Eric Yu Hai Chen

Negative symptoms such as amotivation begin to emerge in the at-risk mental state for psychosis (ARMS), and in some cases, these symptoms are idiopathic (i.e., primary negative symptoms, PNS). While deficits in reinforcement learning (RL) are evident in patients with first-episode and chronic schizophrenia and are associated with the severity of negative symptoms, whether these deficits are present during ARMS warrants further investigation. Additionally, it is unclear whether these deficits, especially those driven by rewards, are particularly characteristic of ARMS individuals with PNS. This study compared 97 ARMS individuals and 37 healthy controls (HC) on probabilistic RL. We then compared ARMS individuals with PNS ( n = 15), those without PNS ( n = 82), and HC on probabilistic RL. Reward- and punishment-driven RL (both trial-by-trial and procedural) and value-guided choice were assessed using two probabilistic RL tasks: Go/NoGo (GNG) and Gain vs. Loss-Avoidance (GLA) tasks. Compared with HC, ARMS individuals showed impairments in overall procedural RL on both RL tasks, as well as subtle, task-specific alterations in value-guided choice. Furthermore, ARMS-PNS individuals, relative to HC, showed particular deficits in reward-driven RL (trial-to-trial RL on GLA task and procedural RL on both tasks), as well as impaired positive expected value representations to guide decision-making on GLA task. Extending the results in patients with established psychosis, our findings indicate that deficits in RL exist before the onset of a psychotic disorder. With a modest sample of ARMS-PNS individuals, preliminary evidence suggests that deficits in reward-driven RL may be more specific to PNS.

Introduction: Suicidal ideation and behaviors (SIB) are common among individuals at clinical high risk for psychosis (CHR‐P), but their relationship with the overall clinical profile remains unclear. This study aimed to identify sociodemographic/clinical factors associated with SIB in CHR‐P individuals and to examine whether subthreshold psychotic symptom severity increases with suicidal risk. Methods: Data from the AMP SCZ initiative included 1443 CHR‐P participants aged 12–30 years. SIB were assessed using the Columbia Suicide Severity Rating Scale (C‐SSRS). Three Elastic Net regression models examined associations between suicidal ideation severity, intensity, and behaviors using 54 variables spanning sociodemographics, general psychopathology, subthreshold psychotic symptoms, and socio‐occupational functioning. Moreover, ANCOVA compared overall psychotic symptom severity across five groups defined by increasing severity on the C‐SSRS. Results: Sixty‐eight percent of participants reported lifetime suicidal ideation, and 26% reported previous suicidal behaviors. Model performance was modest but significant (cross‐validated ideation severity: R ² = 0.161, RMSE = 0.916; ideation intensity: R ² = 0.193, RMSE = 0.898; suicidal behavior: accuracy = 0.685; AUC = 0.675; p < 0.001). Across all models, concurrent depressive symptoms, present/past diagnosis of depression, female sex at birth, cannabis use, visual/gustatory abnormalities, guilt, and lower role functioning were the most consistent correlates of SIB. Ideation was associated with lower disorganized communication expression and lower negative symptoms, whereas behaviors were associated with schizotypal personality disorder. Other core CHR‐P symptoms, including Unusual Thoughts and Experiences, did not contribute to any model. ANCOVA ( p < 0.001, partial η ² = 0.041) indicated increasing overall subthreshold psychotic symptoms across the SIB spectrum. Conclusion: SIB in CHR‐P individuals reflects a multidimensional clinical profile primarily outside of core psychosis‐risk symptoms. Trial Registration: ClinicalTrials.gov identifier: NCT05905003

SUMMARY: The reliable assessment of formal thought disorder (FTD), a collection of observable signs of suspected problems in generating organised thoughts, is the cornerstone of interviewing a person with psychosis. A significant gap persists between the success of assessments reported in published FTD rating scales and the practical constraints of a clinical interview. Validated rating scales largely focus on operationalised criteria for describing items; the procedural aspects of how to elicit these signs often remain implicit. We synthesise the principles and procedures of FTD assessment embedded in rating scales, translating their design into a framework for routine clinical use. Systematic employment of several manoeuvres can help elicit FTD signs: conversational stimulation, cognitive loading, social modulation and pointed clarifications to stress-test thought, language and communication processes. By making these procedures explicit, we aim to equip clinicians and trainees with a strategic, measurement theory-informed approach to the psychiatric interview when assessing for FTD.

