Attenuated Psychosis Syndrome Research Articles

The Italian adaptation of the Mini-SIPS, a tool for early detection of individuals at clinical high risk and first episode of psychosis: A preliminary study of implementation in an Italian FEP program.

The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high risk (CHR) framework, the DSM-5 Attenuated Psychosis Syndrome (APS) and to be implemented in clinical settings. The Mini-SIPS was translated in Italian by a Yale-certified SIPS trainer, then back-translated in English by a trained psychologist, then approved by the Mini-SIPS authors. Since September 2021, the adapted Italian version of the Mini-SIPS has been implemented at the First Episode Psychosis (FEP) Program in Ferrara, Italy. The Italian version of Mini-SIPS was successfully administered to 15 individuals subsequently referred to the First Episode Psychosis service in Ferrara. Within this sample, the tool has proven to be both an effective and efficient tool for the identification of CHR and FEP, and a valid instrument to help with the differential diagnosis. It also performed as a valuable guide for retrieving information about psychiatric history, to date the onset of APS and/or full-blown psychosis, to track the progression from CHR to psychosis or to symptoms resolution and to describe patients' pathways to care. The Mini-SIPS is an efficient and easy-to-use interview to identify the early stages of psychosis and established psychosis in clinical contexts. The Italian adaptation of this interview could be effectively implemented in other Italian FEP Programs as a screening and monitoring tool. Formal validation of the instrument is needed to assessed validity and reliability in the diagnosis of the CHR and FEP.

Psychopathological characteristics in ultra-high risk for psychosis with and without comorbid ADHD.

This study investigates the psychopathological characteristics of a sample of individuals at ultra-high risk for psychosis with and without comorbid attention-deficit hyperactivity disorder (ADHD). Twenty-eight subjects (aged 13-21 years; 13 females) with attenuated psychosis syndrome (APS) were recruited in a cross-sectional study and divided into two groups, each with 14 patients, according to the presence or absence of ADHD. The APS group showed a significantly higher prevalence of negative symptoms than the APS + ADHD group. Other characteristics investigated (positive symptoms, aberrant salience, psychotic-like experiences and prodromal symptoms) did not differ between groups. The different profiles of negative symptoms in the APS with or without ADHD might suggest the presence of a specific subtype among individuals at ultra-high risk for psychosis. Longitudinal studies with larger samples will provide information about the role of negative symptoms in determining conversion to full psychosis in those people with 'pure' APS and those with APS + ADHD.

Impaired insight and error-monitoring deficits among outpatients with attenuated psychosis syndrome and first-episode psychosis

We aimed to determine the relationship between electrophysiological signatures of error monitoring and clinical insight among outpatients with attenuated psychosis syndrome (APS) and first-episode psychosis (FEP). Error-related negativity (ERN), error positivity (Pe), and correct response negativity (CRN) were recorded during a modified flanker task for patients with FEP (n = 32), APS individuals (n = 58), and healthy controls (HC, n = 49). Clinical insight was measured using the Schedule of Assessment of Insight (SAI) and included awareness of illness (SAI-illness), relabeling of specific symptoms (SAI-symptoms), and treatment compliance (SAI-treatment). Compared with HC, patients with FEP showed smaller ERN (p < 0.001) and Pe (p = 0.011) amplitudes and individuals with APS showed smaller ERN amplitude (p = 0.009). No significant difference in CRN amplitude was observed among the groups. A smaller negative amplitude of ERN correlated with a lower score on SAI-symptoms (b = −0.032, 95% CI: 0.062 to −0.002, p = 0.035) and a decreased total score of SAI (b = −0.096, 95% CI: 0.182 to −0.010, p = 0.029). This links were adjusted for age, education, and diagnosis (a dummy variable with FEP = 1 and APS = 0), and was independent of positive symptoms. SAI-illness was predominantly influenced by diagnosis, whereas SAI-treatment was additionally affected by disorganized communications. Neither Pe nor CRN amplitude exhibited an association with clinical insight. Unconscious error detection, as indicated by ERN, may aid individuals at the preliminary stage of psychosis in recognizing the unusual symptoms.

Magnetic resonance advanced imaging analysis in adolescents: cortical thickness study to identify attenuated psychosis syndrome.

