The Concept of Staging in Schizophrenia; 13 Years After the 'Agius Concept of Staging' Was Published.

We review the development of clinical staging models of schizophrenia, which has developed as a logical extension of the Neuro-developmental theory of Schizophrenia. The staging approach, which involves assessing a disorder based on its severity, scope, progression, and characteristics, is gaining growing recognition in the fields of clinical psychology and psychiatry. We review the development of clinical staging models of schizophrenia, which has developed as a logical extension of the Neuro-developmental theory of Schizophrenia. The development of these clinical staging models should be based also on the neuroimaging dana, since this implies actual changes within the brain. There still are some difficulties with these models, but they are gradually providing both more logical ways of understanding the development of psychotic illness and more effective ways of treatment. The Models have contributed to research in several areas of psychiatry.

Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai At Risk for Psychosis (SHARP) program.

BACKGROUND: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program. METHOD: In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC. RESULTS: The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal. CONCLUSIONS: The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.

Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator.

BACKGROUND: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. METHODS: Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). RESULTS: In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. CONCLUSIONS: Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program.

OBJECTIVE: Since only 30% or fewer of individuals at clinical high risk convert to psychosis within 2 years, efforts are underway to refine risk identification strategies to increase their predictive power. The clinical high risk is a heterogeneous syndrome presenting with highly variable clinical symptoms and cognitive dysfunctions. This study investigated whether subtypes defined by baseline clinical and cognitive features improve the prediction of psychosis. METHOD: Four hundred clinical high-risk subjects from the ongoing ShangHai At Risk for Psychosis program were enrolled in a prospective cohort study. Canonical correlation analysis was applied to 289 clinical high-risk subjects with completed Structured Interview for Prodromal Syndromes and cognitive battery tests at baseline, and at least 1-year follow-up. Canonical variates were generated by canonical correlation analysis and then used for hierarchical cluster analysis to produce subtypes. Kaplan-Meier survival curves were constructed from the three subtypes to test their utility further in predicting psychosis. RESULTS: Canonical correlation analysis determined two linear combinations: (1) negative symptom and functional deterioration-related cognitive features, and (2) Positive symptoms and emotional disorganization-related cognitive features. Cluster analysis revealed three subtypes defined by distinct and relatively homogeneous patterns along two dimensions, comprising 14.2% (subtype 1, n = 41), 37.4% (subtype 2, n = 108) and 48.4% (subtype 3, n = 140) of the sample, and each with distinctive features of clinical and cognitive performance. Those with subtype 1, which is characterized by extensive negative symptoms and cognitive deficits, appear to have the highest risk for psychosis. The conversion risk for subtypes 1-3 are 39.0%, 11.1% and 18.6%, respectively. CONCLUSION: Our results define important subtypes within clinical high-risk syndromes that highlight clinical symptoms and cognitive features that transcend current diagnostic boundaries. The three different subtypes reflect significant differences in clinical and cognitive characteristics as well as in the risk of conversion to psychosis.

Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis).

OBJECTIVE: Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. METHOD: A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. RESULTS: Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. CONCLUSIONS: Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

Applying a Transdiagnostic Cognitive-Behavioral Treatment to Adolescents at High Risk for Serious Mental Illness: Rationale and Preliminary Findings.

Given the chronic and deleterious course of serious mental illness (SMI; schizophrenia and bipolar disorder), significant efforts have been undertaken to improve prediction of SMI and provide treatment for adolescents in the early, putatively prodromal stage of these illnesses. While risk assessments and disorder-specific treatments for adolescents at risk for SMI have shown some efficacy, significant issues remain around disorder-specific treatments for these youth. There is substantial heterogeneity of psychopathology within adolescents at high risk for SMI that leads to many false-positives and varying diagnostic outcomes. As a result, initial treatment focusing on broad symptoms and skills has been proposed in place of disorder-specific treatments. We discuss the rationale for providing an already-developed and empirically supported transdiagnostic treatment for emotional disorders (termed the Unified Protocol) as a first-line staging of treatment for adolescents experiencing early SMI symptoms. Additionally, we outline the open trial we are piloting using this transdiagnostic treatment in adolescents between the ages of 13 - 17 who have begun experiencing distressing yet subsyndromal psychosis or bipolar mood symptoms. Preliminary findings suggest feasibility and acceptability as well as initial efficacy in improving psychiatric symptoms, quality of life, and difficulties regulating emotions. We also present case studies from our open trial. A unified, cognitive-behavioral treatment for early presentations of SMI has important clinical and public health benefits, including streamlining treatment and providing broad skills that are applicable to a wide range of psychopathology.

Relationship between duration of untreated prodromal symptoms and symptomatic and functional recovery.

