Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

ZO-1 Serum Levels as a Potential Biomarker for Psychotic Disorder.

OBJECTIVE: There are limited studies in the literature on the relationship between intestinal and blood-brain barrier permeability and the etiology of schizophrenia. We hypothesized that the difference in serum ZO-1 levels in patients with schizophrenia may affect the severity of the disease. The aim of this study was to investigate the role of changes in serum ZO-1 concentrations in the etiopathogenesis of patients with schizophrenia. METHODS: A total of 46 patients, 34 with schizophrenia, 12 with a first psychotic attack, and 37 healthy controls, were included in the study. Symptom severity was determined by applying the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity Scale. Serum ZO-1 levels were measured from venous blood samples. RESULTS: Serum ZO-1 levels were higher in patients with psychotic disorder compared to healthy controls. There was no statistically significant difference between the groups in the first psychotic attack group and the schizophrenia patients. There was a statistically significant positive correlation between serum ZO-1 levels and Positive and Negative Syndrome Scale positive symptom score. CONCLUSIONS: These findings regarding ZO-1 levels suggest that dysregulation of the blood-brain barrier in psychotic disorder may play a role in the etiology of the disorder.

Guiding Ethical Decisions in Cochlear Implantation for the Hearing Impaired with Comorbid Psychosis.

AbstractCochlear implants can restore hearing in people with severe hearing loss and have a significant impact on communication, social integration, self-esteem, and quality of life. However, whether and how much clinical benefit is derived from cochlear implants varies significantly by patient and is influenced by the etiology and extent of hearing loss, medical comorbidities, and preexisting behavioral and psychosocial issues. In patients with underlying psychosis, concerns have been raised that the introduction of auditory stimuli could trigger hallucinations, worsen existing delusions, or exacerbate erratic behavior. This concern has made psychosis a relative contraindication to cochlear implant surgery. This is problematic because there is a lack of data describing this phenomenon and because the psychosocial benefits derived from improvement in auditory function may be a critical intervention for treating psychosis in some patients. The objective of this report is to provide an ethical framework for guiding clinical decision-making on cochlear implant surgery in the hearing impaired with psychosis.

The impact of early intervention psychosis services on hospitalisation experiences: a qualitative study with young people and their carers.

BACKGROUND: While a core aim of early intervention psychosis services (EIPS) is to prevent hospitalisation, many with a first episode of psychosis (FEP) will require inpatient care. We explored young people's (YP) and their carers' hospitalisation experiences prior to and during EIPS engagement and how factors across these services influenced these experiences. METHODS: Using purposive sampling, we recruited twenty-seven YP, all of whom had been involved with the hospital system at some stage, and twelve support persons (parents and partners of YP) from state and federally funded EIPS in Australia with different models of care and integration with secondary mental health care. Audio-recorded interviews were conducted face-to-face or via phone. A diverse research team (including lived experience, clinician, and academic researchers) used an inductive thematic analysis process. RESULTS: Four key themes were identified as influential in shaping participant's hospital experiences and provide ideas for an approach to care that is improved by the effective coordination of that care, and includes this care being delivered in a trauma informed manner: (1) A two-way street: EIPS affected how participants experienced hospitalisation, and vice versa; (2) It's about people: the quality and continuity of relationships participants had with staff, in hospital and at their EIPS, was central to their experience; (3) A gradual feeling of agency: participants viewed EIPS as both reducing involuntary care and supporting their self-management; and (4) Care coordination as navigation for the healthcare system: great when it works; frustrating when it breaks down. CONCLUSIONS: Hospitalisation was viewed as a stressful and frequently traumatic event, but a approach to care founded on trust, transparency, and collaboration that is trauma-informed ameliorated this negative experience. Consistent EIPS care coordination was reported as essential in assisting YP and carers navigate the hospital system; conversely, discontinuity in EIPS staff and lack of integration of EIPS with hospital care undermined the positive impact of the EIPS care coordinator during hospitalisation. Care coordinator involvement as a facilitator, information provider, and collaborator in inpatient treatment decisions may improve the usefulness and meaningfulness of hospital interventions.

Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper.

