Pharmacological and Mechanistic Interventions for Cognitive Impairment Associated With Schizophrenia: A Review of Registered Clinical Trials.

Background: Schizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).

Linguistic Markers of Theory of Mind in Spontaneous Speech: A Narrative Review.

The relationship between theory of mind (ToM) or mentalizing, i.e., the cognitive ability to attribute mental states to oneself and others, and language has been widely explored across disciplines.

Imaging of the superficial white matter in health and disease.

The superficial white matter, the layer of white matter immediately deep to the cortical grey matter, is a highly complex, heterogeneous tissue region comprising dense meshes of neural fibres, a robust population of interstitial neurons, and ongoing glial activity and myelination. It originates from the histologically distinct, developmentally vital subplate in the foetal brain, maintains thalamo-cortical connections throughout adult life, and is a necessary passage for all axons passing between the grey and white matter. Despite these features, the superficial white matter is among the most poorly understood regions of the brain, in part due to its complex makeup and the resulting difficulty of its study.

Task-Related Controllability of Functional Connectome During a Working Memory Task in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

Working memory (WM) deficit is a prominent and common cognitive impairment in major psychiatric disorders (MPDs). Altered control of brain state transitions may underlie the neural basis of WM deficit. We investigate whether shared and illness-specific alterations in controllability underlie WM deficits in MPDs.

Disrupted Glucose Metabolism Covariance Network in Amyotrophic Lateral Sclerosis.

Aims: This study aimed to characterize the topological changes in glucose metabolism covariance networks in amyotrophic lateral sclerosis (ALS).

Methods: We assessed the interregional coordination of F-FDG-PET data to examine topological alterations in individualized glucose metabolism covariance networks in 127 ALS patients compared to 128 healthy controls (HC).

Results: Compared to HC, ALS patients showed reduced small-worldness (lower normalized clustering coefficient, higher normalized characteristic path length) and decreased global and local efficiency, suggesting impaired global integration and local segregation.

Taking a look at your speech: identifying diagnostic status and negative symptoms of psychosis using convolutional neural networks.

Speech-based indices are promising objective biomarkers for identifying schizophrenia and monitoring symptom burden. Static acoustic features show potential but often overlook time-varying acoustic cues that clinicians naturally evaluate-such as negative symptoms-during clinical interviews. A similar dynamic, unfiltered approach can be applied using speech spectrograms, preserving acoustic-temporal nuances.

Early Psychosis Symptoms Noted by Family Physicians in Electronic Medical Records During Help-Seeking Visits in Primary Care: Symptômes précoces de psychose relevés par les médecins généralistes dans les dossiers médicaux électroniques lors de consultations en soins primaires pour demande d'aide.

BackgroundThe objectives of this study were (1) to describe the symptoms noted by family physicians during help-seeking visits for early psychosis, relative to a validated screening tool for early psychosis in primary care, and (2) to examine the referral disposition of patients meeting the screening tool cut-off.MethodsWe constructed a retrospective cohort of Ontario residents aged 14-35 years with an incident diagnosis of non-affective psychotic disorder between 2005-2015 in health administrative data, and at least one visit in the Electronic Medical Record Primary Care database during the 6 months prior to the date of psychotic disorder diagnosis ( = 572). We abstracted symptoms of psychosis noted by the family physician in the electronic medical records and compared these to the Primary Care Checklist (PCCL) for early psychosis.

Brain state dynamics and working memory in patients with schizophrenia and unaffected siblings.

Background: Working memory (WM) deficits are a key feature of schizophrenia and are also seen in unaffected siblings. These deficits might arise  from disrupted transitions from one brain state to another. Using a robust algorithm called the Bayesian Switching Dynamical System (BSDS), we studied hidden brain states and their transitions during a WM task in people with schizophrenia.

Imbalance of thalamocortical structural connectivity in adolescents with early-onset schizophrenia.

Background: Thalamocortical circuit imbalance, characterized by decreased prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity, has been well-documented in adult-onset schizophrenia. We have previously demonstrated functional imbalance of this circuit in adolescents with early-onset schizophrenia (EOS). We now investigate whether this functional imbalance stems from the thalamocortical structural connectivity in EOS, thereby further establishing its relevance to the neurodevelopmental modeling of psychosis.

Norepinephrine system dysconnectivity in major depressive disorder: the effect of short term SSRI treatment.

Despite the long history of norepinephrine hypothesis in depression, the neuropathology involving norepinephrine remains elusive. This study aims to map the whole-brain functional connectivity (FC) of the major norepinephrine nucleus locus coeruleus (LC) and further investigate the effect of escitalopram, an antidepressant with minimal direct norepinephrine effects, on the LCNE system in patients with major depressive disorder (MDD). Totally 253 MDD patients and 227 healthy controls (HCs) were recruited.

Relationship between grammar and schizophrenia: a systematic review and meta-analysis.

Background: Schizophrenia significantly impairs everyday communication, affecting education and employment. Such communication difficulties may arise from deficits in syntax-understanding and generating grammatical structures. Research on syntactic impairments in schizophrenia is underpowered, with inconsistent findings, and it is unclear if deficits are specific to certain patient subgroups, regardless of symptom profiles, age, sex, or illness severity.

