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Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved (“caught up”) to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.

Background Over the last two decades, several randomised controlled trials (RCTs) have indicated that preventive psychosocial, pharmacologic (Van der Gaag et al. 2013), and nutritional interventions (Amminger et al. 2010) are likely to be beneficial in people at ultra-high risk (UHR) of psychosis, in terms of delaying or preventing a transition to psychosis. Antidepressant medication is commonly prescribed in young people at UHR for psychosis; however, the evidence regarding its efficacy for psychosis prevention is limited (Fusar-Poli et al. 2007; Cornblatt et al. 2007; Fusar-Poli et al. 2015). The main aim of the present study is to investigate the impact of concomitant AD medication on the transition to psychosis rate in young people at ultra-high risk of psychosis who participated in the NEURAPRO trial (McGorry et al. 2017). Methods In this secondary analysis, data from 304 participants of a multicenter, double-blind, placebo-controlled, randomized clinical trial (NEURAPRO) of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) were included. During the trial, concomitant antidepressant medication was permitted for treatment of moderate to severe major depressive disorder (a score of ≥ 21 on the Montgomery-Asberg Depression Rating Scale, MADRS) in all participants. Results Of 304 participants, 189 (62.2%) were treated with ADs. 98 (64.1%) of those were in the omega-3 group and 91 (60.3%) in the placebo group. The transition rate to psychosis was higher in individuals who received AD treatment (13.2%; 25 of 189) as in individuals without ADs (6.1%; 7 of 115). The Kaplan-Meier survival curve estimated a group difference of X2 = 3.237, P = .072 (log rank test). Discussion Antidepressants are widely used in early psychosis. This analysis does not support the view that antidepressants may have reduced the transition to psychosis rate in this cohort. The findings are limited by the fact that antidepressants were prescribed based on clinical discretion. A randomised controlled trial is needed to determine whether antidepressants have a role in prevention of transition to psychosis.

Background People with schizophrenia and related psychotic illnesses have poor physical health and are at an increased risk of developing long-term physical health conditions such as diabetes and heart disease. While this may be due to unhealthy lifestyles, such as lack of physical activity, circadian rhythm problems may also play a part. It is therefore important to be able to measure physical activity and sleep patterns in schizophrenia. This study aims to assess for feasibility by comparing ActiGraph accelerometer data, mobile phone app data and questionnaire data. Methods A cross-sectional comparison of different assessment methods of sleep and general activity was used. Assessment methods included: a) ActiGraph wGT3X-BT accelerometers worn on the waist and wrist for 7 days. b) Lenovo A Plus smartphone apps ‘SleepBot’ and ‘Google Fit’ installed for the purposes of gathering data on sleep and physical activity patterns for 7 days. c) Simple Physical Activity Questionnaire taken at baseline and on day 7. At the seven-day assessment participants were interviewed using a topic guide covering their experiences. This explored the feasibility and acceptability of the measures and possible barriers for implementation. Results 14 out of a planned 30 participants who met DSM IV-R criteria for schizophrenia spectrum psychoses have been recruited across Greater Manchester from wards and in the community. All participants were retained for the 7-day study duration. Preliminary assessment has shown concordance between the different measures. 3 out of the 14 participants engaged in vigorous physical activity during the 7 days. All 14 participants spent more than 50% of their time sedentary during the 7 days. Participants showed fragmented sleep with a high number of awakenings. Discussion Using mobile phones and accelerometers are inexpensive and unobtrusive methods for measuring sleep and physical activity. These measures are feasible and acceptable to people with schizophrenia and are therefore suitable for implementation in routine clinical care. The measures can also be used by service users themselves to enhance their ability to monitor their own physical health. Such self-management and monitoring may encourage goal setting and improve autonomy, which have been found to be associated with increased levels of physical activity.

