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A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals. [ABSTRACT FROM AUTHOR]

Background The long-term functional status of subjects at ultra high risk for psychosis (HR) is relatively under investigated. This study explores baseline predictors of long-term functional outcome in HR subjects who did not convert to psychosis during a 6 years follow-up period. Methods A total of 154 HR were followed up for an average of 6 years. The primary outcome variable was global assessment of functioning at the last follow-up visit as assessed with the Global Assessment of Functioning tool. A multinomial logistic regression was performed to identify potential predictors of functional outcome. Results Baseline and follow-up data on functioning was available for 92 HR. Twenty-four (43%) individuals who did not convert to psychosis reported poor functioning at follow-up. Baseline scores in the GAF (Exp(b) = 0.857; 95% CIs: 0.75/0.97), employment status (Exp(b) = 0.029; 95% CIs: 0.00/0.268), and CAARMS total scores (Exp(b) = 1.976; 95% CIs: 1.00/1.14) predicted functional outcome in HR subjects at 6 years. Conclusions Despite the preventive treatments received, many individuals who did not convert to full-blown psychosis in the longer term do not functionally remit. These individuals are lower functioning, unemployed and have higher symptom loading at the time of their presentation to the prodromal clinic. Our study suggests the need for innovative treatments targeting long term functional status beyond the prevention of psychosis onset in the HR population. [ABSTRACT FROM AUTHOR]

BackgroundCannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.MethodLifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.ResultsLifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).ConclusionsIn people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis. [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]

BackgroundAn increased reactivity to stress in the context of daily life is suggested to be an independent risk factor underlying the positive symptoms of psychotic disorder. The aim of this study was to investigate whether positive symptoms moderate the association between everyday stressful events and negative affect (NA), known as stress reactivity. This hypothesis was put to the test in patients with a diagnosis of psychotic disorder.MethodThe Comprehensive Assessment of Symptoms and History (CASH) and the Positive and Negative Syndrome Scale (PANSS) were used to assess positive and negative symptoms. The experience sampling method (ESM), a structured diary technique, was used to measure stress reactivity and psychotic symptoms in daily life.ResultsHigher levels of positive symptoms (CASH: B = 0.14, p = 0.005; PANSS: B = 0.05, p = 0.000; ESM: B = 0.03, p = 0.000) and lower levels of negative symptoms (PANSS: B = − 0.05, p = 0.001) significantly moderate the association between unpleasant events and NA. No significant moderating effect was found for CASH negative symptoms. Moreover, the moderating effect of lifetime and current symptoms on the stress–NA association was significantly larger for those patients with predominantly positive symptoms (CASH: B = 0.09, p = 0.000; PANSS: B = 0.08, p = 0.000; ESM: B = 0.13, p = 0.000).ConclusionsPatients with a ‘psychotic syndrome’ with high levels of positive symptoms and low levels of negative symptoms show increased reactivity to stress in daily life, indicating that stress reactivity is a possible risk factor underlying this syndrome. [ABSTRACT FROM PUBLISHER]

Background. Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis. Method. The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model. Results. Over the initial 12 months from presentation, the costs of the OASIS intervention were £1872 higher than CAU. However, after 24 months they were £961 less than CAU. Conclusions. This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving. [ABSTRACT FROM AUTHOR]

Background: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. Methods: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. Results: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. Conclusion: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population. [ABSTRACT FROM AUTHOR]

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being “hypersensitive” to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms. [ABSTRACT FROM AUTHOR]

