Mentalizing impairments and hypermentalizing bias in individuals with first-episode schizophrenia-spectrum disorder and at-risk mental state: the differential roles of neurocognition and social anxiety.

Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS.

Effectiveness of a two-stage strategy using the 16-item Prodromal Questionnaire (PQ16/fPQ16) and the Comprehensive Assessment of At Risk Mental States (CAARMS) in the early detection of Ultra High Risk (UHR) patients in Lebanon: a cross-sectional pilot study.

OBJECTIVES: This study aims to identify the prevalence of Ultra High Risk (UHR) adults in a sample of patients in Lebanon and to compare screening and diagnostic tools. METHODS: This is a cross-sectional pilot study which targeted patients aged 17-30 years willingly seeking psychiatric care in a university hospital in Beirut, Lebanon. Participants were invited to fill either the English or the French version of the Prodromal Questionnaire (respectively, PQ16 or fPQ16). The abbreviated version of the "Comprehensive Assessment of At-Risk Mental States" (CAARMS) was then administered to all participants. The latter were subsequently sorted into one of the three UHR groups - vulnerability group, attenuated psychosis (APS), intermittent psychosis (BLIPS) - or were diagnosed as suffering from a psychotic disorder. RESULTS: Thirty-one patients participated in this study. The prevalence of positive screening on the PQ16/fPQ16 and positive diagnosis of UHR on the CAARMS were respectively of 61.29% and 45%. The APS group was the most prevalent (71.42%). A positive psychosis screening on PQ16/fPQ16 was statistically related to a UHR diagnosis on CAARMS (p-value: 0.011 on Chi2 test), OR=8.5 (95% CI: 1.4-50.9; p-value: 0.018). No relation was found between PQ16/fPQ16 results and risk stratification or between the number of "True" responses on PQ16/fPQ16 and the intensity of symptoms on CAARMS. PQ16/fPQ16 statements 5, 9, 11 and 16 predicted a UHR diagnosis on CAARMS (p-value of 0.045, 0.006, 0.045 and 0.045, respectively). CONCLUSION: This two-stage strategy for identifying UHR patients can be adopted in a tertiary health care center.

Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk.

BACKGROUND: Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust. METHODS: Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games. RESULTS: Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity. CONCLUSIONS: Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.

Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers.

Magnetic resonance imaging-based markers of schizophrenia have been repeatedly shown to separate patients from healthy controls at the single-subject level, but it remains unclear whether these markers reliably distinguish schizophrenia from mood disorders across the life span and generalize to new patients as well as to early stages of these illnesses. The current study used structural MRI-based multivariate pattern classification to (i) identify and cross-validate a differential diagnostic signature separating patients with first-episode and recurrent stages of schizophrenia (n = 158) from patients with major depression (n = 104); and (ii) quantify the impact of major clinical variables, including disease stage, age of disease onset and accelerated brain ageing on the signature's classification performance. This diagnostic magnetic resonance imaging signature was then evaluated in an independent patient cohort from two different centres to test its generalizability to individuals with bipolar disorder (n = 35), first-episode psychosis (n = 23) and clinically defined at-risk mental states for psychosis (n = 89). Neuroanatomical diagnosis was correct in 80% and 72% of patients with major depression and schizophrenia, respectively, and involved a pattern of prefronto-temporo-limbic volume reductions and premotor, somatosensory and subcortical increments in schizophrenia versus major depression. Diagnostic performance was not influenced by the presence of depressive symptoms in schizophrenia or psychotic symptoms in major depression, but earlier disease onset and accelerated brain ageing promoted misclassification in major depression due to an increased neuroanatomical schizophrenia likeness of these patients. Furthermore, disease stage significantly moderated neuroanatomical diagnosis as recurrently-ill patients had higher misclassification rates (major depression: 23%; schizophrenia: 29%) than first-episode patients (major depression: 15%; schizophrenia: 12%). Finally, the trained biomarker assigned 74% of the bipolar patients to the major depression group, while 83% of the first-episode psychosis patients and 77% and 61% of the individuals with an ultra-high risk and low-risk state, respectively, were labelled with schizophrenia. Our findings suggest that neuroanatomical information may provide generalizable diagnostic tools distinguishing schizophrenia from mood disorders early in the course of psychosis. Disease course-related variables such as age of disease onset and disease stage as well alterations of structural brain maturation may strongly impact on the neuroanatomical separability of major depression and schizophrenia.

