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This workshop summary on natural language processing (NLP) markers for psychosis and other psychiatric disorders presents some of the clinical and research issues that NLP markers might address and some of the activities needed to move in that direction. We propose that the optimal development of NLP markers would occur in the context of research efforts to map out the underlying mechanisms of psychosis and other disorders. In this workshop, we identified some of the challenges to be addressed in developing and implementing NLP markers-based Clinical Decision Support Systems (CDSSs) in psychiatric practice, especially with respect to psychosis. Of note, a CDSS is meant to enhance decision-making by clinicians by providing additional relevant information primarily through software (although CDSSs are not without risks). In psychiatry, a field that relies on subjective clinical ratings that condense rich temporal behavioral information, the inclusion of computational quantitative NLP markers can plausibly lead to operationalized decision models in place of idiosyncratic ones, although ethical issues must always be paramount.

Spoken language is a key source of information for thought disorder evaluation. In the last decades, researchers linked psychopathology phenomena to their counterparts in natural language processing (NLP) analysis. Nonetheless, seemingly opposite traits remain unconciliated. For instance, psychotic speech comprises incoherent trails, but also highly associated ones. In order to address some of the remaining gaps, we leveraged procedures from dynamical systems and graph theory. We examined transcribed interviews of 133 individuals — 60 in at-risk mental states (ARMS) and 73 healthy controls — screened from 4,500 quota-sampled citizens in a large metropolis. SIPS was used to assess psychotic symptoms. NLP features were correlated with psychotic traits (Spearman’s ρ) and ARMS status (Wilcoxon signed-rank tests, general linear models and ensemble machine learning algorithms). The general trait (ω), negative, disorganized and general symptoms were correlated with snippets made of consecutive similar words. Namely, their frequency, average/maximum size, heterogeneity and the average number of unrelated words between such snippets. Positive symptoms were associated with adjective use. Average graph centrality was inversely correlated with the general trait. NLP features presented good performance as input in machine learning classification using the AdaBoost model with Random Forests as base learner (F1 score: 0.83, AUC: 0.93, Balanced Accuracy: 0.86).The existence of loosely connected words (e.g. incoherence, looseness, derailment) is well studied. Conversely, NLP models of perseveration (e.g. higher likelihood of chaining together islands of closely related words) and circumstantiality are brought forth in this work. Evidence shows good performance of NLP for clinical decision support in ARMS screening and assessment of subclinical psychosis. We show that a blueprint for speech-based psychometric evaluation is only a few pieces away. We highlight these fields for future research: clanging (a low hanging fruit), environmental context, task-related differences and interpersonal interactions.

OBJECTIVE Qualitative research can shed light on the subjective experiences of individuals at clinical high risk (CHR) for psychosis, complement quantitative research, broaden our understanding of experiencing CHR, and inform intervention development. The aim of this study was to explore life experiences of individuals at CHR through qualitative research. METHOD Participants were 37 individuals at CHR (20 male, 17 female) aged 16-34 (Mage = 23.32 ± 5.26), and 16 healthy controls (HCs; 7 male, 9 female) aged 18-34 (Mage = 25.37 ± 4.05). Qualitative data were obtained through open-ended interviews (30-45 min). No a priori hypotheses were made, and thematic analyses were used to develop themes. RESULTS Four major themes and one subtheme related to identity were identified through the iterative thematic analysis: defining a self-concept (with a subtheme of creativity),identity development/formation, feeling different from others, and change from a former self. Over 80% of the CHR cohort spontaneously discussed topics related to their identity, compared to 38% of HCs. HCs only reported content within the defining a self-concept theme, while the CHR group reported content within all themes. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The present study demonstrates that identity formation is a major process for youth in general and that psychosis experiences can make this process more challenging. CHR participants spontaneously brought up multiple themes related to identity in open-ended interviews, suggesting the relevance of this topic in this population. Clinicians should continue to probe identity-related concerns on an individual basis and research should focus on integrating this framework into the conceptualization and treatment of CHR. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective. Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic-like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users. Method. Six CHR cannabis users and six psychiatrically-healthy cannabis users comparable in intellectual, demographic, and cannabis use characteristics (including nontreatment-seeking status), participated in the study. Objective and subjective measures of cognition and cannabis reward, were completed before and after smoking half of an active (5.5% Δ9tetrahydrocannabinol [Δ9-THC]) or half of a placebo (0.0% Δ9-THC) cannabis cigarette, under randomized/double-blind conditions. Repeated measures ANOVA tested main effects of drug condition (active vs. placebo) and/or the drug condition × time (baseline vs. post-administration) interactions; groups were analyzed separately due to the small sample size. Results. CHR participants exhibited evidence of decreased objective response inhibition and aversive intoxication following active cannabis, relative to placebo. Psychomotor speed and cannabis-related attentional bias were also affected by cannabis intoxication. No such effects were observed in psychiatrically-healthy cannabis users. Conclusion. These findings provide further preliminary evidence of a deleterious cognitive and reward-related response to cannabis in individuals with preexisting risk for psychosis.