BACKGROUND: Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery. METHODS: The setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.1 million people and including rural, urban and homeless populations. SCOPE comprises (1) formative work to understand care pathways and community resources (resource mapping); examine family context and communication (ethnography); develop valid measures of family communication and personal recovery; and establish platforms for community engagement and involvement of people with lived experience; (2a) a population-based incidence study, (2b) a case-control study and (2c) a cohort study with 12 months follow-up involving 440 people with psychosis (390 rural/Addis Ababa; 50 who are homeless), 390 relatives and 390 controls. We will test hypotheses about incidence rates in rural vs. urban populations and men vs. women; potential aetiological role of khat (a commonly chewed plant with amphetamine-like properties) and traumatic exposures in psychosis; determine profiles of needs at first contact and predictors of outcome; (3) participatory workshops to develop programme theory and inform co-development of interventions, and (4) evaluation of the impact of early identification strategies on engagement with care (interrupted time series study). Findings will inform development of (5) a protocol for (5a) a feasibility cluster randomised controlled trial of interventions for people with recent-onset psychosis in rural settings and (5b) two uncontrolled pilot studies to test acceptability, feasibility of co-developed interventions in urban and homeless populations.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

The inflamed brain.

Autoimmune conditions underlie some cases of psychosis. Scientists are expanding their search for patients, who often benefit from treatment.

Multidimensional Approach to Exploring Neighborhood Determinants and Symptom Severity Among Individuals With Psychosis.

Importance: The impact of cumulative exposure to neighborhood factors on psychosis, depression, and anxiety symptom severity prior to specialized services for psychosis is unknown. Objective: To identify latent neighborhood profiles based on unique combinations of social, economic, and environmental factors, and validate profiles by examining differences in symptom severity among individuals with first episode psychosis (FEP). Design, Setting, and Participants: This cohort study used neighborhood demographic data and health outcome data for US individuals with FEP receiving services between January 2017 and August 2022. Eligible participants were between ages 14 and 40 years and enrolled in a state-level coordinated specialty care network. A 2-step approach was used to characterize neighborhood profiles using census-tract data and link profiles to mental health outcomes. Data were analyzed March 2023 through October 2023. Exposures: Economic and social determinants of health; housing conditions; land use; urbanization; walkability; access to transportation, outdoor space, groceries, and health care; health outcomes; and environmental exposure. Main Outcomes and Measures: Outcomes were Community Assessment of Psychic Experiences 15-item, Patient Health Questionnaire 9-item, and Generalized Anxiety Disorder 7-item scale. Results: The total sample included 225 individuals aged 14 to 36 years (mean [SD] age, 20.7 [4.0] years; 152 men [69.1%]; 9 American Indian or Alaska Native [4.2%], 13 Asian or Pacific Islander [6.0%], 19 Black [8.9%], 118 White [55.1%]; 55 Hispanic ethnicity [26.2%]). Of the 3 distinct profiles identified, nearly half of participants (112 residents [49.8%]) lived in urban high-risk neighborhoods, 56 (24.9%) in urban low-risk neighborhoods, and 57 (25.3%) in rural neighborhoods. After controlling for individual characteristics, compared with individuals residing in rural neighborhoods, individuals residing in urban high-risk (mean estimate [SE], 0.17 [0.07]; P = .01) and urban low-risk neighborhoods (mean estimate [SE], 0.25 [0.12]; P = .04) presented with more severe psychotic symptoms. Individuals in urban high-risk neighborhoods reported more severe depression (mean estimate [SE], 1.97 [0.79]; P = .01) and anxiety (mean estimate [SE], 1.12 [0.53]; P = .04) than those in rural neighborhoods. Conclusions and Relevance: This study found that in a cohort of individuals with FEP, baseline psychosis, depression, and anxiety symptom severity differed by distinct multidimensional neighborhood profiles that were associated with where individuals reside. Exploring the cumulative effect of neighborhood factors improves our understanding of social, economic, and environmental impacts on symptoms and psychosis risk which could potentially impact treatment outcomes.

Faster bi-stable visual switching in psychosis.

Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.

Clozapine Use Among People With Psychotic Disorders Who Experience Specific Indications for Clozapine.

