater functional impairment than urban youth. Substance use was common across the sample of 57 youth (mean age 16.5 years, 56% female) and a history of hazardous substance use was associated with higher levels of depression. Rural youth (n = 32) were more likely than urban youth to be taking antidepressants at baseline (44% compared with 16%). CONCLUSION: Different patterns of help seeking by rural UHR youth suggest a need for greater access to psychosis informed primary care early intervention services. Interventions should target functional decline to prevent adverse outcomes such as reduced community participation and unemployment. In addition, interventions for substance use should be a priority for UHR youth, who should also be screened and monitored for depressive symptoms and treated for depression if indicated.

Effects of Immune Activation during Early or Late Gestation on N-Methyl-d-Aspartate Receptor Measures in Adult Rat Offspring.

BACKGROUND: Glutamatergic receptor [N-methyl-d-aspartate receptor (NMDAR)] alterations within cortex, hippocampus, and striatum are linked to schizophrenia pathology. Maternal immune activation (MIA) is an environmental risk factor for the development of schizophrenia in offspring. In rodents, gestational timing of MIA may result in distinct behavioral outcomes in adulthood, but how timing of MIA may impact the nature and extent of NMDAR-related changes in brain is not known. We hypothesize that NMDAR-related molecular changes in rat cortex, striatum, and hippocampus are induced by MIA and are dependent on the timing of gestational inflammation and sex of the offspring. METHODS: Wistar dams were treated the with viral mimic, polyriboinosinic:polyribocytidylic acid (polyI:C), or vehicle on either gestational day 10 or 19. Fresh-frozen coronal brain sections were collected from offspring between postnatal day 63-91. Autoradiographic binding was used to infer levels of the NMDAR channel, and NR2A and NR2B subunits in cortex [cingulate (Cg), motor, auditory], hippocampus (dentate gyrus, cornu ammonis area 3, cornu ammonis area 1), and striatum [dorsal striatum, nucleus accumbens core, and nucleus accumbens shell (AS)]. NR1 and NR2A mRNA levels were measured by in situ hybridization in cortex, hippocampus, and striatum in male offspring only. RESULTS: In the total sample, NMDAR channel binding was elevated in the Cg of polyI:C offspring. NR2A binding was elevated, while NR2B binding was unchanged, in all brain regions of polyI:C offspring overall. Male, but not female, polyI:C offspring exhibited increased NMDAR channel and NR2A binding in the striatum overall, and increased NR2A binding in the cortex overall. Male polyI:C offspring exhibited increased NR1 mRNA in the AS, and increased NR2A mRNA in cortex and subregions of the hippocampus. CONCLUSION: MIA may alter glutamatergic signaling in cortical and hippocampal regions via alterations in NMDAR indices; however, this was independent of gestational timing. Male MIA offspring have exaggerated changes in NMDAR compared to females in both the cortex and striatum. The MIA-induced increase in NR2A may decrease brain plasticity and contribute to the exacerbated behavioral changes reported in males and indicate that the brains of male offspring are more susceptible to long-lasting changes in glutamate neurotransmission induced by developmental inflammation.

Electrophysiological, cognitive and clinical profiles of at-risk mental state: The longitudinal Minds in Transition (MinT) study.

The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established. Several event-related potential measures, especially mismatch-negativity (MMN), have been identified as potential biomarkers for schizophrenia. In this 12-month longitudinal study, demographic, clinical and neuropsychological data were acquired from 102 anti-psychotic naive UHR and 61 healthy controls, of whom 80 UHR and 58 controls provided valid EEG data during a passive auditory task at baseline. Despite widespread differences between UHR and controls on demographic, clinical and neuropsychological measures, MMN and P3a did not differ between these groups. Of 67 UHR at the 12-month follow-up, 7 (10%) had transitioned to a psychotic illness. The statistical power to detect differences between those who did or did not transition was limited by the lower than expected transition rate. ERPs did not predict transition, with trends in the opposite direction to that predicted. In exploratory analysis, the strongest predictors of transition were measures of verbal memory and subjective emotional disturbance.

Effects of immune activation during early or late gestation on schizophrenia-related behaviour in adult rat offspring.

