Ultra-high Risk Criteria Research Articles

Cortical Volume Differences in Subjects at Risk for Psychosis Are Driven by Surface Area.

In subjects at risk for psychosis, the studies on gray matter volume (GMV) predominantly reported volume loss compared with healthy controls (CON). However, other important morphological measurements such as cortical surface area (CSA) and cortical thickness (CT) were not systematically compared. So far, samples mostly comprised subjects at genetic risk or at clinical risk fulfilling an ultra-high risk (UHR) criterion. No studies comparing UHR subjects with at-risk subjects showing only basic symptoms (BS) investigated the differences in CSA or CT. Therefore, we aimed to unravel the contribution of the 2 morphometrical measures constituting the cortical volume (CV) and to test whether these groups inhere different morphometric features. We conducted a surface-based morphometric analysis in 34 CON, 46 BS, and 39 UHR to examine between-group differences in CV, CSA, and CT vertex-wise across the whole cortex. Compared with BS and CON, UHR individuals presented increased CV in frontal and parietal regions, which was driven by larger CSA. These groups did not differ in CT. Yet, at-risk subjects who later developed schizophrenia showed thinning in the occipital cortex. Furthermore, BS presented increased CSA compared with CON. Our results suggest that volumetric differences in UHR subjects are driven by CSA while CV loss in converters seems to be based on cortical thinning. We attribute the larger CSA in UHR to aberrant pruning representing a vulnerability to develop psychotic symptoms reflected in different levels of vulnerability for BS and UHR, and cortical thinning to a presumably stress-related cortical decomposition.

Clinical profile, conversion rate, and suicidal thinking and behaviour in children and adolescents at ultra-high risk for psychosis: a theoretical perspective.

Over the past years there has been substantial growing interest in the prodromes of psychosis to identify individuals at risk for psychosis prior to their first psychotic episode. Researchers have proposed criteria to detect young adults at Ultra-High Risk (UHR) for psychosis, and these criteria have also been applied to children and adolescents, though few clinical studies have examined this population. This theoretical perspective presents some of the crucial issues in the assessment and treatment of UHR children and adolescents: the presence of a specific clinical profile (i.e., different to that of healthy controls and UHR young adults), the predictive value of UHR criteria, and the presence and clinical significance of suicidal thinking and behaviour. In UHR children and adolescents, like UHR young adults, the presence of Attenuated Psychotic Symptoms (APS) is the most frequently reported inclusion criterion at baseline, with a prevalence of approximately 89–100%. In addition, there are frequently non-psychotic comorbid diagnoses of depressive and anxiety disorders. In contrast to the UHR adult population, UHR children and adolescents demonstrate a lower conversion rate to frank psychosis, most likely due to their high rate of APS. Finally, UHR adolescents report a high prevalence of suicidal ideation and self-injurious behaviour (67.5%), as well as a significantly greater frequency of attempted suicide, relative to adolescents with frank psychosis. On this basis, UHR children and adolescents report a clinical complexity that should be carefully monitored and considered for specific and targeted therapeutic interventions to be planned and developed.

T88. VALIDATION OF THE KOREAN VERSION OF THE 15-ITEM COMMUNITY ASSESSMENT OF PSYCHIC EXPERIENCES (CAPE-15) IN A COLLEGE POPULATION

BackgroundThe Community Assessment of Psychic Experiences-Positive 15-items scale (CAPE-15) is another brief, valid screening tool used to identify people at high risk of psychosis in the community. This study examined the reliability and validity of the Korean version of the CAPE-15 in university students.MethodsThis study had two stages: initial screening with self-report questionnaires including the CAPE-15, and semi-structured interviews to investigate the instrument’s diagnostic validity. The initial screening involved 1,749 college students. The modified Korean version of Prodromal Questionnaire-16 item (mKPQ-16) was also administered. The criteria for ultra-high risk (UHR) of psychosis in the Comprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis.ResultsTwelve of the interviewed subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristic curve was highest (0.936) for the CAPE-15 distress score (p<0.001). The use of 6 as the cutoff for the CAPE-15 distress score resulted in the best balance of sensitivity (91.7%) and specificity (85.2%), with a favorable positive predictive value of 32.4%. The coefficients of correlation between the CAPE-15 and mKPQ-16 were significant.DiscussionThis study showed that the CAPE-15 is a good screening instrument for use in community and school settings. In particular, the better validity of the CAPE-15 suggests that it is a promising alternative to other brief self-report screening tools that are currently used to detect UHR. This validation of a questionnaire with a small number of items may make it feasible to screen large numbers of young adults in the community and shorten the duration of untreated psychosis through prompt early intervention.