Background Ever since the establishment of strategies for identifying people at ultra-high risk (UHR) of developing psychosis about twenty years ago, much research has been conducted in seeking risk factors and in developing prediction models for predicting which UHR individuals will actually make a transition to psychosis. The goal is to provide specific interventions to those of high susceptibility. Such research almost invariably uses fixed predictor variables, typically variables assessed at baseline, i.e. service entry. Interest has now emerged to investigate whether the dynamic nature of psychopathology can be used to improve prediction of the onset of psychosis. As studies on UHR individuals usually require follow-up of participants over time, the longitudinal nature of these studies provides the opportunity to capture the dynamic characteristics of psychopathology by conducting multiple assessments across the study period. The idea is that prediction can be updated continuously as more information about changes in patients’ conditions are obtained. Over the past two decades, statistical methodology that can combine the time-to-transition aspect and the longitudinal aspect of UHR studies into one model has emerged. The methodology is called joint modelling. Methods The aim is to describe the joint modelling methodology and to demonstrate how joint modelling can be used to develop a prediction model for transition to psychosis. The data from the NEURAPRO Study was used for the demonstration. This study was a multi-centre placebo-controlled randomized trial of the effect of omega-3 polyunsaturated fatty acids on transition risk in UHR individuals. The sample size was 304. Study assessments were conducted monthly during the first 6 months and then at months 9 and 12. There were in total 40 known transitions. Results Compared with the conventional approach of using only fixed predictors, joint modelling prediction models showed significantly better sensitivity, specificity and likelihood ratios. Discussion Joint modelling is a useful statistical tool which can improve the prediction of the onset of psychosis and has the potential in guiding the provision of timely and personalized treatment to patients concerned.

BACKGROUND: A number of ethical issues arise in relation to medical research and to the early diagnosis of potentially serious illnesses in medicine. While these apply in a similar way in psychiatry, additional issues have been raised by an ethicist and some critics. These related to stigma and a lack of consensus regarding the nature and course of mental disorders. When the early intervention field was gaining momentum in in the late 1990s, these issues were examined in depth. Since then the evidence base has grown, the stance of critics altered and an expansion to a transdiagnostic perspective and a youth mental health paradigm indicate that another look at the issues is warranted. METHODS: Historical review and analysis. RESULTS: The same considerations as apply to research and treatment in mainstream medicine apply to psychosis, and mental disorders. Potential additional considerations that might increase harm can be addressed through reform of cultures of care, user participation plus advocacy and education targeted at discrimination and stigma. CONCLUSIONS: Ethical issues are crucial in influencing the conduct of research and clinical care.

BACKGROUND Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation. OBJECTIVES To analyse changes in naevi exposed to NB-UVB in a large cohort of patients. METHODS Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry. RESULTS Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%). CONCLUSIONS Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.

Background The clinical high-risk state for psychosis (HRP) is associated with an enhanced probability of developing a psychotic episode over a relatively short period of time. However, the extent to which different diagnostic types of illness develop remains unclear. Methods A systematic review was performed to identify studies of HRP participants reporting International Classfication of Diseases/Diagnostic and Statistical Manual of Mental Disorders diagnostic outcomes at follow-up. Demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. A meta-analysis was performed of transition to schizophrenic (SP) or affective psychoses (AP) and to specific diagnostic categories. Statistical heterogeneity and small study bias were assessed, and meta-regressions were performed. Results Twenty-three studies were retrieved, including a total of 2182 HRP participants, 560 (26%) of them developed a frank psychotic disorder over the follow-up time (mean = 2.35 y). Among HRP participants who developed psychosis, 73% were diagnosed with SP and only 11% with AP (Risk Ratio, RR = 5.43, 95% CI from 3.35 to 8.83). The specific transition risk to ICD/DSM schizophrenia was of 15.7% (over 2.35y). Heterogeneity was statistically significant and moderate in magnitude. Use of basic symptoms criteria in the baseline clinical assessment was associated with a further increase in the proportion progressing to SP vs AP (RR = 17.1). There was no evidence of publication bias and the sensitivity analysis confirmed robustness of the above results. Conclusions The HRP state is heterogeneous in term of longitudinal diagnoses; however, the current HRP diagnostic criteria appear strongly biased toward an identification of early phases of SP rather than AP.

Introduction Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an “ultra high risk” (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder. Methods Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days. Results Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases. Discussion The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further “closing in” on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of “false positive” cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.

Background: The NEURAPRO-E trial is a randomized controlled multicenter trial of long-chain omega-3 polyunsaturated fatty acids in 304 young people at clinical risk of psychosis. The trial failed to replicate the earlier single-center trial in 81 participants (the Vienna omega-3 study). This analysis aims to investigate if antidepressant (AD) use during NEURAPRO-E influenced clinical outcomes. Methods: Secondary analysis of a RCT of omega-3 PUFAs versus placebo involving a total cohort of 304 participants. Randomization was stratified by total score on the Montgomery-Asberg Depression Rating Scale (MADRS score ≥21 vs.