Natural language processing in at-risk mental states: enhancing the assessment of thought disorders and psychotic traits with semantic dynamics and graph theory.

OBJECTIVE: Verbal communication has key information for mental health evaluation. Researchers have linked psychopathology phenomena to some of their counterparts in natural-language-processing (NLP). We study the characterization of subtle impairments presented in early stages of psychosis, developing new analysis techniques and a comprehensive map associating NLP features with the full range of clinical presentation. METHODS: We used NLP to assess elicited and free-speech of 60 individuals in at-risk-mental-states (ARMS) and 73 controls, screened from 4,500 quota-sampled Portuguese speaking citizens in Sao Paulo, Brazil. Psychotic symptoms were independently assessed with Structured-Interview-for-Psychosis-Risk-Syndromes (SIPS). Speech features (e.g.sentiments, semantic coherence), including novel ones, were correlated with psychotic traits (Spearman's-ρ) and ARMS status (general linear models and machine-learning ensembles). RESULTS: NLP features were informative inputs for classification, which presented 86% balanced accuracy. The NLP features brought forth (e.g. Semantic laminarity as 'perseveration', Semantic recurrence time as 'circumstantiality', average centrality in word repetition graphs) carried most information and also presented direct correlations with psychotic symptoms. Out of the standard measures, grammatical tagging (e.g. use of adjectives) was the most relevant. CONCLUSION: Subtle speech impairments can be grasped by sensitive methods and used for ARMS screening. We sketch a blueprint for speech-based evaluation, pairing features to standard thought disorder psychometric items.

Associations between Verbal Fluency and Asymmetry of White Matter Integrity in the Superior Longitudinal Fasciculus in At-Risk Mental States for Psychosis.

Verbal fluency is one of the most severely impaired components of cognitive function in schizophrenia and is also impaired in at-risk mental states (ARMSs) for psychosis. The aim of this study was to explore the markers of disease progression in subjects with ARMSs by comparing the association between the white matter integrity of the superior longitudinal fasciculus (SLF) and verbal fluency in subjects with ARMSs and healthy control (HC) subjects. The correlations of the fractional anisotropy (FA) values on diffusion tensor imaging (DTI) and the laterality index (LI) values of SLF branches I, II, and III with the verbal fluency performance were analyzed in right-handed subjects with ARMSs (ARMS group; n = 18) and HC subjects (HC group; n = 34) aged 18 to 40 years old. In the HC group compared with the ARMS group, the LI values suggested right lateralization of the SLF II and III. Letter fluency was significantly correlated with the LI of the SLF III in both the ARMS and HC groups. The regression coefficient (ß) of this correlation was calculated using the least squares method and yielded a positive number (73.857) in the ARMS group and a negative number (-125.304) in the HC group. The association of the rightward asymmetry of the SLF III with the verbal fluency performance observed in the HC group appeared to be lost in the ARMS group, and this could serve as one of the markers of the pathological progression to psychosis in patients with schizophrenia.

The effectiveness of public health interventions, initiatives, and campaigns designed to improve pathways to care for individuals with psychotic disorders: A systematic review.

PURPOSE: Lengthy duration of untreated psychosis (DUP) and duration of untreated illness (DUI) in people at clinical high-risk for psychosis (CHR-P) and first episode psychosis (FEP) is associated with poorer outcomes. However, individuals with FEP often experience negative pathways to care involving contacts with police, crisis services and requiring compulsory admissions, and evidence suggests individuals with both FEP and CHR-P often experience lengthy delays to treatment. Early detection interventions, such as public health interventions, may be one way to reduce delays. This systematic review aimed to synthesise the available evidence on such interventions. METHODS: The EMBASE, PsychINFO, CINAHL, and MEDLINE databases were searched. Studies were included if they compared an intervention designed to improve timely access to treatment for individuals with FEP or CHR-P to standard treatment provision. Interventions may be targeted at potential patients, their families, the general public, or non-healthcare professionals. Outcomes of interest were DUP or DUI, and/or characteristics of pathways to care. RESULTS: Nineteen studies met the inclusion criteria. All consisted of FEP populations, none of CHR-P populations. Employing narrative synthesis, we found mixed results about the effectiveness of interventions at reducing DUP and interventions appeared to differentially impact groups. Pathways to care information was limited and mixed. CONCLUSION: Findings on the effectiveness of interventions designed to improve timely access to treatment were inconclusive. More research is warranted to better understand where delays occur and factors which may influence this for both FEP and CHR-P populations which may help to develop targeted interventions to address delays.

