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BackgroundCannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).MethodParticipants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).ResultsA history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.ConclusionsFindings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals. [ABSTRACT FROM PUBLISHER]

Schizophrenia is a common disorder, affecting approximately 1 out of every 100 people, with a typical onset during adolescence and early adulthood. The personal and societal costs of schizophrenia are extremely high. Prevention of schizophrenia, would offer substantial benefits to patients, their family members, and the community at large. The prodromal phase of schizophrenia has been recognized since the 19th century. At-risk individuals for psychosis and schizophrenia are the subjects who can provide information for intervention prior to development of frank psychosis. This approach is currently being investigated. The question remains, however, whether it can be a diagnostic category by itself. The proposal for including the risk syndrome is one of the recommendations by the working group on schizophrenia and psychotic disorders for the forthcoming DSM-V. There are differing views in academia regarding this proposal. Prior to becoming fully psychotic, a consistent literature demonstrates that patients generally had suffered from accelerating attenuated symptoms and distress. It is important that the prodromal phase be accurately recognized in order to accomplish the goal of prevention. We can then purposefully engage in early intervention aiming toward prevention. A recent strong resurgent interest in this area stems largely from two developments: First, the identification of the neurobiological deficit processes associated with the severity and chronicity of schizophrenia, and second, the development of reliable criteria for diagnosis. Although the general at-risk construct appears to offer great potential to advance both the treatment and research dealing with psychotic illnesses, it seems premature to many researchers to include the syndrome as an established entity in the text of the new DSM-V. It would be far more appropriate to include this proposed syndrome in the appendix and evaluate the many contemporary issues in future studies. The main issues involved in this discussion are the clinical validity of the syndrome, concern about stigma and unnecessary treatment, and need for responding to patients' distress in addition to the ethical dilemma. In this review we examine the issue of inclusion of the risk syndrome as a diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses the use of evidence-based health care in the early intervention in psychosis. It mentions that the research focuses on the early stage of the disorder which identifies the two classes of patients which include those who have an essentially trivial problem and the other who have a hard time coping up with the disease despite treatments. It affirms that the creation of early psychosis models has been a significant factor in the treatment of the disease.

BackgroundThe ACE project involved 62 participants with a first episode of psychosis randomly assigned to either a cognitive behaviour therapy (CBT) intervention known as Active Cognitive Therapy for Early Psychosis (ACE) or a control condition known as Befriending. The study hypotheses were that: (1) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending; (2) these improvements in symptoms and functioning would be sustained at a 1-year follow-up; and (3) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up.MethodTwo therapists treated the participants across both conditions. Participants could not receive any more than 20 sessions within 14 weeks. Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning: at pretreatment, the middle of treatment, the end of treatment and at 1-year follow-up. An independent pair of raters assessed treatment integrity.ResultsBoth groups improved significantly over time. ACE significantly outperformed Befriending by improving functioning at mid-treatment, but it did not improve positive or negative symptoms. Past the mid-treatment assessment, Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up.ConclusionsThere is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger samples. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Cognitively oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and preventing or alleviating secondary morbidity in the wake of the first psychotic episode. The present study reports on the outcomes of a controlled trial comparing two conditions: COPE versus No-COPE. METHOD: Ninety-one people participated in the trial which was analysed by intention-to-treat, including 12 people who were assigned to COPE but refused to participate. Assessments were conducted at pre-treatment, mid-treatment and post-treatment. Hospital readmission data were obtained through a Psychiatric Case Register. The study was conducted in a front-line public mental health service, the Early Psychosis Prevention and Intervention Centre (EPPIC). Clients in both COPE and No-COPE were provided with full access to the complete range of EPPIC services. RESULTS: There were no significant differences between the two conditions on the nine primary outcome variables. Hospital readmissions were assessed for each client at yearly intervals up to 4 years following the completion of treatment and again there were no significant between-group differences. CONCLUSIONS: The study indicated that there was no significant advantage to COPE over and above routine care at EPPIC. [ABSTRACT FROM AUTHOR]

