Recent Submissions

  • Agoraphobic avoidance in patients with psychosis: Severity and response to automated VR therapy in a secondary analysis of a randomised controlled clinical trial

    O'Regan, Eileen (2022)
    Background: The social withdrawal of many patients with psychosis can be conceptualised as agoraphobic avoidance due to a range of long-standing fears. We hypothesised that greater severity of agoraphobic avoidance is associated with higher levels of psychiatric symptoms and lower levels of quality of life. We also hypothesised that patients with severe agoraphobic avoidance would experience a range of benefits from an automated virtual reality (VR) therapy that allows them to practise everyday anxiety-provoking situations in simulated environments. Method(s): 345 patients with psychosis in a randomised controlled trial were categorised into average, moderate, high, and severe avoidance groups using the Oxford Agoraphobic Avoidance Scale. Associations of agoraphobia severity with symptom and functioning variables, and response over six months to brief automated VR therapy (gameChange), were tested. Result(s): Greater severity of agoraphobic avoidance was associated with higher levels of persecutory ideation, auditory hallucinations, depression, hopelessness, and threat cognitions, and lower levels of meaningful activity, quality of life, and perceptions of recovery. Patients with severe agoraphobia showed the greatest benefits with gameChange VR therapy, with significant improvements at end of treatment in agoraphobic avoidance, agoraphobic distress, ideas of reference, persecutory ideation, paranoia worries, recovering quality of life, and perceived recovery, but no significant improvements in depression, suicidal ideation, or health-related quality of life. Conclusion(s): Patients with psychosis with severe agoraphobic avoidance, such as being unable to leave the home, have high clinical need. Automated VR therapy can deliver clinical improvement in agoraphobia for these patients, leading to a number of wider benefits.
  • A longitudinal qualitative follow-up study of post-traumatic growth among service users who experienced positive change following a first episode of psychosis

    Ng, Fiona (2022)
    Background: Posttraumatic growth refers to the positive psychological changes that people experience following a traumatic or adverse event; and has been reported among people who have experienced a first episode of psychosis. This body of research has an important limitation of not having examined how experiences of posttraumatic growth following a first episode of psychosis change over time. In this study, we examined different aspects and facilitators of posttraumatic growth approximately one year following participants’ initial interview. Methods: Data were collected via semi-structured individual interviews with seven participants and analyzed using thematic analysis. Themes generated from the follow-up interviews were compared with those developed from the initial interviews. Results: Participants experienced challenges at the intersection of trauma, social adversity, and oppression; yet they also reported an improved sense of self; improved relationships with others; embracing existing or new activities; and engaging with and giving back to others. These changes were facilitated by personal resources; social and community-based support; and traditional mental health services and interventions. Discussion: Posttraumatic growth may continue over time. The broader social determinants of health that may lead to a resurgence of psychosis and potential challenges to posttraumatic growth, such as inequality, poverty, and discrimination, should be addressed. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
  • Cortical impoverishment in a stable subgroup of schizophrenia: Validation across various stages of psychosis

    Liddle, Peter F. (2022)
    BACKGROUNDCortical thinning is a well-known feature in schizophrenia. The considerable variation in the spatial distribution of thickness changes has been used to parse heterogeneity. A 'cortical impoverishment' subgroup with a generalized reduction in thickness has been reported. However, it is unclear if this subgroup is recoverable irrespective of illness stage, and if it relates to the glutamate hypothesis of schizophrenia.METHODSWe applied hierarchical cluster analysis to cortical thickness data from magnetic resonance imaging scans of three datasets in different stages of psychosis (n = 288; 160 patients; 128 healthy controls) and studied the cognitive and symptom profiles of the observed subgroups. In one of the samples, we also studied the subgroup differences in 7-Tesla magnetic resonance spectroscopy glutamate concentration in the dorsal anterior cingulate cortex.RESULTSOur consensus-based clustering procedure consistently produced 2 subgroups of participants. Patients accounted for 75%-100% of participants in one subgroup that was characterized by significantly lower cortical thickness. Both subgroups were equally symptomatic in clinically unstable stages, but cortical impoverishment indicated a higher symptom burden in a clinically stable sample and higher glutamate levels in the first-episode sample. There were no subgroup differences in cognitive and functional outcome profiles or antipsychotic exposure across all stages.CONCLUSIONSCortical thinning does not vary with functioning or cognitive impairment, but it is more prevalent among patients, especially those with glutamate excess in early stages and higher residual symptom burden at later stages, providing an important mechanistic clue to one of the several possible pathways to the illness.
  • Trajectories of adolescent psychotic-like experiences and early cannabis exposure: Results from a Finnish Birth Cohort Study

