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An editorial is presented on half of expected relative to the disability and mortality of mental ill health. Topics include Australian mental health researchers publishing more than would be expected given funding and population size and Australian mental health research performs better than research in oncology, endocrinology, cardiovascular disease; and psychological intervention working through targeting behaviours, cognitions or by development of a therapeutic alliance.

Aims: Psychotic‐like experiences (PLEs) are common in adolescents. Their persistence may confer increased susceptibility to psychotic disorder. The early evolution of transient to persistent PLEs is not well known. This study aimed to investigate the early persistence of PLEs (over 6–12 months) in a community sample of adolescents and examine baseline and longitudinal associations of early persistent PLEs. Methods: Five hundred and ninety Year 10 students were administered the community assessment of psychic experiences (CAPE) to measure PLEs at baseline and at follow up 6–12 months later. Persistent PLEs were defined as those present at or above the 90th centile at both time points. Independent variables of depression, psychological distress and functioning were all measured at both baseline and follow up. Self‐esteem, personality and suicidality were assessed at follow up. Results: The study found 5.1% of participants had early persistent PLEs. Persistence was associated positively with depression and distress at both time points, neuroticism and openness at baseline and suicidality at follow up. Persistence was negatively associated with functioning at both time points, agreeableness at baseline and self‐esteem at follow‐up. Only depression remained significantly associated at both time points when accounting for other variables. Thus, depressive symptoms may account for changes in other domains and be a predictor of early PLEs persistence. Conclusions: These results reinforce the importance of monitoring and assessing PLEs in young people especially when associated with depression. Further research is required to investigate PLE persistence over longer periods with increased measurement intervals. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. Results: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Anxiety and depression symptoms are frequently experienced by individuals with psychosis, although prevalence rates have not been reviewed in first-episode psychosis (FEP). The aim of this systematic review was to focus on the prevalence rates for both anxiety and depression, comparing the rates within the same study population. A systematic review and meta-analysis was completed for all studies measuring both anxiety and depression in FEP at baseline. The search identified 6040 citations, of which n = 10 met inclusion criteria. These reported 1265 patients (age 28.3 ± 9.1, females: 39.9%) with diagnosed FEP. Studies which used diagnosis to define comorbidity count were included in separate meta-analyses for anxiety and depression, although the heterogeneity was high limiting interpretation of separate prevalence rates. A random-effects meta-analysis also compared the mean difference between anxiety and depression within the same studies. We show that anxiety and depression co-occur at a similar rate within FEP, although the exact rates are not reliable due to the heterogeneity between the small number of studies. Future research in FEP should consider routinely measuring anxiety and depression using continuous self-report measures of symptoms. Clinically we recommend that both anxiety and depression are equally targeted during psychological intervention in FEP, together with the psychotic symptoms. [ABSTRACT FROM AUTHOR]

The two most used semi‐structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Structured Interview for Psychosis‐Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Developing harmonized psychometric criteria for defining CHR and associated outcomes would be beneficial for future research. This article describes the first step in this process by reporting on a NIMH workshop held in Washington DC, in February 2019 that was attended by experts in the field. The aim of this workshop was to examine the similarities and differences between the two measures and consider how the harmonization process could proceed. [ABSTRACT FROM AUTHOR]

Persistent negative symptoms (PNS) defined as negative symptoms that persist for at least six months in the absence of high levels of positive, depressive and extrapyramidal symptoms, are evident early in the course of schizophrenia from the first episode of psychosis. However, their presence even earlier in the illness, in those at Ultra High Risk of psychosis, has not been investigated. In this study, we examined the prevalence, baseline correlates and outcome of PNS in 363 Ultra High Risk individuals. Assessments were conducted at baseline and 2-14 years later (mean follow up time 7.4 years). Baseline assessments included demographic, clinical and neurocognitive measures, which were repeated at follow up. The prevalence of PNS in the UHR group was 6.1%. Poor premorbid social adjustment, deficits in verbal fluency and childhood maltreatment, specifically emotional neglect, were evident at baseline in the PNS group compared to the group without PNS. PNS were associated with poor psychosocial functioning and deficits in processing speed at follow up. Our findings suggest that PNS can be detected early, allowing for the identification of a subset of Ultra High Risk patients who are likely to have poor outcome. These individuals could be the target for specific intervention. Further research is needed into the pathophysiology of these PNS to develop specific interventions. [ABSTRACT FROM AUTHOR]