Maternal exposure to infectious agents during gestation has been identified as a significant risk factor for schizophrenia. Using a mouse model, past work has demonstrated that the gestational timing of the immune-activating event can impact the behavioural phenotype and expression of dopaminergic and glutamatergic neurotransmission markers in the offspring. In order to determine the inter-species generality of this effect to rats, another commonly used model species, the current study investigated the impact of a viral mimetic Poly (I:C) at either an early (gestational day 10) or late (gestational day 19) time-point on schizophrenia-related behaviour and neurotransmitter receptor expression in rat offspring. Exposure to Poly (I:C) in late, but not early, gestation resulted in transient impairments in working memory. In addition, male rats exposed to maternal immune activation (MIA) in either early or late gestation exhibited sensorimotor gating deficits. Conversely, neither early nor late MIA exposure altered locomotor responses to MK-801 or amphetamine. In addition, increased dopamine 1 receptor mRNA levels were found in the nucleus accumbens of male rats exposed to early gestational MIA. The findings from this study diverge somewhat from previous findings in mice with MIA exposure, which were often found to exhibit a more comprehensive spectrum of schizophrenia-like phenotypes in both males and females, indicating potential differences in the neurodevelopmental vulnerability to MIA exposure in the rat with regards to schizophrenia related changes.

Utility of risk-status for predicting psychosis and related outcomes: evaluation of a 10-year cohort of presenters to a specialised early psychosis community mental health service.

Psychosis transition rates by those at clinical high risk have been highly variable and few studies have compared service presenters across the full psychosis risk spectrum with respect to medium-term outcomes. A 10-year service cohort was examined (N=1997), comprising all presentations to an early psychosis service for young people experiencing a recent psychotic episode or at increased risk ('Psychological Assistance Service', Newcastle, Australia). Baseline and longitudinal service data (median follow-up =7.3 years) were used in a series of logistic regressions to examine relationships between psychosis risk-status and subsequent illness episodes, hospital admissions, and community contacts. Six baseline groups were identified: existing (14.5%) and recent psychosis (19.8%); ultra-high risk (UHR, 9.6%); non-psychotic disorders without (35.4%, the reference group) and with psychiatric admissions (8.3%); and incomplete assessments (12.5%). High comorbidity levels were reported by the cohort (psychosocial problems, 61.1%; depression, 54.1%; substance misuse, 40.7%). UHR clients experienced similar psychosis transition rates to the reference group (17.3% vs. 14.6%; 8.9% vs. 9.1% within 2-years) and comparable rates of subsequent non-psychosis outcomes. A 25.9% conversion rate from early psychosis to schizophrenia was detected. However, among transitioning individuals, UHR clients faired relatively better, particularly with respect to changes in comorbidity and mental health contacts. Interventions tailored to current problems, recovery and psychological strengthening may be more appropriate than those based on estimated psychosis risk, which currently lacks clinical utility.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles.

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition.

BACKGROUND: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. METHODS: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. RESULTS: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. CONCLUSIONS: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

A randomised controlled trial of cognitive behaviour therapy versus non-directive reflective listening for young people at ultra high risk of developing psychosis: The detection and evaluation of psychological therapy (DEPTh) trial.

BACKGROUND: Intervention trials for young people at ultra high risk (UHR) for psychosis have shown cognitive behaviour therapy (CBT) to have promising effects on treating psychotic symptoms but have not focused on functional outcomes. We hypothesized that compared to an active control, CBT would: (i) reduce the likelihood of, and/or delay, transition to psychosis; (ii) reduce symptom severity while improving social functioning and quality of life, whether or not transition occurred. METHOD: This was a single-blind randomised controlled trial for young people at UHR for psychosis comparing CBT to an active control condition, Non Directive Reflective Listening (NDRL), both in addition to standard care, with a 6month treatment phase and 12months of follow-up. Statistical analysis is based on intention-to-treat and used random effect models to estimate treatment effects common to all time-points. RESULTS: Fifty-seven young people (mean age=16.5years) were randomised to CBT (n=30) or NDRL (n=27). Rate of transition to psychosis was 5%; the 3 transitions occurred in the CBT condition (baseline, 2months, 5months respectively). The NDRL condition resulted in a significantly greater reduction in distress associated with psychotic symptoms compared to CBT (treatment effect=36.71, standard error=16.84, p=0.029). There were no significant treatment effects on frequency and intensity of psychotic symptoms, global, social or role functioning. CONCLUSION: Our sample was higher functioning, younger and experiencing lower levels of psychotic like experiences than other trials. The significantly better treatment effect of NDRL on distress associated with psychotic symptoms supports the recommendations for a stepped-care model of service delivery. This treatment approach would accommodate the younger UHR population and facilitate timely intervention. TRIAL REGISTRATION: ANZCTR 12606000101583.