    Sami, Musa (2022)
    BACKGROUNDLongitudinal studies examining the effect of cannabis exposure (CE) on the prognosis of adolescents with psychotic-like experiences (PLEs) are scarce. We examined trajectories of mental health in adolescents with PLEs and cannabis exposure.METHODSThe Northern Finland Birth Cohort 1986 (n = 6552) with linkage to nationwide register data was used. Information on lifetime cannabis exposure was collected when participants were aged 15/16. Register-based outcome data on diagnoses made in clinical practice were obtained until age 33. Logistic regression was used to study the association of PLE/CE patterns and subsequent psychiatric disorders. The group with neither PLEs nor CE was utilized as the reference group. Parental psychiatric disorders, family structure, sex, frequent alcohol intoxications, daily smoking and illicit substance use other than cannabis were adjusted for.RESULTSIn all, 6552 subjects (49.2 % males) were included in analysis. PLEs with cannabis exposure were associated with any psychiatric disorder (OR = 2.59; 95 % CI 1.82-3.68), psychotic disorders (OR = 3.86; 95 % CI 1.83-8.11), mood disorders (OR 4.07; 95 % CI 2.74-6.04), depressive disorders (OR = 4.35; 95 % CI 2.93-6.48), anxiety disorders (OR = 2.06; 95 % CI 1.34-3.17) and substance use disorders (OR = 2.26; 95 % CI 1.13-4.50) compared to reference group. Effect sizes were greater for group with both PLEs and cannabis use than for group with PLEs only.CONCLUSIONSEarly-onset cannabis use is an adverse prognostic marker for adolescents with PLEs after extensive confounder control including other substance use.
  • Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses

    O'Regan, Eileen; Jones, Julia; Martin, Jennifer L.; Hollis, Chris P. (2022)
    BACKGROUNDAutomated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work.METHODSWe did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399.FINDINGSBetween July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference -0·47, 95% CI -0·88 to -0·06; n=320; Cohen's d -0·18; p=0·026) and distress (-4·33, -7·78 to -0·87; n=322; -0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37).INTERPRETATIONAutomated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport.FUNDINGNational Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.
  • Virtual reality (VR) therapy for patients with psychosis: satisfaction and side effects

    O'Regan, Eileen; Jones, Julia
    BACKGROUNDAutomated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.METHODSIn a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.RESULTS79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).CONCLUSIONSPatients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.
  • Imprecise predictive coding is at the core of classical schizophrenia

    Liddle, Peter F.; Liddle, Elizabeth B. (2022)
    Current diagnostic criteria for schizophrenia place emphasis on delusions and hallucinations, whereas the classical descriptions of schizophrenia by Kraepelin and Bleuler emphasized disorganization and impoverishment of mental activity. Despite the availability of antipsychotic medication for treating delusions and hallucinations, many patients continue to experience persisting disability. Improving treatment requires a better understanding of the processes leading to persisting disability. We recently introduced the term classical schizophrenia to describe cases with disorganized and impoverished mental activity, cognitive impairment and predisposition to persisting disability. Recent evidence reveals that a polygenic score indicating risk for schizophrenia predicts severity of the features of classical schizophrenia: disorganization, and to a lesser extent, impoverishment of mental activity and cognitive impairment. Current understanding of brain function attributes a cardinal role to predictive coding: the process of generating models of the world that are successively updated in light of confirmation or contradiction by subsequent sensory information. It has been proposed that abnormalities of these predictive processes account for delusions and hallucinations. Here we examine the evidence provided by electrophysiology and fMRI indicating that imprecise predictive coding is the core pathological process in classical schizophrenia, accounting for disorganization, psychomotor poverty and cognitive impairment. Functional imaging reveals aberrant brain activity at network hubs engaged during encoding of predictions. We discuss the possibility that frequent prediction errors might promote excess release of the neurotransmitter, dopamine, thereby accounting for the occurrence of episodes of florid psychotic symptoms including delusions and hallucinations in classical schizophrenia. While the predictive coding hypotheses partially accounts for the time-course of classical schizophrenia, the overall body of evidence indicates that environmental factors also contribute. We discuss the evidence that chronic inflammation is a mechanism that might link diverse genetic and environmental etiological factors, and contribute to the proposed imprecision of predictive coding.
  • Novice nurses’ communication skills when addressing aggression in individuals experiencing psychosis the role of emotional regulation capacity