Resilience research has documented the ability to cope with traumatic and stressful situations and/or retain functioning given certain risk factors in the context of psychosis. In this study, we conducted the first systematic review of the literature on psychosis-like experiences (PLEs) and resilience. Fifteen articles (from 11 unique study samples) from 10 countries were included in this systematic review, with a total of 11,937 unique study participants. Inclusion criteria were broad, capturing a wide range of individuals with PLEs who have not yet experienced threshold psychosis, such as individuals in the general population with elevated self-reports of PLEs, as well as clinical groups diagnosed by clinician interviews (i.e., clinical- or ultra-high-risk for psychosis [CHR or UHR]). For this review, studies needed to include research aims and empirical research related to resilience, and use an established or author-defined measure of psychological and/or social resilience. Data reporting quality was assessed with the Strengthening the Reporting of Observational Studies in Epidemiology and place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital (PROGRESS) guidelines. Study aims and measurement of key variables varied widely, and all studies were cross-sectional. In 73% of the studies, resilience was inversely associated with PLEs or psychosis risk status (e.g., CHR or UHR). Results related to specific resilience subscales were mixed. Author-defined resilience was typically related to internal/psychological resources. Future research, particularly longitudinal research involving multidimensional measurement of resilience (e.g., internal and external factors), along with well-defined theoretical models, are necessary before drawing firm conclusions on resilience and PLEs. We propose a dynamic, multifaceted, developmentally appropriate, and culturally sensitive model of resilience for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: The COVID-19 pandemic is expected to increase stress and mental health symptoms. We present the case of a young man at risk for psychosis who has paradoxically shown symptomatic and functional improvement as a result of circumstances produced by COVID-19. These changes were unexpected given the client’s persistent mental health struggles in the year leading up to the COVID-19 outbreak in the United States and the expectation of an exacerbation of psychotic-like symptoms. Methods: This report is based on clinical assessments and the client’s first-person account during the height of the pandemic when stay at home orders were in place. Results: During the pandemic, the client demonstrated increased agency by taking on more responsibility at home and obtaining part-time employment. He showed improvement in his mood and relationships with others, had less symptom-related distress, and significantly reduced his cannabis use. The client interpreted these improvements in terms of changing his mindset toward more adaptive thoughts and engaging in healthy coping skills such as praying, reading, and healthy eating. Conclusions: This case highlights the importance of fostering agency in clients during a time of crisis and ensuring that clinicians be aware of potential biases about mental health symptom exacerbation. [ABSTRACT FROM AUTHOR] Copyright of Psychosis is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension (“adaptive salience”). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL.