Psychosis is a symptom common to several mental illnesses and a defining feature of schizophrenia spectrum disorders, whose onset typically occurs in adolescence. Neuroradiological studies have reported evidence of brain structural abnormalities in patients with overt psychosis. However, early identification of brain structural changes in young subjects at risk for developing psychosis (such as those with Attenuated Psychosis Syndrome -APS) is currently lacking. Brain 3D T1-weighted and 64 directions diffusion-weighted images were acquired on 55 help-seeking adolescents (12-17years old) with psychiatric disorders who referred to our Institute. Patients were divided into three groups: non-APS (n = 20), APS (n = 20), and Early-Onset Psychosis (n = 15). Cortical thickness was calculated from T1w images, and Tract-Based Spatial Statistics analysis was performed to study the distribution of white matter fractional anisotropy and all diffusivity metrics. A thorough neuropsychological test battery was adopted to investigate cognitive performance in several domains. In patients with Attenuated Psychotic Syndrome, the left superior frontal gyrus was significantly thinner compared to patients with non-APS (p = 0.048), and their right medial orbitofrontal cortex thickness was associated with lower working memory scores (p = 0.0025, r = -0.668 for the working memory index and p = 0.001, r = -0.738 for the digit span). Early-Onset Psychosis patients showed thinner left pars triangularis compared to non-APS individuals (p = 0.024), and their left pars orbitalis was associated with impaired performance at the symbol search test (p = 0.005, r = -0.726). No differences in diffusivity along main tracts were found between sub-groups (p > 0.05). This study showed specific associations between structural imaging features and cognitive performance in patients with APS. Characterizing this disorder using neuroimaging could reveal useful information that may aid in the development and evaluation of preventive strategies in these individuals.

AI-Based Adherence Prediction for Patients: Leveraging a Mobile Application to Improve Clinical Trials

AbstractIntroductionMedication nonadherence is a public health concern and can impact clinical trial data quality. Traditional compliance collection (pill counts, diaries) can be unreliable in central nervous system trials. As such, strategies such as adherence technologies may play a key role in trial outcomes. AiCure, a computer vision-assisted dosing mobile application (app), collects dosing data and connects patients to sites for dosing support. Phone-based computer vision algorithms confirm dosing and transfer videos for artificial intelligence and human review. Boehringer Ingelheim is partnering with AiCure on pilot trials using AiCure adherence data to improve patient retention and clinical trial data quality. Here we report initial findings.MethodsThis pilot used data from two Phase II trials on the efficacy and safety of BI 409306 in people with schizophrenia (NCT03351244) or Attenuated Psychosis Syndrome (NCT03230097). The AiCure mobile app alerted participants to dosing protocols. The dose event was visually confirmed, providing sites a real-time view of adherence and allowing for targeted outreach and intervention. Adherence data from the first 2 weeks generated quantitative, machine-learning models to predict the individual adherence over the trial. Predictive modeling explored different monitoring periods (7-, 10-, and 14-day) and adherence cutoff points (0.8, 0.7, 0.6).ResultsInitial AiCure assessment identified 43% of participants in NCT03351244 as ≤80% compliant (definition of compliance &gt;80% compliant). Variance in adherence rates between electronic case report forms (eCRF; 78%) and AiCure (26%) data was also observed in the highly compliant/adherent group in NCT03230097. Using the first 2 weeks of adherence data (both studies combined), a participant’s adherence predicted their average adherence for the remainder of the trial. Observation of a participant’s adherence for the latest 4 weeks predicted the probability of premature dropout from the trial. There were further correlations of lower predicted adherence with actual disposition-based dropouts.The early adherence predictive model (0.6 adherence cutoff) identified 22%, 20%, and 19% of patients for trial NCT03351244 (total n=235) as high-risk patients (low-adherence prediction) across 7-, 10-, and 14-day monitoring periods, respectively. Of those high-risk patients, 81%, 90%, and 96%, respectively, were truly nonadherent based on actual adherence data. The 14-day monitoring period model provided the lowest false omission rate, indicative of a better performing model.ConclusionsAiCure data provided insights into patient behavior and adherence patterns which would not be available via CRF. Predictive models developed with AiCure adherence data can identify and predict future poor adherers. This creates opportunities to plan interventions and mitigation strategies to improve patient adherence during trials, thereby providing test drugs the best opportunity at proving efficacy.FundingBoehringer Ingelheim International GmbH (NCT03351244/1289-0049 and NCT03230097/1289-0032)

Symptoms of Attenuated Psychosis Syndrome in Relatives of Clinical High-Risk Youth: Preliminary Evidence.