Validation of the Korean Version of the 15-Item Community Assessment of Psychic Experiences in a College Population.

ObjectiveTo investigate the reliability and validity of the Korean version of the Community Assessment of Psychic Experiences-15 item positive scale (CAPE-15) in college students. MethodsThis study had two stages: initial screening with self-report questionnaires including the CAPE-15, and semi-structured interviews to investigate the instrument’s diagnostic validity. The initial screening involved 1,749 college students. The modified Korean version of Prodromal Questionnaire-16 item (mKPQ-16) was also administered. The criteria for ultra-high risk (UHR) of psychosis in the Comprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis. ResultsTwelve of the interviewed subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristic curve was highest (0.936) for the CAPE-15 distress score (p<0.001). The use of 6 as the cutoff for the CAPE-15 distress score resulted in the best balance of sensitivity (91.7%) and specificity (85.2%), with a favorable positive predictive value of 32.4%. The coefficients of correlation between the CAPE-15 and mKPQ-16 were significant. ConclusionThe Korean version of the CAPE-15 is a good instrument for screening for psychosis risk in collegiate settings. The validation of this scale could contribute to the early identification of psychosis in the Korean community.

Évaluation des états mentaux à risque de transition psychotique dans un échantillon de jeunes détenus de sexe masculin en Tunisie

BackgroundPrevalence of psychotic disorders in a prison population is higher than in the general population. Recent research has shown that early intervention is feasible in prison settings, and that approximately 5% of screened prisoners have met ultra-high-risk (UHR) for psychosis criteria. We aimed to identify the prevalence of the UHR states for developing psychosis in a group of newly incarcerated men in the Jendouba Civil Prison and to analyze the association between UHR states and socio-demographic data and substance use. MethodWe carried-out a cross-sectional study among 120 prisoners. Every prisoner was interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). The Social and Occupational Functioning Assessment Scale (SOFAS) was used to assess the participant's level of functioning. ResultsWe found a prevalence of subjects meeting the UHR criteria of 21.3%. UHR subjects had significantly more psychiatric family history (P=0.035), personal history of suicide attempt(s) (0.035) and self-injury (P=0.013) compared to non-UHR subjects. Clinical self-evaluation found significantly more depression and anxiety in the UHR group (P=0.020 and P=0.035, respectively). In addition, social and occupational functioning was significantly more impaired in the UHR group (P=0.007). UHR subjects used significantly more cannabis in lifetime (P=0.015) as well as in the past year (P=0.022) and had a significantly higher frequency of cannabis use (P=0.01) compared to non-UHRs. ConclusionPrison mental health teams face the challenge of identifying prisoners who need mental health services and providing early care to this vulnerable group; this challenge may offer a unique opportunity for intervention among a population that might not otherwise have had access to it.

Higher order language impairments can predict the transition of ultrahigh risk state to psychosis-An empirical study.