To date, no measures are available that permit differentiation of discrete, clinically distinct subtypes of schizophrenia (SZ) with potential differential underlying pathophysiologies. Over recent years, there has been increasing recognition that SZ is heterogeneously associated with deficits in early auditory processing (EAP), as demonstrated using clinically applicable tasks such as tone-matching task (TMT). Here, we pooled TMT performances across 310 SZ individuals and 219 healthy controls (HC), along with clinical, cognitive, and resting-state functional-connectivity MRI (rsFC-MRI) measures. In addition, TMT was measured in a group of 24 patients at symptomatic clinical high risk (CHR) for SZ and 24 age-matched HC (age range 7–27 years). We provide the first demonstration that the EAP deficits are bimodally distributed across SZ subjects (P d = 2.1) and SZ-EAP+ patients (d = 3.4). The SZ-EAP− group predominated among samples drawn from inpatient sites, showed higher levels of cognitive symptoms (PANSS), worse social cognition and a differential deficit in neurocognition (MATRICS battery), and reduced functional capacity. rsFC-MRI analyses showed significant reduction in SZ-EAP− relative to controls between subcortical and cortical auditory regions. As opposed to SZ, CHR patients showed intact EAP function. In HC age-matched to CHR, EAP ability was shown to increase across the age range of vulnerability preceding SZ onset. These results indicate that EAP measure segregates between discrete SZ subgroups. As TMT can be readily implemented within routine clinical settings, its use may be critical to account for the heterogeneity of clinical outcomes currently observed across SZ patients, as well as for pre-clinical detection and efficacious treatment selection.

The Attenuated Psychosis Syndrome (APS), proposed as a condition warranting further study in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is a controversial diagnostic construct originally developed to identify individuals at clinical high-risk for psychosis. The relationship of APS and Schizotypal Personality Disorder (SPD) remains unclear with respect to their potential co-occurrence and the effect of SPD on risk for conversion to threshold psychosis. We examined the prevalence and effect on conversion of SPD in a cohort of 218 individuals whose symptoms met APS criteria. Results indicated that SPD was highly prevalent (68%), and that SPD did not influence risk for conversion. Rather, total positive symptom burden measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS; OR 1.12, p = 0.02) emerged as the strongest predictor of conversion. These data suggest that when encountering a patient whose presentation meets SPD criteria, the clinician should assess whether APS criteria are also met and, for 1–2 years, carefully monitor positive symptoms for possible conversion to threshold psychosis.

BACKGROUND: Identifying young people as at clinical high-risk (CHR) for psychosis affords opportunities for intervention to possibly prevent psychosis onset. Yet such CHR identification could plausibly increase stigma. We do not know whether these youth already perceive themselves to be at psychosis-risk (PR) or how their being told they are at PR might impact how they think about themselves. METHODS: 148 CHR youth were asked about labels they had been given by others (labeling by others) or with which they personally identified (self-labeling). They were then asked which had the greatest impact on how they thought about themselves. We evaluated whether being told vs. thinking they were at PR had stronger effects. FINDINGS: The majority identified nonpsychotic disorders rather than PR labels as having the greatest impact on sense of self (67.6% vs. 27.7%). However, participants who identified themselves as at PR had an 8.8 (95% CI=2.0-39.1) increase in the odds of the PR label having the greatest impact (p

In medicine, language, such as “history” of present illness and “chief complaints,” is used to understand patients' experience. Language is a rich source of data by which physicians make inferences, build therapeutic alliances, document formulations in the electronic health record, and care for patients. In psychiatry, language is the main source of data as there are no objective laboratory tests for diagnosis of psychiatric illness. It is also a therapeutic tool in psychotherapy. There now exist computer-based automated approaches to language analysis that can serve as tools for diagnosis, documentation, and treatment. Here, we review the history of natural language processing and provide examples of its use in psychiatry, such as psychosis prediction and detection of intoxication, and in extraction of information from psychiatric portions of the electronic health record. We also review future directions for studying discourse (and turn-taking), and potential applications of automated analysis to concurrent modes of communication, including prosody, pauses, face expression, and gesture. [ Psychiatr Ann. 2019;49(5):202–208.]

