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The use of community treatment orders (CTOs) has increased in many jurisdictions despite very limited evidence for their efficacy. In this context, it is important to investigate any differences in outcome by subgroup.
Aims
To investigate the variables associated with CTO placement and the impact of CTOs on admissions and bed-days over the following 12 months, including differences by diagnosis.
Method
Cases and controls from a complete jurisdiction, the state of Queensland, Australia, were analysed. Administrative health data were matched by age, sex and time of hospital discharge (index date) with two controls per case subject to a CTO. Multivariate analyses were used to examine factors associated with CTOs, as well as the impact on admissions and bed-days over the 12 months after CTO placement. Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12624000152527).
Results
We identified 10 872 cases and 21 710 controls from January 2018 to December 2022 (total n = 32 582). CTO use was more likely in First Nations people (adjusted odds ratio = 1.14; 95% CI: 1.06–1.23), people from culturally diverse backgrounds (adjusted odds ratio = 1.45; 95% CI: 1.33–1.59) and those with a preferred language other than English (adjusted odds ratio = 1.21; 95% CI: 1.02–1.44). When all diagnostic groups were considered, there were no differences in subsequent admissions or bed-days between cases and controls. However, both re-admissions and bed-days were significantly reduced for CTO cases compared with controls in analyses restricted to non-affective psychoses (e.g. adjusted odds ratio = 0.77, 95% CI: 0.71–0.84 for re-admission).
Conclusions
Queenslanders from culturally or linguistically diverse backgrounds and First Nations peoples are more likely to be placed on CTOs. Targeting CTO use to people with non-affective psychosis would both address rising CTO rates and mean that people placed on these orders derive possible benefit. This has implications for both clinical practice and policy.
The experience of psychosis in schizophrenia spectrum disorders involves significant distress and functional impairment, contributing to immense social and economic costs. Current gold standard treatment guidelines emphasize the use of antipsychotic medications, though responses to these treatments vary widely, with the potential for detrimental side effects. However, increasing placebo responses in randomized controlled trials since the 1960s complicate the development of new medications. Elevated placebo responses are common in psychiatric populations, including those with psychosis, and are influenced by individual beliefs and prior experiences. Despite extensive research on placebo mechanisms in conditions such as depression and pain, little is known about mechanisms of these effects in psychosis. This narrative review examines the predictors and belief formation processes underlying placebo and nocebo phenomena in psychosis. We discuss features of randomized controlled trials for antipsychotic medications, individual symptom heterogeneity, and contextual factors. Findings related to placebo effects for motivation and cognition-enhancing drugs are also discussed. We then consider the possibility that theories of predictive coding and aberrant salience provide explanation for aspects of both placebo effects and schizophrenia spectrum symptoms. The role of outcome expectations broadly and in the context of reward processing is considered. We conclude with some recommendations for future placebo research in psychosis, emphasizing the diversity of placebo effects, assessment concerns, cultural considerations, and methodological aspects. Future multidisciplinary research is required to further elucidate placebo effects in schizophrenia spectrum disorders.
Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments.
Methods
We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, n = 35), first-episode psychosis (FEP, n = 39), and healthy controls (HC, n = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity.
Results
TNF-α levels were significantly elevated in FEP compared to CHR-P (p = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task (β = 0.28, p = 0.0337) and showed a trend-level association with slower processing speed (β = 0.98, p = 0.075). TNF-α levels predicted poorer facial emotion recognition (β = −1.37, p = 0.0022). IQ and group were significant covariates in most models.
Conclusions
Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention.
Mentalizing defines the set of social cognitive imaginative activities that enable interpretation of behaviors as arising from intentional mental states. Mentalization impairments have been related to childhood trauma (CT) and are widely present in people suffering from mental disorders. Nevertheless, the link between CT exposure, mentalization abilities, and related psychopathology remains unclear. This study aims to systematically review the evidence in this domain.
Methods
A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant systematic review of literature published until December 2022 was conducted through an Ovid search (Medline, Embase, and PsycINFO). The review was registered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42023455602).
