Executive control over low-level information processing is impaired proximal to psychosis onset with evidence of recovery over the first year of illness. However, previous studies demonstrating diminished perceptual modulation via attention are complicated by simultaneously impaired perceptual responses. The present study examined the early auditory gamma-band response (EAGBR), a marker of early cortical processing that appears preserved in first-episode psychosis (FEP), and its modulation by attention in a longitudinal FEP sample.

Magnetoencephalography was recorded from 25 FEP and 32 healthy controls (HC) during active and passive listening conditions in an auditory oddball task at baseline and follow-up (4–12 months) sessions. EAGBR inter-trial phase coherence (ITPC) and evoked power were measured from responses to standard tones. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).

There was no group difference in EAGBR power or ITPC. While EAGBR ITPC increased with attention in HC, this modulation was impaired among FEP. Diminished EAGBR modulation in FEP persisted at longitudinal follow-up. However, among FEP, recovery of EAGBR modulation was associated with reduced PANSS negative scores.

FEP exhibit impaired executive control over the flow of information at the earliest stages of sensory processing within auditory cortex. In contrast to previous work, this deficit was observed despite an intact measure of sensory processing, mitigating potential confounds. Recovery of sensory gain modulation over time was associated with reductions in negative symptoms, highlighting a source of potential resiliency against some of the most debilitating and treatment refractory symptoms in early psychosis.

Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.

First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.

The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.

The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.

The ways in which perceived harm due to substance use affects relationships between psychotic and suicidal experiences are poorly understood. The goal of the current study was to redress this gap by investigating the moderating effects of harm due to substance use on pathways involving positive psychotic symptoms, the perceived cognitive-emotional sequelae of those symptoms, and suicidal ideation.

The design was cross-sectional. Mediation and moderated mediation pathways were tested. The predictor was severity of positive psychotic symptoms. Cognitive interpretative and emotional characteristics of both auditory hallucinations and delusions were mediators. Suicidal ideation was the outcome variable. General symptoms associated with severe mental health problems were statistically controlled for.

There was evidence of an indirect pathway between positive psychotic symptom severity and suicidal ideation via cognitive interpretation and emotional characteristics of both auditory hallucinations and delusions. Harm due to drug use, but not alcohol use, moderated the indirect pathway involving delusions such that it was most prominent when harm due to drug use was at medium-to-high levels. The components of suicidal ideation that were most strongly affected by this moderated indirect pathway were active intent, passive desire, and lack of deterrents.

From both scientific and therapy development perspectives, it is important to understand the complex interplay between, not only the presence of auditory hallucinations and delusions, but the ensuing cognitive and emotional consequences of those experiences which, when combined with harm associated with substance use, in particular drug use, can escalate suicidal thoughts and acts.

Schizophrenia is a complex and heterogeneous syndrome with high clinical and biological stratification. Identifying distinctive subtypes can improve diagnostic accuracy and help precise therapy. A key challenge for schizophrenia subtyping is understanding the subtype-specific biological underpinnings of clinical heterogeneity. This study aimed to investigate if the machine learning (ML)-based neuroanatomical and symptomatic subtypes of schizophrenia are associated.

A total of 314 schizophrenia patients and 257 healthy controls from four sites were recruited. Gray matter volume (GMV) and Positive and Negative Syndrome Scale (PANSS) scores were employed to recognize schizophrenia neuroanatomical and symptomatic subtypes using K-means and hierarchical methods, respectively.

Patients with ML-based neuroanatomical subtype-1 had focally increased GMV, and subtype-2 had widespread reduced GMV than the healthy controls based on either K-means or Hierarchical methods. In contrast, patients with symptomatic subtype-1 had severe PANSS scores than subtype-2. No differences in PANSS scores were shown between the two neuroanatomical subtypes; similarly, no GMV differences were found between the two symptomatic subtypes. Cohen’s Kappa test further demonstrated an apparent dissociation between the ML-based neuroanatomical and symptomatic subtypes (P > 0.05). The dissociation patterns were validated in four independent sites with diverse disease progressions (chronic vs. first episodes) and ancestors (Chinese vs. Western).

These findings revealed a replicable dissociation between ML-based neuroanatomical and symptomatic subtypes of schizophrenia, which provides a new viewpoint toward understanding the heterogeneity of schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) is widely used in schizophrenia and has been divided into distinct factors (5-factor models) and subfactors. Network analyses are newer in psychiatry and can help to better understand the relationships and interactions between the symptoms of a psychiatric disorder. The aim of this study was threefold: (a) to evaluate connections between schizophrenia symptoms in two populations of patients (patients in the acutely exacerbated phase of schizophrenia and patients with predominant negative symptoms [PNS]), (b) to test whether network analyses support the Mohr 5 factor model of the PANSS and the Kahn 2 factor model of negative symptoms, and finally (c) to identify the most central symptoms in the two populations.

Using pooled baseline data from four cariprazine clinical trials in patients with acute exacerbation of schizophrenia (n = 2193) and the cariprazine–risperidone study in patients with PNS (n = 460), separate network analyses were performed. Network structures were estimated for all 30 items of the PANSS.

While negative symptoms in patients with an acute exacerbation of schizophrenia are correlated with other PANSS symptoms, these negative symptoms are not correlated with other PANSS symptoms in patients with PNS. The Mohr factors were partially reflected in the network analyses. The two most central symptoms (largest node strength) were delusions and uncooperativeness in acute phase patients and hostility and delusions in patients with PNS.

This network analysis suggests that symptoms of schizophrenia are differently structured in acute and PNS patients. While in the former, negative symptoms are mainly secondary, in patients with PNS, they are mainly primary. Further, primary negative symptoms are better conceptualized as distinct negative symptom dimensions of the PANSS.

Subjective perceptions of clinical change in patients with schizophrenia are often not congruent to the objective evidence of the same, especially since a lack of insight is part of the symptomatology. However, the exploration of the relationship between clinical judgments from mental health experts and the patients’ perception of symptom change is fairly understudied.

This study aimed to investigate the performance of the Positive and Negative Syndrome Scale (PANSS) as a tool for clinical outcome monitoring in schizophrenia in concordance with the change of self-reported psychopathology assessed with the Frankfurt Complaint Questionnaire (FCQ) in patients with a schizophrenia.

A consecutive sample of patients admitted to a Swiss psychiatric hospital for schizophrenia was assessed with the FCQ at admission and discharge. The PANSS was rated by the responsible clinicians at admission and discharge. Complete data of admission and discharge were available from approximately 60 cases. Reliable change index (RCI) was calculated to determine a clinically meaningful change based on the PANSS scores. Logistic regression models were conducted to explore the link between RCI levels and the change of self-reported perceptions of psychopathology.

Our study found no relationship between the change of PANSS and FCQ from admission to discharge in a sample of patients treated for schizophrenia. Therefore, our findings provide evidence for a large discrepancy between the observed clinical severity and the subjective perception of symptoms in individuals with schizophrenia.

The authors have not supplied their declaration of competing interest.

Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust.

Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games.

Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity.

Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.