Background: Cross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time. Methods: Cross-lagged path modeling was used to analyze bidirectional, longitudinal associations between 4 dimensions of subclinical psychotic experiences (persecutory ideation, bizarre experiences, perceptual abnormalities, and magical thinking) and interpersonal functioning in an adolescent general population sample (N = 881 at T1, N = 652 at T2, and N = 512 at T3) assessed 3 times in 3 years. Results: All symptom dimensions showed some association with interpersonal functioning over time, but only bizarre experiences and persecutory ideation were consistently and longitudinally associated with interpersonal functioning. Poorer interpersonal functioning predicted higher levels of bizarre experiences and persecutory ideation at later measurement points (both T1 to T2 and T2 to T3). Conclusions: Poor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder.

Background The cognitive deficits of schizophrenia have been identified as an unmet clinical need. They are predictive of functional outcome [Green et al., 2000] and quality of life [Fujii et al., 2004], yet there are no treatments able to normalise cognition in schizophrenia. There is increasing evidence that exercise is helpful for these symptoms [Geyer et al., 2012], but the systems involved remain enigmatic. Animal models can be used to scrutinise both the behavioural and biological effects of exercise. The sub-chronic phencyclidine (PCP) rat model for schizophrenia is a well-established and widely utilised model that is used to investigate schizophrenia-like cognitive deficits [Neill et al., 201]. This two-part study investigates whether voluntary wheel running is able to reverse cognitive impairment in the sub-chronic PCP rat model for schizophrenia, and how long the effect of exercise lasts. Methods Female Lister Hooded rats (n=80) were pseudo-randomised into four groups: vehicle-control; vehicle-exercise; PCP-control and PCP-exercise (n=20 per group). Rats were treated either with saline (vehicle) or PCP (2mg/kg, i.p. bi-daily, followed by a seven-day washout period). Vehicle and PCP exercise groups had access to a wheel for 1 hour a day, 5 days a week, for 6 weeks. The vehicle and PCP control groups were treated in the same way, but the wheels were locked. Rats were tested in the novel object recognition (NOR) memory paradigm pre-exercise (time point 1, T1) post-exercise (time point 2, T2), after two weeks rest (time point 3, T3) and four weeks rest (time point 4, T4). Half of the animals from each group (n=10 per group) were sacrificed post exercise (T2), and the remaining animals were sacrificed after 4 weeks rest. For each animal, 1 brain hemisphere was collected for protein analysis and 1 hemisphere was fixed for immunohistochemistry. Behavioural data were analysed using two-way ANOVA and post-hoc t-tests. Results Pre-exercise (T1), in the retention phase both vehicle groups were spent more time exploring the novel over the familiar object, an effect that was not seen in the PCP groups. Post-exercise (T2 & T3), in the retention phase both vehicle groups and the PCP exercise group spent more time exploring the novel over the familiar object, an effect that was not seen in the PCP-control group. Post-exercise (T4) in the retention phase both vehicle groups were spent more time exploring the novel over the familiar object, an effect that was not seen in the PCP groups. Discussion Exercise is able to rescue the NOR cognitive deficit seen in the sub-chronic rat model for schizophrenia. This corresponds with human studies reporting positive effects of exercise in patients with schizophrenia and provides a potential tool to thoroughly investigate the pro-cognitive effects of exercise The benefits of the exercise intervention were observed 2 weeks post-exercise with the deficits returning in the PCP treated animals when they were tested 4 weeks post-exercise. Post-mortem analysis is underway to determine the potential mechanisms by which exercise improves cognitive impairment.

Background The NEURAPRO multicentre randomised controlled trial (RCT) of long-chain polyunsaturated omega-3 fatty acids (ω-3 PUFAs) (‘fish oil’) in combination with high-quality psychosocial intervention (cognitive behavioural case management [CBCM]) vs. placebo in combination with CBCM in young people at ultrahigh risk (UHR) of psychosis showed that the group allocated to fish oil had no clinical benefits over the placebo group. However, a limitation of the trial was that adherence with the study medication was relatively low. Furthermore, although RCTs are placed at the top of the evidence hierarchy, this methodology has limitations in fish oil RCTs, since the test agent is not only present in the intervention group, but ω-3 fats are present in the diet and in the tissues of all participants. A biomarker analysis of ω-3 changes during the trial can ultimately determine the efficacy of ω-3 supplementation in this trial. Methods The NEURAPRO study was conducted from March 2010 to September 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. In this study of 304 young people at UHR for psychotic disorders, 153 (50.3%) were allocated to ω-3 PUFAs and 151 (49.7%) to placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The primary outcome was transition to psychosis assessed with the Comprehensive Assessment of the At-Risk Mental State. Secondary outcomes were levels of psychopathology and functioning assessed by the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales). Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention). We examined changes in cell membrane levels of EPA and DHA, as measures of ω-3 intake independent of source. Data were analysed as a single cohort. Cox proportional hazards models and linear regression analyses were used to examine relationships between the ω-3 index (EPA+DHA) with clinical outcomes at month 6 and 12. Results When analysed as a single cohort, no association was observed between the ω-3 index and transition to psychosis at any follow-up time point but increase of the ω-3 index was found significantly related with most of the functional and symptomatic measures at month 6 and 12, in linear regression models adjusting for relevant baseline factors (i.e., functioning, psychopathology, ω-3 index and smoking). The models revealed consistent results, with low functioning or high psychopathology at baseline, low levels of ω-3s at baseline and increase of the ω-3 index independently predicting clinical improvements at in this sample. Discussion In contrast to our RCT analysis, this study using biomarkers shows that increase in erythrocyte ω-3 PUFAs may improve clinical outcomes of UHR patients. The results also imply that people with low DHA and EPA levels may benefit more from supplementation with fish oil. The analysis also highlights shortcomings of the RCT design in situations when the tested intervention is available outside the study.