The ability to perceive the motion of biological objects, such as faces, is a critical component of daily function and correlates with the ability to successfully navigate social situations (social cognition). Deficits in motion perception in schizophrenia were first demonstrated about 20 years ago but remain understudied, especially in the early, potentially prodromal, stages of the illness. The authors examined the neural bases of visual sensory processing impairments, including motion, in patients with schizophrenia (N=63) and attenuated psychosis (clinical high risk) (N=32) compared with age-matched healthy control subjects (N=67).Electrophysiological recordings during stimulus and motion processing were analyzed using oscillatory (time frequency) approaches that differentiated motion-onset-evoked activity from stimulus-onset sensory-evoked responses. These were compared with functional MRI (fMRI) measures of motion processing.Significant deficits in motion processing were observed across the two patient groups, and these deficits predicted impairments in both face-emotion recognition and cognitive function. In contrast to motion processing, sensory-evoked stimulus-onset responses were intact in patients with attenuated psychosis, and, further, the relative deficit in motion-onset responses compared with stimulus-onset responses predicted transition to schizophrenia. In patients with schizophrenia, motion detection deficits mapped to impaired activation in motion-sensitive visual cortex during fMRI. Additional visual impairments in patients with schizophrenia, not present in patients with attenuated psychosis, implicated other visual regions, including the middle occipital gyrus and pulvinar thalamic nucleus.The study findings emphasize the importance of sensory-level visual dysfunction in the etiology of schizophrenia and in the personal experience of individuals with the disorder and demonstrate that motion-processing deficits may predate illness onset and contribute to impaired function even in patients with attenuated psychosis.

Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types.

Aim The experiences of culturally diverse individuals at clinical high-risk for psychosis (CHR) is not well studied. Exploratory research needs to examine whether differences exist between racial/ethnic groups within the CHR population. Understanding experiences of Latinx patients is of importance, as the Latinx population represents the most rapidly growing paediatric population in the United States and they face significant barriers to mental health treatment. Because Latinx persons experience high rates of mental illness-based stigma and discrimination in their communities, they may face additional stigma-based barriers to CHR treatment. Method Twenty-six participants (15 Latinx, 11 non-Latinx white/NLW) who met CHR criteria based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) were interviewed regarding stigma associated with CHR identification and symptoms. Using a consensus-based open-coding thematic analysis approach, data were analysed for stigma, discrimination, and coping responses. Results Instances of internalization of stereotypes appeared to be more salient to NLW participants than Latinx participants, and Latinx participants reported seemingly more anticipated rejection from stereotypes than NLW participants. Experiences of discrimination also appeared to be more salient to Latinx participants than NLW participants. Moreover, Latinx participants reported evidently greater instances of discrimination across anticipated, individual, and structural discrimination. Finally, while covering strategies appeared to be more salient to NLW's, Latinx clients more often described using secrecy as well as a greater range of coping responses, including empowerment. Conclusion While the experience of anticipated rejection appeared to be more salient to Latinx CHR participants and they seemingly report more secrecy than NLW, they also engaged in empowerment-related coping strategies. Future research should continue to explore the roles of cultural values in influencing coping strategies among CHR individuals.

