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There is a debate in psychiatry regarding whether it is better to use neo-Kraepelinian diagnostic categories or unitary models of psychosis in clinical practice. This article argues that clinicians should use either model as appropriate for the case in question, along with the conceptual framework used in the clinical management of psychosis without a clear biological cause. It first explores the values involved in the development of psychiatric classification systems, the purpose of classification and how we reached the current DSM/ICD and unitary models of psychosis. It then describes a diagnostic approach in which the choice of model should depend on the case in question, and offers a diagnostic protocol to guide the decision.
Whilst Cognitive Behavioural Therapy for Psychosis (CBTp) has been found to reduce psychotic symptoms, most evidence supporting its implementation originates from studies in Western and high-income countries. Furthermore, questions remain regarding the efficacy of CBTp conducted via teleconsultation. Herein we report an ongoing case in Indonesia involving an individual with schizoaffective disorder, who received 60 sessions of CBTp over seven months. Sessions were delivered via a combination of voice and video calls. The patient, a 40-year-old male, was diagnosed with schizoaffective disorder at the age of 26. He exhibited symptoms of paranoid and religious delusions, hallucinations (auditory, visual, and somatic) and disorganised speech during our intake interview. Negative symptoms were not apparent. In the 14 years prior to our initial consultation, the patient was prescribed antipsychotics and demonstrated good adherence. He had no history of psychotherapy independent of our clinic. Treatment involved CBTp techniques, including psychoeducation, a symptom diary, relaxation, and behavioural experiments. Study outcome was assessed with Psychotic Symptom Rating Scales. Both hallucination and delusion subscale scores improved 53% from 53 at intake to 25 during an assessment administered 6 months later. Results from this study demonstrate that the CBTp is both feasible, and beneficial, when conducted via teleconsultation in Indonesia.
Visual experiences such as hallucinations are commonly reported by people with psychosis, psychological trauma and dissociative states, although questions remain about their similarities and differences. For diagnostic and therapeutic purposes, clinical research must better delineate and compare the characteristics of these experiences in post-traumatic stress disorder (PTSD) and in schizophrenia.
To compare visual phenomena and dissociation in participants with a primary psychotic illness and those with a trauma diagnosis.
A quantitative group design study comparing visual phenomena in three participant groups who also have a history of hearing voices: schizophrenia and no trauma history (n = 19), PTSD with dissociation (n = 17) and comorbid schizophrenia and PTSD (n = 20). Validated clinical measures included the North-East Visual Hallucination Interview, PTSD Symptoms Scale Interview, Clinician Administered Dissociative States Scale, Psychotic Symptoms Rating Scales and Positive and Negative Syndrome Scale.
There was a remarkable similarity in visual experiences, including rates of complex visual hallucinations, between the three diagnostic groups. There were no significant differences in the severity or components of distress surrounding the visual experiences. Dissociation predicted visual hallucination severity for the comorbid schizophrenia and PTSD group, but not for PTSD or schizophrenia alone.
Visual experiences in PTSD can include visual hallucinations that are indistinguishable from those experienced in schizophrenia. Multimodal hallucinations are frequently observed in both schizophrenia and PTSD. A model for visual hallucinations in PTSD is suggested, following two separate neurobiological pathways based on distinct responses to trauma.
Additional to a child's genetic inheritance, environmental exposures are associated with schizophrenia. Many are broadly described as childhood adversity; modelling the combined impact of these is complex. We aimed to develop and validate a scale on childhood adversity, independent of genetic and other environmental liabilities, for use in schizophrenia risk analysis models, using data from cross-linked electronic health and social services registers.
A cohort of N = 428 970 Western Australian children born 1980–2001 was partitioned into three samples: scale development sample (N = 171 588), and two scale validation samples (each N = 128 691). Measures of adversity were defined before a child's 10th birthday from five domains: discontinuity in parenting, family functioning, family structure, area-level socioeconomic/demographic environment and family-level sociodemographic status. Using Cox proportional hazards modelling of follow-up time from 10th birthday to schizophrenia diagnosis or censorship, weighted combinations of measures were firstly developed into scales for each domain, then combined into a final global scale. Discrimination and calibration performance were validated using Harrell's C and graphical assessment respectively.