Dysfunctional metacognitive beliefs are common among people with psychosis. In this meta-analysis we examined whether these are also present in people meeting at-risk mental state (ARMS) criteria. We also explored the relationship between metacognitive beliefs and symptoms in the ARMS group. An electronic database search of Ovid MEDLINE, PsycINFO and Embase from inception until August 2016 was conducted using keyword search terms synonymous with ARMS and metacognition. Eligible studies were original research articles that examined metacognitive beliefs using the Metacognitions Questionnaire (MCQ) among people meeting ARMS criteria. Studies included in the meta-analyses also reported comparison MCQ data acquired from healthy controls, help-seeking individuals, or people with psychotic disorders. Eleven eligible studies were identified, reporting data from six unique ARMS samples. People with ARMS did not differ from those with established psychotic disorders on any MCQ subscale, but they reported significantly more dysfunctional metacognitive beliefs than healthy or help-seeking controls. Maladaptive metacognitive beliefs were associated with a range of symptoms in ARMS individuals, but evidence for associations with specific subthreshold psychotic phenomena was inconsistent. This evidence indicates how valuable assessment and treatment of dysfunctional metacognitive beliefs may be but suggests that specific aspects of methodology should be addressed. [ABSTRACT FROM AUTHOR]

Abstract: The Mood and Anxiety Symptoms Questionnaire (MASQ) was developed to measure the symptom-dimensions of the tripartite model of anxiety and depression. A 30-item short adaptation of the MASQ (MASQ-D30) was previously developed and validated in adult psychiatric outpatients. The aim of the present study was to evaluate the validity and reliability of the MASQ-D30 in a sample of adolescents and young adults. Help-seeking adolescents from Australia (N=147; mean age: 17.7 years; 58.8% female) completed the original, 90-item MASQ. Confirmatory Factor Analysis (CFA) was used to evaluate the construct validity (a 3-factor structure) of the original MASQ and the MASQ-D30. Internal consistencies and correlations with other instruments were calculated and compared between versions. CFA showed that the intended 3-factor structure fit adequately to the MASQ-D30 data (CFI=0.95; RMSEA=0.08). Internal consistencies ranged from 0.85 to 0.92 across the scales and patterns of correlations with the Center for Epidemiological Studies-Depression (CES-D) indicated adequate convergent/divergent properties. Importantly, the observed psychometric characteristics were comparable with the original MASQ and alternative short-forms. Results indicated that the MASQ-D30 is a valid and reliable instrument in young people, allowing for quick assessment of the tripartite dimensions of depression and anxiety. [Copyright &y& Elsevier]

Attempts to identify people at imminent risk of psychotic disorder have been made during the past 20 years. High-risk criteria have been developed, and despite findings of a recent decline in the rate of onset of psychosis associated with these criteria, people identified still have a significantly greater risk, compared with the general population. Intervention studies in this group indicate that psychological treatments and fish oil appear to be just as effective as antipsychotics. Future research should refine risk factors for psychosis and examine outcomes other than psychosis. Research is also needed into what harms and benefits are associated with making the high-risk criteria into a formal diagnosis. [ABSTRACT FROM AUTHOR]

The author examines whether it is justifiable to treat people who may be at risk of schizophrenia, and whether these at-risk individuals be given a formal diagnosis. The author discusses the aspects of risk and treatment of schizophrenia in identifying individuals who are at risk of psychotic disorder. In examining the second question, she notes the significance of the Diagnostic and Statistical Manual of Mental Disorders (DSM) to understand the importance of the proposal for a new diagnosis.

Over the last fifteen years, attempts have been made to prospectively identify individuals in the prodromal phase of schizophrenia and other psychotic disorders. The ultra high risk approach, based on a combination of known trait and state risk factors, has been the main strategy used. The validation of the ultra high risk criteria allowed for predictive research in this population in an attempt to identify clinical, neurocognitive and neurobiological risk factors for psychosis onset. It also led to a series of intervention studies in this population, which have included the use of low dose antipsychotic medication, cognitive therapy, and omega-3 fatty acids. Although there is moderate evidence for the effectiveness of specific intervention strategies in this population, the most effective type and duration of intervention is yet to be determined. A current controversy in the field is whether to include an adaption of the ultra high risk criteria (the attenuated psychosis syndrome) in the next version of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). [ABSTRACT FROM AUTHOR]

A new approach to understanding severe mental disorders such as schizophrenia is to adopt a clinical staging model. Such a model defines the extent of the illness such that earlier and milder phenomena are distinguished from later, more impairing features. Specifically, a clinical staging model makes three key predictions. First, pathologic measures should be more abnormal in more severe stages. Second, patients who progress between the stages should show change in these same pathologic measures. Finally, treatment should be more effective in the earlier stages, as well as more benign. In this article, we review the evidence for these three predictions from studies of psychotic disorders, with a focus on neuroimaging data. For all three, the balance of evidence supports the predictions of the staging model. However, there are a number of alternative explanations for these findings, including the effects of medication and symptom heterogeneity. [Copyright &y& Elsevier]