Objective: To show that mental illness affects everyone in society, describe some of the main obstacles to better outcomes, and build confidence that they can be overcome.Methods: A review and analysis of relevant evidence and experience combined with personal advocacy.Results: Mental illnesses are common and seriously under-treated, reform of the system of care has completely stalled, and insidious reinstitutionalization of the modernized system is occurring. A number of contributing factors and possible solutions are identified, including mental health literacy and advocacy campaigns, a focus on young people and early intervention, and functional reintegration of the treatment of mental and substance use disorders.Conclusions: A new wave of reform and major financial investment in the treatment of mental and substance use disorders is overdue. This can be best achieved by combining the evidence-based health care (EBHC) paradigm with a direct appeal to the self-interest of members of the general community. A National Institute of Mental Health and Addiction should be a key element of such reform, which must be a continuing process with substantially increased federal and State funding. [ABSTRACT FROM AUTHOR]

Background: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). Methods: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. Results: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. Conclusion: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes. [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]

Objective: Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment.Method: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status).Results: 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline.Conclusions: Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess young people's mental health literacy in relation to psychosis and depression. It forms part of the baseline measure for the evaluation of a community awareness campaign called The Compass Strategy. A cross-sectional telephone survey using structured interviews was conducted. Vignettes of a person with either depression or psychosis were presented. The randomly selected sample was comprised of 1207 young people aged 12-25 from Melbourne and surrounding rural areas. Overall depression was far more frequently correctly identified than psychosis. A significantly higher proportion of females were able to correctly identify depression and psychosis. Counsellors, family members and friends were the preferred source of help overall followed by General Practitioners and Psychiatrists. However, there were significant differences between disorders in ranking of these sources of help. Vitamins and herbal treatments were rated as more helpful than antidepressants and antipsychotics. To increase early recognition of mental illness by the general public, efforts need to focus on improving knowledge of both signs and symptoms, and effectiveness of treatments. Family, friends and young males are particularly important targets. [ABSTRACT FROM AUTHOR]

Using the lessons gained from implementing the St Vincent Declaration for Diabetes (1990), this declaration details general goals, 5 years targets, performance and outcome measures for the detection and management of early psychosis. Its successful implementation requires integrated partnerships working locally, nationally and internationally to: [ABSTRACT FROM AUTHOR]

Treatment guidelines for first episode psychosis (FEP) recommend at least 1 year of antipsychotic treatment following remission; however, in light of some recent research and the preference of some individuals to discontinue their medication sooner, this recommendation can be questioned. The aim of this article is to appraise the current discontinuation studies given our views on how this field should progress. We conducted a review of randomized controlled trials investigating dose-reduction/medication discontinuation compared with treatment maintenance in clinically remitted FEP patients. Seven trials were identified, and these reported a higher rate of relapse in the dose reduction or discontinuation groups. Relapse rates were higher when a lower threshold for relapse was utilized. However, only three studies specified that concurrent psychosocial interventions were also provided, despite an evidence base for these interventions in reducing symptom severity and relapse. Length of follow-up may also be important, as the study with the longest follow-up (7 years), albeit with some methodological shortcomings, found greater functional recovery in the dose-reduction group and that relapse rates between the two groups (dose-reduction vs. maintenance) were equal after 3 years. Finally, in addition to discontinuation or dose reduction, a diagnosis of schizophrenia, a longer duration of illness, and poor premorbid functioning were associated with a greater risk of relapse. Further trials are needed in this area to establish the long-term risk-benefit ratio of antipsychotic medication in FEP. Meanwhile, young people with FEP who do not fulfil criteria for a diagnosis of a schizophrenia disorder, achieve clinical remission for at least 3 months, attain early functional recovery, and have good social support may be possible candidates for discontinuation of antipsychotic medication bolstered by effective psychosocial interventions provided in the context of a specialized FEP service. [ABSTRACT FROM AUTHOR]

