Improving attitudes toward electroconvulsive therapy.

AIMS AND METHOD: Electroconvulsive therapy (ECT) often causes fear in the general public because of media representation and negative reported side-effects. This study evaluates a new video focusing on experiences of ECT and how this can aid communicating medical information to the public. Knowledge and attitudes toward ECT after watching the video were compared with a group that received no information and a group that read the current NHS leaflet on ECT. The role of empathy was also considered as a covariate. RESULTS: The video was the only condition found to positively affect knowledge and attitudes toward ECT. The video was especially beneficial to those that possessed low perspective-taking trait empathy. CLINICAL IMPLICATIONS: These findings demonstrate the video improved knowledge and attitudes toward ECT compared with current material or no information. We suggest that the addition of personal experiences to public information adds perspective, improving overall attitudes toward health treatments.

Gray matter alterations related to P300 abnormalities in subjects at high risk for psychosis: longitudinal MRI-EEG study.

BACKGROUND: Psychotic disorders are characterized by gray matter and volumetric and electrophysiological abnormalities. The relationship between these factors in the onset of psychotic illness is unclear. METHODS: Eighty English-native right-handed subjects (39 subjects at ultra high risk for psychosis "ARMS" and 41 healthy volunteers) were scanned with MRI, and studied using EEG during an oddball task. Both assessments were performed at first clinical presentation. The ARMS subjects were then followed clinically, with the MRI and EEG assessments repeated in a subgroup of each sample. RESULTS: The P300 amplitude at presentation was significantly lower in the ARMS subjects than in controls. At baseline, the ARMS group showed reduced gray matter volume relative to controls in the right superior frontal gyrus, left medial frontal gyrus, left inferior frontal gyrus, right orbital gyrus and right supramarginal gyrus. Transition to psychosis (26%) was associated with reduced gray matter in the right inferior parietal lobule and in the left parahippocampal gyrus. Within the ARMS group, there was a positive correlation between P300 amplitude and gray matter volume in the right supramarginal gyrus. A significant group by P300 by gray matter interaction was detected in the left medial frontal gyrus. Longitudinal assessment revealed progressive gray matter alterations in prefrontal and subcortical areas of the ARMS but no significant changes in P300 amplitude over time. CONCLUSIONS: P300 abnormalities in the ARMS are related to alterations in regional gray matter volume and represent a correlate of an increased vulnerability to psychosis.

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study.

BACKGROUND: Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis. METHODS: We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an "at-risk mental state" [ARMS]). RESULTS: We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group. LIMITATIONS: The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination. CONCLUSION: P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.

Neural correlates of executive function and working memory in the 'at-risk mental state'.

BACKGROUND: People with prodromal symptoms have a very high risk of developing psychosis. AIMS: To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability. METHOD: Cross-sectional comparison of regional activation in individuals with an'at-risk mental state' (at-risk group: n=17), patients with first-episode schizophreniform psychosis (psychosis group: n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task and an N-back working memory task. RESULTS: A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during the N-back task. CONCLUSIONS: The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.

Insight in individuals with an At Risk Mental State.

PURPOSE: On average, people with an At Risk Mental State (ARMS) for psychosis are more willing to seek and accept clinical help than patients with psychotic disorders, suggesting that insight in this group is relatively less impaired. We compared the level and quality of insight in the ARMS and in first episode psychosis. MATERIALS AND METHODS: Insight about illness was assessed in subjects with an ARMS and in patients with first episode psychosis (FEP) who were and were not help-seeking, using the Schedule for Assessment of Insight (SAI-E). RESULTS: Insight was impaired in ARMS subjects, but there was considerable variability in the insight displayed between subjects. Compared to FEP subjects, ARMS subjects showed greater insight, particularly with respect to Symptom Relabelling. ARMS subjects were more likely to interpret anomalous experiences as symptoms of illness, and to perceive themselves as needing treatment. CONCLUSIONS: Insight in people at high risk for psychosis is impaired, despite the fact that they are help-seeking. Insight varies between subjects, highlighting the need to comprehensively assess all aspects of insight in those with an ARMS. ARMS subjects are impaired in their ability to appraise anomalous experiences as symptoms of illness, but much less impaired than FEP subjects. This is consistent with cognitive models that propose that the way symptoms are appraised determines whether the individual develops a psychotic illness.