Over the last fifteen years attempts have been made to prospectively identify individuals in the prodromal phase of schizophrenia and other psychotic disorders. The 'ultra high risk' approach, based on a combination of known trait and state risk factors, has been the main strategy used. The validation of the ultra high risk criteria led to a series of intervention studies in this population. The aim of this paper is to provide an overview of ultra high risk research. We review studies in this area, focusing on intervention research. Intervention studies have included the use of low dose antipsychotic medication, cognitive therapy, and omega-3 fatty acids. The evidence for specific intervention strategies for this population is moderate and requires replication with larger samples. Recently, it has been proposed to include an adaption of the ultra high risk criteria in the next version of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). This has raised some controversy in the field. The authors conclude that it would be premature to include the Risk Syndrome in the Diagnostic and Statistical Manual of Mental Disorders at this stage. [ABSTRACT FROM AUTHOR]

Abstract: “Transition to psychosis” has been the outcome of interest in Ultra High Risk (UHR) and “prodromal” studies. However, the point at which an individual crosses the line from high risk or prodromal state to psychosis threshold is arbitrary. There have been few attempts to examine whether this threshold has any validity in terms of biological markers or course and outcome. More research is needed to determine if the current point at which a person is declared “psychotic” is valid. Indeed some persons labeled as having developed psychosis may quickly recover. In such a situation their transition could be seen as “trivial”. Others who do not make “transition” may have worse outcomes. Validation of the transition point is an important issue as “risk syndrome for psychosis” (psychosis prodrome) is being considered for inclusion in the DSMV. Further, much research attempts to distinguish markers for psychotic disorders by examining the differences between UHR individuals who do and do not develop psychosis. Thus it behooves us not just to have this risk syndrome validated, but to have the hypothetical endpoint of psychosis validated as well. [Copyright &y& Elsevier]

Abstract: The proposed Risk Syndrome for Psychosis (RS) criteria are derived from the Ultra High Risk criteria (UHR) and prodromal or Clinical High Risk criteria (CHR), and consist of subthreshold or attenuated positive psychotic symptoms with operationalized recency and frequency criteria. The rationale behind the proposed inclusion of the RS in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV) is that several studies have found that the UHR/prodromal/CHR criteria predict onset of psychotic disorder, mainly schizophrenia, within a brief time period of a few years. Identifying individuals meeting these criteria thus affords the possibility of early intervention to prevent or delay onset of full blown psychotic disorder. However, the RS is yet to be properly validated. Additionally, there are potential dangerous unintended consequences of the reification of this syndrome as a formal diagnosis. Thus we feel it is premature to justify inclusion of the RS in the DSM. [Copyright &y& Elsevier]

Aims: Criteria for identifying people likely to develop a first psychotic episode are now used in many clinical services worldwide. In recent years within these services, there has been an increase in the practice of prescribing antipsychotic medication with the aim of reducing symptoms and preventing onset of full-blown disorder. This practice is based on clinical impression of an incipient psychosis, that is, a clinical judgment that a particular patient may soon progress to full-threshold disorder and may therefore benefit from antipsychotics. However, it is unclear how accurate this clinical impression is. If not accurate it could mean that individuals are receiving antipsychotics unnecessarily. In this study, we investigated the predictive validity of clinical impression of whether ultra high risk patients would develop frank psychosis. Methods: Experienced psychologists rated their clinical impression of incipient psychosis in 168 ultra high risk patients. Ratings were made upon entry to the PACE clinic, a clinical service for ultra high risk patients. Psychosis status over the subsequent 12-month period was established using the Comprehensive Assessment of At Risk Mental States or State medical records. Results: A total of 8.9% of the sample transitioned to psychosis over the 12-month follow-up period. There was a sensitivity of 0.80, specificity of 0.84, positive predictive value (PPV) of 0.32 and negative predictive value (NPV) of 0.98 for the prediction of psychosis using the clinical impression ratings. Conclusions: The results indicate that clinical impression is not sufficient for predicting psychosis outcome in ultra high risk cohorts and that ongoing rigorous research into predictors of outcome in such cohorts is required. The results also caution against the prescription of antipsychotic medication based on clinical impression of incipient psychosis. Future work should address the predictive validity of clinical impression with a larger sample and over a longer follow-up period. [ABSTRACT FROM AUTHOR]

Mental distress and mental health disorders are common in young people. Indeed, over 75 % of mental disorders begin before the age of 25 years. Long delays in seeking help for illnesses are common, initial intervention is often ineffective and young people are at risk of disengaging with treatment, particularly when they are expected to move from child and adolescent treating teams to adult services. All of these factors mean that young people are vulnerable to prolonged mental ill-health and its consequences, including educational failure, unemployment, social disengagement and deprivation, and development of further mental health problems including substance misuse. Malla et al. present different service models that attempt to address these issues. Additionally, there needs to be a focus on physical health and social care as these are intertwined with mental health. [ABSTRACT FROM AUTHOR]