Higher order language skills, for example, non-literal language, humour, prosody deal with 'what is meant' and they are necessary for communicative exchange and relationships; No study has investigated their link with conversion to psychosis. The purpose of this study was to determine whether such skills could act as predictors of the onset of psychosis, and compare those of individuals converting and non-converting to psychosis with control of cognitive functions. Seventy-three patients, aged 15 to 32 years, fulfilling ultrahigh risk criteria took part: 14% of whom were receiving antipsychotic drugs. The study was observational, prospective and longitudinal in nature, and scheduled for 60 months. Pragmatic language skills were evaluated using the Polish version of the right hemisphere language battery. The ultrahigh risk (UHR) criteria were evaluated with Comprehensive Assessment of At-Risk Mental States; attention, intelligence and verbal fluency were controlled. The conversion rate was 25%; converters demonstrated impaired humour comprehension and metaphor explanation abilities; composite score of pragmatic language was associated with a hazard ratio of 6.0 (95% CI 1.8-20.5) and AUC of .73. Verbal fluency was an independent predictor of conversion, but attention and intelligence were not; pragmatic language skills were associated with social function but not with prodromal symptoms. The results suggest that deficits in humour comprehension and metaphor explanation could predict conversion to psychosis. These findings could improve diagnosis and create implications for speech and language therapy in UHR groups. Further studies on the mechanisms of pragmatic skills should analyze their relationship with abstract measures and semantic coherence.

Subjective experience of social cognition in adolescents at ultra-high risk of psychosis: findings from a 24-month follow-up study

Deficits in social cognition have been reported in people at ultra-high risk (UHR) of psychosis exclusively using socio-cognitive tasks and in adolescent and young adult mixed population. Aim of this study was (1) to assess subjective experience of social cognition in adolescent help-seekers identified through UHR criteria, (2) to explore its significant correlations with psychopathology and functioning in UHR individuals; and (3) to monitor longitudinally its stability after a 24-month follow-up period. Participants [51 UHR, 91 first-episode psychosis (FEP), and 48 non-UHR/FEP patients], aged 13-18years, completed the comprehensive assessment of at-risk mental states and the GEOPTE scale of social cognition for psychosis. In comparison with non-UHR/FEP patients, both UHR and FEP adolescents showed significantly higher GEOPTE total scores. After 12months of follow-up, UHR individuals had a significant decrease in severity on GEOPTE "Social Cognition" subscore. In the UHR group at baseline, GEOPTE scores had significant positive correlations with general psychopathology, positive and negative dimensions. Across the 2-year follow-up period, social cognition subscores specifically showed more stable associations with general psychopathology and negative symptoms. Social cognition deficits are prominent in UHR adolescents and similar in severity to those of FEP patients at baseline. However, these impairments decreased over time, presumably together with delivery of targeted, specialized models for early intervention in psychosis.

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

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. 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. 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. 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.

Early recognition and prevention of schizophrenia and other psychoses

The last two decades of clinical research have clearly demonstrated the comprehensive benefits of the early recognition and treatment of psychotic disorders. The attenuated and transient positive symptoms according to the ultrahigh risk criteria and the basic symptom criterion "Cognitive disturbances" are the main approaches for an indicated prevention. They have recently been recommended as criteria for aclinical high-risk (CHR) state of psychosis by the European Psychiatric Association (EPA) and, following these, in the German S3 guidelines for the treatment of schizophrenia by the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN); however, the efficacy of early treatment of patients with a CHR for psychoses critically depends on the development of prognostic instruments, which enable healthcare professionals to reliably identify these patients based on the individual objective risk profiles. An important goal is the treatment of functional deficits, which can be identified by an individual risk profile. The treatment of existing comorbid mental disorders, psychosocial problems and the prevention of potential future disorders also characterizes the recommendations of the EPA and DGPPN for early treatment, which favor psychotherapeutic, especially cognitive behavioral interventions over pharmacological treatment. The close interdisciplinary cross-sectoral cooperation between the disciplines of child and adolescent psychiatry, and adult psychiatry is of outstanding importance in this context.