Background: Stress is a key feature of many aetiological models of psychosis and there is considerable empirical evidence implicating stress in the development of psychosis. This paper investigates the role of psychosocial stress in the onset of psychosis by examining the relationship between current and lifetime exposure to traumatic experiences and psychosocial stressors, HPA axis function, and psychopathology in people at high risk of developing psychosis. Methods: Sixty ‘high risk’ (HR) participants were compared with 50 healthy control (HC) participants on measures of exposure to psychosocial stressors. Subgroups of HR and HC participants which provided saliva samples were compared regarding measures of HPA axis function. Results: HR participants were exposed to greater levels of psychosocial stress than HC participants. Specifically, HR participants were more likely to have been separated from their parents (p=.003), report severe parental antipathy (p=.011), and have been bullied while growing up (p=.024). HR participants experienced greater levels of perceived stress than HC participants (p=.001) and were more likely to have had a negative life event in the previous 6 months (p<.001). Positive correlations were found between current stress and number of life events and attenuated psychotic symptoms (r=.585, p<.001, and r=.384, p=< .001, respectively) in the HR participants. Discussion: This study shows that people at high risk of developing psychosis experience greater levels of psychosocial stress than matched healthy control participants throughout the lifetime, from early childhood to the present day, and that current stress is strongly associated with psychotic symptomatology. [ABSTRACT FROM AUTHOR]

Introduction: Individuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms. The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis. Method: Psychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis. A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne. Results: Latent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%). Conclusions: Different constellations of symptomatology are associates with varying levels of risk to of transition to psychosis. [ABSTRACT FROM AUTHOR]

BackgroundEvidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.MethodWe used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.ResultsAssociations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.ConclusionsElevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis. [ABSTRACT FROM AUTHOR]

Background.Recent randomized controlled trials suggest some efficacy for focused interventions in subjects at high risk (HR) for psychosis. However, treating HR subjects within the real-world setting of prodromal services is hindered by several practical problems that can significantly make an impact on the effect of focused interventions.Method.All subjects referred to Outreach and Support in South London (OASIS) and diagnosed with a HR state in the period 2001–2012 were included (n = 258). Exposure to focused interventions was correlated with sociodemographic and clinical characteristics at baseline. Their association with longitudinal clinical and functional outcomes was addressed at follow-up.Results.In a mean follow-up time of 6 years (s.d. = 2.5 years) a transition risk of 18% was observed. Of the sample, 33% were treated with cognitive behavioural therapy (CBT) only; 17% of subjects received antipsychotics (APs) in addition to CBT sessions. Another 17% of subjects were prescribed with antidepressants (ADs) in addition to CBT. Of the sample, 20% were exposed to a combination of interventions. Focused interventions had a significant relationship with transition to psychosis. The CBT + AD intervention was associated with a reduced risk of transition to psychosis, as compared with the CBT + AP intervention (hazards ratio = 0.129, 95% confidence interval 0.030–0.565, p = 0.007).Conclusions.There were differential associations with transition outcome for AD v. AP interventions in addition to CBT in HR subjects. These effects were not secondary to baseline differences in symptom severity. [ABSTRACT FROM AUTHOR]

Abstract: The experience of a first psychotic episode is associated with a marked impairment in psychosocial functioning. However, the decline may be already evident in the pre-psychotic phases and play a significant role in the etiopathology of the disease onset. A sample of subjects at ultra high clinical risk for psychosis (“At Risk Mental State”, ARMS, n =152) was compared with a demographically-matched general population (n =98,072) on different measures of psychosocial functioning. The proportion of subjects with an ARMS living in communal establishments or living at home with their parents was significantly higher than that of the local population (p <0.001). Subjects with an ARMS showed also higher rates of unemployment as compared to the general population (p <0.001). GAF scores at baseline were significantly lower in unemployed ARMS as compared to students and employed ARMS (p =0.002). ARMS subjects living in communal establishments presented higher rates of co-morbid psychiatric conditions (p =0.007) and lower GAF scores at baseline (p =0.017). Finally, baseline unemployment and living in a communal establishment were associated with an increased risk of developing a psychotic episode within the following two years (p <0.05). We concluded that the “At Risk Mental State” is a clinical condition which is characterized by marked psychosocial impairment and by an increased vulnerability to psychosis. Unemployment at the first contact with the prodromal service may be a risk factor for the development of a psychotic episode. [Copyright &y& Elsevier]

