Clinical High Risk Adolescents Research Articles

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery

BackgroundThe effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.MethodsA total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.ResultsDuring the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.ConclusionsEarly use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Social network size in adolescents at clinical high risk for psychosis.

Adolescents and young adults at clinical high risk (CHR) for psychosis report few close friends. Social support has been linked to conversion to psychosis and psychosis relapse in CHR individuals. Expanding earlier research on loneliness and friendships at a single timepoint, this study described composition and changes in social network and its association with clinical and cognitive symptoms among CHR adolescents. Ninety five individuals (46 CHR individuals, 49 healthy volunteers) completed baseline and 1-year follow-up Social Network Index (SNI) evaluations and clinical interviews. Analyses first examined SNI size and composition across 10 categories (e.g., family, close friends, coworkers, classmates) between groups. Then, the relationship between SNI size and baseline social symptoms (i.e., paranoia, social anhedonia, social anxiety, social cognition), social function, and changes in symptoms and social networks over 1-year were examined within the CHR group. CHR individuals showed smaller social networks overall, driven by fewer friendships and family relationships. Social cognition and social anxiety significantly related to SNI size at baseline, but social anhedonia and paranoia did not. SNI size related to social function, but with a modest effect size (r's=.45 and .56). Surprisingly, an increase in positive symptom severity related to an increase in familial but a decrease in coworker social network size. The social support deficits in the CHR group were specific to relatives and friendships, with social anxiety and social cognition as implicated symptoms. Social relationships may serve as a promising early intervention target in individuals at CHR for psychosis.

Neurocognitive Assessments Are More Important Among Adolescents Than Adults for Predicting Psychosis in Clinical High Risk

BackgroundFew studies have examined the effects of age on neurocognition to predict conversion to psychosis in individuals at clinical high risk (CHR). This study aimed to compare the extent and predictive performance of cognitive deficits between adolescents and adults at CHR. MethodsA comprehensive neuropsychological battery was performed on 325 CHR individuals and 365 healthy control (HC) subjects. The subjects were first divided into 189 CHR adolescents (age 12−17 years), 136 CHR adults (age 18−45 years), 88 HC adolescents, and 277 HC adults. CHR subjects were then divided into converters (CHR-Cs) (adolescents, n = 43; adults, n = 34) and nonconverters (CHR-NCs) (adolescents, n = 146; adults, n = 102) based on their 2-year follow-up clinical status. ResultsThe adolescents and adults at CHR performed significantly worse than their control groups on all neurocognitive tests, except for performance on the continuous performance test in adolescents. In the comparison between adolescents and adults, patterns of neurocognitive deficits seemed to vary in HC subjects rather than in CHR subjects. In the comparison between CHR and HC subjects, the rank order of effect sizes across the neurocognitive tests was similar for the top two tests of symbol coding and verbal learning. Comparison between CHR-Cs and CHR-NCs revealed that adolescent CHR-Cs performed significantly worse than CHR-NCs on seven of eight neurocognitive tests; however, adult CHR-Cs performed significantly worse than CHR-NCs only in the visuospatial memory test. ConclusionsThe role of neurocognitive dysfunction may have different patterns and weights during the onset of psychosis in adolescents and adults at CHR, implicating the development of specific strategies that could monitor and improve cognitive function in CHR adolescents.

O1.1. ETRo: EVALUATION OF THE TREATMENT APPROACH “ROBIN” (STANDARDIZED MANUAL AND SMARTPHONE APP) FOR ADOLESCENTS WITH CLINICAL HIGH RISK FOR DEVELOPING A PSYCHOTIC DISORDER