A weighted combination of 42 measures of childhood adversity was derived from the development sample. Independent application to identical measures in validation samples produced Harrell's Concordance statistics of 0.656 and 0.624. Average predicted time to diagnosis curves corresponded with 95% CI limits of observed Kaplan–Meier curves in five prognostic categories.
Our Early Adversity Scale for Schizophrenia (EAS-Sz), the first using routinely collected register data, predicts schizophrenia diagnosis above chance, and has potential to help untangle contributions of genetic and environmental liability to schizophrenia risk.
The antipsychotic clozapine is known to have immune-modulating effects. Clozapine treatment has been reported to be associated with increased risk of COVID-19 infection. However, it remains unclear whether this is because of increased testing of this patient group, who are closely monitored. We linked anonymised health records from mental health services in Cambridgeshire (UK), for patients taking antipsychotic medication, with data from the local COVID-19 testing hub. Patients receiving clozapine were more likely to be tested for COVID-19, but not to test positive. Increased testing in patients receiving clozapine suggests prudent judgement by clinicians, considering the overall health vulnerabilities of this group.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
Difficulty in cognitive adjustment after a conflict or error is a hallmark for many psychiatric disorders, yet the underlying neural correlates are not fully understood. We have previously shown that post-success and post-error cognitive controls are associated with distinct mechanisms particularly related to the prefrontal-cerebellar circuit, raising the possibility that altered dynamic interactions in this circuit may underlie mental illness.
This study included 136 patients with three diagnosed disorders [48 schizophrenia (SZ), 49 bipolar disorder (BD), 39 attention deficit hyperactivity disorder (ADHD)] and 89 healthy controls who completed a stop-signal task during fMRI scans. Brain activations for concurrent, post-success, and post-error cognitive controls were analyzed and compared between groups. Dynamic causal modeling was applied to investigate prefrontal-cerebellar effective connectivity patterns during post-success and post-error processing.
No significant group differences were observed for brain activations and overall effective connectivity structures during post-success and post-error conditions. However, significant group differences were shown for the modulational effect on top-down connectivity from the prefrontal cortex to the cerebellum during post-error trials (pFWE = 0.02), which was driven by reduced modulations in both SZ and ADHD. During post-success trials, there were significantly decreased modulational effect on bottom-up connectivity from the cerebellum to the prefrontal cortex in ADHD (pFWE = 0.04) and decreased driving input to the cerebellum in SZ (pFWE = 0.04).
These findings suggest that patients with SZ and ADHD are associated with insufficient neural modulation on the prefrontal-cerebellar circuit during post-success and post-error cognitive processing, a phenomenon that may underlie cognitive deficits in these disorders.
There is increasing evidence that assessing outcomes in terms of capability provides information beyond that of health-related quality of life (HRQoL) for outcome evaluation in mental health research and clinical practice.
To assess similarities and differences in the measurement properties of the ICECAP-A capability measure and Oxford Capabilities Questionnaire for Mental Health (OxCAP-MH) in people with schizophrenia experiencing depression, and compare these measurement properties with those of (a) the EuroQol EQ-5D-5L and EuroQol Visual Analogue Scale (EQ-VAS) and (b) mental health-specific (disease-specific) measures.
Using data for 100 patients from the UK, measurement properties were compared using correlation analyses, Bland–Altman plots and exploratory factor analysis. Responsiveness was assessed by defining groups who worsened, improved or remained unchanged, based on whether there was a clinically meaningful change in the instrument scores between baseline and 9-month follow-up assessments.
The two capability instruments had stronger convergent validity with each other (Spearman's rho = 0.677) than with the HRQoL (rho = 0.354–0.431) or the mental health-specific (rho = 0.481–0.718) instruments. The OxCAP-MH tended to have stronger correlations with mental health-specific instruments than the ICECAP-A, whereas the ICECAP-A had slightly stronger correlation with the EQ-VAS. Change scores on the capability instruments correlated weakly with change scores on the HRQoL scales (rho = 0.131–0.269), but moderately with those on mental health-specific instruments for the ICECAP-A (rho = 0.355–0.451) and moderately/strongly on the OxCAP-MH (rho = 0.437–0.557).