Rationale: Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects. Objectives: We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients. Methods: Thirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week. Results: One-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p =.005) on cortisol reactivity as well as a significant (p =.003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p =.003), and in HC compared with CHR-CBD (p =.014), but was not different between CHR-P and CHR-CBD (p =.70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p's <.02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change. Conclusions: Our findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms. [ABSTRACT FROM AUTHOR]

Over the last two decades, there has been a rapid increase of studies testing the efficacy and acceptability of virtual reality in the assessment and treatment of mental health problems. This systematic review was carried out to investigate the use of virtual reality in the assessment and the treatment of psychosis. Web of Science, PsychInfo, EMBASE, Scopus, ProQuest and PubMed databases were searched, resulting in the identification of 638 articles potentially eligible for inclusion; of these, 50 studies were included in the review. The main fields of research in virtual reality and psychosis are: safety and acceptability of the technology; neurocognitive evaluation; functional capacity and performance evaluation; assessment of paranoid ideation and auditory hallucinations; and interventions. The studies reviewed indicate that virtual reality offers a valuable method of assessing the presence of symptoms in ecologically valid environments, with the potential to facilitate learning new emotional and behavioural responses. Virtual reality is a promising method to be used in the assessment of neurocognitive deficits and the study of relevant clinical symptoms. Furthermore, preliminary findings suggest that it can be applied to the delivery of cognitive rehabilitation, social skills training interventions and virtual reality-assisted therapies for psychosis. The potential benefits for enhancing treatment are highlighted. Recommendations for future research include demonstrating generalisability to real-life settings, examining potential negative effects, larger sample sizes and long-term follow-up studies. The present review has been registered in the PROSPERO register: CDR 4201507776. [ABSTRACT FROM PUBLISHER]

Background Subjects at ultra high-risk (UHR) for psychosis have an enhanced vulnerability to develop the disorder but the risk factors accounting for this accrued risk are undetermined. Method Systematic review of associations between genetic or environmental risk factors for psychosis that are widely established in the literature and UHR state, based on comparisons to controls. Results Forty-four studies encompassing 170 independent datasets and 54 risk factors were included. There were no studies on association between genetic or epigenetic risk factors and the UHR state that met the inclusion criteria. UHR subjects were more likely to show obstetric complications, tobacco use, physical inactivity, childhood trauma/emotional abuse/physical neglect, high perceived stress, childhood and adolescent low functioning, affective comorbidities, male gender, single status, unemployment and low educational level as compared to controls. Conclusions The increased vulnerability of UHR subjects can be related to environmental risk factors like childhood trauma, adverse life events and affective dysfunction. The role of genetic and epigenetic risk factors awaits clarification. [ABSTRACT FROM AUTHOR]

Objective About one-third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis ( FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. Method Retrospective study comparing duration of hospital admission, referral-to-diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high-risk service ( n = 164) to patients with FEP who initially presented to conventional mental health services ( n = 2779). Regression models were performed, controlling for several confounders. Results FEP patients who had presented to a high-risk service spent 17 fewer days in hospital [95% CI: −33.7 to (−0.3)], had a shorter referral-to-diagnosis time [B coefficient −74.5 days, 95% CI: −101.9 to −(47.1)], a lower frequency of admission [ IRR: 0.49 (95% CI: 0.39-0.61)] and a lower likelihood of compulsory admission [ OR: 0.52 (95% CI: 0.34-0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. Conclusion Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic. [ABSTRACT FROM AUTHOR]

Background.The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown.Method.We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses.Results.The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive–compulsive disorder symptoms.Conclusions.Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state. [ABSTRACT FROM AUTHOR]