BackgroundThe construct of a clinical high-risk (CHR) state of psychosis has been established to describe potentially prodromal symptoms which typically appear during adolescence and young adulthood. This is a very sensitive developmental period and the clinical high risk (CHR) is associated with increased functional impairment. However, there is a lack of research on age-appropriate treatment strategies for this vulnerable age group. To fill this gap, the experts from the specialized outpatient care unit for early intervention in psychosis at the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital, of the University Zürich (CAPS), have developed the combined treatment program “Robin” (standardized manual and smartphone App). The therapy program is targeting at risk-symptoms and aims to improve of quality of life as well as daily functioning. The smartphone application “Robin Z” is an add-on treatment tool to support the patients between the sessions. While a number of trials with smartphone applications in therapy have shown promising effects with adult patient with psychosis, there is little known about using them in the therapy with minor patients. “Robin Z” is one of the first smartphone applications addressing adolescent patients with at risk- symptoms or full-blown psychotic symptoms. Since September 2017, the efficacy of this combined treatment approach is being evaluated with the systematic clinical intervention trial ETRo (Evaluation of the treatment approach “Robin“). The study has been registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03829527) and the study protocol has been published June 2019 in the journal “Frontiers in Psychiatry”.MethodsThe ETRo trial is a prospective, naturalistic, follow up study with a matched control design. Participants from a former early recognition study are included for the control condition (treatment as usual). For the intervention condition (16 weekly individual sessions + a minimum 4 family sessions), 30 help seeking CHR adolescents, aged 14–18, are being recruited. At-risk and comorbid symptoms, functioning, self-efficacy and quality of life are monitored at six time points (baseline, during the treatment period, immediately after intervention, and 6, 12, and 24 months later) and compared to the respective measures of the active control group.ResultsThe data from a pilot investigation showed, that “Robin” was accepted by clinicians and patients. Therefore, the authors hypothesize that the “Robin” will enhance the treatment engagement. Within the first 2 years of the systematic evaluation, 18 CHR individuals (61% female, mean age 16.1) have been included in the intervention condition. In Florence, the preliminary results and their implications will be presented. This will include baseline data of the first patients in the intervention group, the intraindividual changes in symptomatology and well-being after 6 months of treatment and data about the treatment satisfaction.Discussion“Robin” is a newly developed treatment approach for adolescents at clinical high risk (CHR) of developing a psychotic disorder combining a standardized treatment manual with a smartphone application. To the best of the author’s knowledge, this is the first controlled trial to test the efficacy of a specific early psychosis treatment in combination with a smartphone application for CHR adolescents. The results of the study are of clinical importance and expected to add essential information in the fields of eMental Health as well as in prevention and early intervention in psychosis.

Conversion to psychosis in adolescents and adults: similar proportions, different predictors.

Age effects may be important for improving models for the prediction of conversion to psychosis for individuals in the clinical high risk (CHR) state. This study aimed to explore whether adolescent CHR individuals (ages 9-17 years) differ significantly from adult CHR individuals (ages 18-45 years) in terms of conversion rates and predictors. Consecutive CHR individuals (N = 517) were assessed for demographic and clinical characteristics and followed up for 3 years. Individuals with CHR were classified as adolescent (n = 244) or adult (n = 273) groups. Age-specific prediction models of psychosis were generated separately using Cox regression. Similar conversion rates were found between age groups; 52 out of 216 (24.1%) adolescent CHR individuals and 55 out of 219 (25.1%) CHR adults converted to psychosis. The conversion outcome was best predicted by negative symptoms compared to other clinical variables in CHR adolescents (χ2 = 7.410, p = 0.006). In contrast, positive symptoms better predicted conversion in CHR adults (χ2 = 6.585, p = 0.01). Adolescent and adult CHR individuals may require a different approach to early identification and prediction. These results can inform the development of more precise prediction models based on age-specific approaches.

Depression, family interaction and family intervention in adolescents at clinical-high risk for psychosis.

The relationship between family behaviour and depression in adolescents at clinical high risk (CHR) for psychosis remains understudied despite high rates of depression in this population. This study examines the relationship between family problem-solving behaviours and depression in CHR adolescents and the impact of family interventions targeting subthreshold symptoms of psychosis on reducing symptoms of depression over 2-years. Participants were a subset of the North American Prodrome Longitudinal Study who were randomized to 6-months of family focused therapy for individuals at CHR or family psychoeducational treatment. We evaluated the relationship between communication during family conflict discussion and adolescents' symptoms of depression before treatment. At follow-up assessments the family treatment groups were compared on depression. Finally, we compared those in family treatment with matched controls. Adolescents' constructive communication was associated with less severe symptoms of depression before treatment. Symptoms of depression improved for adolescents in both family treatment groups. However, there were no significant group by treatment interactions. When adolescents who participated in either type of family intervention were compared to CHR adolescent controls, symptoms of depression improved for adolescents in treatment and control groups, but there were no significant time by treatment interactions. The communication skills of CHR adolescents are related to both depression and their parents' communication skills pre-treatment. However, reductions in depression over the course of the treatment trial cannot be attributed to family treatment. It is imperative to incorporate interventions that directly target depression into future family treatment studies.

Personality Traits as Markers of Psychosis Risk in Kenya: Assessment of Temperament and Character.

Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (n = 268) and controls (n = 251), aged 15–25 years. CHR status was estimated using the Structured Interview of Psychosis-Risk Syndromes (SIPS) and the Washington Early Psychosis Center Affectivity and Psychosis (WERCAP) Screen. Student’s t-tests were used to assess group differences on the Temperament and Character Inventory (TCI). Neurocognitive functioning, stress severity, and substance use were correlated with the TCI, correcting for psychosis severity. CHR participants were more impulsive (ie, higher novelty seeking [NS]) and asocial (ie, lower reward dependence) than controls. They were also more schizotypal (ie, high self-transcendence [ST] and lower self-directedness [SD] and cooperativeness [CO] than controls). CO was related to logical reasoning, abstraction, and verbal memory. Stress severity correlated with high HA and schizotypal character traits. Lifetime tobacco use was related to NS, and lifetime marijuana use to high NS, low SD and high ST. Temperament and character of Kenyan CHR youth is similar to that observed in schizophrenia. Psychosis risk in Kenya is associated with impulsive, asocial, and schizotypal traits. CHR adolescents and young adults with schizophrenia-specific personality traits may be most at risk for developing a psychotic disorder and to require early intervention to improve outcomes.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning

BackgroundThe ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. Methods24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. ResultsPrevious work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. ConclusionsThese findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

Comorbid Mental Disorders and 6-Month Symptomatic and Functioning Outcomes in Chinese University Students at Clinical High Risk for Psychosis.

High rates of non-psychotic psychopathological symptoms have been observed in clinical population at clinical high risk (CHR) for psychosis. These comorbid disorders affected the baseline functional level of CHR patients. However, little is known about the comorbid mental disorder in CHR individuals in non-clinical adolescent population. This study aimed to investigate the comorbid mental disorder in non-clinical CHR adolescents and the impact on attenuated psychosis symptoms (APS) as well as clinical outcome. The sample consisted of 32 CHR students, who were screened from 2,800 university students. CHR status was evaluated with the Structured Interview of Prodromal Syndromes, comorbid mental disorder diagnoses with the International Neuropsychiatric Interview. In the CHR sample, 46.9% was found at least one non-psychotic comorbid mental disorder. The CHR participants presenting comorbid mental disorder had significantly more severity of APS than those without comorbid mental disorders, and the remission rate at 6-month follow-up is significantly higher in the individuals without comorbid mental disorders at baseline. In the non-clinical sample of individuals at CHR, non-psychotic comorbid mental disorders are common and anxiety disorder is most frequent. Copresence of anxiety and/or depression is related to higher level of attenuated psychotic symptoms and unfavorable clinical outcome at 6-month follow-up. Assessment and intervention in anxiety and depression for non-clinical CHR adolescents are suggested.

An Overview of Recent Findings on Social Anxiety Disorder in Adolescents and Young Adults at Clinical High Risk for Psychosis.

Background: Some studies have shown that anxiety is particularly frequent in the Clinical High Risk (CHR) for psychosis population. Notably, social anxiety disorder is identified as one of the most common anxiety disorders in CHR adolescents and young adults. Despite this, the frequency and the clinical significance of social anxiety in this population have been underestimated. Methods: A selective review of literature published between 2011 and 2017 on social anxiety disorder in CHR adolescents and young adults. Results: Five studies are included. In particular, three studies demonstrated that CHR adolescents and young adults have higher levels of anxiety compared to controls. Furthermore, anxiety, including social anxiety, is related to the severity of psychotic symptoms. The other studies included show inconsistent results regarding the possible relationship between social anxiety and social functioning. Conclusions: To date, the eidence concerning the comorbidity of social anxiety disorder and CHR in adolescents and young adults is not sufficient to provide clear guidelines for clinical practice. Future longitudinal studies on larger samples of the CHR adolescents and young adults are required to examine the relationship between social anxiety disorder and the presence of attenuated psychotic symptomatology.

Clinical high risk for psychosis in children and adolescents: a systematic review.