ImportanceThe ENIGMA clinical high risk for psychosis (CHR) initiative, the largest pooled CHR-neuroimaging sample to date, aims to discover robust neurobiological markers of psychosis risk in a sample with known heterogeneous outcomes.ObjectiveWe investigated baseline structural neuroimaging differences between CHR subjects and healthy controls (HC), and between CHR participants who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). We assessed associations with age by group and conversion status, and similarities between the patterns of effect size maps for psychosis conversion and those found in other large-scale psychosis studies.Design, Setting, and ParticipantsBaseline T1-weighted MRI data were pooled from 31 international sites participating in the ENIGMA CHR Working Group. MRI scans were processed using harmonized protocols and analyzed within a mega- and meta-analysis framework from January-October 2020.Main Outcome(s) and Measure(s)Measures of regional cortical thickness (CT), surface area (SA), and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR, HC) and conversion status (CHR-PS+, CHR-PS-, HC).ResultsThe final dataset consisted of 3,169 participants (CHR=1,792, HC=1,377, age range: 9.5 to 39.8 years, 45% female). Using longitudinal clinical information, we identified CHR-PS+ (N=253) and CHR-PS- (N=1,234). CHR exhibited widespread thinner cortex compared to HC (average d=-0.125, range: -0.09 to -0.17), but not SA or subcortical volume. Thinner cortex in the fusiform, superior temporal, and paracentral regions was associated with psychosis conversion (average d=-0.22). Age showed a stronger negative association with left fusiform and left paracentral CT in HC, compared to CHR-PS+. Regional CT psychosis conversion effect sizes resembled patterns of CT alterations observed in other ENIGMA studies of psychosis.Conclusions and RelevanceWe provide evidence for widespread subtle CT reductions in CHR. The pattern of regions displaying greater CT alterations in CHR-PS+ were similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread CT disruptions coupled with abnormal age associations in CHR may point to disruptions in postnatal brain developmental processes.Key PointsQuestionHow do baseline brain morphometric features relate to later psychosis conversion in individuals at clinical high risk (CHR)?FindingsIn the largest coordinated international analysis to date, reduced baseline cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in CHR, in a manner highly consistent with thinner cortex in established psychosis. Regions that displayed greater cortical thinning in future psychosis converters additionally displayed abnormal associations with age.MeaningCHR status and later transition to psychosis is robustly associated with reduced cortical thickness. Abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in CHR, including pruning and myelination.

Objective: Obstacles for computational tools in psychiatry include gathering robust evidence and keeping implementation costs reasonable. We report a systematic review of automated speech evaluation for the psychosis spectrum and analyze the value of information for a screening program in a healthcare system with a limited number of psychiatrists (Maputo, Mozambique). Methods: Original studies on speech analysis for forecasting of conversion in individuals at clinical high risk (CHR) for psychosis, diagnosis of manifested psychotic disorder, and first-episode psychosis (FEP) were included in this review. Studies addressing non-verbal components of speech (e.g., pitch, tone) were excluded. Results: Of 168 works identified, 28 original studies were included. Valuable speech features included direct measures (e.g., relative word counting) and mathematical embeddings (e.g.: word-to-vector, graphs). Accuracy estimates reported for schizophrenia diagnosis and CHR conversion ranged from 71 to 100% across studies. Studies used structured interviews, directed tasks, or prompted free speech. Directed-task protocols were faster while seemingly maintaining performance. The expected value of perfect information is USD 9.34 million. Imperfect tests would nevertheless yield high value. Conclusion: Accuracy for screening and diagnosis was high. Larger studies are needed to enhance precision of classificatory estimates. Automated analysis presents itself as a feasible, low-cost method which should be especially useful for regions in which the physician pool is insufficient to meet demand.

The diagnosis and treatment of psychiatric disorders depends on the analysis of behavior through language by a clinical specialist. This analysis is subjective in nature and could benefit from automated, objective acoustic and linguistic processing methods. This integrated approach would convey a richer representation of patient speech, particularly for expression of emotion. In this work, we explore the potential of acoustic and prosodic metrics to infer clinical variables and predict psychosis, a condition which produces measurable derailment and tangentiality in patient language. To that purpose, we analyzed the recordings of 32 young patients at high risk of developing clinical psychosis. The subjects were evaluated using the Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms (SIPS/SOPS) criteria. To analyze the recordings, we examined the variation of different acoustic and prosodic metrics across time. This preliminary analysis shows that these features can infer negative symptom severity ratings (i.e., SIPS-Btotal), obtaining a Pearson correlation of 0.77 for all the subjects after cross-validated evaluation. In addition, these features can predict development of psychosis with high accuracy above 90%, outperforming classification using clinical variables only. This improved predictive power ultimately can help provide early treatment and improve quality of life for those at risk for developing psychosis.