At-risk mental states and personality traits: A cluster analysis approach on a group of help-seeking young adults.

INTRODUCTION: Research on the relationship between personality and psychosis onset is growing, with the goal of preventing or intervening early in patients' vulnerability. The identification of individuals with at-risk mental states has enabled the development of early intervention strategies, such as Programma 2000, a youth mental health service that was implemented in Milan (Italy). AIMS: Focusing on the 18-25 age range-the time window with the highest incidence of psychotic onset-this study aims to identify the personality traits that may characterize the at-risk mental states and the social functioning of a group of help-seeking young adults. METHODS: The sample includes 169 people (48.5% males and 51.5% females). Data were collected during an initial assessment that comprised the Social and Occupational Functioning Assessment Scale, the Personality Inventory for DSM-5, the Checklist ERIraos and a clinical session. RESULTS: Results identified a three-cluster solution based on the Checklist scores: Cluster 1 'Not at psychotic risk'; Cluster 2 'At intermediate risk'; Cluster 3 'With psychotic onset'. The multivariate analysis of the variance of personality traits shows significant differences among the clusters in negative affect, detachment and disinhibition. Higher scores in these traits may distinguish individuals, not at psychotic risk from those at intermediate risk or with psychotic onset. Moreover, social functioning was found to be negatively associated with clusters of psychotic risk. CONCLUSION: Findings from this study highlighted the need to evaluate personalized interventions targeting such personality traits that could prevent psychotic transition and promote psychological well-being.

Translation and cross-cultural adaptation to Brazilian Portuguese of two brief screening tools for at-risk psychosis youth: the Prodromal Questionnaire (PQ-16) and the PRIME-Screen.

INTRODUCTION: Prodromal characteristics of psychosis have been described for more than a century. Over the last three decades, a variety of studies have proposed methods to prospectively identify individuals (and youth in particular) who are at high risk of developing a psychotic disorder. These studies have validated various screening instruments and made them available in several languages. Here, we describe the translation into Brazilian Portuguese and cross-cultural adaptation of two such screening tools - the Prodromal Questionnaire-16 (PQ-16) and the Prevention through Risk Identification, Management, and Education (PRIME)-Screen. METHOD: Two bilingual native speakers of Brazilian Portuguese translated the questionnaires from English. A native English speaker then performed back-translations into English. These back-translated versions were submitted to the original authors. They provided feedback and later approved the final versions. RESULTS: After translation and cross-cultural adaptation, no items needed to be changed in the adapted PQ-16 and four items were revised in the PRIME-Screen. After the peer-review process, we included two suggestions in the PQ-16 to facilitate use of the tool in our cultural and social contexts. The PRIME-Screen did not need further changes. CONCLUSION: These new instruments can help screen Brazilian Portuguese-speaking patients who are at risk of psychosis in primary care.

Mentalizing in individuals with state and trait risk for psychosis: a systematic review.