Protocol for a multicentre study to assess feasibility, acceptability, effectiveness and direct costs of TRIumPH (Treatment and Recovery In PsycHosis): integrated care pathway for psychosis.

INTRODUCTION: Duration of untreated psychosis (time between the onset of symptoms and start of treatment) is considered the strongest predictor of symptom severity and outcome. Integrated care pathways that prescribe timeframes around access and interventions can potentially improve quality of care. METHODS AND ANALYSIS: A multicentre mixed methods study to assess feasibility, acceptability, effectiveness and analysis of direct costs of an integrated care pathway for psychosis. A pragmatic, non-randomised, controlled trial design is used to compare the impact of Treatment and Recovery In PsycHosis (TRIumPH; Intervention) by comparison between NHS organisations that adopt TRIumPH and those that continue with care as usual (Control). Quantitative and qualitative methods will be used. We will use routinely collected quantitative data and study-specific questionnaires and focus groups to compare service user outcomes, satisfaction and adherence to intervention between sites that adopt TRIumPH versus sites that continue with usual care pathways. SETTING: 4 UK Mental health organisations. Two will implement TRIumPH whereas two will continue care as usual. PARTICIPANTS: Staff, carers, individuals accepted to early intervention in psychosis teams in participating organisations for the study period. INTERVENTION: TRIumPH-Integrated Care Pathway for psychosis that has a holistic approach and prescribes time frames against interventions; developed using intelligence from data; co-produced with patients, carers, clinicians and other stakeholders. OUTCOMES: Feasibility will be assessed through adherence to the process measures. Satisfaction and acceptability will be assessed using questionnaires and focus groups. Effectiveness will be assessed through data collection and evaluation of patient outcomes, including clinical, functional and recovery outcomes, physical health, acute care use. Outcome measures will be assessed at baseline, 12 and 24 months to measure whether there is an effect and if so, whether this is sustained over time. Outcomes measures at the adopter sites will be compared to their own baseline and against comparator sites. ETHICS AND DISSEMINATION: Ethics approval was obtained from East of Scotland Research Ethics Service (REC Ref no: LR/15/ES/0091). The results will be disseminated through publications, conference presentations, reports to the organisation. STUDY REGISTRATION: UK Clinical Research Network Portfolio: 19187.

What causes the onset of psychosis?

It has become increasingly clear that the simple neurodevelopmental model fails to explain many aspects of schizophrenia including the timing of the onset, and the nature of the abnormal perceptions. Furthermore, we do not know why some members of the general population have anomalous experiences but remain well, while others enter the prodrome of psychosis, and a minority progress to frank schizophrenia. We suggest that genes or developmental damage result in individuals vulnerable to dopamine deregulation. In contemporary society, this is often compounded by abuse of drugs such as amphetamines and cannabis, which then propel the individual into a state of dopamine-induced misinterpretation of the environment. Certain types of social adversity such as migration and social isolation, as well as affective change can also contribute to this. Thereafter, biased cognitive appraisal processes result in delusional interpretation of the abnormal perceptual experiences. Thus, a plausible model of the onset of psychosis needs to draw not only on neuroscience, but also on the insights of social psychiatry and cognitive psychology.

Outreach and support in south London (OASIS): implementation of a clinical service for prodromal psychosis and the at risk mental state.

BACKGROUND: While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear. AIMS: To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor. METHOD: Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months. RESULTS: People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year. CONCLUSION: It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.

Jumping to perceptions and to conclusions: specificity to hallucinations and delusions.