The concept of being at risk for psychosis has been introduced both for adults and children and adolescents, but fewer studies have been conducted in the latter population. The aim of this study is to systematically review the articles associated with clinical description, interventions, outcome and other areas in children and adolescents at risk for psychosis. We searched in MEDLINE/PubMed and PsycINFO databases for articles published up to 30/06/16. Reviewed articles were prospective studies; written in English; original articles with Clinical High Risk (CHR) for psychosis samples; and mean age of samples younger than 18years. From 103 studies initially selected, 48 met inclusion criteria and were systematically reviewed. Studies show that CHR children and adolescents present several clinical characteristics at baseline, with most attenuated positive-symptom inclusion criteria observed, reporting mostly perceptual abnormalities and suspiciousness, and presenting comorbid conditions such as depressive and anxiety disorders. CHR children and adolescents show lower general intelligence and no structural brain changes compared with controls. Original articles reviewed show rates of conversion to psychosis between 17 and 20% at 1 year follow-up and between 7 and 21% at 2 years. While 36% of patients recovered from their CHR status at 6-year follow-up, 40% still met CHR criteria. Studies in children and adolescents with CHR were conducted with different methodologies, assessments tools and small samples. It is important to conduct studies on psychopharmacological and psychological treatment, as well as replication of the few studies found.

The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis

BackgroundProdromal syndromes often begin in adolescence — a period of neurodevelopmental changes and heightened stress sensitivity. Research has shown elevated stress and cortisol in individuals at clinical high risk (CHR) for psychosis. This cross-sectional study examined relations of age and pubertal status with cortisol and self-reported stress in healthy controls (HCs) and CHR adolescents. It was hypothesized that the relations of age and pubertal stage with cortisol and stress would be more pronounced in CHR youth. MethodsParticipants were 93 HCs and 348 CHR adolescents from the North American Prodrome Longitudinal Study (NAPLS). At baseline, measures of stress (Daily Stress Inventory — DSI), Tanner stage (TS), and salivary cortisol were obtained. ResultsANCOVA revealed increased DSI scores with age for both groups, and higher DSI scores in CHR adolescents than HCs, with a more pronounced difference for females. Contrary to prediction, with age controlled, HCs showed greater TS-related DSI increases. Analysis of cortisol showed no significant interactions, but a main effect of age and a trend toward higher cortisol in the CHR group. Correlations of cortisol with TS were higher in HC than CHR group. ConclusionsStress measures increased with age in HC and CHR adolescents, and DSI scores also increased with TS in HCs. The results do not support a more pronounced age or TS increase in stress measures in CHR adolescents, but instead suggest that stress indices tend to be elevated earlier in adolescence in the CHR group. Potential determinants of findings and future directions are discussed.

Longitudinal investigation of the relationship between family history of psychosis and affective disorders and Child Behavior Checklist ratings in clinical high-risk adolescents

This is the first study to investigate whether positive family history (FH) of psychosis and affective disorders moderates the relationship between child diagnostic status and parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) in clinical high-risk adolescents. This longitudinal investigation assessed 122 participants (mean age=14.25±1.8years) from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. As predicted, there was a main effect of FH for a number of CBCL scales indicating higher scores for adolescents with positive FH. The findings also demonstrate a significant Diagnostic Status×Family History interaction for several behavioral scales providing support for FH as a concurrent and longitudinal moderator of the relationship between diagnostic status and CBCL scales. The moderating effect is present for areas of functioning associated with depression, anxiety, social adjustment, thought problems, attention problems, and aggressive behavior. The findings also indicate that both positive and negative symptoms are related to the genetic vulnerability for developing psychosis in clinical high-risk individuals, particularly those symptoms reflective of emotional, attentional, and interpersonal functioning. The present findings are novel and have significant clinical and research implications. This investigation provides a platform for future studies to clarify further the role of FH in clinical high-risk individuals and contributes to integration of this knowledge in the development of early intervention and prevention approaches in at-risk populations for the emergence of severe mental illness.

Psychosis risk screening in clinical high-risk adolescents: A longitudinal investigation using the Child Behavior Checklist

This is the first study to investigate whether parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) can be used for psychosis risk screening and the identification of at-risk youth in the general population. This longitudinal investigation assessed 122 adolescent participants from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. The findings indicate that two individual CBCL rating scales, Withdrawn/Depressed and Thought Problems, have clinical and diagnostic utility as an adjunctive risk screening measure to aid in early detection of at-risk youth likely to develop psychosis. Furthermore, the findings shows that a cost-effective, general screening tool with a widespread use in community and pediatric healthcare settings has a promise to serve as a first step in a multi-stage risk screening process. This can potentially facilitate increased screening precision and reduction of high rate of false-positives in clinical high-risk individuals who present with elevated scores on psychosis-risk measures, but ultimately do not go on to develop psychosis. The findings of the present study also have significant clinical and research implications for the development of a broad-based psychosis risk screening strategy, and novel prevention and early intervention approaches in at-risk populations for the emergence of severe mental illness.

Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis

Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14–21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant.

Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: A preliminary study

Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.