Our previous study has found that a long duration of untreated prodromal symptoms (DUPrS) does not increase the conversion risk to psychosis in individuals with attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to other poor outcomes remains unknown. The purpose of this study was to analyse the association between the DUPrS and outcomes (symptomatic and functional recovery) in APS population. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. Of total 391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82 (24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic outcome. A significant correlation between GAF scores and DUPrS was observed in the non-converter group, but not in the converters. Individuals with APS who had a longer DUPrS were correlated with poorer functional outcome. However, it was not correlated with poorer symptomatic outcome. While a longer DUPrS was not related to poor symptomatic outcome, it was significantly related to poor functional outcome. Our findings highlight the importance of reducing DUPrS to decrease future functional impairment in populations at risk for psychosis.

Duration of untreated prodromal symptoms in a Chinese sample at a high risk for psychosis: demographic, clinical, and outcome.

BACKGROUND: The duration of untreated psychosis (DUP) has been widely studied. However, for individuals with attenuated psychosis syndrome (APS), it is unclear whether the duration of untreated prodromal symptoms (DUPrS) also has a negative effect on the progression of psychosis. Our aim was to identify demographic and clinical factors contributing to the DUPrS in a large sample of individuals with APS, and to evaluate the association between DUPrS and the conversion to psychosis. METHOD: A sample of 391 individuals with APS, who were identified through a structured interview for prodromal syndromes, were included in this study, of whom a total of 334 patients had completed at least a 1-year clinical follow-up. A total of 57 individuals had converted to psychosis. RESULTS: The average DUPrS was 4.8 months for the whole sample. Individuals with a longer DUPrS were likely to be men, non-local residents, with abnormal thought symptoms, a higher severity level of negative symptoms, the lower severity level of general symptoms, and lower level of general function before the onset of attenuated positive symptoms. A DUPrS of less than 2 months, or more than 6 months, lowered the risk for conversion to psychosis. CONCLUSIONS: Our data suggested that the association between the DUPrS and outcome in individuals with APS were likely to be different, which is either long or short DUPrS was not related to future psychosis onset. Individuals with APS were more likely to have a group of features associated with a longer DUPrS.

Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort.

BACKGROUND: DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD: We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS: The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS: NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

Faux pas recognition performance in a help-seeking population at clinical high risk of psychosis.

There is a growing body of evidence suggesting that patients with psychosis show impaired theory of mind (ToM). However, much remains to be understood as to whether ToM deficits occur in the premorbid or post-onset period of psychosis. Our primary aim was to examine empirically impairment on ToM tasks in a group of individuals with clinical high risk (CHR) of psychosis. Fifty CHR participants identified through the Structured Interview for Prodromal Syndromes and 52 age-/education-matched controls were assessed with a complete standard neuropsychological battery (the MCCB, MATRICS Consensus Cognitive Battery) and a social cognition assessment (Faux Pas Test, FPT). We then examined the association of baseline FPT performance with conversion to psychosis at 12-month follow-up. Compared with controls, the CHR group showed significantly poorer performances on the FPT and most MCCB domains. Significant positive correlations were found between faux pas detection and the MCCB domains of Attention/Vigilance and Working Memory in CHR participants when controlling for age and years of education. Mean scores on the FPT in 14 converters who were diagnosed with full-blown psychosis within 12 months were significantly lower than they were for non-converters. Impairments in ToM ability are acquired earlier in the prodromal stage of psychosis, along with general cognition (such as memory function) deficits. Declines in ToM ability may overlap with the progress of psychosis (the gradual loss insight), sharing similar neural substrates, and reflected by impairments in basic cognitive function.

Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Introduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

Multivariate joint models for the dynamic prediction of psychosis in individuals with clinical high risk.

This study attempted to construct and validate dynamic prediction via multivariate joint models and compare the prognostic performance of these models to both static and univariate joint models. Individuals with clinical high risk(CHR)(n = 289) were recruited and re-assessed for positive symptoms, general functions, and conversion to psychosis at 2-months, 1-year, and 2-years to develop the dynamic models. A multivariate joint model of positive psychotic symptoms was assessed using the Structured Interview for Prodromal Symptoms(SIPSp) and general function assessed by global assessment of functioning scores(GAFs) with time-to-conversion to psychosis. The area under the receiver operating characteristic(ROC) curve(AUC) was used to test the accuracy of the models. Among 298 CHR individuals, 68 converted to psychosis within 2 years after the initial assessments. Multivariate joint models showed that declining GAFs and increasing SIPSp corresponded to significant and trending to significantly increased risk of psychosis onset and had much higher prognostic accuracy (cross-validated AUC=0.9) compared to the static model(AUC=0.6) and univariate joint models(cross-validated AUC=0.6-0.8). Our results showed that multivariate joint models could be highly efficient in forecasting psychosis onset for CHR individuals. Longitudinal assessments for psychopathology and general functions can be useful for dynamically predicting the prognosis of the pre-morbid phase of psychosis.

