Cognitive control refers to the ability to dynamically guide behavior by maintaining goal context and filtering out irrelevant information. Cognitive control deficits are well-documented in people with schizophrenia (PSZ), but the degree of impairment varies considerably depending upon the type of control being assessed. The present study examined three domains of cognitive control-selective attention to context, rule switching, and response conflict management-within a single paradigm to characterize different facets of cognitive control dysfunction in PSZ. Thirty-eight PSZ and 35 healthy control subjects (HCS) completed a cued task-switching paradigm that required participants to make a button-press response to different features of a target stimulus (letter, number, or color) depending upon the location that the target appeared on each trial. Prior to target onset, participants were presented with a cue indicating which stimulus dimension would be probed. PSZ were able to utilize the cue as effectively as HCS; however, when the relevant target dimension switched between trials (thus requiring a different stimulus-response mapping), PSZ showed greater switch costs compared to HCS. Finally, PSZ showed modestly impaired response conflict management when the irrelevant stimulus dimensions of the target corresponded to a different (incongruent) response compared to the relevant stimulus dimension. These findings suggest that selective attention to context is mostly intact, but response rule switching and response conflict management are impaired in PSZ.

AIMS:Negative symptoms are a core component of schizophrenia, affecting up to 60% of individuals with the disorder. They are categorised into primary negative symptoms (PNS), which are intrinsic to the illness, and secondary negative symptoms, which arise from external factors such as depression or medication side effects. They can also be divided into diminished expression and amotivation/anhedonia subtypes. While inflammation has been implicated in schizophrenia and linked to negative symptoms, little is known about whether inflammatory profiles differ between negative symptom subtypes in individuals at Ultra-High Risk (UHR) for psychosis. METHODS:We conducted a secondary analysis of 147 UHR participants from the Staged Treatment in Early Psychosis (STEP) study to examine whether inflammatory markers (Alpha-2-Macroglobulin, IL-6, CRP, sICAM-1, sVCAM-1, and suPAR) differed across negative symptom subgroups, using multinomial and binomial logistic regression models adjusted for age, sex, smoking, and BMI. RESULTS:Overall, most inflammatory markers were not significantly associated with negative symptom subgroups. However, higher sICAM-1 levels were asscoiated with lower odds of primary negative symptoms compared with no negative symptoms. Additionally, younger age was associated with increased odds of PNS and amotivation, while smoking was associated with higher odds of secondary negative symptoms compared with no negative symptoms. DISCUSSION:These findings suggest that inflammation may not broadly distinguish negative symptom subtypes at the UHR stage, although sICAM-1 may play a role in early illness processes. Limitations include sample ascertainment, potential misclassification of negative symptoms, and the relatively small number of participants with PNS. Future studies with larger samples and longitudinal designs are needed to clarify whether inflammatory changes contribute to the emergence of specific negative symptom subtypes.

BACKGROUND:The current study combined behavioral and EEG measures to investigate variations in attentional state during comprehension of spoken stories in a clinical sample that included participants with several major mental health disorders that often feature attentional control difficulties. METHODS:Participants with schizophrenia (N=62), bipolar disorder (N=44), major depressive disorder (N=51) and psychiatrically healthy controls (N=82) completed a story-listening task and were periodically interrupted by attention probes. Attention probes assessed three different states of engagement via self-reports: on-task attention, partially off-task split-attention, and fully off-task lapsed attention. EEG was recorded to examine corresponding changes in periodic alpha-band (8-13 Hz) power. RESULTS:We found that all patient groups reported significantly less time fully on-task during story listening than did control participants, but that individual patient groups reported distinct patterns of off-task attention. Whereas reports of fully-lapsed attention dominated off-task reports for participants with schizophrenia, participants with major depressive disorder reported a higher incidence of experiencing a distracted or split attentional state. The EEG results provided additional evidence that the three self-report attention probe categories tapped into biologically distinguishable attentional states, with split attention and fully lapsed attention associated with distinct neural signatures relative to on-task attention. Periodic alpha power was modulated by attentional state in all groups, although there were significant group differences. CONCLUSIONS:Our results demonstrate distinct behavioral and neurophysiological attentional control profiles in schizophrenia and major depressive disorder compared to control participants during language comprehension.

BACKGROUND AND HYPOTHESIS:People who hear voices may have strong prior expectations of speech, so that noisy auditory signals are resolved as speech. Data in non-clinical voice hearers suggest that voice hearing may involve sensitivity to speech in degraded stimuli. This has yet to be examined in people with schizophrenia (SZ). STUDY DESIGN:In this case-control study, we presented sine-wave-speech (SWS; made by replacing the formants in speech with pure tone whistles) to people with SZ (n = 63) and healthy controls (HC; n = 27). SWS is typically unintelligible on first exposure. However, once the listener knows that it is potentially intelligible as speech (by exposure to the unaltered speech template, which thus serves as a prior expectation), relatively high levels of comprehension are achieved. Our participants first listened to intelligible and unintelligible SWS and reported whether they heard speech. They were then exposed to the speech templates, and then the first phase was repeated. STUDY RESULTS:Compared to HC, people with SZ reported hearing more speech before template exposure. The Reveal increased both groups' false alarms and reporting of speech, but there was no interaction with group. Change in hit rates after the Reveal correlated with hallucinations, which is consistent with a greater influence of the priors enhancement in SZ patients who hear voices. CONCLUSIONS:These findings suggest that people with SZ have stronger expectations of speech. This task has validity for hallucinatory voice hearing. It is also simple and convenient to administer, and may prove useful in detecting prodromal risk, as well as acute exacerbation in voice hearing.