Distress related to psychotic symptoms in individuals at high risk of psychosis

This study assessed the relationship between distress, severity and frequency of attenuated psychotic symptoms in individuals meeting Ultra High Risk (UHR) criteria, both at baseline and over time. It also assessed distress in relation to attenuated symptoms and whether cognitive behavioural therapy (CBT) reduced distress over time by symptom type. At baseline a combined total of 592 UHR participants (mean age 19.9; males, 53.9%) from two studies were assessed using a confirmatory factor analysis (CFA). Change over time from this baseline point was assessed using latent growth curve (LGC) models, based on participants from one of the studies. Distress associated with psychotic symptom was shown to be a separate psychological construct from severity and frequency. Distress was also significantly associated with severity but not frequency. Longitudinal LGC models with 244 participants showed that distress, severity and frequency all reduced over six months, although the rate of distress reduction varied across symptom type. Non-bizarre ideas (NBI) were more distressing and had the fastest rate of distress reduction over time. The baseline distress for some symptoms also strongly predicted the symptom severity change over time, suggesting that distress may cause change in the UHR criteria for unusual thought content (UTC) and NBI symptoms. CBT was not shown to be significantly different from treatment as usual (TAU) in its effect on distress. However, distress reduces over time, particularly in the first 3 months after presentation. We recommend that distress should be used as an outcome in future research and as a clinical indicator.(250 words)

The reality of at risk mental state services: a response to recent criticisms.

In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Anomalous self-experiences are strongly associated with negative symptoms in a clinical high-risk for psychosis sample

ObjectiveAnomalous self-experiences (ASE) are considered as central features of the schizophrenia spectrum disorders and prodromal schizophrenia. We investigated total and single-item prevalence of these phenomena in a clinical high-risk (CHR) for psychosis sample, and associations with conventional psychosis-risk symptoms, present and childhood global/psychosocial functioning, and childhood trauma. MethodsThe sample (n = 38) included 31 CHR, according to ultra-high risk or cognitive basic symptoms (COGDIS) criteria, and seven with non-progressive attenuated positive symptoms. Psychopathological evaluations included the Examination of Anomalous Self-Experience (EASE), Structured Clinical Interview for Prodromal Syndromes (SIPS), Schizophrenia Proneness Instrument – Adult (SPI-A) (only the COGDIS-criteria), a diagnostic interview (SCID-I), Global Assessment of Functioning – Split version (S-GAF), Premorbid Adjustment Scale (PAS) and Childhood Trauma Questionnaire (CTQ). ResultsThe mean total EASE score was in line with reports from other CHR samples, and was particularly enhanced in schizotypal personality disorder and in subjects fulfilling COGDIS-criteria. The four most frequent EASE-items were present in two-thirds or more of the participants. EASE total was significantly associated with negative and disorganization symptoms. A multiple regression analysis revealed that the level of negative symptoms explained most of the variance in EASE total. ConclusionsThese results corroborates other findings that anomalous self-experiences are frequent and important features in CHR conditions and in the schizophrenia spectrum. The strong associations with negative symptoms and cognitive disturbances (COGDIS) should be investigated in longitudinal studies to address causality, psychopathological pathways and schizophrenia spectrum specificity. The weaker correlation between EASE total and positive symptoms may partly be related to a restricted range of positive symptoms.

Anhedonia in adolescents at ultra-high risk (UHR) of psychosis: findings from a 1-year longitudinal study.

Previous findings suggested deficits in pleasure experience in schizophrenia, but little is known in psychosis risk prodrome, especially in adolescence. Aim of this study was (1) to assess anhedonia in distinct help-seeking subgroups of adolescents identified through the ultra-high risk (UHR) criteria, (2) to explore any association of anhedonia with other psychopathological aspects in the UHR group, and (3) to monitor longitudinally the stability of anhedonia in UHR individuals across 1-year follow-up period. 123 participants (13-18years) completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II, the Schizotypal Personality Questionnaire-Brief version, the Brief-O-LIFE questionnaire (BOL), and the Brief version of the World Health Organization Quality of Life scale (WHOQOL-BREF). Two different indexes of anhedonia were used: CAARMS "Anhedonia" item 4.3 and BOL "Introvertive Anhedonia" subscale scores. No difference in anhedonia levels between UHR and First Episode Psychosis (FEP) groups was found. UHR adolescents showed higher CAARMS and BOL anhedonia scores than non-UHR/FEP. After 1-year follow-up period, UHR adolescents had a significant decrease in severity only in CAARMS anhedonia subscores. In UHR subgroup, CAARMS anhedonia measures showed significant correlations with impaired role functioning and negative symptoms, while BOL anhedonia was significantly correlated with specific schizotypal personality traits concerning interpersonal deficits. Anhedonia is prominent in the psychosis prodrome, also in adolescence. Its severity is not statistically different from that of FEP adolescents and is related to more severe functioning impairment and a worse quality of life.

