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Aims: Ongoing NICE guidance recommends research on the clinical and cost effectiveness of psychological treatment alone, compared to antipsychotic medication and compared to psychological treatment and antipsychotic medication combined. The COMPARE study (Cognitive behaviour therapy or Medication for Psychosis- A Randomised Evaluation) was a pilot trial designed to inform a definitive trial to answer this question. Method: COMPARE was a single-site pilot randomised controlled trial to compare a standardised Cognitive Behaviour Therapy (CBT) intervention to treatment with antipsychotic medication (APs) and a combined treatment (CBT plus APs) in adults with psychosis. Participants were assessed using the Positive and Negative Syndrome Scale (PANSS) and followed up at 6, 12, 24 and 52 weeks. The primary outcomes were recruitment and retention of participants. We surveyed a wider population of staff and service users to further inform feasibility of a definitive trial. Results: We report the characteristics of the recruited sample at baseline (n = 75) and results from surveys. Conclusions: The study recruited to target demonstrating it is feasible to identify and recruit participants to a study of this kind. The survey results also suggest that such trials are feasible. [ABSTRACT FROM AUTHOR]

The article discusses the transition outcomes in individuals at high clinical risk. In the study's context, a substantial proportion of people at clinical high risk of psychosis will develop a psychotic disorder over time. Twenty-seven studies met the inclusion criteria for the study, comprising a total of 2,502 patients. The transition risk varies with patient age, nature of provided treatment and the way the syndrome and transition to psychosis are defined.

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

Background: Morphological abnormalities of the superior temporal gyrus have been consistently reported in schizophrenia, but the timing of their occurrence remains unclear.Aims: To determine whether individuals exhibit superior temporal gyral changes before the onset of psychosis.Method: We used magnetic resonance imaging to examine grey matter volumes of the superior temporal gyrus and its subregions (planum polare, Heschl's gyrus, planum temporale, and rostral and caudal regions) in 97 antipsychotic-naive individuals at ultra-high risk of psychosis, of whom 31 subsequently developed psychosis and 66 did not, and 42 controls.Results: Those at risk of psychosis had significantly smaller superior temporal gyri at baseline compared with controls bilaterally, without any prominent subregional effect; however, there was no difference between those who did and did not subsequently develop psychosis.Conclusions: Our findings indicate that grey matter reductions of the superior temporal gyrus are present before psychosis onset, and are not due to medication, but these baseline changes are not predictive of transition to psychosis. [ABSTRACT FROM AUTHOR]

Aim: Although the different approaches to psychosis research have made significant advances in their own fields, integration between the approaches is often lacking. This paper attempts to integrate a strand of cognitive research in psychotic disorders (specifically, social cognition research) with phenomenological accounts of schizophrenia and other psychotic disorders. Method: The paper is a critical investigation of phenomenological models of disturbed selfhood in schizophrenia in relation to cognitive theories of social cognition in psychotic disorders. Results: We argue that disturbance of the basic sense of self, as articulated in the phenomenological literature, may underlie the social cognition difficulties present in psychotic disorders. This argument is based on phenomenological thinking about self-presence (‘ipseity’) being the primary or most basic ground for the intentionality of consciousness – that is, the directedness of consciousness towards others and the world. A disruption in this basic ground of conscious life has a reverberating effect through other areas of cognitive and social functioning. We propose three routes whereby self-disturbance may compromise social cognition, including dissimilarity, disruption of lived body and disturbed mental coherence. Conclusions: If this model is supported, then social cognition difficulties may be thought of as a secondary index or marker of the more primary disturbance of self in psychotic disorders. Further empirical work examining the relationship between cognitive and phenomenological variables may be of value in identifying risk markers for psychosis onset, thus contributing to early intervention efforts, as well as in clarifying the essential psychopathological features of schizophrenia and other psychotic disorders. [ABSTRACT FROM AUTHOR]

Aim: Costs associated with mental health treatment for young persons at ‘ultra’ high risk (UHR) of developing a psychotic disorder have not previously been reported. This paper reports cost implications of providing psychological and pharmacological intervention for individuals at UHR for psychosis compared with minimal psychological treatment. Method: Mental health service costs associated with a randomized controlled trial of two treatments (Specific Preventive Intervention: SPI and Needs-Based Intervention: NBI) for UHR young persons were estimated and compared at three time points: treatment phase, short-term follow up and medium-term follow up. Results: Although the SPI group incurred significantly higher treatment costs than the NBI group over the treatment phase, they incurred significantly lower outpatient treatment costs over the longer term. Conclusion: This study indicates that specific interventions designed to treat young persons who are identified as being at UHR of psychosis might be associated with some cost savings compared with non-specific interventions. [ABSTRACT FROM AUTHOR]