Background: Mentalization is an umbrella concept defined as the ability to interpret one's and others' mental states. Previous studies have hypothesized that mentalization may be a crucial resilience factor that significantly moderates the likelihood of developing psychotic disorders in individuals with both state and trait risk factors for the illness. Purpose: The study reviews the role of mentalizing abilities (e.g., reflective functioning, Theory of Mind (ToM), and metacognition) in young adults with At-Risk Mental States (ARMS) and schizotypal traits. Specifically, the objective is to include articles that (a) evaluate the links between low mentalizing and both state (ARMS/CHR) and trait (schizotypy) risk for psychosis (b) compare the differences in mentalizing abilities between individuals with ARMS, schizotypy, full-blown psychosis, and healthy controls. Method: Electronic databases (PsycINFO, PubMed, Scopus, and Google Scholar) were used to search for articles, while Rayyan was employed to facilitate the screening and selection of studies. Eligible studies are original English-language; peer-reviewed research articles on populations that met validated risk diagnostic criteria for psychosis, ARMS, and healthy controls; empirical studies evaluating the association or differences between psychotic risk and mentalizing abilities. Non-English language studies, the ones not considering state or trait risk for psychosis, and qualitative studies were excluded. After the application of the PRISMA checklist and the inclusion and exclusion criteria previously mentioned, 10 articles were extracted. The systematic review has been registered on Prospero (CRD42023397594). Results: Low levels of reflective functioning and metacognition may predict a transition to psychosis. In addition, reflective functioning and metacognitive impairments are associated with attenuated psychotic symptoms in both state risk groups and in non-clinical individuals with schizotypal traits. Concerning ToM tasks, mixed results emerged. Conclusion: The results obtained from the review suggest that the application of strategies to attenuate maladaptive metacognitive beliefs and low mentalization may be equally effective in improving psychotic symptoms. The assessment of mentalization and metacognition could potentially provide additional prognostic value over factors predisposing to psychosis. Good mentalization and metacognition functioning should be considered as protective factors able to minimize the transition to psychosis.

High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers.

The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism (SNP) rs6265C > T, Val66Met, affects BDNF secretion and has been related to inflammatory processes. Both the rs6265 and BDNF protein levels have been widely investigated in neuropsychiatric disorders with conflicting results. In the present study we examined BDNF mRNA expression in blood considering the SNP rs6265 and its relationship with inflammatory markers in the early stages of psychosis. The rs6265 genotype and blood BDNF mRNA levels were measured in 34 at-risk mental states (ARMS) individuals, 37 patients with first-episode psychosis (FEP) and 42 healthy controls (HCs) by quantitative PCR and reverse transcription (RT)-qPCR using validated TaqMan assays. We also obtained measures of interleukin-6 (IL6) mRNA levels, fibrinogen, neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein. We identified that BDNF mRNA levels were associated with the rs6265 genotype in an allele-dose-dependent manner, with low expression levels associated with the T allele (Met substitution). Thus, we controlled for the rs6265 genotype in all analyses. Blood BDNF mRNA levels differed between diagnostic groups: patients with FEP exhibited higher blood BDNF mRNA levels than ARMS individuals, and the lowest levels were observed in HC. In addition, we observed significant correlations between BDNF mRNA levels and inflammatory markers (IL6 mRNA levels and NLR), controlled by the rs6265 genotype, in ARMS and FEP groups. This exploratory study suggests that the rs6265 genotype is associated with differential blood mRNA expression of BDNF that increases with illness progression and correlated with inflammation in the early stages of psychosis.

Personality traits and transition to psychosis one year after the first assessment.

Introduction: Several studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process. Aims: The current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk. Methods: The sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests' assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample. Results: Overall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits. Conclusion: Results obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported.

Corrigendum: Personality traits and transition to psychosis one year after the first assessment.

[This corrects the article DOI: 10.3389/fpsyg.2023.1096626.].

Clinical and Functional Differences Between Mexican Youth at Clinical High Risk for Psychosis and With Familial High Risk.

Few studies have explored the differences in clinical psychopathology between youth at high risk for psychosis and those at familial high risk for psychosis. This study seeks to describe and compare the sociodemographic, clinical, and functional characteristics of At-Risk Mental State (ARMS) for psychosis youth and those with a first- or second-degree relative with psychosis (Familial High-Risk: FHR) in a Mexican sample. Twenty-one ARMS individuals and 21 with FHR were evaluated for sociodemographic characteristics, psychopathological symptoms, and functional impairment. ARMS individuals were significantly younger, had fewer years of schooling, and were more likely to be male than those in the FHR group. Groups did not differ as regards marital status or occupation. The ARMS group showed greater severity of prodromal symptoms, schizotypal personality traits, and general psychopathology than the FHR group. In addition, they reported more premorbid adjustment deficit from early adolescence than the FHR group. Current overall social and role functioning was significantly lower in the ARMS group. Findings are consistent with ARMS studies from other countries. First- or second-degree relatives of patients with psychosis should be considered a vulnerable group as they display several symptoms of general psychopathology and may experience social adjustment problems in their adult lives. The lack of early detection and intervention psychosis programs in Mexico underlines the need to prioritize the development of preventive strategies to help close the care gap.