Selective Insensitivity to Global Versus Local Linguistic Context in Speech Produced by Patients With Untreated Psychosis and Positive Thought Disorder.

Background: Early psychopathologists proposed that certain features of positive thought disorder, the disorganized language output produced by some people with schizophrenia, suggest an insensitivity to global, relative to local, discourse context. This idea has received support from carefully controlled psycholinguistic studies in language comprehension. In language production, researchers have so far remained reliant on subjective qualitative rating scales to assess and understand speech disorganization.

Neurite Density and Kurtosis in the Gray Matter of People With Early Schizophrenia.

Background: Classic models of diffusion-weighted imaging, especially diffusion tensor imaging, are unsuitable for application to the cortical gray matter given its high microstructural complexity. As such, most neuroimaging studies have focused on gross structural effects of schizophrenia, such as cortical thickness differences. More recently developed models, such as neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging (DKI), incorporate higher-resolution data and may provide more sensitive descriptions of schizophrenia pathology with more specific interpretations.

Distinct structural deficits in treatment-resistant schizophrenia and their putative neurotransmitter basis: a source-based morphometry analysis.

Schizophrenia is associated with widespread gray matter reduction. This is influenced by the underlying connectivity, resulting in covarying patterns of structural changes that are more pronounced in treatment-resistant individuals. However, it remains uncertain whether a distinct network of brain regions, with specific neurotransmitter basis, forms the substrate for treatment resistance in schizophrenia.

Symptom networks and working memory in schizophrenia: a multi-methodological cross-sectional study from phenotype to endophenotype.

Background: A notable deficit in working memory (WM) is well established in schizophrenia. Nevertheless, the intricate relationship between various symptoms and WM impairment is still not fully understood. We use three distinct methodologies-symptom network analysis (SNA), Connectome-Based Predictive Modeling (CPM), and brain gene annotation enrichment analysis-to explore the connectome patterns that link WM deficits and symptoms, and their related gene expression.

Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence.

Cerebral asymmetry, fundamental to various cognitive functions, is often disrupted in neuropsychiatric disorders. While brain growth has been extensively studied, the maturation of brain asymmetry in children and the factors influencing it in adolescence remain poorly understood. We analyze longitudinal data from 11,270 children aged 10-14 years in the Adolescent Brain Cognitive Development (ABCD) study.

Latent Trajectories of Positive, Negative Symptoms and Functioning in Early Intervention Services for First-Episode Psychosis: A 2-Year Follow-Up Study.

Background: From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to examine latent trajectories of positive and negative symptoms and functioning among FEP individuals undergoing EIS.

Study Design: The Prevention and Early Intervention Program for Psychoses (PEPP-Montreal) is a 2-year EIS for FEP that conducted longitudinal assessments of 689 individuals aged 14-35, including sociodemographics, cognition, psychopathology, and functioning.

Stable White Matter Structure in the First Three Years After Psychosis Onset.

Background: White matter alterations observed using diffusion weighted imaging have become a hallmark of chronic schizophrenia, but it is unclear when these changes arise over the course of the disease. Nearly all studies reported to date have been cross-sectional, so despite their large sample sizes, they cannot determine whether changes accumulate as a degenerative process or patients with preexisting white matter damage are predisposed to more chronic forms of schizophrenia.

Methods: We examined 160 scans comprising 2 years of annual follow-up data from 42 control participants and 28 patients with schizophrenia recruited in the first 2 years since their diagnosis, totaling 2 to 3 scans per participant.

Convergence of Cannabis and Psychosis on the Dopamine System.

Importance: Despite evidence that individuals with a cannabis use disorder (CUD) are at elevated risk of psychosis and that the neurotransmitter dopamine has a role in psychosis, the mechanism linking cannabis use and psychosis remains unclear.

Objective: To use neuromelanin-sensitive magnetic resonance imaging (MRI), referred to as the neuromelanin-MRI signal, a practical, proxy measure of dopamine function, to assess whether a common alteration in the dopamine system may be implicated in CUD and psychosis and whether this alteration can be observed in those with a CUD whether or not they have a diagnosis of first-episode schizophrenia (FES).

Design, Setting, And Participants: This longitudinal observational cohort study recruited individuals from 2019 to 2023 from an early psychosis service and the surrounding communities in London, Ontario.

Disorganisation and depression: a re-examination of how we think and speak when depressed.

Disorganised thinking in severe mental illness seriously cripples social functions. Historically, the study of disorganisation has primarily concentrated on schizophrenia, utilizing tools designed to assess formal thought disorder (FTD). This review examines the characteristics, prevalence, and possible neural correlates of FTD within the framework of depressive disorders.

Speaking of yourself: A meta-analysis of 80 years of research on pronoun use in schizophrenia.

People with schizophrenia experience significant language disturbances that profoundly affect their everyday social interactions. Given its relevance to the referential function of language, aberrations in pronoun use are of particular interest in the study of schizophrenia. This systematic review and meta-analysis, adhering to PRISMA guidelines, examines the frequency of pronoun use in schizophrenia.

Seminal Contributions of Timothy J. Crow.

We recall the life and work of Timothy J. Crow, whose contributions provided great insights into the pathophysiology of schizophrenia and continue to shape many questions in the field. We compile his key works relating to psychotic disorders, focusing on the trajectory of his theoretical stance.