Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

The relationship between subjective sleep disturbance and attenuated psychotic symptoms after accounting for anxiety and depressive symptoms.

BACKGROUND AND HYPOTHESES: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. DESIGN: Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. RESULTS: Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. CONCLUSIONS: The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship.

The phenomenology of auditory verbal hallucinations in emotionally unstable personality disorder and post-traumatic stress disorder.

OBJECTIVE: To explore the phenomenology of auditory verbal hallucinations (AVHs) in a clinical sample of young people who have a 'non-psychotic' diagnosis. METHODS: Ten participants aged 17-31 years with presentation of emotionally unstable personality disorder or post-traumatic stress disorder and frequent AVHs were recruited and participated in a qualitative study exploring their subjective experience of hearing voices. Photo-elicitation and ethnographic diaries were used to stimulate discussion in an otherwise unstructured walking interview. RESULTS: 'Non-psychotic' voices comprised auditory qualities such as volume and clarity. Participants commonly personified their voices, viewing them as distinct characters with which they could interact and form relationships. There appeared to be an intimate and unstable relationship between participant and voice, whereby voices changed according to the participants' mood, insecurities, distress and circumstance. Equally, participants reacted to provocation by the voice, leading to changes in mood and circumstance through emotional and physical disturbances. In contrast to our previous qualitative work in psychosis, voice hearing was not experienced with a sense of imposition or control. CONCLUSIONS: This phenomenological research yielded in-depth and novel accounts of 'non-psychotic' voices which were intimately linked to emotional experience. In contrast to standard reports of voices in disorders such as schizophrenia, participants described a complex and bi-directional relationship with their voices. Many other features were in common with voice hearing in psychosis. Knowledge of the phenomenology of hallucinations in non-psychotic disorders has the potential to inform future more successful management strategies. This report gives preliminary evidence for future research.

Has improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts?

BACKGROUND: The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment ('treatment as usual') to this decline. METHOD: An audit was conducted on 105 clinical files of patients who received standard care at a specialised ultra-high-risk service. The session notes of these files were quantified, allowing examination of treatment quantity, targets, psychotherapy, and medication. Differences in these aspects across patients' year of clinic entry were assessed. Variables with significant differences across years were examined using cox regression to assess their contribution to psychosis transition rates. RESULTS: Findings were that, as a function of patients' year of clinic entry, there were increases in: patients' number of sessions, cognitive behavioural therapy (CBT), problem and solving therapy. There was a relationship between baseline year cohort and psychosis transition rate, with lower rates observed in more recent cohorts. When changes in treatment between cohorts were adjusted for, the relationship between baseline year cohort and transition rate disappeared. The relationship between baseline year and transition rate was attenuated most by increases in CBT. CONCLUSION: Changes in standard treatment, particularly increases in CBT, may have contributed to the decline in psychosis risk observed in recent ultra-high-risk cohorts, although these variables do not fully explain this trend. Implications for clinical practice, prediction and intervention research are discussed. Future ultra-high-risk research should investigate the impact of other treatment factors, such as therapeutic alliance.

Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.

Impact of Age, Frailty, and Dementia on Prescribing for Type 2 Diabetes at Hospital Discharge 2012-2016.

BACKGROUND: The risks of intensive blood glucose lowering may outweigh the benefits in vulnerable older people. OBJECTIVES: Our primary aim was to determine whether age, frailty, or dementia predict discharge treatment types for patients with type 2 diabetes (T2D) and related complications. Secondly, we aimed to determine the association between prior hypoglycemia and discharge treatment types. DESIGN, SETTING AND PARTICIPANTS: We conducted a cohort study involving 3,067 patients aged 65-99 years with T2D and related complications, discharged from Melbourne's Eastern Health Hospital Network between 2012 and 2016. MEASUREMENTS: Multinomial logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for the association between age, frailty, dementia and hypoglycemia, and being prescribed insulin-only, non-insulin glucose-lowering drugs (GLDs) or combined insulin and non-insulin GLDs compared to no GLD. International Classification of Diseases-10 codes were used to identify dementia status and prior hypoglycemia; frailty was quantified using the Hospital Frailty Risk Score. RESULTS: Insulin-only, non-insulin GLDs, combined insulin and non-insulin GLDs, and no GLDs were prescribed to 19%, 39%, 20%, and 23% of patients, respectively. Patients >80 years were less likely than patients aged 65-80 to be prescribed any of the GLD therapies, (eg. non-insulin GLDs [OR 0.67; 95%CI 0.55-0.82]), compared to no GLD. Similarly, high vs. low frailty scores were associated with not being prescribed any of the three GLD therapies, (eg. non-insulin GLDs [OR 0.63; 95%CI 0.45-0.87]). However, dementia was not associated with discharge prescribing of GLD therapies. Patients with a hypoglycemia-related admission were more likely than those not hospitalized with hypoglycemia to receive insulin-only (OR 4.28; 95%CI 2.89-6.31). CONCLUSIONS: Clinicians consider age and frailty when tailoring diabetes treatment regimens for patients discharged from hospital with T2D and related complications. There is scope to optimize prescribing for patients with dementia and for those admitted with hypoglycemia.

Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

BACKGROUND: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. METHODS: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. RESULTS: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. CONCLUSIONS: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

Pharmacological treatment initiation for type 2 diabetes in Australia: are the guidelines being followed?

AIM: To determine the patterns and predictors of pharmacological treatment initiation for type 2 diabetes and whether treatment initiation is consistent with Australian clinical practice guidelines that recommend metformin monotherapy. METHODS: Individuals aged 40-99 years initiating a non-insulin type 2 diabetes medication between July 2013 and February 2018 were identified from a 10% random national sample of pharmacy dispensing data. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the predictors of initiating sulfonylurea monotherapy, non-guideline monotherapy and combination therapy compared with metformin monotherapy. Predictors included age, sex, initiation year and comorbidities determined using the Rx-Risk comorbidity index. RESULTS: Of the 47 860 initiators, [47% women, mean age 60.7 (sd 12.1) years], 85.8%, 4.6%, 1.9% and 7.7% received metformin monotherapy, sulfonylurea monotherapy, non-guideline monotherapy and combination therapy, respectively. Increasing age was associated with increasing odds of initiating sulfonylurea monotherapy and non-guideline monotherapy. Combination therapy initiation was less likely in women (OR 0.74, 95% CI 0.69-0.79) and people with more comorbidities (e.g. OR 0.36, 95% CI 0.29-0.44 for seven or more comorbidities vs. no comorbidities) but more likely in congestive heart failure (OR 1.42, 95% CI 1.22-1.65), cerebrovascular disease (OR 1.50, 95% CI 1.32-1.69) and dyslipidaemia (OR 1.29, 95% CI 1.19-1.40). CONCLUSION: Treatment initiation in Australia is largely consistent with clinical practice guidelines, with 86% of individuals initiating metformin monotherapy. Initiation on combination therapy was more common in men and in those with fewer comorbidities.

The prognostic significance of attenuated psychotic symptoms in help-seeking youth.

BACKGROUND: Recent findings suggest that attenuated psychotic symptoms (APS) might serve as a risk factor for general mental health impairment in help-seeking youth. The current study was designed to test this possibility by examining the prognostic significance of APS in a large cohort of help-seeking youth not selected for psychosis risk. METHOD: 465 youth aged 12-25 referred to general youth mental health services were grouped as either APS + or APS- based on whether or not they met 'ultra high risk' for psychosis APS risk criteria as assessed using the Comprehensive Assessment of At Risk Mental States (CAARMS). They completed clinical assessments at baseline and at 12-month follow-up, measuring a range of psychopathology (depression, anxiety, eating disorders, general psychological distress, substance abuse) and psychosocial functioning. RESULTS: APS + had significantly poorer outcomes at 12-months on a range of clinical variables, even after adjusting for baseline scores and amount of treatment received. However, the APS + group showed greater improvement in functioning at follow-up compared to APS-. CONCLUSION: Attenuated psychotic symptoms are a prognostic indicator of persistent transdiagnostic mental health problems and reduced response to treatment in help-seeking youth over the short term. Hence, it is critical to screen and assess attenuated psychotic symptoms at the primary and secondary mental health services level, especially given that these subclinical symptoms are rarely voluntarily reported.

Vulnerability to psychosocial disability in psychosis.

Psychosocial disability affects a number of individuals with psychosis and often begins years before the formal onset of disorder. This suggests that for many, their psychosocial disability is enduring, and targeted interventions are therefore needed earlier in their developmental trajectories to ensure that psychosocial disability does not become entrenched. Poor psychosocial functioning also affects individuals with a range of different emerging mental health problems, putting these young people at risk of long-term social marginalisation and economic disadvantage; all of which are known risk factors for the development of psychosis. Identification of the markers of poor psychosocial functioning will help to inform effective treatments. This editorial will discern the early trajectories and markers of poor psychosocial outcome in psychosis, and highlight which individuals are most at risk of having a poor outcome. This editorial will also discuss whether early interventions are currently being targeted appropriately and will propose how intervention and preventative strategies can be implemented, to restore psychosocial trajectories in a way that enables young people to maximise their life chances.

Neural correlates of multi-day learning and savings in sensorimotor adaptation.