Attenuated Psychosis Syndrome (APS) impacts functioning and predicts increased risk of psychosis. Risk for developing APS itself has received minimal attention. Knowledge of familial and environmental contributions to APS symptoms would advance understanding of APS and risk for psychosis. As an initial step, this report presents the first data on APS symptoms in family members of APS patients. This study utilized a discordant sibling-pair family study design. The Structured Interview for Psychosis-risk Syndromes (SIPS) was administered to 17 APS probands and 26 non-APS biological siblings. Probands and siblings were compared on positive, negative, disorganized, and general SIPS symptom scales and factors derived from those scales. There was significantly greater symptom severity in probands compared to siblings on nine of 19 SIPS scales. Negative/anxiety, functioning, and positive symptom factors were identified. Probands showed significantly greater severity than siblings on the negative/anxiety and positive factors. Elevated pathology on the negative/anxiety factor best differentiated between probands and siblings, over and above the contribution of the positive factor. No difference was found for the functioning factor. Results support the importance of non-familial effects on risk for APS and suggest differences in familial contribution to APS symptoms. Understanding the relative contribution of familial and environmental effects on APS symptoms may reveal important differences among APS patients, with implications for risk characterization, symptom course, and treatment selection.

The Mini-SIPS: development of a brief clinical structured interview guide to diagnosing DSM-5 Attenuated Psychosis Syndrome and training outcomes

ObjectiveThe Mini-SIPS, a condensed version of the Structured Interview for Psychosis-Risk Syndromes (SIPS), is intended to efficiently identify for clinicians the minimum information needed to support a DSM-5 Attenuated Psychosis Syndrome (APS) diagnosis.MethodsThe instrument and the DSM-5 criteria are accessible through the online training program.ResultsMost individuals (67.5%) in the first 212 to complete the training program indicated an intended use of the Mini-SIPS exclusively for clinical purposes. Performance on the post-training quiz was excellent for those with and without prior training in structured diagnostic interviewing.ConclusionThe Mini-SIPS, and accompanying training program, are offered as public-domain clinical resources to the mental health community.

Clinical profile and conversion rate to full psychosis in a prospective cohort study of youth affected by autism spectrum disorder and attenuated psychosis syndrome: A preliminary report.

Psychosis can occur at high rates in individuals with autism spectrum disorder (ASD). However, the detection of prodromal psychotic symptoms, including attenuated psychosis syndrome (APS), conditions at high risk of converting to full psychosis, has not been extensively investigated in ASD. We longitudinally evaluate a sample of young ASD individuals (age, mean ± SD: 13 ± 2.9) with (n = 13) or without (n = 18) concomitant APS through a standardized assessment of autistic (Autism Diagnostic Observation Schedule–Second Edition; ADOS−2) and psychotic (Structured Interview for Psychosis-Risk Syndromes, SIPS) symptoms and cognitive and adaptive skills. Individuals with other neuropsychiatric disorders were excluded. We estimated the conversion rate to full psychosis (according to SIPS criteria) over time (39.6 ± 11.5 months) and explored the role of clinical variables at baseline in the transition to full psychosis. A conversion rate to full psychosis of 30.7% was found in ASD/APS. Conversion to full psychosis was not affected by the severity of the autistic and psychotic symptoms. At baseline, young individuals with ASD/APS who later converted to full psychosis showed lower cognitive performance (d = 2.05) and greater impairment of adaptive social functioning profile (d = 1.2) than those with ASD. The results of this preliminary report revealed that nearly a third of young individuals with ASD/APS convert to full psychosis over time. Conversion to full psychosis is affected by decreased cognitive and adaptive skills. Further investigations are needed to confirm the utility of APS detection and to better characterize the psychotic developmental trajectory in ASD, with consequent important implications on prognosis and therapeutic strategies.