    Ng, Fiona (2022)
    Effective nursing practice is linked to a nurse’s ability to regulate emotions and ef-fectively communicate with patients. Novice nurses can feel unprepared when approaching individuals with psychosis who show aggressive behaviors. The current descriptive correlational study aimed to examine relationships among novice nurses’ emotional regulation (ER) capacity, length of service, and communication skills, and investigate the predictive capacity of ER on communication skills in deal-ing with aggression among individuals with psychosis. A convenience sample of 133 novice nurses was obtained. Nurses who had been working for 19 to 24 months demonstrated significantly higher overall communication skills than those who had been working for 12 to 18 months and those who had been working <12 months (mean = 45.05 [SD = 10.89], mean = 41.43 [SD = 12.16], and mean = 38.44 [SD = 9.33], respectively; p = 0.03). In addition, a strong positive correlation was detected between ER strategies and communication skills. ER strategies were identified as in-dependent precursors of novice nurses’ communication skills. Incorporating ER and communication skills training in mental health nursing curricula is recommended. © SLACK INCORPORATED.
  • Associations between personal recovery and service user-rated versus clinician-rated clinical recovery, a cross-sectional study

    Slade, Mike (2022)
    BACKGROUNDThis study examined the relationship between service user-rated personal recovery and clinician-rated and service user-rated clinical recovery. The relationships between different subdomains of clinical recovery and personal recovery were also assessed.METHODSIn total, 318 mental health service users with a psychosis diagnosis and their clinicians from 39 sites across Norway completed standardized questionnaires regarding personal recovery, clinical symptoms and psychosocial functioning. Regression models were used to investigate the relationship between personal and clinical recovery.RESULTSOverall, clinical recovery was positively associated with personal recovery, when rated both by service users and by clinicians. Personal recovery was associated with lower levels of depression, self-harm and problems with relationships when rated by the service users. Among the subdomains rated by the clinicians, personal recovery was associated with fewer problems with relationships and higher aggressiveness.CONCLUSIONSThese findings suggest that affective symptoms are associated with personal recovery, indicating the need for greater focus on depression treatment among people with psychosis. Improving social connections is of importance for personal recovery, and might be an area where clinicians and service users can meet and find agreement on important treatment goals.
  • Positive psychotherapy for psychosis in Hong Kong: A randomized controlled trial

    Slade, Mike (2022)
    Recovery-oriented practice has been advocated in mental health services in Hong Kong since 2009. Well-being has become an important area of focus for mental health services. Positive Psychotherapy for Psychosis (PPP) is a well-being-focused intervention for use in psychosis, with preliminary evidence from a randomized controlled trial in the United Kingdom of impact on well-being and symptomatology. The aim of this study was to test the effectiveness of PPP on the well-being of people with psychosis in Hong Kong. The study was a randomized controlled trial with two-arm parallel groups. Both groups received treatments as usual, and in addition the intervention group received a 13-session intervention based on a Cantonese Chinese translation of the PPP manual. Intention-to-treat analysis was used. The trial was registered (ANZCTR: ACTRN12620000464965). A total of 154 participants (78 intervention, 76 control) were recruited. As compared to control group, intervention group participants showed significant changes over time on the primary outcome of well-being assessed using the Chinese Short Warwick-Edinburgh Mental Well-being Scale (p = 0.001) and on secondary outcomes of hope (Agency subscale: p = 0.029) and self-efficacy (p = 0.001). Positive Psychotherapy for Psychosis was found to be an effective treatment in improving the well-being and other mental health outcomes for people with psychosis. It can be recommended for use in mental health services to promote recovery.
  • Characterization of hemodynamic alterations in schizophrenia and bipolar disorder and their effect on resting-state fMRI functional connectivity