Background: Specialised early intervention (SEI) programs have offered individuals with psychotic disorders and their families new hope for improving illness trajectories and outcomes. The Early Psychosis Prevention and Intervention Centre (EPPIC) was one of the first SEI programs developed in the world, providing services for young people experiencing their first episode of psychosis.Methods: We conducted a narrative synthesis of controlled and uncontrolled studies that have been conducted at EPPIC.Discussion: The history of the EPPIC model is first described. This is followed by a discussion of clinical research emerging from EPPIC, including psychopharmacological, psychotherapeutic trials and outcome studies. Neurobiological studies are also described. Issues pertaining to the conduct of clinical research and future research directions are then described. Finally, the impact of the EPPIC model on the Australian environment is discussed. [ABSTRACT FROM AUTHOR]

Background: headspace centres provide enhanced primary mental healthcare for young people. A priority is to provide services for all young people irrespective of a range of social disadvantages or social exclusion. The aims of this study were to: (i) delineate extent of social inclusion across domains of housing, studying/employment, functioning, alcohol, and other drug use; and (ii) map profiles of young people deemed vulnerable to experiencing additional barriers to accessing services based on their social inclusion domains (e.g., those living in unstable housing, not in employment/education, and/or experiencing intersecting or multiple forms of disadvantage or difficulties), including detailing their clinical characteristics. Methods: Young people were recruited from five headspace centres. Data relevant to social inclusion were examined. Multivariate logistic regression models were used to determine overlap between vulnerable groups, functional, social, clinical, and behavioural factors. Results: 1107 young people participated, aged 12–25 years (M = 18.1 years, SD = 3.3), most living in stable housing (96.5%) and engaged in studying/employment (84.8%). Specific vulnerabilities were evident in young people with NEET status (15.2%); in unstable accommodation (3.5%); of culturally diverse backgrounds (CALD) (12.2%); living in regional areas (36.1%); and identifying as lesbian, gay, bisexual, transgender, intersex, queer/questioning, and asexual plus (LGBTIQA+; 28.2%). Higher levels of distress, substance use, functional impairment, and lower social support were reported by those who were NEET and/or in unstable housing. LGBTIQA+ status was associated with high distress, depressive symptoms, and suicidal ideation. Conclusions: Most participants reported good social support, stable housing, and engagement in work or education. Those deemed vulnerable were likely to experience social exclusion across multiple domains and reported more mental health problems. The co-occurrence of mental ill-health and social exclusion highlights the importance of integrated mental healthcare. [ABSTRACT FROM AUTHOR]

BackgroundThe past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field.MethodWe undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health.ResultsThe HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to ‘HR criteria’ alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined ‘transition’ obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of ‘schizophrenia light progressing to schizophrenia’ is inadequate.ConclusionsIn the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss aspects of the editorial "Should the diagnostic boundaries of schizophrenia be expanded?," by Anthony S. David. They state that David's commentary argues against the inclusion of the study "Prodromal Risk Syndrome," by W. T. Carpenter in the book "Diagnostic and Statistical Manual of the American Psychiatric Association" (DSM). Furthermore, the authors say that David's editorial intends to expand the boundaries of schizophrenia and early intervention.

Presents a study on brain structure abnormalities before the onset of psychosis. Prevalence of grey matter in the cortex of individuals with psychosis; Application of magnetic resonance imaging in the study; Significance of the study.