Background Converging evidence suggests that people at ultra-high risk (UHR) for psychosis have depleted levels of several fatty acids (FAs), and that changes in omega-3 (n-3) FA levels may indicate a higher risk for transition to psychosis. However, limited information is available on how FA deficiencies relate to psychopathology in individuals with UHR phenotypes. Here, we report the relationship between membrane FA levels and symptom severity in a study of individuals at UHR for psychosis. Methods Data from 280 of 304 (92%) of participants of the NEURAPRO study, a multi-centre randomized-controlled trial of omega-3 fatty acids versus placebo, were used for the present analysis. All participants were aged between 13 and 40 years and met criteria for UHR for psychosis. Blood samples were collected at study baseline and month 6 (end-of-intervention). Membrane fatty acids were analysed using mass spectrometry as percentage of total fatty acids in erythrocytes. Pearson correlation coefficients were calculated between baseline erythrocyte fatty acid levels and scores on the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS). Results Negative symptoms were positively correlated with one saturated FA (Tetracosanoic acid [24:0], R=0.272, p

Summary Background Teledermatology is a rapidly growing field with studies showing high diagnostic accuracy when compared with face-to-face diagnosis. Teledermoscopy involves the use of epiluminescence microscopy to increase diagnostic accuracy. The utility of teledermoscopy as a triage tool has not been established. Objectives To assess teledermoscopy as a triage tool for a hospital skin lesion clinic. Methods Patients referred to a dermatology skin lesion clinic were recruited. Digital and dermoscopic photographs were taken of skin lesions of concern and the patients were then seen independently face-to-face by two out of three dermatologists. The digital images were evaluated 4 weeks later, as a teledermoscopy consultation, by two of these dermatologists. The diagnosis and management from both types of consultation were compared. Results Two hundred patients with a total of 491 lesions were seen. There was excellent agreement between teledermoscopy and face-to-face diagnosis with only 12·3% of lesions having disparate diagnoses of clinical significance. Twelve of 491 (2·4%) lesions appeared to have been under-reported by teledermoscopy when compared with face-to-face diagnosis. However, when histopathology became available, only one malignant lesion had been missed (a basal cell carcinoma diagnosed as solar keratosis) by teledermoscopy. Teledermoscopy approximated 100% sensitivity and 90% specificity for detecting melanoma and nonmelanoma skin cancers. Importantly, 74% of all lesions were determined to be manageable by the general practitioner without needing to be seen face-to-face by a dermatologist. Conclusions This use of teledermoscopy as a triage tool offers the potential to shorten waiting lists and thus improve healthcare access and delivery.

Summary Background The pulsed dye laser (PDL) is the treatment of choice for port wine stains (PWS); however, some patients' PWS become refractory to further treatments. Technological advances have enabled new machines with the advent of surface cooling devices to deliver longer wavelengths and higher fluence more safely. These advances have the potential to achieve improved response rates in refractory PWS. There are few studies comparing the efficacy of standard PDL treatments for refractory PWS with the wider choice of treatment variables available from newer PDL machines. Objectives To determine if there is any advantage of using a longer wavelength (595 nm) and pulse widths (1·5 ms, 6 ms and 20 ms) over conventional PDL settings (wavelength 585 nm, pulse width 1·5 ms) in refractory PWS. Methods Eighteen consecutive consenting patients with Fitzpatrick skin types 1–4 with a mean age 35 years (range 17–59 years) with refractory PWS were treated routinely with three separate test areas using 595-nm PDL (using three different pulse width settings of 1·5 ms, 6 ms and 20 ms), compared with test areas treated with 585-nm PDL (pulse width 1·5 ms). All test areas were treated with an identical fluence (15 J cm−2), spot size (7 mm) and cooling setting (dynamic cooling 60 ms, delay 60 ms). Results We found a statistically significant advantage of 595-nm PDL (pulse width 1·5 ms) over 595-nm PDL (pulse width 6 ms) (P

The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.