    Liddle, Peter F. (2021)
    Common and distinct neural bases of Schizophrenia (SZ) and bipolar disorder (BP) have been explored using resting-state fMRI (rs-fMRI) functional connectivity (FC). However, fMRI is an indirect measure of neural activity, which is a convolution of the hemodynamic response function (HRF) and latent neural activity. The HRF, which models neurovascular coupling, varies across the brain within and across individuals, and is altered in many psychiatric disorders. Given this background, this study had three aims: quantifying HRF aberrations in SZ and BP, measuring the impact of such HRF aberrations on FC group differences, and exploring the genetic basis of HRF aberrations. We estimated voxel-level HRFs by deconvolving rs-fMRI data obtained from SZ (N = 38), BP (N = 19), and matched healthy controls (N = 35). We identified HRF group differences (P < .05, FDR corrected) in many regions previously implicated in SZ/BP, with mediodorsal, habenular, and central lateral nuclei of the thalamus exhibiting HRF differences in all pairwise group comparisons. Thalamus seed-based FC analysis revealed that ignoring HRF variability results in false-positive and false-negative FC group differences, especially in insula, superior frontal, and lingual gyri. HRF was associated with DRD2 gene expression (P < .05, 1.62 < |Z| < 2.0), as well as with medication dose (P < .05, 1.75 < |Z| < 3.25). In this first study to report HRF aberrations in SZ and BP, we report the possible modulatory effect of dopaminergic signalling on HRF, and the impact that HRF variability can have on FC studies in clinical samples. To mitigate the impact of HRF variability on FC group differences, we suggest deconvolution during data preprocessing.
  • Post-traumatic growth in psychosis: a systematic review and narrative synthesis

    Ng, Fiona; Rennick-Egglestone, Stefan; Newby, Christopher; Hare-Duke, Laurie; Llewellyn-Beardsley, Joy; Yeo, Caroline; Slade, Mike (2021)
    BACKGROUND AND OBJECTIVEPeople with psychosis report experiences of highly traumatic events. Positive change or post-traumatic growth (PTG) can occur as a result of traumatic experiences. Yet there is limited attention on PTG in psychosis, possibly due to the negative impact of psychotic symptoms on functioning and quality of life. The aim of this review was to identify significant correlates and mediators of PTG in psychosis, and to develop a conceptual framework synthesising facilitators of PTG in psychosis.METHODTen electronic databases were searched in seven languages, and five journals and grey literature were searched in English. Quantitative studies were eligible if examining correlates, mediators, or the temporal relationship between PTG and one or more variables. Qualitative studies were eligible if describing PTG arising from experiences of psychosis. Findings from quantitative papers were grouped by analysis method, with significant correlates, mediators, and temporal relationships descriptively reported upon. Narrative synthesis was conducted on findings in qualitative papers.RESULTSThirty-seven papers were included. Significant correlates and mediators of PTG were identified. Mediators of PTG in psychosis included meaning in life, coping self-efficacy, core beliefs, and self-reported recovery. No studies describing the temporal relationship between PTG and psychosis were identified. The narrative synthesis identified seven facilitators of PTG in psychosis: Personal identity and strength, Receiving support, Opportunities and possibilities, Strategies for coping, Perspective shift, Emotional experience, and Relationships, giving the acronym PROSPER.CONCLUSIONSIndividuals with psychosis can be supported to grow from traumatic experiences. Clinicians can support PTG through the provision of trauma-informed care that supports positively valued identity changes. For researchers, the findings provide an evidence-based theoretical framework for conceptualising PTG, which can be validated through longitudinal cohort studies and underpin the development of new clinical interventions.
  • The relationships between childhood abuse and neglect, sub-clinical symptoms of psychosis and self-harm in a non-clinical community sample