Background. Abnormalities in the semantic and syntactic organization of speech have been reported in individuals at clinical high-risk (CHR) for psychosis. The current study seeks to examine whether such abnormalities are associated with changes in brain structure and functional connectivity in CHR individuals. Methods. Automated natural language processing analysis was applied to speech samples obtained from 46 CHR and 22 healthy individuals. Brain structural and resting-state functional imaging data were also acquired from all participants. Sparse canonical correlation analysis (sCCA) was used to ascertain patterns of covariation between linguistic features, clinical symptoms, and measures of brain morphometry and functional connectivity related to the language network. Results. In CHR individuals, we found a significant mode of covariation between linguistic and clinical features (r = 0.73; p = 0.003), with negative symptoms and bizarre thinking covarying mostly with measures of syntactic complexity. In the entire sample, separate sCCAs identified a single mode of covariation linking linguistic features with brain morphometry (r = 0.65; p = 0.05) and resting-state network connectivity (r = 0.63; p = 0.01). In both models, semantic and syntactic features covaried with brain structural and functional connectivity measures of the language network. However, the contribution of diagnosis to both models was negligible. Conclusions. Syntactic complexity appeared sensitive to prodromal symptoms in CHR individuals while the patterns of brain-language covariation seemed preserved. Further studies in larger samples are required to establish the reproducibility of these findings.

Background: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. Method: Response to points of critique. Results: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not ���extremely difficult���; e) the pattern of progression, although heterogenous, is discernible; f) ���psychosis-like symptoms��� are common but are not used to identify CHR; and g) on the point described as ���the real risk,��� CHR diagnosis does not frequently cause harmful stigma. Discussion: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the ���real risk��� of stigma associated with a CHR ���label,��� however, our view is that avoiding words like ���risk��� and ���psychosis��� reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

Human ratings of conceptual disorganization, poverty of content, referential cohesion and illogical thinking have been shown to predict psychosis onset in prospective clinical high risk (CHR) cohort studies. The potential value of linguistic biomarkers has been significantly magnified, however, by recent advances in natural language processing (NLP) and machine learning (ML). Such methodologies allow for the rapid and objective measurement of language features, many of which are not easily recognized by human raters. Here we review the key findings on language production disturbance in psychosis. We also describe recent advances in the computational methods used to analyze language data, including methods for the automatic measurement of discourse coherence, syntactic complexity, poverty of content, referential coherence, and metaphorical language. Linguistic biomarkers of psychosis risk are now undergoing cross-validation, with attention to harmonization of methods. Future directions in extended CHR networks include studies of sources of variance, and combination with other promising biomarkers of psychosis risk, such as cognitive and sensory processing impairments likely to be related to language. Implications for the broader study of social communication, including reciprocal prosody, face expression and gesture, are discussed.

Introduction: In the past two decades, there have been a number of studies that test preventive intervention strategies for young people at imminent and elevated clinical risk for psychosis. We review these studies, integrate their findings, and lay out a framework for future clinical trials.

BackgroundThe authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.MethodsBaseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center. Each patient was followed for up to 2 years or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting procedure was used to construct a model for conversion specifically to a psychotic disorder.ResultsAt 2 years, 64 patients (32.2%) converted to a psychotic disorder. The top five variables with relatively large standardized effect sizes included SIPS subscales of visual perceptual abnormalities, dysphoric mood, unusual thought content, disorganized communication, and violent ideation. The concordance index (c-index) was 0.73, indicating a moderately strong ability to discriminate between converters and non-converters.ConclusionsThe prediction model performed well in classifying converters and non-converters and revealed SIPS measures that are relatively strong predictors of conversion, comparable with the risk calculator published by NAPLS (c-index = 0.71), but requiring only a structured clinical interview. Future work will seek to externally validate the model and enhance its performance with the incorporation of relevant biomarkers.