Importance:Healthy individuals typically show attractive serial dependence in working memory tasks, with responses biased toward recent inputs, whereas people with schizophrenia (SZ) reliably show the opposite-repulsive biases. Determining whether individuals with bipolar disorder (BD) and a history of psychosis exhibit similar or distinct serial-dependence patterns is essential for clarifying shared vs disorder-specific cognitive mechanisms across the psychosis spectrum. Objective:To determine whether people with BD exhibit the repulsive bias seen in people with SZ or the attractive bias seen in healthy control (HC) individuals. Design, Setting, and Participants:This case-control study included individuals who met DSM-5 criteria for SZ or BD with a history of psychosis, along with matched HC participants recruited across 5 US sites. Clinical samples were recruited from outpatient psychiatric clinics and day programs, and HC participants were recruited from the community. A working memory task was used in which participants remembered the orientation of a teardrop-shaped object and reproduced it using a computer mouse after a variable delay. The Brief Psychiatric Rating Scale was used to quantify symptom severity. The study was conducted from September 2023 to April 2025. Main Outcomes and Measures:The primary outcome measure was the bias index, used to evaluate the extent to which current-trial responses were biased toward or away from previous-trial targets. Exposures:Diagnostic group and the orientation of the previous trial's target during a spatial working memory paradigm. Results:A total of 41 participants were included in BD group (21 [51%] male; mean [SD] age, 37.02 [11.53] years), 30 in the SZ group (18 [60%] male; mean [SD] age, 37.5 [9.04] years), and 27 in the HC group (16 [59%] male; mean [SD] age, 39.98 [11.01] years). Overall bias differed across groups, with people with SZ (mean, -1.99; 95% CI, -2.74 to 1.23) demonstrating significantly greater repulsive bias than both people with BD (mean, 0.44; 95% CI, -0.25 to 1.13) and HC individuals (mean, 1.82; 95% CI, 1.31 to 2.32). Fifteen of 27 HC individuals exhibited attractive bias, with none showing repulsive bias, whereas 17 of 30 people with SZ exhibited repulsive bias, with none showing attractive bias. Attractive bias was common in people with BD (13 of 41), but some exhibited a repulsive bias (7 of 41). Conclusions and Relevance:In this case-control study, attractive and repulsive serial biases differed between HC individuals and people with SZ, with some people with BD showing the HC pattern and few showing the SZ pattern. These results suggest that serial bias may serve as a valuable biomarker for pathophysiology and precision psychiatry.

AIM:This study assessed the feasibility of a stepped-care model for those at clinical high-risk for psychosis (CHRp) within a coordinated specialty care clinic in the United States. METHODS:Youth aged 12-30 completed a 12-month, three-step intervention where persistent or worsening symptoms received increasingly intensive treatment including Supportive Problem Solving, Cognitive Behavioural Case Management, and a Selective Serotonin Reuptake Inhibitor. RESULTS:Of 32 CHR youth admitted to the clinic over 18 months, 12 were eligible for the study, 10 consented (83.3% consent rate at 0.56 recruitment rate), eight participated, and five completed (62.5% completion rate). Reasons for ineligibility were mostly unrelated to the treatment, including disengagement before recruitment, pressing comorbid concerns that required other specialty care, and medication preferences. Those who completed treatment showed clinically significant improvements in social functioning, depression, and attenuated psychosis symptoms by 12-month follow-up, but sample size precluded statistical analysis. Three discontinued due to medication needs (more intensive care, perceived side effects). CONCLUSIONS:This small preliminary study supports larger scale trials of stepped-care interventions for CHRp in the US, but also illuminates key features of the US healthcare system that must shape implementation. The stepped-care intervention appeared tolerable and feasible in those who were eligible and engaged; clinical outcomes were promising. Comorbid treatment needs in this heterogenous population, including medication needs/preferences, and disengagement during referral to psychosis specialty care precluded participation for many. Future studies should evaluate larger samples, account for needs and preferences for medication, and place screening and early steps in general outpatient mental health services to evaluate real-world effectiveness.