Prognostic Accuracy of DSM-5 Attenuated Psychotic Symptoms in Adolescents: Prospective Real-World 5-year Cohort Study

IntroductionThere is limited research in adolescent at risk for psychosis. The new criteria of Attenuated Psychosis Syndrome (APS) of Diagnostic and Statistical Manual of Mental Disorders- 5 (DSM-5) have not been validated.ObjectivesThe aims of this study were to: 1) characterize adolescent’s profile with APS (DSM-5 APS) compared to adolescents with early onset psychosis (EOP) and with other psychiatric disorders (non-APS); 2) to estimate their long-term risk of transition to psychosis and prognostic accuracy of DSM-5 APS.Methods243 adolescents, aged 12-17, were included (October 2012- July 2019) and dived in three sub-groups (110 DSM-5 APS, 31 EOP, 102 non-APS). All underwent a comprehensive assessment evaluating: sociodemographic characteristics, family and personal history of any DSM-5 psychiatric disorders, psychopathological assessment and level of functioning. An annual follow-up evaluation was carried out (up to 7 years) including a clinical interview to investigate DSM-5 criteria for transition to psychosis.ResultsDSM-5 APS adolescents had on average higher comorbid disorders (2.3) and intermediate psychopathological and functioning profile between non-APS/EOP. The cumulative risk of transition at 1,2,3, 4-5 years was 13%, 17%, 24.2%, 26.8% and 26.8% in DSM-5 APS group, 0%, 0%, 3.2%, 3.2% and 3.2% in the non-APS. The 5-year prognostic accuracy of the DSM-5 APS in adolescent was adequate (Area Under the Curve=0.77) with high sensitivity (91.3%) and suboptimal specificity (63.2%).ConclusionsThe DSM-5 APS diagnosis can be used to detect help-seeking adolescents at risk of psychosis and predict their long-term outcomes, leading the way to new preventive approaches.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Neurocognitive Functioning of Adolescents with Clinical High Risk for Psychosis, other Psychiatric Symptoms, and Psychosis

IntroductionClinical High Risk of Psychosis (CHR-P) condition and the clinical validity of at-risk criteria are still little studied in child and adolescent population.ObjectivesThis study aimed to discover neurocognitive profiles of adolescents with CHR-P, compared with adolescents with psychosis and youth with other psychiatric symptoms that do not meet CHR-P criteria.MethodsWe divided 116 adolescents (12-18 years old) in three groups according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): psychosis, attenuated psychosis syndrome (APS), non-APS. Moreover, we administered Wechsler scales to assess the IQ, Wisconsin Card Sorting Test to assess abstract reasoning and flexibility, Rey-Osterrieth complex figure to assess planning and attention, and Trail Making Test to assess psychomotor speed, visual attention and task switching. We administered BVN 12-18 subtests to assess lexical denomination, verbal and nonverbal working memory, selective auditory, visual attention, phonemic and categorial fluency, reasoning and problem solving.ResultsNineteen adolescents met criteria for psychosis, 47 for APS, and 50 did not meet criteria neither for psychosis nor for APS. APS group performed better than psychosis group and similar to non-APS group in processing speed, planning, visual attention, and categorial fluency. APS did not show a significant difference from the other groups in working memory and backward digit span, showing an intermediate profile; non-APS and psychosis groups still differed significantly in these functions.ConclusionsIdentifying typical neurocognitive profiles leads to more accurate diagnoses and early intervention that can lead to better patient outcomes.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Predicting Psychosis: Field Moves From Assessment of Clinical Risk to Search for Biomarkers

Predicting Psychosis: Field Moves From Assessment of Clinical Risk to Search for Biomarkers

Antipsychotics prescribed for one in three children at clinical high risk for psychosis

In an editorial in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry, researchers focus on what they admit is a “delicate, complex, and often divisive issue” — prescribing antipsychotics for children and adolescents who have conditions which carry an “established higher risk of imminent development of an overt psychotic state.” This risk, known as clinical high risk for psychosis (CHR‐P), is not the same as, for example, a genetic risk. It is specifically related to the DSM‐5 attenuated psychosis syndrome (APS) which falls below the severity threshold for a diagnosis of schizophrenia and other psychotic disorders.