Sensory processing deficits are core features of schizophrenia, reflected in impaired generation of event-related potential (ERP) measures such as auditory mismatch negativity (MMN) and visual P1. To understand the potential time course of development of deficits in schizophrenia, we obtained MMN to unattended duration, intensity and frequency deviants, and visual P1 to attended LSF stimuli, in 43 healthy individuals ages 6 to 25 years (mean 17), and compared results to data from 30 adult schizophrenia patients (mean age 38). We analyzed “time-domain” measures of amplitude and latency, and event-related spectral perturbation (ERSP, “time-frequency”) to evaluate underlying neurophysiological mechanisms. Duration and intensity MMN amplitudes increased from childhood to late adolescence, while frequency MMN reached maximum amplitude during early development. As reported previously, in ERSP analyses, MMN activity corresponded primarily to theta-band (4–7 Hz) activity, while responses to standards occurred primarily in alpha (8–12 Hz) across age groups. Both deviant-induced theta and standard-induced alpha activity declined significantly with age for all deviant types. Likewise, visual P1 also showed an amplitude decline over development, reflecting a reduction in both evoked power and ITC. While MMN “difference” waveform ERP data suggest failure of maturation in schizophrenia, MMN ERSP analyses instead support a neurodegenerative process, as these isolate responses to deviants and standards, showing large low-frequency evoked power for both in children. Neurodegenerative processes are also supported by large visual P1 amplitudes and large low-frequency evoked power in children, in contrast with adult schizophrenia. Sensory processing deficits in schizophrenia may be related to accelerated synaptic pruning.

Aim We sought to examine attenuated first-rank symptoms (FRS) and subcomponents of the Unusual Thought Content (P.1.) section of the Structured Interview for Psychosis-Risk Syndromes (SIPS) to investigate the robust relationship between total P.1. and conversion. We hypothesized that attenuated FRS would drive the association and, additionally, be most predictive of a schizophrenia diagnosis. Method We assessed 189 clinical high-risk participants. Two independent raters separately scored attenuated FRS and each subcomponent of P.1. as if each were the only symptom reported. Total P.1. was also scored. Participants were evaluated for conversion up to 2 years. Results While total P.1. score significantly predicted conversion in the 54 converters, attenuated FRS, which were relatively uncommon in this sample, nor any subcomponent of P.1., was independently predictive. FRS did not predict conversion to schizophrenia among 35 subjects. Conclusion Although attenuated FRS, and subcomponents of P.1. of the SIPS, did not significantly predict transition to psychosis, our results support previous research affirming the value of total P.1. score as a tool for predicting conversion to psychosis.

Objective Among individuals at clinical high risk (CHR) for psychosis, processing speed (PS) has been related to social and role functioning regardless of conversion to schizophrenia. This information processing dysfunction is a gateway to broader behavioral deficits such as difficulty executing social behaviors. We examined the feasibility of improving information processing relevant to social situations in CHR, including its sustainability at 2-month follow-up, and its association with concurrent social function. Method This was a double-blind RCT in which 62 CHR participants were randomized to Processing Speed Training (PST) or an active control matched for training format and the same dose and duration of treatment. PST is a tablet-based program that uses pupillometry-based neurofeedback to continually adjust training parameters for an optimal neurocognitive load and to improve visual scanning efficiency by inhibiting selection of nonessential targets and discriminating figure-ground details. Results The PST group showed faster motoric and nonmotoric PS at post training and 2-month follow-up. At 2 month follow-up, the PST group reported better overall social adjustment. Changes in PS from baseline to 2 months were correlated with overall social adjustment and social avoidance in the entire sample. Conclusions and implications for practice This is the first study to test focal neurofeedback-based cognitive training for PS deficits in the putatively prodromal phase of schizophrenia to address associated social morbidity. Targeting PS appears to be a promising pathway to decreasing comorbidity and mitigating a risk factor for psychosis. (PsycINFO Database Record