Psychological Pathways to Paranoia and Psychotic-Like Experiences in Daily-Life: The Mediating Role of Distinct Affective Disturbances.

BACKGROUND AND HYPOTHESIS: Influential models of psychosis indicate that the impact of putative causal factors on positive symptoms might be explained partly through affective disturbances. We aimed to investigate whether pathways from stress and self-esteem to positive symptoms, as well as reversal pathways from symptoms to stress and self-esteem, were mediated through specific affective disturbances across the extended psychosis phenotype. STUDY DESIGN: Using experience sampling methodology, 178 participants (65 high-schizotypy, 74 at-risk mental state, and 39 first-episode psychosis) were assessed on levels of momentary stress, self-esteem, anxiety, sadness, psychotic-like experiences (PLE), and paranoia. Multilevel mediation models were fit to examine indirect effects of each of these pathways. Considering evidence of mediation, each indirect pathway will be combined in a single model to explore their relative contributions. STUDY RESULTS: Anxiety, sadness, and self-esteem mediated the pathways from stress to PLE and paranoia in daily-life. In the pathway to paranoia, sadness, and self-esteem showed larger contributions than anxiety. Pathways from self-esteem to PLE and paranoia were mediated by anxiety and sadness, the later showing a larger contribution. Pathways from symptoms to stress, but not from symptoms to self-esteem, were differently explained by emotional states; sadness lost its mediating effect and anxiety was the most important mediator. Few differences across groups were found. CONCLUSIONS: This study lends support to psychological models of psychosis that highlight the relevance of affective disturbances in the risk and expression of psychosis. Furthermore, specific influences of different negative emotional states were identified, which could enhance psychological treatments.

Shared Decision Making With Young People at Ultra High Risk of Psychotic Disorder.

Introduction: While the majority of young people who meet the criteria for being considered at increased risk of psychosis do not go on to develop a psychotic disorder, young people are currently being identified and treated in early intervention services. Ethical concerns have been raised concerning the decision about whether or not to provide treatment, and if so, what type of treatment. This study sought to support young people themselves to make these decisions with support from their clinician through a shared decision-making approach, facilitated by an online decision aid. Methods: This project used the International Patient Decision Aid Standards (IPDAS) to guide the development and piloting of an online decision aid across two phases: (1) qualitative, semi-structured focus groups with young people who were past clients and clinicians from an early psychosis service; and (2) pilot testing of the decision aid with clinicians and young people who were current clients to finalize the development. Results: Issues discussed by clinicians in the focus group were grouped into three main areas: (1) engagement phase; (2) assessment and priorities for treatment; and (3) initial and ongoing decision making. Clients focused on the context in which the decisions were made, including as they experienced initial feelings of resistance, and then acceptance of efforts made to describe and treat their mental health challenges. Clients highlighted the need for collaboration between themselves and their clinician, and the need to be equipped with the knowledge and tools to take care of themselves. These focus group data were used to refine the online decision aid. Pilot testing revealed that while it was overall useful and relevant, important limitations were noted by both clients and clinicians. Discussion: The use of a decision aid to facilitate shared decision making (SDM) in this area is feasible and has utility for both clients and clinicians. Use of such a tool can help to address the need to uphold the rights of young people as decision makers about their own care. Future efforts should embed decision aids within complex SDM interventions, and research to understand issues relating to implementation of these interventions.

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.

Establishing a clinical high-risk program in Tunisia, North Africa: A pilot study in early detection and identification.