Objective: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. Method: Totally 340 clinical MRI reports [Controls (n =98), first-episode psychoses (n =152), chronic schizophrenia (n =90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). Results: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. Conclusion: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning. [ABSTRACT FROM AUTHOR]

Purpose: Headspace services provide treatment options to young people seeking mental healthcare. To obtain a better understanding of needs and characteristics of this population, and effectively evaluate services, we require novel youth-specific outcome measures. As part of our broad research program to establish such measures, a sample of young people were recruited and assessed. The study describes (i) methodology used to obtain clinical, functioning, and substance use characteristics of young people presenting to headspace services; and (ii) an overview of these characteristics.Methods: Young people presenting to headspace centres were recruited. Multidimensional information was obtained relating to clinical and functional outcomes, demographic information, and lifestyle factors.Results: 1107 young help-seeking individuals were recruited. Participants were most likely young adults aged M = 18.1 years, SD = 3.3, with diagnoses of depression and/or anxiety (76.6%, n = 801), engaged in work and study (84.9%, n = 890), and living with parent(s) (68.9%, n = 736). Impairments in functioning were moderate as indicated by the Social and Occupational Functioning Assessment Scale (M = 65.2, SD = 9.5), substance use was common (alcohol 62.7%, n = 665; illicit substances 30.5%, n = 324), and current suicidal ideation was reported by a third (33.6%, n = 358).Conclusions: A broad dataset was obtained providing an insight into key clinical, functional and quality of life characteristics of these individuals. We observed that young people present with complex problems, comorbid diagnoses, moderate levels of symptomatology, impairments in functioning, substance use, and suicidal ideation. This work provides the foundation for our broader research program aiming to develop novel, relevant and youth-specific, change and outcome measures. [ABSTRACT FROM AUTHOR]

Background: Two common barriers to help-seeking are lack of awareness of appropriate services, and low mental health literacy. The headspace awareness campaigns are designed to address these factors. Aims: To examine whether distance from a headspace centre affects community awareness of headspace, and whether general awareness of headspace changed between 2008 and 2015. Method: Responses from 4707 participants aged 12–25 years, collected in 2008 and 2015, were analysed. The effect of headspace centre location on awareness of services was assessed by comparing awareness between those living in headspace areas (within 20 km of a centre) and those who were not. Change in awareness between 2008 and 2015 was assessed. Results: Awareness of headspace and its services was significantly greater among those living in headspace areas than among those living further away. Within headspace areas, awareness increased by 27% between 2008 and 2015. Prompted and unprompted awareness were significantly greater in 2015 than in 2008. Conclusions: Awareness of headspace has increased over time; however, innovative awareness campaigns are needed for those residing in non-headspace areas. Continued funding to increase headspace's national coverage, improving mental health literacy and service access for youth and their families, particularly those living in non-headspace areas, is needed. [ABSTRACT FROM AUTHOR]

Background: Certain migrant groups are more likely to develop a psychotic disorder compared to the native‐born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra‐high risk for psychosis (UHR) compared to native‐born young people and whether migrant status was associated with the risk of transition to a full‐threshold psychotic disorder. Methods: The cohort included all young people aged 15–24 who were identified as UHR at a specialist clinic over a five‐year period (2012–16). Australian census data were used to obtain the at‐risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. Results: 467 young people were identified as UHR, of which 13.5% (n = 63) were born overseas. First‐generation migrants were 2.6‐fold less likely to be identified as UHR compared to Australian‐born young people (IRR = 0.39, 95% CI [0.30, 0.51], P < 0.001). There was no difference between migrant and native‐born young people in their risk of transitioning to a psychotic disorder (HR = 0.90, 95% CI [0.39, 2.08], P = 0.81). Conclusions: UHR first‐generation migrants may be under‐accessing mental health services. [ABSTRACT FROM AUTHOR]

Background: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP). Method: MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. Results: The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES −0.213, 95% confidence interval (CI) (−0.344 to −0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES −0.031, 95% CI (−0.048 to −0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. Conclusion: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking. [ABSTRACT FROM AUTHOR]

Background. Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. Methods. In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. Results. Visuospatial and verbal associative memoryat baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. Results. Visuospatial and verbal associative memoryat baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. [ABSTRACT FROM AUTHOR]

BackgroundWhite matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.MethodsDiffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).ResultsCompared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).ConclusionsConnectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia. [ABSTRACT FROM PUBLISHER]