Objective: Studies conducted in community samples suggest that psychotic-like experiences are common in the general population, leading to suggestions that they are either variations of normal personality or are different expressions of underlying vulnerability to psychotic disorder. Different types of psychotic symptoms may exist, some being normal variants and some having implications for mental health and functioning. The aim of the present study was to determine if different subtypes of psychotic-like experiences could be identified in a community sample of adolescents and to investigate if particular subtypes were more likely to be associated with psychosocial difficulties, that is, distress, depression and poor functioning, than other subtypes. Method: Eight hundred and seventy-five Year 10 students from 34 schools participated in a cross-sectional survey that measured psychotic-like experiences using the Community Assessment of Psychic Experiences; depression using the Centre for Epidemiologic Studies Depression Scale; and psychosocial functioning using the Revised Multidimensional Assessment of Functioning Scale. Factor analysis was conducted to identify any subtypes of psychotic experiences. Results: Four subtypes of psychotic-like experiences were identified: Bizarre Experiences, Perceptual Abnormalities, Persecutory Ideas, and Magical Thinking. Intermittent, infrequent psychotic experiences were common, but frequent experiences were not. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas were strongly associated with distress, depression and poor functioning. Magical Thinking was only weakly associated with these variables. Overall these findings may suggest that infrequent psychotic-like experiences are unlikely to be a specific risk factor for onset of a psychotic disorder in community samples. Conclusions: Given that the different subtypes had varying associations with current difficulties it is suggested that not all subtypes confer the same risk for onset of psychotic disorder and poor outcome. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas may represent expressions of underlying vulnerability to psychotic disorder, but Magical Thinking may be a normal personality variant. [ABSTRACT FROM AUTHOR]

There is a higher incidence of psychotic disorders in more socially deprived neighbourhoods and a higher risk in migrants living in neighbourhoods of low ethnic density. Yet it is unclear at what stage these neighbourhood environmental factors exert an influence on the risk for psychosis. 166 Ultra high risk for psychosis young people were included in this study. Neighbourhood data were obtained from the Australian Bureau of Statistics. There was a trend for UHR individuals to reside in relatively more deprived areas and there was no association between the rate of identification of UHR migrants and neighbourhood ethnic density. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults have a high incidence and prevalence of mental disorders, which can be disabling, chronic and lead to the development of further mental health problems. Yet their needs are not being adequately met by existing health structures. We set out to examine the extent of met and unmet need in young people by assessing referrals to a public mental health service for 15 - 24 year olds. We sought to identify differences between young people who were accepted into the service and those who were not with respect to psychiatric diagnosis, subthreshold symptoms, and psychosocial functioning. Method: All young people aged 15 - 24 years who were referred to the service from April to September 2003 for assistance with non-psychotic disorders were approached for assessment. Results: 204 individuals were referred to the service with non-psychotic problems over the data collection period, and 150 consented to participate in the study. Fifty nine percent of participants (n = 88) were accepted into the service (the RA group). They were more likely to have a current diagnosis than those not accepted into the service (the RNA group; n = 62). The RA group had higher levels of depression and anxiety, and lower psychosocial functioning, compared to the RNA group. The RNA group group were also unwell: nearly 63% had at least one diagnosis at the time of referral. Both the RA and RNA groups showed functional impairment. Conclusions: Limited services are denying assistance to young people with significant morbidity and associated functional impairment. We suggest a range of reforms that would benefit the mental health of society by focussing on those most in need and those most likely to respond to early intervention: our young people. [ABSTRACT FROM AUTHOR]

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis. Methods: Participants underwent baseline magnetic resonance imaging and were followed-up over 12–24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR individuals who developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and healthy control subjects (n = 33). Results: Relative to control subjects, UHR-P individuals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP individuals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by individuals subsequently diagnosed with a schizophrenia spectrum psychosis. Conclusions: These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR individuals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to individuals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker. [Copyright &y& Elsevier]

Abstract: An increased prevalence of large cavum septum pellucidum (CSP), a marker of midline neurodevelopmental abnormality, has been reported in schizophrenia. However, not all studies have been able to replicate this finding and very few studies have been conducted in large samples. In the current study, magnetic resonance imaging was used to assess the presence of an abnormal CSP in 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, 135 ultra high-risk (UHR) individuals, and 87 controls. The prevalence of a large CSP (>5.6 mm) did not differ between the groups (9.3% of the FEP patients, 11.2% of the chronic schizophrenia patients, 11.1% of the UHR individuals, and 11.5% of the controls). The length of the CSP was not associated with sulcal morphology of the anterior cingulate cortex (ACC), suggesting different biological processes responsible for the CSP enlargement versus ACC folding. These findings suggest that the CSP is not a neurodevelopmental marker of psychosis and cast doubt over the notion that it plays a major role in the neurobiology of psychosis. [Copyright &y& Elsevier]