Does a parent-report measure of behavioral problems enhance prediction of conversion to psychosis in clinical high-risk adolescents?

Recent research on risk for psychosis has focused on youth who manifest subclinical signs that are often associated with the prodrome to psychosis. Standardized measures of prodromal symptoms have been shown to significantly enhance prediction of risk for conversion to an Axis I psychotic disorder. In the present study, a widely used parent-report measure of behavioral problems, the Child Behavior Checklist (CBCL) was administered to examine the clinical and diagnostic utility of the measure as an adjunctive screening instrument in the identification of at-risk youth. The CBCL, the Structured Interview for Prodromal Syndromes (SIPS), and other diagnostic measures were administered at baseline and at one year follow-up assessments to adolescents (n=41) at clinical high-risk for the development of a psychotic disorder. Analyses were conducted to compare the 14 at-risk adolescents who subsequently converted to psychosis to the 27 who did not. Conversion to psychosis was defined as conversion to an Axis I psychotic disorder or affective disorder with psychotic features. Consistent with expectations, at one year follow-up, compared to the Non-Converted participants, the Converted participants manifested significantly higher scores on the prodromal symptom scales of the SIPS. There were, however, no differences in CBCL social and behavioral ratings as a function of conversion status. It is concluded that the CBCL does not show promise as an alternative or adjunctive predictor of conversion to psychosis in at-risk adolescents.

The relationship between psychotic-like symptoms and neurocognitive performance in a general adolescent psychiatric sample

Introduction The current criteria for detecting a Clinical High-Risk (CHR) state for psychosis do not address cognitive impairment. A first step for identifying cognitive markers of psychosis risk would be to determine which aspects of neurocognitive performance are related with more severe psychotic-like symptoms. This study assessed cognitive impairment associated with prodromal symptoms in adolescents receiving public psychiatric treatment. Methods 189 adolescents were recruited from consecutive new patients aged 15–18 attending mainly outpatient adolescent psychiatric units in Helsinki. They had been screened for prodromal symptoms using the Prodromal Questionnaire, and all screen-positives as well as a random sample of screen-negatives were interviewed using the Structured Interview for Prodromal Symptoms (SIPS) and underwent testing using a large, standardized neurocognitive test battery. The sample included 62 adolescents who met the CHR criteria (CHR) and 112 who did not (non-CHR). A healthy control sample ( n = 72) was also included to provide age- and gender-matched norms. Results The CHR group performed worse on visuospatial tasks than the non-CHR group. Among CHR adolescents, negative symptoms were associated with slower processing speed and poorer performance on verbal tasks. Among non-CHR adolescents, positive symptoms were associated with poorer performance on visuospatial tasks, and negative symptoms with poorer performance on verbal tasks. Conclusion Clinical high-risk status is associated with impaired visuospatial task performance. However, both positive, psychotic-like symptoms and negative symptoms are associated with lower levels of neurocognitive functioning among adolescents in psychiatric treatment regardless of whether CHR criteria are met. Thus, even mild positive and negative symptoms may have clinical relevance in adolescents in psychiatric care. Adolescents with both psychotic-like symptoms and neurocognitive deficits constitute a group requiring special attention.

Spatial working memory deficits in adolescents at clinical high risk for schizophrenia

Identifying endophenotypic markers is crucial to schizophrenia research for finding appropriate preventive strategies. Working memory (WM) deficit has been suggested as a marker for schizophrenia but its presence in adolescents at high risk is understudied. We piloted a test of spatial WM function in adolescents at clinical high risk (CHR) for schizophrenia and in age- and IQ-matched low-risk control subjects. CHR adolescents showed deficits in spatial WM compared with controls but showed intact performance on a non-WM-demanding spatial control task. Although based on a small pilot study, the results strongly suggest that WM deficit may be a risk factor for psychosis.

Cyclosporin A in cadaveric organ transplantation.

The use of cyclosporin A (CyA) with a protocol designed to avoid the effects of nephrotoxicity resulted in a one-year survival of 86% in recipients of renal allografts from unmatched cadaveric donors. The drug also controlled rejection of liver and pancreatic allografts. It was possible to change patients initially treated with CyA to azathioprine and corticosteroids and vice versa, thus enlarging the potential value of CyA in organ allografting. Of 34 recipients of renal allografts, 29 were currently receiving only CyA as immunosuppressive treatment. Twelve patients never required any adjuvant steroid treatment. These results suggest that CyA is an effective immunosuppressant, and if used with care side effects need not be severe.