Saccadic eye movements in different dimensions of schizophrenia and in clinical high-risk state for psychosis

BackgroundOculomotor dysfunction is one of the most replicated findings in schizophrenia. However the association between saccadic abnormalities and particular clinical syndromes remains unclear. The assessment of saccadic movements in schizophrenia patients as well as in clinical high-risk state for psychosis individuals (CHR) as a part of schizophrenia continuum may be useful in validation of saccadic movements as a possible biomarker.MethodsThe study included 156 patients who met the ICD-10 criteria for schizophrenia: 42 individuals at clinical high-risk-state for psychosis and 61 healthy controls. The schizophrenia patients had three subgroups based on the sum of the global SAPS and SANS scores: (1) patients with predominantly negative symptoms (NS, n = 62); (2) patients with predominantly positive symptoms (PS, n = 54) (3) patients with predominantly disorganization symptoms (DS, n = 40). CHR subjects were characterized by the presence of one of the groups of criteria: (1) Ultra High Risk criteria, (2) Basic Symptoms criteria or (3) negative symptoms and formal thought disorders. Horizontal eye movements were recorded by using videonystagmograph. We measured peak velocity, latency and accuracy in prosaccade, antisaccade and predictive saccade tasks as well as error rates in the antisaccade task.ResultsSchizophrenia patients performed worse than controls in predictive, reflexive and antisaccade tasks. Oculomotor parameters of NS were different from the other groups of patients. Latencies of predictive and reflexive saccades were significantly longer than in controls only in the NS group. The accuracy of predictive saccades was also different from controls only in the NS schizophrenia group. More prominent loss of accuracy of reflexive saccades was found in the DS group and it significantly differed from the one in other groups. Participants from DS group made more errors in antisaccade task compared to NS and PS groups. CHR subjects performed worse than controls as measured by the accuracy of reflexive saccades and antisaccades.ConclusionsThe study confirms the existence of different relations between the symptom dimensions of schizophrenia and saccades tasks performances. Saccadic abnormalities were revealed in the clinical (schizophrenia) and pre-clinical (clinical high risk) populations that provide further evidence for assessing saccadic abnormalities as a possible neurobiological marker for schizophrenia.

Two-Year Clinical and Functional Outcomes of an Asian Cohort at Ultra-High Risk of Psychosis.

Background: To determine the 2-year clinical and functional outcomes of an Asian cohort at ultra-high risk (UHR) of psychosis.Method: This was a longitudinal study with a follow-up period of 2 years on 255 help-seeking adolescents and young adults at UHR of psychosis managed by a multi-disciplinary mental health team in Singapore. Clients received case management, psychosocial, and pharmacological treatment as appropriate. Data comprising symptom and functional outcomes were collected over the observation period by trained clinicians and psychiatrists.Results: The 2-year psychosis transition rate was 16.9%, with a median time to transition of 168 days. After 2 years, 14.5% of the subjects had persistent at-risk symptoms while 7.5% developed other non-psychotic psychiatric disorders. 38.4% of the cohort had recovered and was discharged from mental health services. The entire cohort's functioning improved as reflected by an increase in the score of the Social and Occupational Functioning Assessment Scale during the follow-up period. Predictors to psychosis transition included low education level, baseline unemployment, a history of violence, and brief limited intermittent psychotic symptoms, while male gender predicted the persistence of UHR state, or the development of non-psychotic disorders.Conclusion: Use of the current UHR criteria allows us to identify individuals who are at imminent risk of developing not just psychosis, but also those who may develop other mental health disorders. Future research should include identifying the needs of those who do not transition to psychosis, while continuing to refine on ways to improve the UHR prediction algorithm for psychosis.