Abstract: Background: Identification of individuals “prodromal” for schizophrenia and other psychotic disorders relies on criteria that predict onset within a brief period. Previous trials and biological research have been predicated on the view that certain “ultra high risk” (UHR) criteria detect “the prodrome”, but there is a need to test the validity of these criteria. Aim: To assess the predictive validity of the UHR criteria in a clinical population. Method: The presence of UHR criteria was determined in 292 help-seeking individuals. At 2 year follow-up the number of new cases of psychotic disorder was assessed. Results: The criteria significantly predicted onset of psychotic disorder within 2 years. The transition rate of 16% was much lower than in initial cohorts (over 40%). Conclusions: The predictive validity of UHR criteria depends on the sample to which they are applied. Although young help-seekers meeting these criteria are at greater risk of psychotic disorder than those who do not meet them, caution is needed in their management, since a high transition rate can no longer be assumed. [Copyright &y& Elsevier]

Aim: To describe the development of the field of prodromal intervention in psychotic disorders and to summarize the findings from the PACE Clinic, the inaugural service devoted to this area. Method: A review of the PACE Clinic studies, with reference to the work of other groups. Results: The aims of intervention before the onset of psychosis are to alleviate current distress and impairment and to either prevent, delay or ameliorate the onset of more severe psychotic disorder. To do this, it is necessary to be able to first accurately identify those in the earliest stages of a potentially serious psychotic disorder, and second to effectively slow or prevent progression to more advanced illness. Criteria have been developed which have predicted onset of psychotic disorder inover 30% of so-called ‘ultra high risk’ individuals. Treatment trials have been promising, and to date have examined the effects of antipsychotic medication, cognitive therapy and a combination of the two. Recently, omega-3 fatty acids have also been shown to be effective. However, there are also pitfalls of working in the prodromal area, including ethical concerns and more recently the possibility that there is a decline in the rate of transition from ultra-high-risk state to first-episode psychosis. Conclusions: The field of prodromal intervention in psychotic disorders is an exciting one as it offers the possibility of prevention of full-blown disorder and its related negative sequelae. However, there are many issues that need to be dealt with in order to achieve this goal, and ongoing evaluation of methods to identify and treat such individuals is needed. [ABSTRACT FROM AUTHOR]

Objective. To examine the discriminant validity of the Mood and Anxiety Symptom Questionnaire (MASQ) in a sample of young help-seekers. Method. 136 young people referred to a psychiatric service completed a diagnostic interview and the MASQ. Results. Participants were classified according to diagnostic status: Mood Only; Anxiety Only; Mixed Anxiety-Depression; Other DSM-IV Disorder; and No Axis-I Disorder. Participants in the Mood Only and Mixed groups scored significantly higher than the remaining groups on all MASQ scales. Participants in the Anxiety Only group did not score significantly higher than participants in the Other DSM-IV or No Diagnosis groups for any scale. Conclusion. Our finding supported the specificity of the depression-specific scale, however the purported anxiety-specific scale did not distinguish between those with and those without Anxiety disorders. It was hypothesised that in clinical samples, the MASQ may measure general psychological distress. [ABSTRACT FROM AUTHOR]

The current paper examines a neglected function of ‘ultra high risk’ (UHR) clinics: to detect first-episode psychosis (FEP) mistakenly identified as a prodrome. A clinical audit was conducted of referrals to a UHR service, the Personal Assessment and Crisis Evaluation Clinic, over a 12-month period (April 2005–March 2006). In this audit, 11.4% of the total number of referrals ( n= 149) and 11.9% of those who attended a first appointment were psychotic on referral. These figures indicate that a substantial proportion of individuals thought to be prodromal are in fact suffering FEP. UHR clinics minimize duration of untreated psychosis for FEP patients mistaken as prodromal. [ABSTRACT FROM AUTHOR]

Abstract: Psychotic-like experiences (PLEs) are used to identify individuals considered to be at Ultra High Risk (UHR) of, or prodromal for, psychotic disorder. They are also common in the general population and in clinical samples of non-psychotic individuals. Depression has been found to be an important factor in mediating outcome in those with PLEs in both community and UHR populations. It is associated with increased risk of transition to psychotic disorder in the UHR group, and with need for care in relation to PLEs in community samples. In this study we aimed to examine the 6-month outcome of PLEs in a sample of help-seeking young people aged 15 to 24 years in relation to their level of depression. Subjects (n =140) were assessed at baseline and 6 months for PLEs and depression. PLEs were measured by the Community Assessment of Psychic Experiences (CAPE). Depression was assessed as a continuous measure using the Mood and Anxiety Symptom Questionnaire (MASQ) and categorically according to DSM-IV diagnosis of mood disorder. PLEs reduced in conjunction with an improvement in depression level and with remission of diagnosis of mood disorder. It is important to assess depression in those with PLEs and consider the need for treatment of the comorbid depressive syndrome. This may reduce the risk of worsening of PLEs and transition to psychotic disorder. [Copyright &y& Elsevier]