Objective: To examine rates of clozapine use among people with psychotic disorders who experience specific indications for clozapine.Methods: Records data from 11 integrated health systems identified patients aged 18 years or older with recorded International Classification of Diseases, Tenth Revision, Clinical Modification, diagnoses of schizophrenia, schizoaffective disorder, or other psychotic disorder who experienced any of the 3 events between January 1, 2019, and December 31, 2019, suggesting indications for clozapine: a diagnosis of self-harm injury or poisoning, suicidal ideation diagnosed or in response to standardized assessments, and hospitalization or emergency department (ED) care for psychotic disorder despite treatment with 2 or more antipsychotic medications. Prescription dispensing data identified all clozapine use prior to or in the 12 months following each indication event. Analyses were conducted with aggregate data from each health system; no individual data were shared.Results: A total of 7,648 patients with psychotic disorder diagnoses experienced at least 1 indication event. Among 1,097 experiencing a self-harm event, 32 (2.9%) had any prior clozapine use, and 10 (0.9%) initiated clozapine during the following 12 months. Among 6,396 with significant suicidal ideation, 238 (3.7%) had any prior clozapine use, and 70 (1.1%) initiated clozapine over 12 months. Among 881 with hospitalization or ED visit despite pharmacotherapy, 77 (8.7%) had any prior clozapine treatment, and 41 (4.7%) initiated clozapine over 12 months. Among those with significant suicidal ideation, rates of both prior clozapine treatment and subsequent initiation varied significantly by race and ethnicity, with rates among Hispanic and non-Hispanic Black patients lower than among non Hispanic White patients.Conclusions: Initiating clozapine treatment is uncommon among people with psychotic disorders who experience events suggesting clozapine is indicated, with even lower rates among Black and Hispanic patients.

Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland.

BACKGROUND: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term. METHODS: We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study. FINDINGS: We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis. INTERPRETATION: The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis. FUNDING: Northwell Health and Sigrid Jusèlius Foundation.

Qatar's National Mental Health Study-The World Mental Health Qatar.

BACKGROUND: We provide an overview of Qatar's first epidemiological study on prevalence, predictors, and treatment contact for mood and anxiety disorders. AIMS: We highlight the importance of the three-pronged study, its aims, and its key components. MATERIALS & METHODS: The first component comprised a probability-based representative survey of Qatari and non-Qatari (Arab) adult males and females recruited from the general population and interviewed using the International Diagnostic Interview (CIDI version 3.3). The second component, a clinical reappraisal study, assessed concordance between diagnoses based on the CIDI and independent clinical assessments conducted by trained clinical interviewers. The third component comprised a resting-state functional magnetic resonance imaging study of healthy survey respondents who were matched to patients with psychosis. RESULTS: 5000 survey interviews provided data on prevalence and treatment of common mental disorders. Clinical re-interviews (N = 485) provided important diagnostic validity data. Finally, state-of-the art structural and functional brain markers for psychosis were also collected (N = 100). DISCUSSION: Descriptive epidemiological data were collected to inform future mental health priorities in Qatar and situates these within a global context. CONCLUSION: The study fills important gaps in regional and global estimates and establish necessary baseline to develop comprehensive risk estimates for mental health in Qatar's young population.

Neuroimaging alterations and relapse in early-stage psychosis.

BACKGROUND: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis. METHODS: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls. We divided patients into 2 groups, namely those who did not experience relapse between disease onset and the magnetic resonance imaging (MRI) scan (no-relapse group) and those who did experience relapse between these 2 timings (relapse group). We analyzed 3003 functional connectivity estimates between 78 regions of interest (ROIs) derived from resting-state functional MRI data by adjusting for demographic and clinical confounding factors. RESULTS: We studied 85 patients, incuding 54 in the relapse group and 31 in the no-relapse group, along with 94 healthy controls. We observed significant differences in 47 functional connectivity estimates between the relapse and control groups after multiple comparison corrections, whereas no differences were found between the no-relapse and control groups. Most of these pathological signatures (64%) involved the thalamus. The Jonckheere-Terpstra test indicated that all 47 functional connectivity changes had a significant cross-group progression from controls to patients in the no-relapse group to patients in the relapse group. LIMITATIONS: Longitudinal studies are needed to further validate the involvement and pathological importance of the thalamus in relapse. CONCLUSION: We observed pathological differences in neuronal connectivity associated with relapse in early-stage psychosis, which are more specifically associated with the thalamus. Our study implies the importance of considering neurobiological mechanisms associated with relapse in the trajectory of psychotic disorders.