Background. Interpersonal sensitivity is a personality trait described as excessive awareness of both the behaviour and feelings of others. Although interpersonal sensitivity has been found to be one of the vulnerability factors to depression, there has been little interest in its relationship with the prodromal phase of psychosis. The aims of this study were to examine the level of interpersonal sensitivity in a sample of individuals with an at-risk mental state (ARMS) for psychosis and its relationship with other psychopathological features. Method. Sixty-two individuals with an ARMS for psychosis and 39 control participants completed a series of self-report questionnaires, including the Interpersonal Sensitivity Measure (IPSM), the Prodromal Questionnaire (PQ), the Ways of Coping Questionnaire (WCQ) and the Depression and Anxiety Stress Scale (DASS). Results. Individuals with an ARMS reported higher interpersonal sensitivity compared to controls. Associations between interpersonal sensitivity, positive psychotic symptoms (i.e. paranoid ideation), avoidant coping and symptoms of depression, anxiety and stress were also found. Conclusions. This study suggests that being 'hypersensitive' to interpersonal interactions is a psychological feature of the putatively prodromal phase of psychosis. The relationship between interpersonal sensitivity, attenuated positive psychotic symptoms, avoidant coping and negative emotional states may contribute to long-term deficits in social functioning. We illustrate the importance, when assessing a young client with a possible ARMS, of examining more subtle and subjective symptoms in addition to attenuated positive symptoms. [ABSTRACT FROM AUTHOR]

Abstract: We followed up a cohort (n =35) of clients with an “At Risk Mental State” (ARMS) for almost 2 years (mean 21.3 months). At baseline, these clients had taken part in research looking at the relationship between reasoning biases, memory, personality styles and delusional ideation. During the follow-up period, clients underwent a package of intervention from a specialist early detection team. Eighty percent (n =28) of these clients were successfully re-interviewed. There was improvement across the cohort as a whole, however five participants (17.9%) had made the transition to psychosis at follow-up. Those who had become psychotic had lower levels of manic symptomatology at baseline than those who did not enter the first episode. Further, across the cohort, impaired working memory and delusional ideation at baseline combined to predict 45% of the delusional ideation at follow-up. These preliminary findings suggest that working memory impairments may be linked to the persistence of delusional ideation and that manic symptoms in someone with an ARMS may suggest that such an individual is less likely to develop a frank psychotic episode. [Copyright &y& Elsevier]

Abstract: Background: Several studies have indicated that people with prodromal signs of psychosis show alterations in the structure and function of the brain when they first present to clinical services. However, the longitudinal course of these abnormalities, and how they relate to subsequent clinical and functional outcome is relatively unclear. Methods: A cohort of subjects at ultra high risk of psychosis were studied using functional magnetic resonance imaging (fMRI) in conjunction with the N-Back task, and volumetric MRI at first clinical presentation and again after one year. Levels of psychopathology and global functioning were assessed at the same time points using the CAARMS, PANSS, and the GAF scale. Results: At baseline, the high risk group showed reduced activation during the task in the left middle frontal gyrus, supramarginal gyrus and inferior parietal lobule, and reduced gray matter volume in the left middle and medial frontal gyri, left insula and the right anterior cingulate gyrus. Within the high-risk group, there was a positive correlation between the magnitude of the functional and structural alterations in the left middle frontal gyrus. Between presentation and follow up, the severity of perceptual disorder and thought disorder (rated by the CAARMS), and of general psychopathology (rated by the PANSS general score) decreased, and the level of global functioning improved. This clinical and functional improvement was associated with a longitudinal increase in activation in the anterior cingulate and right parahippocampal gyrus. The change in anterior cingulate response was directly correlated with the improvement in the GAF score. Conclusions: In subjects presenting with prodromal signs of psychosis, reduced prefrontal activation during a working memory task is associated with a reduction in gray matter volume in the same area. Changes in anterior cingulate activation were correlated with functional improvement in this group, consistent with the role of this region in multiple cognitive and social processes. [Copyright &y& Elsevier]

