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Objective: Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis., Methods: Ventricular volumes were measured using a semi-automated and highly reliable method, for 89 established schizophrenia, 162 first-episode psychosis, 135 ultra high-risk for psychosis and 87 healthy controls using 1.5T magnetic resonance images. Clinical outcome diagnoses for ultra high-risk for psychosis were evaluated at long-term follow-up (mean: 7.5 years)., Results: Compared to controls, we identified significant ventricular enlargement of 36.2% in established schizophrenia ( p < 0.001). Ventricular enlargement was not significant in first-episode psychosis (6%) or ultra high-risk for psychosis (-3%). Examination across stages of schizophrenia-spectrum diagnoses subgroups revealed a significant linear trend ( p = 0.006; established schizophrenia = 36.2%, first-episode psychosis schizophrenia = 18.5%, first-episode psychosis schizophreniform = -4.2% and ultra high-risk for psychosis-schizophrenia converters = -18.5%)., Conclusion: Ventricular enlargement is apparent in patients with established schizophrenia but is not a feature at the earliest stages of illness (ultra high-risk for psychosis and first-episode psychosis). Further research is needed to fully characterize the nature and timing of ventricular volume changes early in the course of illness and how these changes impact outcomes.

Background: A clinical and research challenge is to identify which depressed youth are at risk of "early transition to bipolar disorders (ET-BD)." This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings., Methods: Fifty cases with reliably ascertained, ET-BD I and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes., Results: Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these "BAR-Depression" criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7., Conclusions: Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: The 'ultra-high-risk' criteria identify a clinical population at substantially increased risk for progressing to schizophrenia and other psychotic disorders. Although a number of clinical variables predictive of transition to psychotic disorder have been identified within this population, the predictive value of the level of distress associated with attenuated psychotic symptoms has not yet been examined. This was the aim of the present study., Method: The level of distress (0-100) associated with attenuated psychotic symptoms was recorded for 70 ultra-high-risk (UHR) patients using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Transition to psychosis was assessed over a 16-month follow-up period., Results: Of the 70 UHR patients, 15 transitioned to psychosis (21.4%). Of the four CAARMS subscales measuring attenuated positive symptoms, Perceptual Abnormalities was rated as the most distressing. There were no differences in CAARMS scales rated as the most distressing between those who transitioned to psychosis and those who did not. There was also no association between higher levels of distress associated with attenuated psychotic symptoms and transition to psychosis., Conclusion: Although the findings require replication, they indicate that the degree of distress associated with attenuated psychotic symptoms should not be used as a criterion for enriching UHR samples for risk of frank psychotic disorder., (© 2015 Wiley Publishing Asia Pty Ltd.)

Objectives: There are no established tools to identify individuals at risk for developing bipolar disorder. We developed a set of ultra-high-risk criteria for bipolar disorder [bipolar at-risk (BAR)]. The primary aim of the present study was to determine the predictive validity of the BAR criteria., Methods: This was a 12-month prospective study that was conducted at Orygen Youth Health Clinical Program, a public mental health program for young people aged 15-24 years in metropolitan Melbourne, Australia. At intake, BAR screen-positive individuals and a matched group of individuals who did not meet BAR criteria were observed over a period of 12 months. The BAR criteria include general criteria such as being in the peak age range for the onset of the disorder, as well as sub-threshold mania, depression plus cyclothymic features, and depression plus genetic risk. Conversion to first-episode mania/hypomania was defined by the presence of DSM-IV manic symptoms for more than four days, in line with the DSM-IV definition of hypomania/mania., Results: A total of 559 help-seeking patients were screened. Of the eligible participants, 59 (10.6%) met BAR criteria. Thirty-five participants were included in the BAR group and 35 matched participants were selected to be in the control group. During the follow-up, five BAR patients out of 35 (14.3%) converted to first-episode hypomania/mania as opposed to none in the non-BAR group [χ(2) (1) = 5.38, p = 0.020]. Four out of these five converters had a DSM-IV diagnosis of bipolar I or bipolar II disorder., Conclusions: These findings support the possibility of identification of persons prior to the onset of mania/hypomania. The proposed criteria need further evaluation in larger, prospective studies with longer follow-up periods., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The article presents a prospective study focusing on whether youth at high risk of illness progression can be identified by measures of rumination, depression and sleep-wake disturbance. Topics include the use of clinical staging to investigate and identify risk factors for illness progression, and the tendency for common dimensions between rumination and sleep-wake disturbance to indicate illness progression in youth.

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients. [ABSTRACT FROM PUBLISHER]

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During recent years, a decrease has been noted in the rate of transition of ultra-high risk (UHR) clients to a psychotic disorder. Although important to the concept of the at-risk mental state, the reasons for this decline remain largely unknown. We investigated the possibility of a 'dilution effect' in contributing to the decline, i.e. if later UHR cohorts present with less severe clinical intake characteristics than earlier cohorts. Firstly, clinical intake characteristics of a large UHR sample (n=397) were compared across baseline year epochs (1995-2006). Characteristics showing significant differences were included in a Cox-regression to examine if they could explain the decline in transition rates. Secondly, because later cohorts show lower transition rates, 'more stringent' UHR-criteria were retrospectively applied to these cohorts (post-2000, n=219), investigating if this resulted in a higher transition rate. Results indicated that earlier cohorts presented with (1) a larger array of attenuated psychotic symptoms, (2) higher ratings on conceptual disorganization (formal thought disorder) and (3) a higher proportion of individuals with trait risk factor (all P<.001). However, these factors could not fully account for the decline in transition rates. Applying more stringent UHR-criteria to the post-2000-subsample did not substantially change the rate of transition. Our study suggests that later UHR cohorts presented with different clinical intake characteristics than earlier cohorts. While this may have contributed to the observed decrease in transition rates to psychosis, it does not appear to fully account for this decline, suggesting other factors have also impacted on transition rates over time. [ABSTRACT FROM AUTHOR]

Abstract: Valid criteria to identify young people who are believed to be at ultra high risk (UHR) of developing a psychotic episode were developed over the last decade. The first randomized controlled trial of treatment in a UHR cohort indicated that specific pharmacotherapy and psychotherapy delayed onset of disorder, and possibly reduced incidence. This paper reports results of follow-up of that trial. 41 of the 59 (69.5%) participants in the original study agreed to follow-up. No differences were found in transition rate, level of symptomatology or functioning between participants who received a combination of psychological treatment and anti-psychotic medication compared to those who received supportive therapy alone. A significant proportion of both treatment groups reported moderate levels of psychiatric morbidity and a continuing need and desire for care at this follow-up. Low levels of hospitalisation were noted for those who did progress to psychosis. Conclusions that can be drawn from this exploratory study are limited by the relatively small number of participants in the original study and the failure to follow-up the entire cohort. Although participants may have been treated too briefly to result in enduring positive effects, there appear to have been some cost savings in inpatient mental health treatment required after the end of the trial for individuals in both treatment groups who developed psychosis. [Copyright &y& Elsevier]