    Green, Kathleen; Webster, Anthony (2021)
    There is now substantial evidence that childhood adverse events are a significant risk factor for symptoms of psychosis in both clinical and community samples. Both childhood trauma and positive symptoms of psychosis are associated with an increased risk of self-harming behaviours. Therefore the current study aimed to consider the relationship between retrospective reports of childhood adversity, sub-clinical positive symptoms of psychosis and self-harm in a non-clinical community sample. The study employed a cross-sectional survey design, distributed online. Participants were asked to complete psychometric assessments relating to: demographic characteristics including past-year substance misuse; childhood adversity; sub-clinical symptoms of psychosis (delusions and hallucinations) and self-harming behaviours. The results found that, after controlling for substance misuse, childhood adversity predicted significant variance in sub-clinical delusions and hallucinations in the general population. Both symptoms of psychosis and childhood adversity increased the risk of self-harming behaviours. Positive symptoms partially mediated the relationship between early adversity and self-harming behaviours. For some people, the sequelae of early adversity including sub-clinical delusions and hallucinations may increase the risk of self-harming behaviours. Future research would benefit from considering the role of dissociation in these relationships and the affective impact of pseudo-psychotic experiences. Practitioners should consider the impact of childhood adversity, unusual perceptual experiences and distorted beliefs when working with people who self-harm. The current research was limited by the cross-sectional survey design and non-random sampling methodology.
  • Psychoses in global context: Do not forget the Muslim world

    Sami, Musa (2021)
    Comment: I wish to congratulate Craig Morgan and colleagues1 on their ambitious proposal to set up a Lancet Psychiatry Commission on Psychoses in Global Context. The Commission has an opportunity to remedy an important oversight among psychosis researchers and policy makers: the often neglected plight of Muslim populations struggling with mental illness.
  • Development and validation of a nonremission risk prediction model in first-episode psychosis: An analysis of 2 longitudinal studies

    Liddle, Peter F. (2021)
    Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.
  • The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study

    Liddle, Peter F. (2021)
    BACKGROUNDFormal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition.METHODS279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).RESULTSThe results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (pfdr < 0.001) and role (pfdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (pfdr < 0.001) and phonological verbal fluency (pfdr < 0.001), short-term verbal memory (pfdr = 0.002) and abstract thinking (pfdr = 0.010), in comparison to FTD-Low group.CONCLUSIONSClustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.
  • Audit on clozapine dose and plasma level correlation for patients with chronic treatment-resistant psychosis

    Macnamara, Olivia; Lawton, John D.; Lankappa, Sudheer (2021)
    Aims Clozapine is associated with a risk of severe adverse events for which there are current monitoring systems are in place; however, there are no established regimens for monitoring of clozapine plasma levels. Recent Medicines and Healthcare products Regulatory Agency (MHRA) guidance advises clozapine levels should be monitored in certain clinical situations where toxicity may be suspected. This audit aimed to evaluate current practice of clozapine level monitoring within one Local Mental Health Team (LMHT). Method Electronic (RiO) records of 41 patients (33 male, 8 female; aged from 27 to 76 years; mean age 45 years) registered to the ZTAS system within the Nottingham City Central LMHT were reviewed. 46% had been on clozapine for over 16 years. 73.3% of patients were within clusters 12 and 13; 25.4% of patients were in cluster 11, with one patient in cluster 8. Dates of clozapine plasma level tests for each patient between 2006 and 2020 were found on the electronic NoTIS system, along with clozapine, norclozapine and total clozapine levels. Concurrent clozapine dose and regimens were obtained from pharmacy records from 2018 onwards. Result 273 clozapine plasma levels were conducted between 2006 and 2020. The average interval between levels taken was 10 months, 2 weeks but had a wide range, the shortest interval being 2 days, the longest being 13 years. 88 levels taken were >600 ug/L, suggesting increased toxicity risk. 108 levels were <350 ug/L, suggesting possible sub-optimal dosing or non-compliance. Statistical tests on correlation coefficient, although statistically non-significant (R = 0.37), showed a positive trend between total clozapine dose and the plasma level between all 3 parameters (i.e. clozapine, norclozapine and total clozapine). Conclusion There does not appear to be any routine plasma clozapine level monitoring throughout the LMHT with an average interval between tests of 10 months. There was a non-significant but positive trend between total daily dose of clozapine and clozapine level. 32% of clozapine levels returned were higher than the recommended level. We would recommend as suggested in the guidelines from MHRA, clozapine plasma levels should be monitored in certain clinical situations with increased toxicity risk. Trough levels should be taken with records of time of previous dose taken. Limitations of this study included a small sample size (41 patients) with data collection reliant on electronic systems. It was unclear if these results represent trough levels, making values difficult to interpret. Multifactorial impact on clozapine metabolism causes wide patient variability in plasma levels.
  • Quantfying the disorganization and the core deficit in classical schizophrenia

