Schizophrenia Bulletin

BackgroundAll perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research ...

BackgroundA growing body of neuroimaging research has revealed a relationship between blunted activation of the ventral striatum (VS) and apathy in schizophrenia. In contrast, the association between reduced striatal volume and apathy is less well established, while the relationship between VS function and structure in patients with schizophrenia remains an open question. Here, we aimed to replicate previous structural findings in a larger independent sample and to investigate the relationship b...

Background and HypothesisAuditory-verbal hallucinations (AVH), hearing voices without external speakers, are a core symptom of schizophrenia. A prominent account proposes that AVH reflect failures to recognize self-generated speech. Similar effects in hallucination-prone individuals suggest that these mechanisms span a continuum from subclinical to clinical manifestations. We used a self-other voice discrimination (SOVD) task, previously identified as a potential biomarker of self-disturbance, t...

Data-driven phenotypes have the potential to accelerate biomedical research but must be vetted thoroughly for robustness, interpretability, and generalizability. This study sought to create and evaluate the predictive validity of empirical phenotypes derived from assessments of signs and symptoms of psychopathology collected in a large cohort of patients using a validated semi-structured clinical interview based on the OPCRIT system. Data was available for N = 17,719 individuals diagnosed with s...

Recent research highlights the critical role of white matter (WM) alterations in psychosis and schizophrenia (SZ), reporting volumetric and structural brain changes in affected individuals. In this study, we explored the role of astroglia in SZ, which is believed to play a role in white matter integrity. We investigated for the first time the associations between advanced diffusion Magnetic Resonance Imaging (dMRI) measures of WM microstructure, and Magnetic Resonance Spectroscopy (MRS)-derived ...

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, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were ...

BackgroundRecent evidence suggests that patients with schizophrenia may show advanced brain ageing, particularly evident after the first year of onset. However, it is unclear if accelerated ageing relents, persists or continues to increase over time. The underlying causal factors are also poorly understood. Disruptions in glutamate function, oxidative stress, and inflammation may all contribute to progressive brain changes in people with schizophrenia. We examine whether brain ageing differs bet...

BackgroundStudies have linked auditory hallucinations (AH) in schizophrenia-spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the neuroanatomical distribution and specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI). MethodsWe included patients with SCZ with (AH+; n=59) and without (AH-; n=81) cur...

BackgroundEEG microstates provide a window into rapid, large-scale brain network dynamics. Despite showing alterations in schizophrenia, evidence in first-episode schizophrenia spectrum psychosis (FESSP) is limited. We assessed whether microstate temporal and transition features could identify a multivariate signature of FESSP, and whether these dynamics can track symptom severity. MethodsResting-state EEG was analysed in 69 participants (FESSP n=41, mean age: 22.49 years; healthy controls n=28...

Schizophrenia is extremely heterogenous, and the underlying brain mechanisms are not fully understood. Many attempts have been made to substantiate and delineate the relationship between schizophrenia and the brain through unbiased exploratory investigations of resting-state functional magnetic resonance imaging (rs-fMRI). The results of numerous data-driven rs-fMRI studies have converged in support of the disconnection hypothesis framework, reporting aberrant connectivity in cortical-subcortica...

In schizophrenia spectrum disorders (SSD), structural alterations of the gray matter (GM) and white matter (WM) have been widely described. However, the complex interplay between early disease-related changes and ongoing brain maturation challenges our ability to identify early biomarkers. In this study, we investigated structural abnormalities and their association with symptoms in a drug-naive or minimally medicated sample comprising 113 patients with SSD and 112 neurotypical controls. Specifi...

BackgroundThere has been increasing interest in the study of brain gyrification in schizophrenia since it may provide additional useful information on the cytoarchitecture and connectivity of the brain. Various methods have been developed to estimate brain gyrification that, so far, have yielded mixed and inconclusive results in schizophrenia studies. To the best of our knowledge, an alternative method to compute brain gyrification, known as surface ratio (SR), has not yet been applied to a schi...

BackgroundSchizophrenia is associated with widespread functional dysconnectivity, but the spatial scale and structural correlates of these alterations remain unclear. Short-range connectivity, in particular, has received limited attention due to methodological constraints, despite its relevance to local microcircuit dysfunction. MethodsWe applied a vertex-wise, distance-dependent analysis of functional connectivity strength (FCS) to resting-state fMRI data from 86 schizophrenia patients and 99 ...

Background and HypothesisMotion processing deficits in schizophrenia have been linked to impairments in higher-order social-cognitive processes. The neural underpinnings are not fully understood but it has been hypothesized that middle temporal area (MT+) may serve as a bridge between purely sensory and more cognitive proceseses. We investigated the interrelationship between MT+ sensory processing deficits and impairments in higher-order processing using naturalistic videos with explicit motion ...

BackgroundSchizophrenia is associated with aberrant gamma band power, hypothesized to reflect imbalance in the excitation-inhibition (E/I) ratio and undermine neural signal efficiency. Relationships between resting-state gamma, E/I balance, and regional hemodynamics from the fMRI BOLD signal are unknown. MethodsWe recorded simultaneous EEG-fMRI at rest, with eyes open, in people with schizophrenia (n= 57) and people without a psychiatric diagnosis (n= 46) and identified gamma and aperiodic EEG ...

BackgroundImpairments in language comprehension and production are core symptoms of schizophrenia spectrum disorders (SSD). Predictive processing, a Bayesian framework of brain function, provides an explanatory account of both language processing and psychotic symptom formation. Within SSD, neurobiological correlates of alterations in predictive language processing are poorly understood. Here, we investigate if glutamatergic neurotransmission and functional connectivity (FC) within the language ...

Psychotic symptoms occur in a majority of schizophrenia patients, and in approximately 50% of all Parkinsons disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little, however, is known about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as schizophrenia and PD. The present study investigated a large, multicenter sample containing 722 participants: 146 patients with fir...

BackgroundThere is growing evidence for inflammatory mechanisms in schizophrenia spectrum disorders (SSD) that have been associated with blood-brain barrier (BBB) disruption. Previous studies investigating the BBB in SSD focused on cerebrospinal fluid (CSF) markers, that cannot adequately assess BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) represents a sensitive method for investigating subtle barrier breakdown in vivo. So far, only one pilot study has investigat...

BackgroundPeople with schizophrenia exhibit notable difficulties in the use of everyday language. This directly impacts ones ability to complete education and secure employment. An impairment in the ability to understand and generate the correct grammatical structures (syntax) has been suggested as a key contributor; but studies have been underpowered, often with conflicting findings. It is also unclear if syntactic deficits are restricted to a subgroup of patients, or generalized across the bro...

Key PointsO_ST_ABSQuestionC_ST_ABSIs variation in global functioning among people with schizophrenia associated with genetic differences? FindingsIn this genetic association study of 5991 adults with schizophrenia and 59,795 hospitalizations, polygenic scores for schizophrenia and educational attainment predicted global functioning at psychiatric admission and discharge, as well as the magnitude of functional improvement during hospitalization. Higher polygenic burden for schizophrenia was cons...