Results
Twenty-nine studies were included in the qualitative synthesis. Twenty studies (69%) showed a significant negative correlation between CT and mentalization. There was solid evidence for this association in patients with psychotic disorders, as almost half the studies focused on this population. The few studies focusing on unipolar depression, personality disorders, and opioid addiction also reported a negative impact of CT on mentalization. In contrast, evidence for post-traumatic stress disorder was inconsistent, and no evidence was found for bipolar disorder. When stratifying for subtypes of CT, there was solid evidence that neglect (physical and emotional) decreased mentalization capacity, while abuse (physical, emotional, or sexual) was not associated with mentalization impairments.
Conclusions
Although causality cannot be established, there was substantial evidence that CT negatively affects mentalization across various psychiatric disorders, particularly psychotic disorders. These findings highlight the potential of targeting mentalization impairments in prevention and treatment strategies aiming to reduce the incidence and the social functioning burden of mental illness.
Easily accessible, impactful, evidence-based resources are needed to assist mental health workers to best support voice-hearers in managing and living well with voices. Let’s Talk About Voices (LTAV) is an innovative suite of resources designed for mental health workers to use in supporting voice-hearers.
Aim
This study aimed to assess the impact of LTAV on mental health workers’ self-reported capacity to work with voice-hearers.
Method
A randomised, controlled crossover design was used, with assessment at three time points. The assessment measure was co-developed by researchers, clinicians, peer workers and voice-hearers based on the aims of LTAV and the Theory of Planned Behaviour. Participants were randomised into two groups. The immediate group received access to LTAV following the first assessment; the delayed group received access following the second assessment. In total, 256 mental health workers commenced the study, with 120 completing all assessments.
Results
Between-group comparisons for change between times 1 and 2 found a significant difference with a large effect size (F = 40.2, P < 0.001, ηp2 = 0.19). Significance remained on intention-to-treat analysis (F = 22.9, P < 0.001, ηp2 = 0.08). Pairwise repeated-measures comparisons found a significant increase in scores for both groups following access to LTAV, which was sustained at follow-up. Fourteen of 24 individual items showed significant change. Changes were consistent across professions, work settings and experience working with voice-hearers, but those with less confidence in working with voice-hearers on intake showed significantly stronger improvements.
Conclusions
This research indicates that LTAV has the potential to substantially improve mental health workers’ attitudes and confidence in supporting voice-hearers.
Virtual reality (VR) may improve psychological treatments for psychotic disorders. We investigated the effects of VR-based cognitive behavior therapy for paranoid ideation (VR-CBTp) compared to standard CBTp.
Methods
We conducted a pragmatic, single-blind, randomized clinical trial in seven mental health centers across the Netherlands and Belgium. A total of 98 participants with a psychotic spectrum disorder and paranoid ideation were randomized to a maximum of 16 sessions of VR-CBTp (n = 48) or CBTp (n = 50). The primary outcome was momentary paranoia, measured with the experience sampling method (ESM) at posttreatment. Secondary measures, assessed at baseline, posttreatment, and 3-month follow-up, included symptoms (paranoia, hallucination, depression, cognition, and anxiety related), social functioning, self-esteem, and schemes.
Results
Both groups showed reductions in momentary paranoia between baseline and posttreatment (n = 56, b = −15.0, effect size [ES] = 0.65), but those were greater for VR-CBT (interaction b = 8.3, ES = 0.62). Reductions remained at follow-up (n = 50, b = −10.7, ES = 0.57) but not the interaction. Limited ESM compliance resulted in data loss; however, secondary paranoia measures did confirm improvements (ES range = 0.66–1.15, n = 78–81), but not the interaction. Both groups improved in symptoms, self-esteem, and social functioning. Interaction effects in favor of VR-CBTp were found for safety behavior, depression, and self-esteem at posttreatment, and self-esteem and anxiety at follow-up. For VR-CBTp, 37.5% did not complete treatment; for CBTp, this was 24.0%. Completers, on average, received 12.7 (VR-CBTp: standard deviation [SD] = 3.9) and 15.1 (CBTp: SD = 2.5) sessions.
Conclusions
Both CBTp and VR-CBTp are efficacious treatments for paranoid ideation, but VR-CBTp may be somewhat more effective. Limitations concern missing primary outcome data and a lower sample size than anticipated.
Based on an efficacious face-to-face theory-driven psychological therapy for persecutory delusions in the context of psychosis, we set out to develop a scalable guided 6-month online program. The aim was an intervention that patients can easily access and use, produces large clinical effects, and can be supported by a range of mental health professionals in less contact time than face-to-face therapy. We report here the proof-of-concept testing. At least moderate-sized clinical effects were required to progress to a randomized controlled trial (RCT).