Background: The overlap between Depression and Anxiety has led some researchers to conclude that they are manifestations of a broad, non-specific neurotic disorder. However, others believe that they can be distinguished despite sharing symptoms of general distress. The Tripartite Model of Affect proposes an anxiety-specific, a depression-specific and a shared symptoms factor. Watson and Clark developed the Mood and Anxiety Symptom Questionnaire (MASQ) to specifically measure these Tripartite constructs. Early research showed that the MASQ distinguished between dimensions of Depression and Anxiety in non-clinical samples. However, two recent studies have cautioned that the MASQ may show limited validity in clinical populations. The present study investigated the clinical utility of the MASQ in a clinical sample of adolescents and young adults. Methods: A total of 204 Young people consecutively referred to a specialist public mental health service in Melbourne, Australia were approached and 150 consented to participate. From this, 136 participants completed both a diagnostic interview and the MASQ. Results: The majority of the sample rated for an Axis-I disorder, with Mood and Anxiety disorders most prevalent. The disorder-specific scales of the MASQ significantly discriminated Anxiety (61.0%) and Mood Disorders (72.8%), however, the predictive accuracy for presence of Anxiety Disorders was very low (29.8%). From ROC analyses, a proposed cut-off of 76 was proposed for the depression scale to indicate 'caseness' for Mood Disorders. The resulting sensitivity/specificity was superior to that of the CES-D. Conclusion: It was concluded that the depression-specific scale of the MASQ showed good clinical utility, but that the anxiety-specific scale showed poor discriminant validity. [ABSTRACT FROM AUTHOR]

Abstract: Criteria for identifying individuals at imminent risk for onset of a psychotic disorder, that is “prodromal” for psychosis, have recently been described. The current study set out to test the predictive validity of these criteria in a sample of help-seeking young people aged 15–24 years who were referred to, but not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status was determined at baseline and psychosis status was assessed at 6 month follow up. Baseline psychosocial functioning was also assessed as a possible predictor of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one person not meeting UHR criteria developed psychosis in the follow up period. Sensitivity, specificity, positive predictive value and negative predictive value of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI 0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994 (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become psychotic than UHR− individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group. The transition to psychosis rate was much lower than in previous samples. This may be a due to the sample being a more general one, not identified as possibly “prodromal”. Other potential causes of this reduction in transition are also explored. [Copyright &y& Elsevier]

Objective: Recognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS. Method: Several methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To assess concurrent validity, CAARMS-defined UHR criteria were compared to the existing criteria for identifying the UHR cohort. To assess predictive validity, the CAARMS-defined UHR criteria were applied to a sample of 150 non-psychotic help-seekers and rates of onset of psychotic disorder at 6-month follow-up determined for the CAARMS-positive (i.e. met UHR criteria) group and the CAARMS-negative (i.e. did not meet UHR criteria) group. The inter-rater reliability of the CAARMS was assessed by using pairs of raters. Results: High CAARMS score in the UHR group was significantly associated with onset of psychotic disorder. The control group had significantly lower CAARMS scores than the UHR group. The UHR criteria assessed by the CAARMS identified a similar group to the criteria measured by existing methodology. In the sample of non-psychotic help-seekers those who were CAARMS-positive were at significantly increased risk of onset of psychotic disorder compared to those who were CAARMS-negative (relative risk of 12.44 (95% CI = 1.5–103.41, p = 0.0025)). The CAARMS had good to excellent reliability. Conclusions: In these preliminary investigations, the CAARMS displayed good to excellent concurrent, discriminant and predictive validity and excellent inter-rater reliability. The CAARMS instrument provides a useful platform for monitoring subthreshold psychotic symptoms for worsening into full-threshold psychotic disorder. [ABSTRACT FROM AUTHOR]

The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at ‘ultra high risk’ for schizophrenia and other psychotic disorders by virtue of having a family history of psychotic disorder combined with some functional decline or the presence of subthreshold or self-limiting psychotic symptoms. All subjects were therefore symptomatic, but not psychotic, at intake. Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months.Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months. Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis. A combination of family history of psychosis, a recent significant decrease in functioning and recent experience of subthreshold psychotic symptoms was also predictive of psychosis. Combining highly predictive variables yielded a method of psychosis prediction at 12 months with good positive predictive value (80.8%), negative predictive value (81.8%) and specificity (92.6%) and moderate sensitivity (60.0%).Within our symptomatic high-risk group, therefore, it appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia. Given the very high PPV and low false positive rate with this two-step process, it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments depending on clinical condition. This indicated prevention approach could be further developed and preventive strategies in the psychoses refined. [Copyright &y& Elsevier]

