Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FAT) and higher extracellular free water (FW).

Thirty-seven SZ and 129 healthy controls (HC) were grouped into the ‘none/low’ or ‘high’ CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FAT and FW.

SZ displayed lower FAT within the corpus callosum and corona radiata compared to HC (p < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FAT (p < 0.05, TFCE) and higher FW (p < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group (p > 0.05, TFCE).

These novel findings suggest that the impact of CT on lower FAT may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.

This study aimed to provide information about pathways to care and clinical response to community-based brief interventions for improving youth mental health through evaluating the Mindspace Mayo service.

Participants were 1,184 individuals aged 12–25 years (Mean = 17.92, SD = 2.66) who engaged with the Mindspace service. Demographic information included gender, age and living situation. The Clinical Outcome in Routine Evaluation (CORE) was used to measure psychological distress before and after attending the Mindspace service between February 2015 and 2022.

On average, individuals received six sessions of therapeutic support. Analyses indicated that most referrals were made by either a parent (40%) or self-referral (38%). The most frequent reason for referral was mood and anxiety-related issues. Across the entire sample, reductions in CORE scores were both statistically and clinically significant. Neither the source of the referral nor living situation significantly predicted intervention response. Complexity of issues presented at referral significantly predicted a reduction in psychological distress post-intervention in young people aged over 17 years.

This study highlighted the value of primary care mental health services for young people aged 12–25 years, and underlined the importance of recording electronic data to track referral pathways, reasons for referral and the intervention outcomes over time.

Schizophrenia represents one of the most stigmatised of mental disorders. Despite public awareness campaigns to raise awareness and increase understanding of mental health disorders, schizophrenia continues to be poorly understood. In this context, this study aims to provide a descriptive analysis of reporting on schizophrenia in the Irish online print news media.

Online printed news articles which made reference to schizophrenia or related terms in 2021, the latest year for which full date was available, were collected. A list of criteria considered good reporting practise on mental illness in the media was curated. Additionally, a scale was developed based on these criteria to assign a valence to each article in terms of characteristics that were either stigma reinforcing or stigma challenging.

A total of 656 articles were included in the analysis. A majority of articles were found to avoid stigma reinforcing criteria (e.g. use of pejorative language). By contrast, few characteristics considered stigma challenging criteria were being endorsed (e.g. inclusion of a first person account). Overall sample valences show good reporting practises, but also suggested targets for improvement.

While Irish online print news reports on schizophrenia and related illnesses avoid many stigmatising characteristics, many opportunities to challenge stigma remain.

Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia.

To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort.

Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479).

In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort.

These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.

Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.

Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.

Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.

These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the ‘dysconnectivity hypothesis’ of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.

To present a systematic review of the literature on the associations between early social environment, early life adversity, and social cognition in major psychiatric disorders, including schizophrenia, bipolar disorder, borderline personality disorder, major depressive disorder and posttraumatic stress disorder.

Relevant studies were identified via electronic and manual searches of the literature and included articles written in English and published in peer-reviewed journals up to May 2018. Quality assessment was performed using the quality evaluation scale employed in previous systematic reviews.

A total of 25 studies were included in the systematic review with the quality assessment scores ranging from 3 to 6 (out of 6). The vast majority of the studies reviewed showed a significant association between early childhood social experience, including both insecure attachment and adversity relating to neglect or abuse, and poorer social cognitive performance.

We discuss these findings in the context of an attachment model, suggesting that childhood social adversity may result in poor internal working models, selective attention toward emotional stimuli and greater difficulties with emotional self-regulation. We outline some of the steps required to translate this understanding of social cognitive dysfunction in major psychiatric disorders into a target for interventions that mitigate the adverse effects of childhood maltreatment and poor parental attachment on social cognition.

A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown.

To determine the impact of the rs7914558 risk ‘A’ allele on measures of neurocognition, social cognition and brain structure.

Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39).

No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples.

Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.

Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.

In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.

Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1–3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.

These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.