Background: Grey matter changes have been described in individuals who are pre- and peri-psychotic, but it is unclear if these changes are accompanied by changes in white matter structures.Aims: To determine whether changes in white matter occur prior to and with the transition to psychosis in individuals who are pre-psychotic who had previously demonstrated grey matter reductions in frontotemporal regions.Method: We used magnetic resonance imaging (MRI) to examine regional white matter volume in 75 people with prodromal symptoms. A subset of the original group (n=21) were rescanned at 12-18 months to determine white matter volume changes. Participants were retrospectively categorised according to whether they had or had not developed psychosis at follow-up.Results: Comparison of the baseline MRI data from these two subgroups revealed that individuals who later developed psychosis had larger volumes of white matter in the frontal lobe, particularly in the left hemisphere. Longitudinal comparison of data in individuals who developed psychosis revealed a reduction in white matter volume in the region of the left fronto-occipital fasciculus. Participants who had not developed psychosis showed no reductions in white matter volume but increases in a region subjacent to the right inferior parietal lobule.Discussion: The reduction in volume of white matter near the left fronto-occipital fasciculus may reflect a change in this tract in association with the onset of frank psychosis. [ABSTRACT FROM AUTHOR]

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

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

Objective : An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. Method : The‘ultra’ high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. Results : Obstetric complications were not associated with the later development of psychosis in the UHR group included in this study. Conclusions : This study does not support a role for OCs as a risk factor for the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area. Australian and New Zealand Journal of Psychiatry 2005; 39:460–466 [ABSTRACT FROM AUTHOR]

Objective: While cognitive deficits are frequently reported in psychotic disorders, it is unclear whether these impairments predate the onset of illness and to what extent they are predictive of later transition to psychosis. Method: The authors studied 37 healthy volunteers and 98 symptomatic, help- seeking patients meeting the inclusion criteria of a treatment program for people at ultra-high risk for psychosis. Of the ultra-high-risk patients, 34 (34.7%) developed psychosis over the course of the investigation. Premorbid and current IQ, attention, memory, and executive functioning were measured with instruments including subtests from the Wechsler Memory Scale-Revised (WMS-R). Analyses compared the ultra-high-risk patients who became psychotic, those who did not become psychotic, and the comparison subjects. Results: Overall, the ultra-high-risk subjects had significantly lower performance lQs than the comparison subjects. Further, impairments were also found in the visual reproduction subtest and the verbal memory index (predominantly owing to lower logical memory scores) of the WMS-R that were specific to the ultra-high-risk-patients who developed psychosis. No other memory, attentional, or executive tasks discriminated between any of the groups. Conclusions: These findings suggest that visuospatial processing impairment and some memory deficits were apparent before the full expression of psychotic illness. Cognitive performance on more complex tasks requiring rapid registration and efficient recall may be compromised before development of first-episode psychosis. Further experimental tasks that challenge these cognitive domains are required to clarify the predictive value of these results. [ABSTRACT FROM AUTHOR]

Background: Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown.Aims: To examine pituitary volume variation in people at different stages of psychotic disorder.Method: Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls.Results: Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics.Conclusions: The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity. [ABSTRACT FROM AUTHOR]

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

Abstract: Objective: Studies conducted in community samples indicate that psychotic-like experiences (PLEs) are common in the general population; it has been suggested that such experiences are either variations in normal personality or different expressions of vulnerability to psychotic disorders. The aim of this study was to determine whether different subtypes of PLEs could be identified in a community sample of adolescents and young adults, and to investigate whether particular subtypes of PLEs were more likely to be associated with psychosocial difficulties, i.e. distress, depression and poor functioning, than other subtypes. Method: 1882 students from high schools and universities participated in a cross-sectional multisite survey that measured i) PLEs using the Positive Scale of the Community Assessment of Psychic Experiences (CAPE), ii) depression and distress using the CAPE Depression and Distress Subscales, and iii) functioning using the General Health Questionnaire-12. Factor analysis was conducted to identify any subtypes of PLEs. Results: Four subtypes of PLEs were identified: bizarre experiences (BE), perceptual abnormalities (PA), persecutory ideas (PI) and grandiosity (GR). Intermittent, infrequent psychotic experiences were common, whereas frequent experiences were not. BE and PI were strongly associated with distress, depression and poor functioning. PA and GR were associated with these variables to a lesser degree. Conclusions: Different subtypes of PLEs were identified in this large sample, confirming the findings of our previous studies. These subtypes seem to have different psychopathological meaning and may therefore indicate different levels of risk of severe psychiatric disorders, which suggests it is misleading to define PLEs as a homogenous entity. [Copyright &y& Elsevier]