Pseudo-inflammatory tumours are a poorly defined group of tumours, with indeterminate malignant potential, which can occur at almost any site of the body. The optimal treatment of inflammatory pseudo-tumours is yet to be elucidated. Surgical excision has been the most frequently reported treatment in the literature. We report a case of solitary cutaneous inflammatory pseudo-tumour.

The development of a new frontier for research and early intervention in psychotic disorders is highly dependent on the construction of synergistic clinical infrastructures. This has catalyzed great progress in the recognition, enhanced treatment, and study of first episode psychosis, and the task is even more challenging when the boundaries are extended to include the earliest clinical phase of illness, the prodromal or prepsychotic phase. This article describes the conceptual and practical building blocks for the construction of service models for intervention in the postonset clinical phase prior to the attainment of current diagnostic thresholds. This is best regarded as indicated prevention, a form of very early secondary prevention, which involves a blend of immediate clinical care combined with research-oriented preventive intervention. The experience of the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne across several stages of growth is described and contrasted with that of several emerging centers in Europe and North America. The progress to date, the lessons learned, and the unresolved challenges and opportunities are detailed. It is concluded that service models can be developed that are acceptable and helpful to young people and their families, and that create a unique environment for the study of the transition to frank psychotic disorder. The ultimate clinical utility and general safety of this approach and the range of effective treatments remain unclear, and will be determined by more extensive research. Such research must be conducted in a logical and rigorous manner with the best designs possible, sensitive to input from consumers and caregivers and to ethical considerations.

Background: A number of interventions have been trialed in the ultra-high risk for psychosis population with the aim of preventing onset of psychotic disorder and improving outcomes. Among the most promising has been dietary supplementation with long-chain omega-3 polyunsaturated acids (PUFA), which in a single-center study involving 81 participants, was shown to significantly reduce the risk of transition to psychosis over a 12-month period as well as improving symptomatic and functional outcomes, an effect that persisted long term (median 6.7 years). The current trial aimed to replicate these findings in a large-scale multicenter study. The objective of the RCT was to determine whether treatment with PUFA, in combination with a high-quality psychosocial intervention, cognitive–behavioral case management (CBCM), is more effective than placebo plus CBCM in preventing transition to psychosis and improving outcomes in young people at ultra-high risk for psychosis. Here we report the medium term (>2 years) outcome of the trial.

Background: Clinical criteria for Ultra-High Risk of psychosis (UHR) show moderate specificity for the prediction of the first psychotic episode (FEP), with an average true positive rate of approximately 30% at 3 years. We have recently developed a multimodal probabilistic model using the odds ratio form of Bayes’ rule that achieved sensitivity=73% and specificity=96% for FEP combining clinical data and biological data in a small sample of UHR patients. To validate this approach, we built a similar model using cognitive and clinical data from the Personal Assessment and Crisis Evaluation (“PACE 400”) study.

We report a 44-year-old man who presented with recurrent unexplained encephalopathy and myositis despite extensive neurological and metabolic investigations. Eventually, he was noted to have multiple asymptomatic flesh-coloured papules suggestive of scleromyxoedema, which was confirmed by histology. Although primarily a cutaneous disease, extracutaneous features of scleromyxoedema may dominate the clinical picture of this rare mucin-deposition disorder.

Pustular vasculitis of the hands is a distinctive clinical entity. It has recently been proposed by some authors to rename pustular vasculitis of the hands as 'neutrophilic dermatosis of the hands' to reflect its histological resemblance to the neutrophilic dermatoses. We report the case of a 66-year-old woman who presented with clinical appearances resembling pustular vasculitis of the hands associated with palmo-plantar pustulosis due to Streptococcus-induced 'pustular vasculitis'.

This article describes the theoretical background, origins, and development of a new clinical service for intervention in the putatively prodromal phase of schizophrenia and other psychotic disorders. Establishing such a service required examination of conceptual issues such as the meaning of the prodrome in psychosis and its association with risk of subsequent psychosis, and of practical issues related to identifying prodromal patients in the community and engaging them in monitoring and treatment. Patients' needs, timing, and mode of treatment had to be considered. Preliminary data from the service's 20-month pilot phase are presented to help inform these issues.

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