Assessing outcomes in terms of capabilities for people with schizophrenia and depression provided more relevant, mental health-specific information than the EQ-5D-5L or the EQ-VAS. The ICECAP-A and the OxCAP-MH demonstrated similar psychometric properties, but the OxCAP-MH was more correlated with disease-specific instruments.
The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable.
Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages.
Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex.
Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.
People with severe mental illness (SMI) are more likely to have obesity and engage in health risk behaviours than the general population. The aims of this study are (1) evaluate the effectiveness of interventions that focus on body weight, smoking cessation, improving sleeping patterns, and alcohol and illicit substance abuse; (2) Compare the number of interventions addressing body weight and health risk behaviours in low- and middle-income countries (LMICs) v. those reported in published systematic reviews focusing on high-income countries (HICs).
Intervention studies published up to December 2020 were identified through a structured search in the following database; OVID MEDLINE (1946–December 2020), EMBASE (1974–December 2020), CINAHL (1975–2020), APA PsychoINFO (1806–2020). Two authors independently selected studies, extracted study characteristics and data and assessed the risk of bias. and risk of bias was assessed using the Cochrane risk of bias tool V2. We conducted a narrative synthesis and, in the studies evaluating the effectiveness of interventions to address body weight, we conducted random-effects meta-analysis of mean differences in weight gain. We did a systematic search of systematic reviews looking at cardiometabolic and health risk behaviours in people with SMI. We compared the number of available studies of LMICs with those of HICs.
We assessed 15 657 records, of which 9 met the study inclusion criteria. Six focused on healthy weight management, one on sleeping patterns and two tested a physical activity intervention to improve quality of life. Interventions to reduce weight in people with SMI are effective, with a pooled mean difference of −4.2 kg (95% CI −6.25 to −2.18, 9 studies, 459 participants, I2 = 37.8%). The quality and sample size of the studies was not optimal, most were small studies, with inadequate power to evaluate the primary outcome. Only two were assessed as high quality (i.e. scored ‘low’ in the overall risk of bias assessment). We found 5 reviews assessing the effectiveness of interventions to reduce weight, perform physical activity and address smoking in people with SMI. From the five systematic reviews, we identified 84 unique studies, of which only 6 were performed in LMICs.
Pharmacological and activity-based interventions are effective to maintain and reduce body weight in people with SMI. There was a very limited number of interventions addressing sleep and physical activity and no interventions addressing smoking, alcohol or harmful drug use. There is a need to test the feasibility and cost-effectiveness of context-appropriate interventions to address health risk behaviours that might help reduce the mortality gap in people with SMI in LMICs.
Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown.
We searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using 18FDG-PET, in schizophrenia/first-episode psychosis v. controls. Effect sizes (Hedges g) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus.
Thirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's g = −0.74 ± 0.54, p = 0.01; I2 = 67%) and metabolism relative to whole brain (g = −0.44 ± 0.34, p = 0.01; I2 = 55%) were lower in schizophrenia v. controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic (g = −1.18 ± 0.73) v. first-episode patients (g = −0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (−1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia v. controls (−0.25 ± 0.24, p = 0.049; I2 = 5%). Studies identified reporting voxel-based morphometry measures of absolute 18FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower 18FDG uptake in the left anterior cingulate gyrus (Z = −4.143; p = 0.007) and the left inferior orbital frontal gyrus (Z = −4.239; p = 0.02) in schizophrenia.
We report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.
This chapter describes the phenomenon of psychosis and how it presents in patients with PWS. Characteristics of psychosis, including delusions, hallucinations, disorganized thinking, abnormal motor behavior, or negative symptoms are described. Although the classical presentation of schizophrenia, schizophreniform, and other schizoid disorders is uncommon in PWS, there are other less-recognized psychotic presentations that are explained in the text. Delirium, despite not being considered a psychotic disorder, is important to recognize due to its association with medications patients with PWS are prescribed. Cycloid psychosis is another phenomenon that, although not formally recognized in the DSM-5, is frequently seen in PWS. The sudden onset and cycling between normalcy and psychosis makes it difficult to diagnose for providers who are unfamiliar with it. We emphasize the need for immediate medical attention and treatment in the case of suspected psychosis. Some commonly used strategies for management are discussed. Continued monitoring by mental healthcare providers and need for maintenance treatment is discussed.