Objectives: Bipolar Disorder (BD)-characterized by mania, affective lability, and elevated psychosis risk-is associated with sustained attention deficits. However, evidence regarding performance on the AX-Continuous Performance test task (AX-CPT), a task reliably impaired in schizophrenia-spectrum psychosis, is mixed. This study examined whether individual differences in mania/affective lability risk and psychosis risk, across cohorts of BD and BD-at-risk individuals, were associated with altered AX-CPT performance. Methods: The standard measures d'context and A-cue bias quantified AX-CPT performance. Factors from the Mood Spectrum Self Report (MOODS-SR-L) indexed lifetime mania/affective lability risk (psychomotor activation, suicidality, and mixed instability) and lifetime psychosis risk. Linear regressions were performed for dimensional continuous aims (Aims 1-2) for both d'context and A-cue bias. Tests between BD with low and high-risk groups (Aims 3-4) were completed with ANCOVAs for both AX-CPT output measures. Results: In the final sample of euthymic BD (n = 27) and at-risk individuals (n = 121), higher levels of psychosis and mania/affective lability risk were associated with reduced target discrimination (d'context; absolute t's > 2.015, p's < 0.047), but not with altered A-cue bias. Group comparisons showed no significant differences for either AX-CPT measure. Associations with d'context from Aims 1-2 remained after covarying for current depressive symptoms but were removed when covarying for current mania severity (absolute t's < 1.26, all p's > 0.203). Conclusions: Target discrimination deficits were associated dimensionally with psychosis and mania/affective lability risk but not categorically with BD diagnosis. This suggests scope for dimensional risk models for understanding sustained attention deficits in BD and at-risk individuals and highlights contributions of mania/affective lability and psychosis risk.

Computational psychiatry aims to quantify individual patients' psychiatric pathology by measuring behavior during psychophysical tasks and characterizing the neurocomputational parameters underlying specific decision-making systems. While this approach has great potential for informing us about specific computational processes associated with psychopathology, the fundamental psychometric properties of computational assessments remain understudied. Optimizing these psychometric properties, including test-retest reliability, is essential for clinical utility. To address this gap, we assessed the test-retest reliability of manifest behavior and computational model parameters of a probabilistic reward and reversal learning task, two-armed Bandit, using intraclass correlations (ICCs) in 179 adults, including those with various psychosis-spectrum disorders and undiagnosed controls. We studied two computational models from recent literature: regression modeling of choice strategies and a hidden Markov model. The test-retest reliability for both manifest behavior (0.24 ≤ ICCs ≤ 0.54) and computational parameters (0.30 ≤ ICCs ≤ 0.61) ranged from poor to moderate, which was not explained by practice effects. Computational parameters did not outperform manifest behavior parameters. The reliability of computational parameters was generally-though not significantly-higher in healthy adults, which may potentially reflect the internal heterogeneity of categorical psychiatric diagnoses. Computational modeling holds promise, but tasks and analyses must be optimized for greater reliability before proceeding into clinical use. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Neuromelanin (NM) magnetic resonance imaging (MRI) is a relatively new, noninvasive method used as a proxy measure of midbrain dopamine function. Previous studies in schizophrenia have found evidence of enhanced signal in patients that are associated with positive psychotic symptoms. However, there are limited data available comparing methods of computing signal in substantia nigra (SN). We sought to examine the reliability and validity of manual tracing vs template-defined methods to help guide the field in identifying optimal approaches in NM imaging. NM-MRI was performed on 22 participants (18 with early psychosis (EP) and 4 healthy controls (HCs)) scanned twice over a 1-14 week period. Mean SN NM signal was calculated using template-defined and manual tracing methods to define SN ROIs. Intraclass correlation coefficients (ICCs) based on absolute agreement were calculated between test and retest. Correlations between NM signal for each method and symptoms in EP were also examined. ICCs for the template-defined were in the excellent range (.81-.85) and manual tracing methods were in the poor to fair range (-.14 to .56). The template-defined method showed a trend positive relationship with reality distortion symptoms (r = .45, p = .06) and the manual tracing method showed a significant positive relationship (r = .47, p = .05). Supplemental analyses highlighted the importance of thresholding and using the mode to compute CNR for identifying these relationships to symptomatology. While both methods showed clinical validity, the excellent reliability of the template-defined method suggests this technique is the preferred strategy for NM-MRI analysis.

Inflammatory changes have been widely reported in psychosis. Cannabis use has been consistently related to increased risk of psychosis, earlier onset, higher rates of relapse and poorer treatment response. However, it is unclear how cannabis use interacts with brain inflammatory changes in psychosis. In this cross-sectional study we used diffusion imaging to measure extracellular free water in the brain (FW), a measure that has been associated with inflammation, in 62 individuals with recent onset psychosis (ROP) and 38 controls, with and without cannabis use. Past cannabis use was associated with lower FW in controls, and conversely, to elevated FW in ROP. This group x past cannabis use interaction was found significant in average GM (p = 0.049), and in cortical regions, including the temporal lobe expanding to parietal regions (TFCE p-FWE < 0.05). Within ROP, antipsychotic exposure was related to lower FW in gray matter and white matter only in the non-cannabis users, with no significant association in cannabis users (p interaction in WM = 0.005, in GM = 0.073). Our results demonstrate a differential effect of cannabis use on FW, a surrogate marker of neuroinflammatory processes and suggest that past cannabis use may influence the effects of antipsychotic medication on the brain. However, given the cross-sectional design and moderate sample size, causal interpretations are limited, and further longitudinal studies are warranted.