BACKGROUND: Face processing deficits characterize schizophrenia, including in prodromal stages. Baseline face processing deficits predict psychosis onset in clinical high-risk (CHR) youths, specifically in fear/anger processing (Corcoran, 2015). Here, we evaluate the predictive value for psychosis onset, specifically of speed of face processing in CHR youths. METHODS: In a cohort of 49 CHR patients (of whom 7 later transitioned to psychosis), and 31 healthy controls, we examined reaction times for face processing using the UPenn battery, including the Emotion Recognition (ER-40; Kohler 2005), Emotion Discrimination (EMODIFF), Emotional Acuity (PEAT), Facial Identification, as well as motor praxis. RESULTS: CHR converters had significantly slower reaction time for face emotion recognition (FER) (p=.008), but not discrimination, acuity or facial identification. They also had slower motor praxis and greater baseline prodromal symptom severity (p

Aim Early detection and intervention (EDI) is a main challenge in psychosis research. The Chilean schizophrenia (SZ) national program has universal support and treatment by law for all SZ patients, but this does not yet extend to earlier stages of illness. Therefore, we have piloted an ultra-high risk (UHR) program to demonstrate the utility and feasibility of this public health approach in Chile. Methods We introduce "The University of Chile High-risk Intervention Program," which is the first national EDI program for UHR youths. Longitudinal follow-up included clinical and cognitive assessments, and monitoring of physiological sensory and cognitive indices, through electroencephalographic techniques. Results We recruited 27 UHR youths over 2 years. About 92.6% met criteria for attenuated psychosis syndrome (APS). Mean Scale of Psychosis-Risk Symptoms (SOPS) ratings in the cohort were 6.9 (SD 4.6) for positive, 9.1 (SD 8.3) for negative, 5.4 (SD 5.3) for disorganized and 6.3 (SD 4.1) for general symptoms. About 14.8% met criteria for comorbid anxiety disorders and 44.4% for mood disorders. Most participants received cognitive behavioural therapy (62.9%) and were prescribed low dose antipsychotics (85.2%). The transition rate to psychosis was 22% within 2 years. Conclusions We describe our experience in establishing the first EDI program for UHR subjects in Chile. Our cohort is similar in profile and risk to those identified in higher-income countries. We will extend our work to further optimize psychosocial and preventive interventions, to promote its inclusion in the Chilean SZ national program and to establish a South American collaboration network for SZ research.

The past two decades have marked an increase in research on the prodromal stages of schizophrenia that precede a first episode of psychosis. Criteria for a clinical high risk (CHR) state for psychosis have been validated and included in the DSM-5 as the attenuated psychosis syndrome and as requiring further study. This was hotly debated, given the concern of stigmatizing young people who would receive this psychosis risk label. In this article, I review ethical issues related to the psychosis risk label, including the potential harm of stigma and paternalism if risk labels are withheld in the context of the observed low predictive power of the psychosis risk designation. I review data that supports that the psychosis risk label need not be harmful, and could even confer benefit, and set out strategies for reducing stigma through individualized risk assessment and public health education.

Marijuana use is associated with psychosis, but its effects are understudied in individuals with preexisting risk for psychotic disorders. This preliminary study examined the acute psychological and physiological effects of smoked marijuana (0.0% or 5.5% Δ9-THC) in marijuana users at clinical high-risk (CHR; n = 6) to develop a psychotic disorder, and those not at risk (n = 6), under controlled laboratory conditions. CHR marijuana users exhibited temporary increases in psychotic-like states and decreases in neurocognitive performance during marijuana intoxication but control marijuana smokers did not. These findings, if replicated, may support a psychotogenic role for marijuana in CHR individuals.