Objective: To discuss the rationale for early intervention in psychotic disorders and to explore why the widespread implementation of early intervention services has stalled. Method: Four central questions are explored regarding early intervention in psychosis: (i) what is the rationale for early intervention services in psychosis and is it justified? (ii) what are the obstacles to the implementation of early intervention services throughout Australia? (iii) how could some of these obstacles be overcome? and (iv) what else needs to occur? Results: Early intervention in psychosis aims to improve recognition and access, promote recovery from the initial psychotic episode, minimize secondary morbidity and reduce collateral damage. It may also prevent some brain dysfunction and damage, which may otherwise occur later in the illness. Despite the now growing body of evidence supporting the idea of early intervention, obstacles remain to its widespread adoption in policy and implementation, principally related to chronic under-funding of the public mental health system. Among the solutions proposed is the need to develop services with a youth focus, able to cater for young people with both psychotic and non-psychotic psychiatric disorders. These services should be well integrated with primary care and other youth orientated agencies. Conclusions: We are hopeful that strong investment in early intervention and better services for young people will be among the highest priorities of the Third National Mental Health Plan. This is not only where the greatest public health burden lies, but also where cost-effectiveness of intervention is likely to be maximal. [ABSTRACT FROM AUTHOR]

Objective: To evaluate current practice at a generic adult mental health service, St Vincent's Mental Health Service (SVMHS) in relation to management of patients with early psychosis. A further aim was to compare treatment of early psychosis patients within this generic service with management of a similar group in a specialized early psychosis service. Method: A case file audit of all patients identified as having early psychosis (within the first 2 years of treatment) was undertaken using a standardized audit tool. Variables including proportion of early psychosis admitted as inpatients to the psychiatric unit, average length of stay (LOS), use of seclusion, involvement of police in admission process, mean neuroleptic dose and estimated duration of untreated psychosis (DUP) were studied. Results of this audit were then compared with published evaluative data from the Early Psychosis Prevention and Intervention Centre (EPPIC), a service specifically catering for young people with early psychosis (within the first 18 months of treatment). Results: Data were collected on 62 of 68 patients identified as having early psychosis. Within the generic service, mean DUP was found to be about 15 months, a high proportion (81%) of patients were admitted and secluded (22% of those admitted), average length of stay was 46.5 days and use of police in the admission process was also high (40% of those admitted). This compares unfavourably with the EPPIC data of mean DUP of just over 6 months, 64.1% of patients admitted, 10.3% secluded, average LOS 12.9 days, and police involved in 3.8% of admissions. Conclusions: We believe that practice at SVMHS in relation to early psychosis patients is fairly typical of management of these patients within generic services as a whole. These services tend to focus on the needs of the majority of their patients, those with chronic schizophrenia, rather than the small group of patients with early psychosis (who make up about 8% of current... [ABSTRACT FROM AUTHOR]

Intervention in the prodromal phase of schizophrenia and related psychoses may result in attenuation, delay or even prevention of the onset of psychosis in some individuals. However, a “prodrome” is difficult to recognise prospectively because of its nonspecific symptoms.This study set out to recruit and follow up subjects at high risk of transition to psychosis with the aim of examining the predictive power for psychosis onset of certain mental state and illness variables.Symptomatic individuals with either a family history of psychotic disorder, schizotypal personality disorder, subthreshold psychotic symptoms or brief transient psychotic symptoms were assessed and followed up monthly for 12 months or until psychosis onset.Twenty of 49 subjects (40.8%) developed a psychotic disorder within 12 months. Some highly significant predictors of psychosis were found: long duration of prodromal symptoms, poor functioning at intake, low-grade psychotic symptoms, depression and disorganization. Combining some predictive variables yielded a strategy for psychosis prediction with good sensitivity (86%), specificity (91%) positive predictive value (80%) and negative predictive value (94%) within 6 months.This study illustrates that it is possible to recruit and follow up individuals at ultra high risk of developing psychosis within a relatively brief follow-up period. Despite low numbers some highly significant predictors of psychosis were found. The findings support the development of more specific preventive strategies targeting the prodromal phase for some individuals at ultra high risk of schizophrenia. [Copyright &y& Elsevier]