In the present study we evaluated changes in neural activation that occur over the time course of multiple days of sensorimotor adaptation, and identified individual neural predictors of adaptation and savings magnitude. We collected functional MRI data while participants performed a manual adaptation task during four separate test sessions over a three-month period. This allowed us to examine changes in activation and associations with adaptation and savings at subsequent sessions. Participants exhibited reliable savings of adaptation across the four sessions. Brain activity associated with early adaptation increased across the sessions in a variety of frontal, parietal, cingulate, and temporal cortical areas, as well as various subcortical areas. We found that savings was positively associated with activation in several striatal, parietal, and cingulate cortical areas including the putamen, precuneus, angular gyrus, dorsal anterior cingulate cortex (dACC), and cingulate motor area. These findings suggest that participants may learn how to better engage cognitive processes across days, potentially reflecting improvements in action selection. We propose that such improvements may rely on action-value assignments, which previously have been linked to the dACC and striatum. As correct movements are assigned a higher value than incorrect movements, the former are more likely to be performed again.

Multi-day Adaptation and Savings in Manual and Locomotor Tasks.

Using an individual differences approach, we evaluated whether manual and locomotor adaptation are associated in terms of adaptation and savings across days, and whether they rely on shared underlying mechanisms involving visuospatial working memory or visual field dependence. Participants performed a manual and a locomotor adaptation task during 4 separate test sessions over a 3-month period. Reliable adaptation and savings were observed for both tasks. It was further found that higher visuospatial working memory performance and lower visual field dependence scores were associated with faster learning in the manual and locomotor tasks, respectively. Moreover, adaptation rates were correlated between the 2 tasks in the final test session, suggesting that people may gradually be learning something generalizable about the adaptation process.

The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo.

Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set of standardised criteria including presumed genetic vulnerability (Trait), or a recent history of Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS). Recent calls to revise these criteria have arisen from evidence that Trait, APS and BLIPS groups may transition to psychosis at different rates. Concurrently, it has become clear that the UHR status confers clinical risk beyond transition to psychosis. Specifically, most UHR individuals will not develop psychosis, but will experience high rates of non-psychotic disorders, persistent APS and poor long-term functional outcomes. Rather than focus on transition, the present study investigated whether UHR groups differ in their broader clinical risk profile by examining baseline clinical characteristics and long-term outcomes other than transition to psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any BLIPS. Participants (N=702) were recruited upon entry to early intervention services and followed-up over a period of up to 13years (mean=4.53, SD=3.84). The groups evidenced similar symptom severity (SANS for negative symptoms, BPRS for positive and depression/anxiety symptoms) and psychosocial functioning (SOFAS, GAF, QLS) at baseline and follow-up as well as similar prevalence of non-psychotic disorders at follow-up. Our findings demonstrate that UHR groups evidence a similar clinical risk profile when we expand this beyond transition to psychosis, and consequently support maintaining the existing UHR criteria.

Deterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study.

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 memory at 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. CONCLUSIONS: Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.

Lithium suppression of tau induces brain iron accumulation and neurodegeneration.

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

Substance use in youth at risk for psychosis.

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.

Risk factors for development of primary bladder squamous cell carcinoma.

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients.

Cannabis-induced attenuated psychotic symptoms: implications for prognosis in young people at ultra-high risk for psychosis.

BACKGROUND: Cannabis 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). METHOD: Participants 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). RESULTS: A 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. CONCLUSIONS: Findings 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.

Visual-spatial processing and working-memory load as a function of negative and positive psychotic-like experiences.

INTRODUCTION: Patients with schizophrenia show impairments in working-memory and visual-spatial processing, but little is known about the dynamic interplay between the two. To provide insight into this important question, we examined the effect of positive and negative symptom expressions in healthy adults on perceptual processing while concurrently performing a working-memory task that requires the allocations of various degrees of cognitive resources. METHODS: The effect of positive and negative symptom expressions in healthy adults (N = 91) on perceptual processing was examined in a dual-task paradigm of visual-spatial working memory (VSWM) under three conditions of cognitive load: a baseline condition (with no concurrent working-memory demand), a low VSWM load condition, and a high VSWM load condition. RESULTS: Participants overall performed more efficiently (i.e., faster) with increasing cognitive load. This facilitation in performance was unrelated to symptom expressions. However, participants with high-negative, low-positive symptom expressions were less accurate in the low VSWM condition compared to the baseline and the high VSWM load conditions. CONCLUSIONS: Attenuated, subclinical expressions of psychosis affect cognitive performance that is impaired in schizophrenia. The "resource limitations hypothesis" may explain the performance of the participants with high-negative symptom expressions. The dual-task of visual-spatial processing and working memory may be beneficial to assessing the cognitive phenotype of individuals with high risk for schizophrenia spectrum disorders.