Longitudinal assessment of negative symptoms in early onset first episode psychosis

Anomalous self-experiences (ASE) are considered as central features of the schizophrenia spectrum disorders and prodromal schizophrenia. We investigated total and single-item prevalence of these phenomena in a clinical high-risk (CHR) for psychosis sample, and associations with conventional psychosis-risk symptoms, present and childhood global/psychosocial functioning, and childhood trauma.The sample (n = 38) included 31 CHR, according to ultra-high risk or cognitive basic symptoms (COGDIS) criteria, and seven with non-progressive attenuated positive symptoms. Psychopathological evaluations included the Examination of Anomalous Self-Experience (EASE), Structured Clinical Interview for Prodromal Syndromes (SIPS), Schizophrenia Proneness Instrument – Adult (SPI-A) (only the COGDIS-criteria), a diagnostic interview (SCID-I), Global Assessment of Functioning – Split version (S-GAF), Premorbid Adjustment Scale (PAS) and Childhood Trauma Questionnaire (CTQ).The mean total EASE score was in line with reports from other CHR samples, and was particularly enhanced in schizotypal personality disorder and in subjects fulfilling COGDIS-criteria. The four most frequent EASE-items were present in two-thirds or more of the participants. EASE total was significantly associated with negative and disorganization symptoms. A multiple regression analysis revealed that the level of negative symptoms explained most of the variance in EASE total.These results corroborates other findings that anomalous self-experiences are frequent and important features in CHR conditions and in the schizophrenia spectrum. The strong associations with negative symptoms and cognitive disturbances (COGDIS) should be investigated in longitudinal studies to address causality, psychopathological pathways and schizophrenia spectrum specificity. The weaker correlation between EASE total and positive symptoms may partly be related to a restricted range of positive symptoms.

Prevalence, course and psychosis-predictive value of negative symptoms in 22q11.2 deletion syndrome

BackgroundThe 22q11.2 deletion syndrome (22q11DS) is one of the highest known risk factors for schizophrenia and recent findings have highlighted the clinical relevance of ultra-high risk (UHR) criteria in this population. However, studies in other at-risk populations have shown that the presence of negative symptoms (NS) is also of clinical relevance in predicting transition to psychosis. The present study examined in detail the presence and course of NS in 22q11DS, as well as their value in predicting transition to psychosis. MethodsA total of 111 participants aged between 8 and 33 years were assessed with the Structured Interview for Psychosis-Risk Syndromes (SIPS). A follow-up assessment was available for 89 individuals. ResultsCore NS of at least moderate severity were present in 50.5% of the sample and were more severe in individuals meeting UHR criteria. They predominantly remained stable over time and their emergence between baseline and follow-up assessment was associated with significant functional decline. Some NS were significant predictors of conversion to psychosis and the emergence/persistence of psychosis risk. ConclusionsAltogether, these findings highlight that NS are core manifestations of psychosis in individuals with 22q11DS that strongly impact global functioning. The presence of NS should be a primary target of early therapeutic intervention in this population.

A Mini Review on the Contribution of the Anterior Cingulate Cortex in the Risk of Psychosis in 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that causes a high risk of developing schizophrenia, thus representing a unique model for the investigation of biomarkers of psychosis. Cognitive and clinical risk factors have been identified as reliable predictors of schizophrenia in patients with 22q11DS and are currently used in the clinical practice. However, biomarkers based on neuroimaging are still lacking, mainly because of the analytic approaches adopted so far, which are almost uniquely based on the comparison of 22q11DS patients with healthy controls. Such comparisons do not take into account the heterogeneity within patients with 22q11DS, who indeed show various clinical manifestations. More recently, a number of studies compared measures of brain morphology and connectivity between patients with 22q11DS with different symptomatic profiles. The aim of this short review is to highlight the brain alterations found in patients with 22q11DS fulfilling ultra-high risk (UHR) criteria. Findings point to alterations in brain morphology and connectivity in frontal brain regions, and in particular in the anterior cingulate cortex, in patients with 22q11DS presenting UHR symptoms. These alterations may represent valuable biomarkers of psychosis in 22q11DS.