Objective Some people with major depressive disorder ( MDD) may be at a pre-onset stage for bipolar disorder ( BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. Methods Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios ( OR) for baseline predictors. Results From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12-18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01-4.14, N = 7), earlier age of onset of depression ( g = −0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79-12.66, N = 5). Conclusions Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered. [ABSTRACT FROM AUTHOR]

Background: People with schizophrenia have high rates of substance use which contributes to co-morbidity and premature mortality. Some evidence suggests people at-risk for psychosis have high rates of substance use. We aimed to assess substance use in a help-seeking cohort, comparing those at-risk and not at-risk for psychosis, and to establish any relationship with clinical symptoms.Method: Participants were help-seeking youth presenting to mental health services in Sydney and Melbourne. 279 (34.8%) were at-risk for psychosis, and 452 (56.4%) did not meet criteria for a psychotic disorder or risk for psychosis. The excluded individuals were made up of 59 (7.4%) young people who met criteria for a psychotic disorder and 11 (1.4%) who were unable to be evaluated. We assessed the association of substance use involvement with risk status and clinical symptoms using multivariate regression.Results: Individuals at-risk for psychosis had significantly higher tobacco, alcohol and cannabis use than those not at-risk. Multivariate analysis revealed at-risk status was significantly associated with higher alcohol involvement scores when adjusting for age and gender, but no association was found for cannabis or tobacco. At-risk status was no longer associated with alcohol involvement when cannabis or tobacco use was added into the analysis.Conclusion: Tobacco smoking, alcohol consumption and cannabis use are common in help-seeking youth, particularly those at-risk for psychosis. It is important to consider co-occurring use of different substances in adolescents. Early substance misuse in this phase of illness could be targeted to improve physical and mental health in young people. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The Need for Drug-Naive Research in First-Episode Psychosis," by J. Moncrieff and J. Leo in a 2010 issue.

Introduction Role functioning is key to optimal health and inoculates against life-long inequality. Depression is a leading cause of functional disability. In most cases, improved symptomatology corresponds with improved functioning; however, functioning does not always return to “normal”, despite symptom remission. Furthermore, the relationship between symptom remission and the likelihood of being Not in Employment, Education or Training (NEET) is unknown. Objectives and aim To examine the temporal associations between depression course, functioning, and NEET status in young adults with mental health problems. Methods A prospective and multisite clinical cohort study of young people aged 15–25 years seeking help from a primary mental health service ( n = 448). Participants completed a clinical interview (incl. QIDS-C16) and self-report battery (incl. WHODAS 2.0, employment, education) at baseline which was repeated at 12-month follow-up whilst continuing treatment as usual. Results Remitted depression was significantly associated with improved functioning; however, 12 month functioning was still lower than the normative ranges for age-matched peers. Remittance of depression did not change the likelihood of being NEET. Only 10% of those who were NEET had received vocational support during the study. Conclusion Remittance of depression was associated with improved functioning but it did not reduce the likelihood of being NEET. This may be explained by economic influences or alternatively, a time lag may exist where improvements in functioning do not immediately correspond with reduced NEET rates. Lastly, there may be a scarring effect of depression such that change in NEET status requires an additional intervention to depression treatment. [ABSTRACT FROM AUTHOR]

Background.Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study.Method.Participants were 268 (152 females, 116 males) individuals identified as UHR 2–14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS).Results.Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups.Conclusions.Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia. [ABSTRACT FROM PUBLISHER]

BackgroundWhether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses.MethodCortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined.ResultsThe effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms.ConclusionsOur results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness. [ABSTRACT FROM PUBLISHER]

BackgroundThere are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.MethodThe 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.ResultsThe 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.ConclusionsOur findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness. [ABSTRACT FROM PUBLISHER]