BACKGROUND: There is evidence that people with psychosis display a "jump-to-conclusions" (JTC) reasoning style, and that this bias may be specific to delusions. A "jump-to-perceptions" (JTP) cognitive bias has also been found and is typically linked to hallucinations. However, there is some evidence for an association between JTP and delusions, and its specificity to hallucinations remains unclear. It has been suggested that these biases are related and products of shared cognitive processes. METHODS: This study examined the symptom specificity of JTC and JTP, and the relationship between them, in a sample of 98 individuals with delusions divided into 'hallucinators' (n=51) and 'non-hallucinators' (n=47). Biases were assessed using the beads task and visual and auditory perceptual tasks. RESULTS: As predicted, both groups demonstrated a JTC bias, but the 'hallucinators' showed a more pronounced JTP style in both modalities. The presence of JTC and JTP biases did not co-occur: making a decision on the beads task after two or fewer draws was not related to visual JTP, and was associated with a less marked JTP bias in the auditory perceptual task. No differences were found in JTP or JTC between participants with and without a schizophrenia diagnosis. JTP, but not JTC, was associated with the presence of hallucinations. CONCLUSIONS: These findings suggest that the JTC and JTP biases show specificity to delusions and hallucinations, respectively, and not to diagnosis. There was no evidence that they are the product of shared cognitive processes, further supporting their specificity.

Spatial working memory ability in individuals at ultra high risk for psychosis.

The goal of this investigation was to clarify the nature of spatial working memory difficulties in individuals at ultra high risk (UHR) for psychosis. We evaluated spatial working memory and intelligence in 96 individuals at UHR for psychosis, 28 patients with first episode psychosis (FEP), and 23 healthy controls. Fourteen UHR individuals developed a psychotic disorder during follow-up. Compared to controls, the UHR group was impaired in both the short-term maintenance of material and in the effective use of strategy, but not more immediate memory. These impairments were not as severe as those in the FEP group, as the UHR group performed better than the FEP group. A similar pattern of results was found for the intelligence measures. Discriminant function analyses demonstrated short-term maintenance of material significantly differentiated the UHR and healthy control groups even when accounting for full scale intelligence quotient (IQ); whereas full scale IQ significantly differentiated the UHR and FEP groups and FEP and control groups. Notably, within the UHR group, impaired spatial working memory performance was associated with lower global functioning, but not full scale IQ. The subgroup of UHR individuals who later developed psychosis was not significantly more impaired on any aspect of working memory performance than the group of UHR individuals who did not develop psychosis. Given, the relationship between spatial working memory deficits and functional outcome, these results indicate that cognitive remediation could be useful in individuals at UHR for psychosis to potentially improve functioning.

Reduced mismatch negativity predates the onset of psychosis.

BACKGROUND: Individuals with an "At Risk Mental State" have a 20-30% chance of developing a psychotic disorder within two years; however it is difficult to predict which individuals will become ill on the basis of their clinical symptoms alone. We examined whether mismatch negativity (MMN) could help to identify those who are particularly likely to make a transition to psychosis. METHOD: 41 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 50 controls performed a duration-deviant passive auditory oddball task whilst their electroencephalogram was recorded. The amplitude of the MMN wave was compared between groups using linear regression. The ARMS subjects were then followed for 2 years to determine their clinical outcome. RESULTS: The MMN amplitude was significantly reduced in the ARMS group compared to controls. Of the at-risk subjects who completed followed up (n=41), ten (24% of baseline sample) subsequently developed psychosis. The MMN amplitude in this subgroup was significantly smaller across all three recording sites (FZ, F3 and F4) than in the ARMS individuals who did not become psychotic. CONCLUSION: Among those with the ARMS, MMN amplitude reduction is associated with an increased likelihood of developing frank psychosis.

Elevated striatal dopamine function linked to prodromal signs of schizophrenia.

CONTEXT: A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. OBJECTIVES: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. DESIGN: Case-control study of in vivo striatal dopaminergic function. SETTING: Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging. RESULTS: Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. CONCLUSIONS: These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.

Abnormal P300 in people with high risk of developing psychosis.

BACKGROUND: Individuals with an "at-risk mental state" (or "prodromal" symptoms) have a 20-40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable. METHOD: 35 cases meeting PACE criteria for the at-risk mental state (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression. RESULTS: The P300 amplitude was significantly reduced in the ARMS group [8.6+/-6.4 microvolt] compared to controls [12.7+/-5.8 microvolt] (p<0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. CONCLUSION: Reduction in the amplitude of the P300 is associated with an increased vulnerability to psychosis. Neurophysiological and other biological markers may be of use to predict clinical outcomes in populations at high risk.