The effect of BI 409306 on heart rate in healthy volunteers: a randomised, double-blind, placebo-controlled, crossover study

PurposeThe potent, selective phosphodiesterase-9A inhibitor BI 409306 may be beneficial for patients with attenuated psychosis syndrome and could prevent relapse in patients with schizophrenia. Transient BI 409306-dependent increases in heart rate (HR) demonstrated previously necessitated cardiac safety characterisation. We evaluated cardiac effects of BI 409306 in healthy volunteers during rest and exercise.MethodsIn this double-blind, three-way crossover study, volunteers received placebo, BI 409306 50 mg or 200 mg in randomised order (same treatment on Days 1 [resting] and 3 [exercise]). Cardiopulmonary exercise testing was performed twice post treatment on Day 3 of each period. BI 409306-mediated effects on placebo-corrected change from baseline in resting HR (ΔΔHR) were evaluated based on exposure–response analysis and a random coefficient model. Adverse events (AEs) were recorded.ResultsOverall, 19/20 volunteers completed. Resting ΔΔHR versus BI 409306 concentration yielded a slope of 0.0029 beats/min/nmol/L. At the geometric mean (gMean) maximum plasma concentration (Cmax) for BI 409306 50 and 200 mg, predicted mean (90% CI) ΔΔHRs were 0.80 (− 0.76, 2.36) and 5.46 (2.44, 8.49) beats/min, respectively. Maximum adjusted mean differences from placebo (90% CI) in resting HR for BI 409306 50 and 200 mg were 3.85 (0.73, 6.97) and 4.93 (1.69, 8.16) beats/min. Maximum differences from placebo in resting HR occurred at/near gMean Cmax and returned to baseline after approximately 4 h. The proportion of volunteers with AEs increased with BI 409306 dose.ConclusionObserved hemodynamic effects following BI 409306 administration were of low amplitude, transient, and followed the pharmacokinetic profile of BI 409306.

Patients’, carers’ and clinicians’ attitudes towards alternative terms to describe the at-risk for psychosis state

ObjectiveLanguage used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the ‘at-risk mental state’ (ARMS) concept and to investigate what young people, their caregivers and clinicians thought about them as well as terms commonly used in early intervention clinics. Another aim was to understand participants preference related to the best timing to introduce the at-risk concept and the extent and context of the information presented. MethodsNew terms illustrating the at-risk concept have been generated by a youth reference group with lived experience of mental illness: ‘pre-diagnosis stage’ (PDS), potential of developing a mental illness (PDMI) and disposition for developing a mental illness (DDMI). A specifically designed questionnaire was administered to 46 patients with ARMS, 24 caregivers and 52 clinicians to obtain their feedback on newly proposed terms and on the terms already used in clinical practice and research. ResultsThe preferred terms were PDS, PDMI and ARMS. The least favoured terms were Ultra High Risk and Attenuated Psychosis Syndrome, which were thought to be associated with the most stigma. Most participants agreed that disclosure about diagnosis should be delivered early by the key clinician. ConclusionsPatients generated terms such as PDS, PDMI, alongside ARMS should be considered to be used in clinical practice. They present with low stigma and are illustrative of young peoples difficulties.

Antipsychotics and Attenuated Psychosis Syndrome: Transdiagnostic assessment and discontinuation strategies

Antipsychotics and Attenuated Psychosis Syndrome: Transdiagnostic assessment and discontinuation strategies

Autism Spectrum Disorder and Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis

Psychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.

Attenuated Psychosis Syndrome Should Be Moved to the Main Section in DSM-5-TR

This Viewpoint reviews the history of the clinical high risk for psychosis construct, discusses developments from research and clinical practice that inform this dilemma, and argues for including attenuated psychosis syndrome in the main section of the upcoming DSM-5 text revision.

Symptomatic and preventive effects of the novel phosphodiesterase-9 inhibitor BI 409306 in an immune-mediated model of neurodevelopmental disorders

BI 409306, a phosphodiesterase-9 inhibitor under development for treatment of schizophrenia and attenuated psychosis syndrome (APS), promotes synaptic plasticity and cognition. Here, we explored the effects of BI 409306 treatment in the polyriboinosinic-polyribocytidilic acid (poly[I:C])-based mouse model of maternal immune activation (MIA), which is relevant to schizophrenia and APS. In Study 1, adult offspring received BI 409306 0.2, 0.5, or 1 mg/kg or vehicle to establish an active dose. In Study 2, adult offspring received BI 409306 1 mg/kg and/or risperidone 0.025 mg/kg, risperidone 0.05 mg/kg, or vehicle, to evaluate BI 409306 as add-on to standard therapy for schizophrenia. In Study 3, offspring received BI 409306 1 mg/kg during adolescence only, or continually into adulthood to evaluate preventive effects of BI 409306. We found that BI 409306 significantly mitigated MIA-induced social interaction deficits and amphetamine-induced hyperlocomotion, but not prepulse inhibition impairments, in a dose-dependent manner (Study 1). Furthermore, BI 409306 1 mg/kg alone or in combination with risperidone 0.025 mg/kg significantly reversed social interaction deficits and attenuated amphetamine-induced hyperlocomotion in MIA offspring (Study 2). Finally, we revealed that BI 409306 1 mg/kg treatment restricted to adolescence prevented adult deficits in social interaction, whereas continued treatment into adulthood also significantly reduced amphetamine-induced hyperlocomotion (Study 3). Taken together, our findings suggest that symptomatic treatment with BI 409306 can restore social interaction deficits and dopaminergic dysfunctions in a MIA model of neurodevelopmental disruption, lending preclinical support to current clinical trials of BI 409306 in patients with schizophrenia. Moreover, BI 409306 given during adolescence has preventive effects on adult social interaction deficits in this model, supporting its use in people with APS.