Longitudinal Cognitive Changes in Young Individuals at Ultrahigh Risk for Psychosis

Cognitive deficits are a key feature of risk for psychosis. Longitudinal changes in cognitive architecture may be associated with the social and occupational functioning in young people. To examine longitudinal profiles of cognition in individuals at ultrahigh risk (UHR) for psychosis, compared with healthy controls, and to investigate the association of cognition with functioning. This study has a multiple-group prospective design completed in 24 months and was conducted from January 1, 2009, to November 11, 2012, as part of the Longitudinal Youth at-Risk Study conducted in Singapore. Participants either were recruited from psychiatric outpatient clinics, educational institutions, and community mental health agencies or self-referred. Follow-up assessments were performed every 6 months for 2 years or until conversion to psychosis. Individuals with medical causes for psychosis, current illicit substance use, or color blindness were excluded. Data analysis was conducted from June 2014 to May 2018. Neuropsychological, perceptual, and social cognitive tasks; semi-structured interviews, and the Structured Clinical Interview for DSM-IV Axis I disorders were administered every 6 months. The UHR status of nonconverters, converters, remitters, and nonremitters was monitored. Cognitive domain scores and functioning were investigated longitudinally. In total, 384 healthy controls and 173 UHR individuals between ages 14 and 29 years were evaluated prospectively. Of the 384 healthy controls, 153 (39.8%) were female and 231 (60.2%) were male with a mean (SD) age of 21.69 (3.26) years. Of the 173 individuals at UHR for psychosis, 56 (32.4%) were female and 117 (67.6%) were male with a mean (SD) age of 21.27 (3.52) years). After 24 months of follow-up, 383 healthy controls (99.7%) and 122 individuals at UHR for psychosis (70.5%) remained. Baseline cognitive deficits were associated with psychosis conversion later (mean odds ratio [OR], 1.66; combined 95% CI, 1.08-2.83; P = .04) and nonremission of UHR status (mean OR, 1.67; combined 95% CI, 1.09-2.95; P = .04). Five cognitive components-social cognition, attention, verbal fluency, general cognitive function, and perception-were obtained from principal components analysis. Longitudinal component structure change was observed in general cognitive function (maximum vertical deviation = 0.59; χ2 = 8.03; P = .01). Group-by-time interaction on general cognitive function (F = 12.23; η2 = 0.047; P < .001) and perception (F = 8.33; η2 = 0.032; P < .001) was present. Changes in attention (F = 5.65; η2 = 0.013; P = .02) and general cognitive function (F = 7.18; η2 = 0.014; P = .01) accounted for longitudinal changes in social and occupational functioning. Individuals in this study who met the UHR criteria appeared to demonstrate cognitive deficits, and those whose UHR status remitted were seen to recover cognitively. Cognition appeared as poor in nonremitters and appeared to be associated with poor functional outcome. This study suggests that cognitive dimensions are sensitive to the identification of young individuals at risk for psychosis and to the longitudinal course of those at highest risk.

Exploring the predictive power of the unspecific risk category of the Basel Screening Instrument for Psychosis.

Ultrahigh risk (UHR) criteria, consisting of brief limited intermittent psychotic symptoms (BLIPS), attenuated psychotic symptoms (APS) and genetic risk and deterioration (GRD) syndrome are the most widely used criteria for assessing the clinical high-risk state for psychosis (CHR-P). The Basel Screening Instrument for Psychosis (BSIP) includes a further risk category, the unspecific risk category (URC). However, little is known about the predictive power of this risk category compared to other risk categories. Two hundred CHR-P patients were detected as part of the Früherkennung von Psychosen (FePsy) study using the BSIP. Transition to psychosis was assessed in regular intervals for up to 7 years. Patients meeting only the URC criterion (n = 40) had a significantly lower risk of transition to psychosis than the UHR group (including BLIPS, APS and GRD) (HR 0.19 [0.05; 0.80] (P = 0.024). Furthermore, the URC only risk group had a lower transition risk than the APS without BLIPS group (P = 0.015) and a trendwise lower risk than the BLIPS group (P = 0.066). However, despite the lower transition risk in the URC only group, there were still two patients (5%) in this group with a later transition to psychosis. The URC includes patients who have a lower risk of transition than those included by the UHR categories and thereby increases the sensitivity of the BSIP. This offers the possibility of a stratified intervention, with these subjects receiving low intensity follow-up and treatment.