Objective It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. Method We conducted meta-analyses of studies comparing familial-high risk ( FHR) or ultra-high risk ( UHR; n = 2113) and healthy controls ( n = 1748) in youth studies in which the mean age was between 15 and 29. Results Compared with controls, high risk subjects were impaired in each domain in both UHR ( d = 0.34-0.71) and FHR ( d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis ( I2 = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains ( d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. Conclusion Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits. [ABSTRACT FROM AUTHOR]

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA2) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA2 and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA2 were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA2 activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA2 activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA2 activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis. [ABSTRACT FROM AUTHOR]

BackgroundGrey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.MethodWe examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.ResultsAt baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.ConclusionsThese data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences. [ABSTRACT FROM AUTHOR]

BackgroundMany research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the course and outcome based on individual symptoms scores.MethodData from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes.ResultsLCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate–severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning.ConclusionsThe different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms. [ABSTRACT FROM PUBLISHER]

Omega-3 fatty acid supplementation studies are inconclusive. We performed two intervention studies. The first study (Berger et al 2007) was a double blind, placebo-controlled randomized trial comparing 2g Ethyl-eicosapentaenoic acid (EPA) versus placebo in addition to antipsychotic medication in 79 first episode psychosis patients. Mixed model analysis suggests that EPA augmented first episode psychosis patients respond quicker compared to placebo for time to response (p=0.06). Post hoc analysis for cumulative response rates confirm a higher response rate at week 6 (42.9% versus 17.6% for all subjects, p=.036; 54,2% versus 17.2% for non-affective psychosis, p=.008) that was not significant anymore at week 12 (potential ceiling effect). In the second study (Amminger et al, 2010) using 840mg EPA and 700mg docosahexaenoic acid per day as sole treatment in 81 prodromal adolescents only 1 of 38 UHR adolescents (2.6%) in the EPA/DHA group compared to 8 of 38 (21.1%) prodromal adolescents in the placebo group met exit criteria for psychotic disorder (Chi-square Fisher''s exact test =6.2, df=1, p=0.028; OR=9.9). The change from baseline on the PANSS total symptom score (p=0.006), and the GAF score (p=0.025) were also significant between the treatment groups showing a clinically relevant advantage of EPA/DHA over placebo. Stage of illness may be more relevant for the use of the benign treatments such as omega-3 fatty acids in emerging psychosis and explain previous inconclusive findings. Research designs for future omega-3 fatty acid intervention trials and potential pitfalls will be discussed. [Copyright &y& Elsevier]

BackgroundIn recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables.MethodAltogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR.ResultsRemission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators.ConclusionsThese findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery. [ABSTRACT FROM PUBLISHER]

Abstract: There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways. [ABSTRACT FROM AUTHOR]

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria (n = 48) were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time. [ABSTRACT FROM AUTHOR]

Bechdolf A, Thompson A, Nelson B, Cotton S, Simmons MB, Amminger GP, Leicester S, Francey SM, McNab C, Krstev H, Sidis A, McGorry PD, Yung AR. Experience of trauma and conversion to psychosis in an ultra-high-risk (prodromal) group. Objective: We aimed to replicate a recent finding of high prevalence of trauma history in patients at ‘ultra-high risk’ (UHR) of psychotic disorder and to investigate whether trauma predicts conversion to psychosis in this population. Method: A consecutive sample of UHR patients was assessed. History of trauma was accessed with the General Trauma Questionnaire. Cox regression models were used to explore relationship between conversion to psychosis and trauma. Results: Of 92 UHR patients nearly 70% had experienced a traumatic event and 21.7% developed psychosis during follow-up (mean 615 days). Patients who had experienced a sexual trauma (36%) were significantly more likely to convert to first-episode psychosis (OR 2.96) after controlling for meeting multiple UHR intake groups. Conclusion: UHR patients have a high prevalence of history of trauma. Previous sexual trauma may be a predictor of onset of psychotic disorder in this population. [ABSTRACT FROM AUTHOR]