Lost in Translation: Challenges in the Diagnosis and Treatment of Early-Onset Schizophrenia.

Early-onset schizophrenia (EOS) is a heterogeneous condition that has a serious, insidious clinical course and poor long-term mental health outcomes. The clinical presentations are highly complex due to the overlapping symptomatology with other illnesses, which contributes to a delay in the diagnosis. The objective of the review is to study if an earlier age of onset (AAO) of EOS has poor clinical outcomes, the diagnostic challenges of EOS, and effective treatment strategies. The review provides a comprehensive literature search of 5966 articles and summarizes 126 selected for empirical evidence to methodically consider challenges in diagnosing and treating EOS for practicing clinicians. The risk factors of EOS are unique but have been shared with many other neuropsychiatric illnesses. Most of the risk factors, including genetics and obstetric complications, are nonmodifiable. The role of early diagnosis in reducing the duration of untreated psychosis (DUP) remains critical to reducing overall morbidity. Many specific issues contribute to the risk and clinical outcomes. Therefore, issues around diagnostic ambiguity, treatment resistance, nonadherence, and rehospitalizations further extend the DUP. There is hesitancy to initiate clozapine early, even though the empirical evidence strongly supports its use. There is a growing body of research that suggests the use of long-acting injectables to address nonadherence, and these measures are largely underutilized in acute settings. The clinical presentations of EOS are complex. In addition to the presence of specific risk factors, patients with an early onset of illness are also at a higher risk for treatment resistance. While there is a need to develop tools for early diagnosis, established evidence-based measures to address nonadherence, psychoeducation, and resistance must be incorporated into the treatment planning.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

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. Methods: 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.

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.

Neural Correlates of Facial Emotion Recognition in Non-help-seeking University Students With Ultra-High Risk for Psychosis.

Background: Since the introduction of the neurodevelopmental perspective of schizophrenia research on individuals at ultra-high risk for psychosis (UHR) has gained increasing interest, aiming at early detection and intervention. Results from fMRI studies investigating behavioral and brain functional changes in UHR during facial emotion recognition, an essential component of social cognition, showed heterogenous results, probably due clinical diversity across these investigations. This fMRI study investigated emotion recognition in a sub-group of the UHR spectrum, namely non-help-seeking, drug-naïve UHR with high cognitive functioning to reveal the neurofunctional underpinnings of their social functioning in comparison to healthy controls. Methods: Two large cohorts of students from an elite University (n 1 = 4,040, n 2 = 4,364) were screened firstly with the Prodromal Questionnaires and by surpassing predefined cut-offs then interviewed with the semi-structured Interview for Psychosis-Risk Syndromes to verify their UHR status. Twenty-one identified non-help-seeking UHR and 23 non-UHR control subjects were scanned with functional magnetic resonance imaging while classifying emotions (i.e., neutral, happy, disgust and fear) in a facial emotion recognition task. Results: Behaviorally, no group differences were found concerning accuracy, reaction times, sensitivity or specificity, except that non-help-seeking UHR showed higher specificity when recognizing neutral facial expressions. In comparison to healthy non-UHR controls, non-help-seeking UHR showed generally higher activation in the superior temporal and left Heschl's gyrus as well as in the somatosensory, insular and midcingulate cortex than the control subjects during the entire recognition task regardless of the emotion categories. In an exploratory analysis, in the non-help-seeking UHR group, functional activity in the left superior temporal gyrus was significantly correlated with deficits in the ability to experience emotions at uncorrected statistical thresholds. Conclusions: Compared to healthy controls, non-help-seeking UHR show no behavioral deficits during facial emotion recognition, but functional hyperactivities in brain regions associated with this cognitive process. Our study may inspire future early intervention and provide loci for treatment using neural stimulation.

Predictors of remission from the ultra-high risk state for psychosis.