BACKGROUND: Early identification and prevention research has provided huge advances in our understanding of early screening and identification of young people at clinical high-risk (CHR). Most of these procedures were developed in high-income countries, yet middle-income countries in North Africa such as Tunisia can benefit from these empirically-based assessment approaches. METHODS: Using established procedures, nine Tunisian psychiatric raters were trained on structured assessments: the CAARMS, BPRS, and SCID to high standards of interrater reliability. These raters developed a clinical high-risk program (CHiRP) in Tunisia and recruited 10 patients who were exhibiting possible signs of CHR. These patients were evaluated to determine if they met criteria for a CHR group, such as Attenuated Psychosis. RESULTS: Trained raters met the following interrater reliability criteria for the CAARMS and BPRS (ICC = .80 or greater) and the SCID (Kappa = .75 or greater). Of 10 pilot patients, six were classified as CHR and belonging to the Attenuated Psychosis Group. One of the six patients converted to psychosis 3 months after study entry for a conversion rate of 17% which is comparable with currently published rates globally. DISCUSSION: The first CHR program has been established in Tunisia, a middle-income country using methods developed in high income countries. Efforts aimed at assembling a group of prevention-oriented psychiatrists, obtaining administrative support, and training raters to high levels of interrater reliability were successful. The feasibility was demonstrated for screening, assessing, treating, and following-up of 10 CHR patients suggesting that conversion rates are comparable to those of Western and European countries.

Anxiety sensitivity dimensions in young individuals with at-risk-mental states.

Anxiety Sensitivity (AS) is a transdiagnostic risk factor involved in the development and maintenance of different psychopathological conditions including anxiety disorders and psychosis. It consists of Physical Concerns (e.g., the belief that palpitations lead to a cardiac arrest), Social Concerns (the belief that observable anxiety reactions will elicit social rejection), and Cognitive Concerns (the belief that cognitive difficulties lead to mental incapacitation). No study investigated whether specific AS dimensions are related to At-Risk Mental States (ARMS). This study compared AS dimensions between young individuals with ARMS, patients after a recently occurred First-Episode Psychosis (FEP) and matched community controls. Based on models of ARMS and previous evidence, it was hypothesized that ARMS individuals have higher physical, social and cognitive concerns than FEP patients and controls. Thirty individuals with ARMS and 30 with FEP and 30 controls recruited from the general population completed the Anxiety Sensitivity Index-3 (ASI-3) and Penn State Worry Questionnaire. ARMS and FEP individuals had higher scores than controls on ASI-3 Cognitive Concerns [F( 2,87)= 11.48, p<.001]. Individuals with ARMS had higher ASI-3 Physical Concerns scores than FEP patients [F( 2,87)= 5.10, p<.01] and at a marginal significance level than controls. No between-group difference was found on Social Concerns. Higher ASI-3 Physical Concerns scores [B = -.324, Wald's χ2 (1) = 8.29, p < .01] and psychiatric comorbidities [B = -2.726, Wald's χ2 (1) = 9.33, p < .01] were significantly related to ARMS than FEP. Higher ASI-3 Social Concerns scores were related to FEP, despite at a marginal significance level [B =.213, Wald's χ2 (1) = 3.79, p = .052]. Interventions for AS Cognitive/Physical Concerns could be incorporated in the treatment of ARMS. A replication of the findings is required. Future longitudinal studies should examine whether Cognitive Concerns predict development of FEP in ARMS to improve early detection and prevention strategies.

Association of preceding psychosis risk states and non-psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS-2 cohort.

The validity and clinical utility of the concept of "clinical high risk" (CHR) for psychosis have so far been investigated only in risk-enriched samples in clinical settings. In this population-based prospective study, we aimed - for the first time - to assess the incidence rate of clinical psychosis and es-timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM-IV diagnoses of non-psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person-years. The mutually-adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12-36.49), psychosis high-risk state (HR=7.86, 95% CI: 2.76-22.42) and drug use disorders (HR=5.33, 95% CI: 1.61-17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6-94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4-82.9), psychosis high-risk state (PAF=36.9, 95% CI: 11.3-55.1), and drug use disorders (PAF=18.7, 95% CI: -0.9 to 34.6) as the most important factors. Although the psychosis high-risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high-risk states in the population. These findings provide empirical evidence for the "prevention paradox" of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis-focused approach for achieving population-based improvements in prevention of psychotic disorders.