BackgroundInternational agreement dictates that clients must be help-seeking before any assessment or intervention can be implemented by an ‘at-risk service’. Little is known about individuals who decline input. This study aimed to define the size of the unengaged population of an ‘at-risk service’, to compare this group to those who did engage in terms of sociodemographic and clinical features and to assess the clinical outcomes of those who did not engage with the service.MethodGroups were compared using data collected routinely as part of the service's clinical protocol. Data on service use and psychopathology since referral to Outreach and Support in South London (OASIS) were collected indirectly from clients' general practitioners (GPs) and by screening electronic patient notes held by the local Mental Health Trust.ResultsOver one-fifth (n=91, 21.2%) of those referred did not attend or engage with the service. Approximately half of this group subsequently received a diagnosis of mental illness. A diagnosis of psychosis was given to 22.6%. Nearly 70% presented to other mental health services. There were no demographic differences, except that those who engaged with the service were more likely to be employed.ConclusionsOver one-fifth of those referred to services for people at high risk of psychosis do not attend or engage. However, many of this group require mental health care, and a substantial proportion has, or will later develop, psychosis. A more assertive approach to assessing individuals who are at high risk of psychosis but fail to engage may be indicated. [ABSTRACT FROM PUBLISHER]

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age- matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age- matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

Broome MR, Matthiasson P, Fusar-Poli P, Woolley JB, Johns LC, Tabraham P, Bramon E, Valmaggia L, Williams SCR, Brammer MJ, Chitnis X, McGuire PK. Neural correlates of movement generation in the ‘at-risk mental state’. Objective: People with ‘prodromal’ symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task. Method: Cross-sectional comparison of individuals with an ARMS ( n = 17), patients with first episode schizophreniform psychosis ( n = 10) and healthy volunteers ( n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. Results: During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. Conclusion: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neurocognitive impairments in executive and mnemonic domains are already evident in the pre-psychotic phases. The longitudinal dynamic course of the neurofunctional abnormalities underlying liability to psychosis and their relation to clinical outcomes is unknown. Methods: In this study we used functional magnetic resonance imaging (fMRI) in a cohort of subjects at ultra high clinical risk for psychosis (with an “At Risk Mental State”, ARMS) and in healthy controls. Images were acquired at baseline and again after one year on a 1.5 Tesla Signa, while patients were performing a visuospatial working memory task. Psychopathological assessment of the prodromal symptoms was conducted at the same time points by using the CAARMS and the PANSS instruments. Results: There were no significant differences between the ARMS and control groups with respect to age or IQ. Although both groups performed the PAL task with a high degree of accuracy, the ARMS showed an increased latency in answers during the most demanding level of the task. At baseline, such cognitive impairment was associated with reduced activation in the left precuneus, left superior parietal lobule, right middle temporal gyrus in the ARMS as compared to controls. In addition, the ARMS failed to activate parietal areas with increasing difficulty of the task. Between presentation and follow-up the overall clinical status of the ARMS sample improved, despite 2 out of the 15 subjects having developed a full-blown psychosis: the CAARMS (perceptual disorder and thought disorder subscales) and the PANNS general scores decreased, while the GAF score increased. Such clinical amelioration was associated with a longitudinal compensatory increase in occipitoparietal regions. Conclusions: The prodromal phase of psychosis is associated with functional alterations in parietal and temporal networks subserving visuospatial working memory which are more evident under high cognitive loads. The clinical improvement at one year is associated with a compensatory increase in occipitoparietal regions. [Copyright &y& Elsevier]

Experimental research is increasingly important in developing the understanding of paranoid thinking. An assessment measure of persecutory ideation is necessary for such work. We report the reliability and validity of the first state measure of paranoia: The State Social Paranoia Scale. The items in the measure conform to a recent definition in which persecutory thinking has the 2 elements of feared harm and perpetrator intent. The measure was tested with 164 nonclinical participants and 21 individuals at high risk of psychosis with attenuated positive symptoms. The participants experienced a social situation presented in virtual reality and completed the new measure. The State Social Paranoia Scale was found to have excellent internal reliability, adequate test-retest reliability, clear convergent validity as assessed by both independent interviewer ratings and self-report measures, and showed divergent validity with measures of positive and neutral thinking. The measure of paranoia in a recent social situation has good psychometric properties. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding progressive increase in striatal dopamine synthesis capacity as patients develop psychosis. The study utilizes the positron emission tomography to measure the longitudinal change in presynaptic striatal dopaminergic function within subjects as it progressed from a prodromal phase to the first episode of psychosis. Findings of the study reveal that dopaminergic dysregulation progressively increases with the development of psychosis.