AIM: A significant proportion of individuals at Ultra-High Risk (UHR) for psychosis do not transition to manifest psychosis. Many non-transitioning UHR individuals do, however, display poor long-term outcomes such as persistence of attenuated psychotic symptoms. Evidence is scarce on which variables may predict a better clinical and functional prognosis such as remission from the UHR state. METHODS: A total of 146 UHR individuals were enrolled in a randomized clinical trial (RCT), with this being analyses secondary to the RCT. Participants were assessed on multiple domains of symptoms, functioning, neuro- and social cognition. Regression analyses elucidated on the predictive power of these measures to remission from the UHR status (ie, not meeting UHR criteria) at 12-month follow-up. RESULTS: Of the 91 UHR individuals attending 12-month follow-up, 33 (36%) exhibited remission from the UHR state. Regression analyses revealed baseline functioning to be a significant predictor of risk remission, and this was maintained when controlling for the effect of antipsychotic medication, gender and estimated IQ. The individuals with remission from the UHR state showed lower attenuated psychotic- and depressive symptoms along with better functioning at 12-month follow-up. CONCLUSION: Our findings indicate functioning to be a contributor to the symptomatic recovery of UHR individuals, but a large amount of the variance on risk remission is, however, explained by other factors. Additionally, our findings suggest that UHR individuals with better functioning at ascertainment may present with a better clinical and functional prognosis, which may inform on the need for monitoring and intervention in this subgroup.

Changes in the cognitive function of Chinese college students with a clinical high risk of psychosis.

The purpose of our study was to explore the value of measuring cognitive functions for predicting the conversion to psychosis in Chinese college students with a clinical high risk (CHR). A total of 115 CHR students and 99 healthy controls were enrolled. All included participants were recruited from colleges in Wuhan, China. The MATRICS Consensus Cognitive Battery was used to evaluate cognitive function. CHR individuals were followed for 2 years, and the cognitive function of CHR individuals who later converted to psychosis (CHR-C) was compared to CHR individuals who did not convert (CHR-NC). Of the 107 CHR individuals that completed the 2- year follow-up, 29 (27.1%) developed a psychotic disorder. CHR individuals demonstrated poorer performance on all cognitive function tests compared to controls. CHR-C participants exhibited poorer performance on all cognitive tests except the Trail Making Test A and Continuous Performance Test-Identical Pairs compared to CHR-NC participants. The most significant differences displayed between CHR-C and CHR-NC groups were in visual learning, working memory, and reasoning and problem solving. The degree of cognitive impairment in visual learning and working memory may be a predictive marker for individuals who are at risk of developing psychosis.

Decreasing risk of psychosis by sulforaphane study protocol for a randomized, double-blind, placebo-controlled, clinical multi-centre trial.

AIM: A growing number of studies suggest a role of neuroinflammation and oxidative stress in the pathophysiology of psychosis. Sulforaphane (SFN), a natural compound extracted from cruciferous vegetables, has shown anti-inflammatory and anti-oxidative effects which imply a potential effect on decreasing the risk of psychosis. However, there is no study testing the efficacy of SFN for this purpose. It's necessary to evaluate its efficacy on individuals at clinical high risk (CHR) for psychosis. METHODS: This is a randomized, double-blind, placebo-controlled, multi-centre trial. A total of 300 CHR subjects will be identified in the course of face-to-face interviews using the Structured Interview for Prodromal Syndromes. All participants will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The study duration includes an intervention for 52 consecutive weeks, and additional 1-year follow-up. RESULTS: The primary outcome is 2-year conversion rate of psychosis. Secondary outcomes include 1-year conversion rate of psychosis, the severity and duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and peripheral blood biomarkers of inflammation, oxidative stress and metabolism. Safety monitoring will be performed using scales for side effect, serious adverse events recording, and laboratory tests. CONCLUSION: This trial is expected to clarify the efficacy of SFN in improving prodromal symptoms, and its role in decreasing the risk and conversion rate of psychosis among CHR subjects. The results will also provide solid evidence about the efficacy and safety of SFN in CHR population. Potential challenges and their solutions in performing the present trial are discussed.

Pathways to care in at-risk mental states: A systematic review.

AIM: Pathways to care are well studied in the First Episode Psychosis field, but less attention has been given to At-Risk Mental States or prodromal psychosis. This is important because accessing appropriate help at the earliest opportunity is likely to improve outcomes, particularly for those who make transition to psychosis. The present systematic review aimed to synthesize the available literature on pathways to care in ARMS or prodromal psychosis, and investigate the barriers and facilitators to receiving care for ARMS. METHODS: The CINAHL Complete, EMBASE, Medline Complete, PsycINFO and PubMED databases were searched. Studies were included if they were published in English between 1985 and 2019, where reported data came exclusively from an At-Risk Mental State population, and the study described or related to pathways to care. RESULTS: Ten studies met the inclusion criteria, of which 8 were quantitative. Screening tools and pathways to care instruments varied. Mental health professionals, and general practitioners played a key role in help seeking. Family involvement was also found to be an important factor. CONCLUSIONS: Pathways to care research in At-Risk Mental States are more scarce than in the field of First Episode Psychosis. More research is warranted, especially concerning the role of patient-level characteristics on pathways to care. A validated measure of pathways to care may also be of benefit.