Introduction: Two thirds of individuals identified as ultra-high risk (UHR) for psychosis do not transition to psychosis over the medium to long-term (non-transition; UHR-NT). Nevertheless, many of these individuals have persistent attenuated psychotic symptoms (APS). The current study examined whether there were differences in baseline grey matter volume (i.e. at initial identification as UHR) in UHR-NT individuals whom had APS compared to those without APS (No-APS) at medium to long-term follow-up.Methods: Participants were help-seeking individuals who were identified as being at UHR for psychosis between 2 and 12years previously (mean=7.5). The sample consisted of 109 participants who underwent a Magnetic Resonance Imaging scan at baseline and who had not been observed to develop a psychotic disorder over the follow-up period (UHR-NT). Using voxel-based morphometry, baseline grey matter volume (GMV) was compared between participants with (N=30) and without (N=79) APS at follow-up.Results: At baseline, the APS and No-APS groups were clinically indistinguishable. At follow-up, the APS group had significantly worse symptoms and impaired functioning. Individuals with APS had reduced baseline GMV in frontal, temporal, posterior and cingulate regions compared to those without APS at follow-up. Reduced GMV was associated with more severe positive, negative and depressive symptoms and lower global functioning in the combined UHR-NT cohort. These associations were independent of later APS outcome.Discussion: This study found that differences in regional GMV are discernible at an early stage of UHR and may be specific to individuals who have APS and psychopathology at follow-up. Our findings suggest that lower GMV at baseline may confer neurobiological risk for later APS and/or increased psychopathology while the absence of these structural abnormalities might be protective. [ABSTRACT FROM AUTHOR]

We have previously reported an association between childhood sexual trauma and transition to psychosis in an Ultra High Risk (UHR) population. We aimed to investigate if this association was mediated by affective or dissociative symptoms. Data were from a large UHR for psychosis cohort study. None of the potential mediators (depression, anxiety, dissociation, mood swings and mania, assessed by the HAM-D, HAM-A and the CAARMS symptom scales) significantly mediated the total association between sexual abuse scores and transition. At the point of transition, the mechanistic pathway from sexual trauma to psychosis does not appear to operate through affective symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Valid criteria to identify young people who are believed to be at ultra high risk (UHR) of developing a psychotic episode were developed over the last decade. The first randomized controlled trial of treatment in a UHR cohort indicated that specific pharmacotherapy and psychotherapy delayed onset of disorder, and possibly reduced incidence. This paper reports results of follow-up of that trial. 41 of the 59 (69.5%) participants in the original study agreed to follow-up. No differences were found in transition rate, level of symptomatology or functioning between participants who received a combination of psychological treatment and anti-psychotic medication compared to those who received supportive therapy alone. A significant proportion of both treatment groups reported moderate levels of psychiatric morbidity and a continuing need and desire for care at this follow-up. Low levels of hospitalisation were noted for those who did progress to psychosis. Conclusions that can be drawn from this exploratory study are limited by the relatively small number of participants in the original study and the failure to follow-up the entire cohort. Although participants may have been treated too briefly to result in enduring positive effects, there appear to have been some cost savings in inpatient mental health treatment required after the end of the trial for individuals in both treatment groups who developed psychosis. [Copyright &y& Elsevier]

Abstract: Early detection of imminent psychosis allows for the possibility of interventions to prevent onset, or to minimise severity and disability. It also has potential to enhance knowledge of the factors important in the etiology of psychotic illnesses. Neurocognitive deficits are well documented in psychotic illnesses and there is evidence to suggest that such deficits are present in individuals long before they develop the illness. Further, it has been proposed that such impairments may indicate an underlying predisposition to develop psychosis and may thus be described as ‘vulnerability indicators’. This study aimed to investigate the proposed vulnerability indicator of impaired sustained attention in young people thought to be at ultra high-risk of developing psychosis imminently to see whether it would improve the prediction of psychosis in this group. The Continuous Performance Test – Identical Pairs (CPT-IP) version performance of an ultra high-risk group (UHR, N =70) was compared with that of a healthy comparison group (NC, N =51) and a first-episode psychosis group (FEP, N =32). The UHR group exhibited performance deficits compared to the NC group and performed at a level similar to that of the FEP group. However, within the UHR group, those who developed psychosis within the timeframe of the study did not differ from those who did not develop psychosis on their CPT-IP performance. These results support sustained attention as an indicator of vulnerability to psychosis, but suggest that CPT-IP performance does not help to predict transition to psychosis in an ultra high-risk group. [Copyright &y& Elsevier]

Summary: Background: Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis. Methods: We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people. Findings: In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum. Interpretation: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression. [ABSTRACT FROM AUTHOR]