    Rathnaiah, Mohanbabu; Faruqi, Catherine; Kelly, Christina; Gill, Malkeet (2021)
    Aims To derive scores for mental disorganization and impoverishment from commonly used rating scales, and test the hypothesis that disorganization and impoverishment, along with impaired cognition and role-function reflect a latent variable that is a plausible candidate for the putative core deficit. Background For more than 100 years, disorganization and impoverishment of mental activity have been recognised as fundamental symptoms of schizophrenia. These symptoms may reflect a core brain process underlying persisting disability. Delusions and hallucinations have been regarded as accessory features. The psychopathological processes predisposing to persisting disability in schizophrenia are poorly understood. The delineation of a core deficit underlying persisting disability would be potentially of great value in predicting outcome and developing improved treatment. Method Patients aged 18–55 years were included if: they satisfied DSM IV criteria for schizophrenia or schizoaffective disorder. Healthy controls were recruited by public advertisement and selected to match the patient group in age and sex. Study sample included 39 participants with schizophrenia, 1 with schizoaffective disorder and 44 matched healthy controls. We derived disorganization and impoverishment scores from three symptom scales: PANSS, SSPI and CASH. We computed composite scores for disorganization and for impoverishment and employed Confirmatory Factor Analysis to test the hypothesis that a single factor accounts for the relationships between disorganization, impoverishment, cognitive impairment and impaired role function. We assessed the relationship between this latent “core deficit” and diminished Post Movement Beta Rebound (PMBR), an electrophysiological measure from Magnetoencephalography (MEG), associated with persisting brain disorders. Result Fit indices for the single factor model from CFA indicated a good fit: χ2(2) = 1.817, p = .403; RMSEA <.001 GFI = .979. PMBR was significantly reduced in the schizophrenia group compared to healthy controls, t (68) = 3.55, p < .001. Within the patient group, PMBR was significantly and negatively correlated with the CFA factor scores representing the Core Deficit score, r=−.543, p < .01, indicating that high core deficit scores were associated with reduced PMBR. PMBR was significantly correlated with the composite Disorganization score, r=−.521, p < .001. Conclusion Our findings demonstrate that the shared variance between impoverishment (psychomotor poverty); disorganization; cognitive impairment; and impaired role function can be accounted for by a latent variable that can reasonably be described as the core deficit of classical schizophrenia. The demonstration that the severity of the putative core deficit is correlated with the reduction in PMBR provides evidence that the core deficit is associated with an identifiable abnormality of brain dysfunction.
  • Oxidative stress and the pathophysiology and symptom profile of schizophrenia spectrum disorders

    Katshu, Mohammad Z.; Liddle, Peter F. (2021)
    Schizophrenia is associated with increased levels of oxidative stress, as reflected by an increase in the concentrations of damaging reactive species and a reduction in anti-oxidant defences to combat them. Evidence has suggested that whilst not the likely primary cause of schizophrenia, increased oxidative stress may contribute to declining course and poor outcomes associated with schizophrenia. Here we discuss how oxidative stress may be implicated in the aetiology of schizophrenia and examine how current understanding relates associations with symptoms, potentially via lipid peroxidation induced neuronal damage. We argue that oxidative stress may be a good target for future pharmacotherapy in schizophrenia and suggest a multi-step model of illness progression with oxidative stress involved at each stage.
  • Acute psychotic presentation in syphilis-the great imitator is back

    Katshu, Mohammad Z. (2021)
    In the late 19th and the early 20th century, general paresis of the insane, as it was known historically, or neurosyphilis was a common cause of new-onset psychosis. Symptomatic neurosyphilis was reported in 10-20% patients with syphilis (Singh & Romanowski 1999). The widespread use of penicillin resulted in a marked reduction in syphilis (Kim 1965). Towards the end of the 20th century, syphilis was considered a rare disease and its relevance in clinical training and practice in general, and in neuropsychiatric settings in particular, diminished (Ropper 2019). Unfortunately, there has been a global resurgence of syphilis over the past decade. In England, between 2010 and 2019, the number of newly diagnosed syphilis patients increased from 2646 to 7982 (Mitchell et al. 2020). A similar increase from 45844 to 115045 was observed in the USA between 2010 and 2018 (Centers for Disease Control and Prevention 2019). Despite these increasing numbers, the clinical interest in syphilis, known for its protean manifestations earning the name of the 'great imitator', remains low.

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