Overweight and obesity are twice as likely to develop in people living with severe mental illness (SMI), compared with those without. Many factors contribute to this, such as reduced physical activity and the use of certain medications that induce weight gain. Obesity contributes to the premature mortality seen in people living with SMI, as it is one of the fundamental risk factors for cardiovascular disease and diabetes. Bariatric surgery is an effective treatment option, although patients living with SMI might face stigma when being considered for surgical intervention. This article proposes a discussion around obesity and bariatric surgery in patients living with SMI. It will also reflect on the challenges faced by healthcare professionals and patients living with SMI and obesity, when considering appropriate treatments for weight loss. The paper utilises a fictional case, informed by contributions from a lived experience author, to explore bariatric surgery in people living with SMI.
Food insecurity occurs when an individual lacks the financial resources to ensure reliable access to sufficient food to meet their dietary, nutritional and social needs. Adults living with mental ill health, particularly severe mental illness, are more likely to experience food insecurity than the general adult population. Despite this, most interventions and policy reforms in recent years have been aimed at children and families, with little regard for other vulnerable groups. Initiating a conversation about access to food can be tricky and assessing for food insecurity does not happen in mental health settings. This article provides an overview of food insecurity and how it relates to mental ill health. With reference to research evidence, the reader will gain an understanding of food insecurity, how it can be assessed and how food-insecure individuals with severe mental illness can be supported. Finally, we make policy recommendations to truly address this driver of health inequality.
Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.
Baseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.
Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.
The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.
Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder.
The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status.
Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001).
Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.
The Cognitive Neuroscience of Religious Experience, now updated and expanded in a new edition, updates key topics covered in the first edition including: decentering and self-transformation, supernatural agent cognitions, mystical states, religious language, ritualization and religious group agency. It expands upon the first edition to include major findings on the brain and religious experience over the past decade, focusing on methodology, future thinking and psychedelics. It provides an up-to-date review of brain-based accounts of religious experiences, and systematically examines the rationale for utilizing neuroscience approaches to religion. While it is primarily intended for religious studies scholars, people interested in comparative religion, philosophy of religion, cultural evolution and personal self-transformation will find an account of how such transformation is accomplished within religious contexts.
The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning.
A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15–28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA.
We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning.
Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.
Despite a large descriptive literature linking creativity and risk for psychiatric illness, the magnitude and specificity of this relationship remain controversial.
We examined, in 1 137 354 native Swedes with one of 59 3-digit official and objective occupational codes in managerial and educated classes, their familial genetic risk score (FGRS) for ten major disorders, calculated from 1st through 5th degree relatives. Mean FGRS across disorders were calculated, in 3- and 4-digit occupational groups, and then controlled for those whose disorder onset preceded occupational choice. Using sequential analyses, p values were evaluated using Bonferroni correction.
3-digit professions considered to reflect creativity (e.g. ‘artists’ and ‘authors’) were among those with statistically significant elevations of FGRS. Among more specific 4-digit codes, visual artists, actors, and authors stood out with elevated genetic risks, highest for major depression (MD), anxiety disorders (AD) and OCD, more modest for bipolar disorders (BD) and schizophrenia and, for authors, for drug and alcohol use disorders. However, equal or greater elevations in FGRS across disorders were seen for religious (e.g. ministers), helping (e.g. psychologists, social workers), and teaching/academic occupations (e.g. professors). The potential pathway from FGRS → Disorder → Occupation accounts for a modest proportion of the signal, largely for MD and AD risk.
While traditional creative occupations were associated with elevated genetic risk for a range of psychiatric disorders, this association was not unique, as similar, or greater elevations were seen for religious, helping and teaching professions and was stronger for internalizing than psychotic disorders.