Prognostic Accuracy of DSM-5 Attenuated Psychosis Syndrome in Adolescents: Prospective Real-World 5-Year Cohort Study.

There is limited research in adolescents at risk for psychosis. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition attenuated psychosis syndrome (DSM-5 APS) criteria have not been validated in this group. We conducted a RECORD-compliant, real-world, prospective, 5-year cohort study addressing clinical profile, transition to psychosis, and prognostic accuracy of DSM-5 APS in help-seeking inpatient/outpatient adolescents accessing Children and Adolescent Neuropsychiatric services at IRCCS Mondino Foundation (Pavia, Lombardy, Italy) between 2012 and 2019. About 243 adolescents (31 early-onset psychosis [EOP]; 110 meeting DSM-5 APS criteria, DSM-5 APS; 102 not meeting psychotic or DSM-5 APS criteria, non-APS) were included. At baseline, DSM-5 APS adolescents (aged 15.4 ± 1.6) had on average 2.3 comorbid disorders (higher than EOP/non-APS, P < .001). DSM-5 APS adolescents had an intermediate psychopathological profile between non-APS/EOP (P < .001) and worsen Clinical Global Impression-Severity than non-APS (P < .001). DSM-5 APS functioning was intermediate between non-APS and EOP. 39.1% of DSM-5 APS were treated with psychotropic drugs (average = 64 days); 53.6% received psychotherapy. Follow-up of DSM-5 APS and non-APS groups lasted 33 and 26 months, respectively (median). The cumulative risk of transition at 1-5 years was 13%, 17%, 24.2%, 26.8%, and 26.8% in the DSM-5 APS group, 0%, 0%, 3.2%, 3.2%, and 3.2% in the non-APS group. The 5-year prognostic accuracy of the DSM-5 APS in adolescent was adequate (area under the curve = 0.77; Harrell's C = 0.736, 95%CI 0.697-0.775), with high sensitivity (91.3%) and suboptimal specificity (63.2%). The DSM-5 APS diagnosis can be used to detect help-seeking adolescents at risk of psychosis and predict their long-term outcomes. Future research should consolidate these findings.

Reinforcement learning abnormalities in the attenuated psychosis syndrome and first episode psychosis

Prior studies indicate that chronic schizophrenia (SZ) is associated with a specific profile of reinforcement learning abnormalities. These impairments are characterized by: 1) reductions in learning rate, and 2) impaired Go learning and intact NoGo learning. Furthermore, each of these deficits are associated with greater severity of negative symptoms, consistent with theoretical perspectives positing that avolition and anhedonia are associated with impaired value representation. However, it is unclear whether these deficits extend to earlier phases of psychotic illness and when individuals are unmedicated. Two studies were conducted to examine reinforcement learning deficits in earlier phases of psychosis and in high risk patients. In study 1, participants included 35 participants with first episode psychosis (FEP) with limited antipsychotic medication exposure and 25 healthy controls (HC). Study 2 included 17 antipsychotic naïve individuals who were at clinical high-risk for psychosis (CHR) (i.e., attenuated psychosis syndrome) and 18 matched healthy controls (HC). In both studies, participants completed the Temporal Utility Integration Task, a measure of probabilistic reinforcement learning that contained Go and NoGo learning blocks. FEP displayed impaired Go and NoGo learning. In contrast, CHR did not display impairments in Go or NoGo learning. Impaired Go learning was not significantly associated with clinical outcomes in the CHR or FEP samples. Findings provide new evidence for areas of spared and impaired reinforcement learning in early phases of psychosis.