Background: The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychotic experiences. This issue deserves attention as delays to help-seeking and poor engagement with treatment predict worsened clinical and functional outcomes for people with psychosis. The present protocol describes the methodology for a scoping review which will aim to identify barriers and facilitators faced by LGBTQA+ individuals across the psychosis spectrum in help-seeking and accessing mental health support. Methods: A comprehensive search strategy will be used to search Medline, PsycINFO, Embase, Scopus, LGBTQ+ Source, and grey literature. Original studies of any design, setting, and publication date will be included if they discuss barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with experiences of psychosis. Two reviewers will independently screen titles/abstracts and full-text articles for inclusion in the review. Both reviewers will then extract the relevant data according to pre-determined criteria, and study quality will be assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Key data from included studies will be synthesised in narrative form according to the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. Discussion: The results of this review will provide a comprehensive account of the current and historical barriers and facilitators to mental healthcare faced by LGBTQA+ people with psychotic symptoms and experiences. It is anticipated that the findings from this review will be relevant to clinical and community services and inform future research. Findings will be disseminated through publication in a peer-reviewed journal and presented at conferences. Scoping review registration: This protocol is registered in Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/AT6FC). [ABSTRACT FROM AUTHOR]

Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS- kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. ARMS- kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. The term ARMS- kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages. • Existing terms for psychosis high-risk status may lead to stigma. • Patients, family members, and clinicians were surveyed about high-risk terms. • ARMS- kokoro was most preferred and least stigmatizing among high-risk terms. • Ultra-high risk and other terms including 'psychosis' were not preferred. [ABSTRACT FROM AUTHOR]

Background: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders.Methods: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups.Results: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups.Conclusion: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis. [ABSTRACT FROM AUTHOR]

The article discusses early intervention (EI) in psychosis and analyses evidence, evidence gaps, criticism, and confusion related to it. EI can be effective if duration of untreated psychosis (DUP) is decreased. Specialized services of EI for first-episode psychosis (FEP) are superior to generic services. EI services are also criticized for disruption of continuity of care and considered as preventing psychotic disorder by treatment of nonpsychotic individuals.

The author discusses the therapeutic efficacy of administering antipsychotic medications to individuals with ultra-high risk (UHR) psychosis, in relation to the North American Prodome Longitudinal Study (NAPLS) on the treatment history of UHR patients. He describes the proportion of individuals receiving such treatment, noting the significant number of young people that receive the medications off-label. He explains his belief that clinicians also use antipsychotic drugs to prevent the onset of psychotic disorders.

Aim Methods Results Conclusions Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side‐effect profile) of lithium in a sample of young people identified at ultra‐high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU).Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side‐effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes.Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side‐effect assessment indicated that lithium was well‐tolerated. 64% (n = 16) of participants in the lithium group were lithium‐adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time.With a side‐effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort. [ABSTRACT FROM AUTHOR]

Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth. Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention. A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was −5.8 in the n-3 PUFA group and −5.6 in the placebo group (mean difference, 0.2; 95% CI, −1.1 to 1.5; p =.75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups. This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder. [ABSTRACT FROM AUTHOR]

The article discusses the need of extending the upper age range for early intervention for psychosis services. Topics include expanding the clinical focus to emerging and early phases of a range of psychiatric illnesses; high rates of comorbidity between anxiety, depression and sub-threshold psychotic symptoms in young people; and concerns about the privatization of National Health Service (NHS) in the Great Britain such as lack of transparency about profits, costs, and level of care.

• Active neuroinflammation may contribute to the onset of schizophrenia. • Anti-inflammatory treatments in the at-risk mental state could reduce risk of onset. • Minocycline and omega-3, neither alone nor together, reduced transition to psychosis. • Omega-3 supplementation improved nonpsychotic general and transdiagnostic symptoms. Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. 10,173 help-seeking individuals aged 16–35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. The study was funded by the Stanley Research Medical Institute. [ABSTRACT FROM AUTHOR]

Objectives: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people. Methods: We used data from the Transitions Study, a longitudinal investigation of young people attending headspace youth mental health services in Australia between January 2011 and August 2012. Participants were 775 young people aged 12–25. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania and psychosis symptoms than with any one in isolation. Results: Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%). Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain. More severe childhood trauma was more strongly associated with the co-occurrence of symptoms than with any one symptom domain in isolation, such that more severely trauma-exposed young people were more likely to experience increased symptom clustering. Conclusions: Childhood trauma is pervasive in youth mental health services and associated with a symptom profile that cuts across traditional diagnostic boundaries. [ABSTRACT FROM AUTHOR]

Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders. [ABSTRACT FROM AUTHOR]

The article presents the author's views on a study on the neurodevelopmental theory of schizophrenia published in this issue. He opines on the vulnerability indicators including cognitive deficits and social and role difficulties used in the study. He comments on the use of a model to generate a prognostic score for each high-risk individual in the study.

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). [ABSTRACT FROM AUTHOR]

Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field. [ABSTRACT FROM AUTHOR]