Background: Major depressive episodes (MDEs) are highly recurrent in clinical samples. However, the course of MDEs and predictors of their endurance are unclear in the general youth population. Methods: We investigated prospective factors associated with enduring MDE (the presence of 12-month DSM-IV MDE at baseline and 1 year using the Composite International Diagnostic Interview–Screening Scales) in 1,833 participants of a 1-year epidemiological youth cohort study in Hong Kong. Multivariable logistic regression models were used to examine the influences of a range of personal and environmental factors. Results: At baseline, 13.7% participants had MDEs, among whom 21.1% presented enduring MDEs. More severe symptoms of post-traumatic stress disorder (adjusted odds ratio [aOR] = 5.54, confidence interval [CI] = 2.14–14.38), depression (aOR = 3.92, CI = 1.79–8.62), and generalized anxiety (aOR = 2.27, CI = 1.21–4.25) at baseline were among the strongest associated factors for enduring MDE, with trends of associations observed for psychotic-like experiences (aOR = 1.98, CI = 0.98–4.02) and eating disorder symptoms (aOR = 1.88, CI = 0.90–3.95). Among various types of stressors, only dependent stressors at follow-up showed a clear association with enduring MDE (aOR = 4.22, CI = 1.81–9.83). Those with enduring MDE showed poorer functioning and mental health-related quality of life at follow-up, with only 35.6% having sought any psychiatric/psychological help during the past year. Conclusions: Detecting comorbid symptoms in those with prior MDEs and reducing the impact of dependent stressors may help reduce their long-term implications. Enhancing the accessibility and acceptability of youth-targeted mental health services would also be crucial to improve help-seeking.

Speech-based detection of early psychosis is progressing at a rapid pace. Within this evolving field, the Accelerating Medicines Partnership® in Schizophrenia (AMP® SCZ) is uniquely positioned to deepen our understanding of how language and related behaviors reflect early psychosis. We begin with detailed standard operating procedures (SOPs) that govern every stage of collection. These SOPs specify how to elicit speech, capture facial expressions, and record acoustics in synchronized audio–video files—both on-site and through remote platforms. We then explain how we chose our sampling tasks, hardware, and software, and how we built streamlined pipelines for data acquisition, aggregation, and processing. Robust quality-assurance and quality-control (QA/QC) routines, along with standardized interviewer training and certification, ensure data integrity across sites. Using natural language processing parsers, large language models, and machine-learning classifiers, we analyzed Data Release 3.0 to uncover systematic grammatical markers of psychosis risk. Speakers at clinical high risk (CHR) produced more referential language but fewer adjectives, adverbs, and nouns than community controls (CC), a pattern that replicated across sampling tasks. Some effects were task-specific: CHR participants showed elevated use of complex syntactic embeddings in two elicitation conditions but not the third, underscoring the importance of the language sampling task. Together, these results demonstrate how computational linguistics can turn everyday speech into a scalable, objective biomarker, paving the way for earlier and more precise detection of psychosis. Video Link: https://vimeo.com/1112291965?fl=pl&fe=sh

Objective: Non-adherence is an important factor in clinical trials, which has not been investigated in people at ultra-high risk (UHR) of developing a first episode of psychosis. Methods: Exploratory analysis of data from NEURAPRO, a multicenter, placebo-controlled trial of long-chain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in 304 individuals at UHR. We examined correlates of non-adherence with study medication (omega-3 PUFAs or placebo), including patient, illness and treatment factors, plus transition to psychosis. Non-adherence was defined as p = 0.001), independent of omega-3 PUFA treatment status. Similarly, Cox regression analysis, covarying for the aforementioned factors significantly associated with non-adherence, also revealed non-adherence as an independent predictor of transition to psychosis ( B = 1.452, p = 0.005). Finally, non-adherence was also significantly associated with transition to psychosis, even when defining non-adherence by number of returned pills. Conclusion: Non-adherence predicted a higher risk of progressing to psychosis in UHR individuals. Further studies are needed to better understand factors contributing to non-adherence and how non-adherence is related to transition to psychosis.