Methods
In the 6-month Feeling Safer online program, a certified medical device, patients complete a brief assessment and then are provided with up to 10 modules that match their difficulties. Regular remote meetings with a mental health professional also take place. These may be supplemented by in-person visits. A pre- to post-treatment cohort trial was conducted with 14 patients with persistent persecutory delusions. The primary outcome was the Psychotic Symptoms Rating Scale (PSYRATS)-Delusions.
Results
Satisfaction and usability ratings of the program were high. Very large reductions in persecutory delusions were observed (PSYRATS mean reduction = 7.1, 95% C.I. = 3.4, 10.8, n = 13, Cohen’s d = 3.0). There were large improvements in paranoia, anxiety, depression, agoraphobic distress, psychological wellbeing, meaningful activity, personal recovery, recovering quality of life, and moderate improvements in insomnia, agoraphobic avoidance, and quality of life.
Conclusions
The clinical effects associated with Feeling Safer were very high, comparable to those seen in the evaluations of the face-to-face therapy, and enable progression to an RCT.
Psychotic-like experiences (PLEs) are associated with cognitive impairment and premature mortality, which may be indicative of accelerated biological ageing. Epigenetic clocks provide a measure of biological age based on DNA methylation, yet the long-term relationship between epigenetic ageing and PLEs remains largely unclear. We tested the relationship between epigenetic ageing and PLEs using a 17-year longitudinal approach.
Methods
Epigenetic ageing was calculated using four epigenetic clocks (DunedinPACE, Cortical EpiAge, Horvath, and PCGrimAge) in a sample from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large population-based birth cohort (n = 1840, 56.8% females). We modeled epigenetic ageing from up to three repeated measures collected between ages 7 and 24 using a linear mixed-effects model to calculate (1) average epigenetic age [mean-centered intercept] and (2) rate of epigenetic ageing over this 17-year period [slope]. We then compared these two measures between individuals who developed PLEs in early adulthood (n = 95) against those who did not (n = 1745).
Results
Results showed that a faster rate (slope) of longitudinal PCGrimAge was predictive of PLEs (OR = 1.79, 95% CI [1.13–2.85], p = .014), although this association was no longer significant after adjusting for smoking. There was a non-significant effect in the same direction for other clocks. Average epigenetic age (mean-centered intercept) was not associated with PLEs.
Conclusions
Our findings suggest that the observed association between accelerated rate of epigenetic ageing, measured with PCGrimAge, from childhood to early adulthood, and the development of PLEs in early adulthood may be explained by smoking.
The prevalence of psychiatric disorders in people with epilepsy is as high as 43% and, among them, psychoses represent a severe comorbidity.
Aims
This is a narrative review discussing the interplay between epilepsy and psychosis and identifying challenges in diagnosing and managing psychotic symptoms in epilepsy, focusing on the past 10 years.
Method
Articles published between June 2014 and December 2024 were identified through searches in PubMed using the search terms ‘psychosis’, ’seizure, epilepsy and convulsion’, ‘epile*’, ’seizure*’ and ‘convuls*’.
Results
The association between epilepsy and psychosis was shown to be bidirectional, with people with psychosis being at increased risk of epilepsy. In epilepsy, psychotic symptoms may occur in three clinical scenarios, with clinical presentation and management varying in relationship to these: seizure-related (peri-ictal), treatment-related or independent of the former.
Conclusions
There are no guidelines for the management of psychotic symptoms in epilepsy, but it is possible to apply policies for the treatment of psychoses, taking into account the peculiarities and needs of people with epilepsy.
Psychotic disorders are frequently preceded by depressive disorders, and it has been hypothesized that treatment of depression in youth may reduce risk for later psychosis. Using quasi-experimental methods, we estimated the causal relationship between the treatment of adolescent depression with selective serotonin reuptake inhibitors (SSRIs) and the risk of later psychosis.
Methods
We used data linkage from multiple national Finnish registries for all individuals (n = 697,289) born between 1987 and 1997 to identify depression diagnosed before age 18, cumulative SSRI treatment within three years of diagnosis, and diagnoses of non-affective psychotic disorders by end of follow-up (age 20–29). We used instrumental variable analyses, exploiting variability in prescribing across hospital districts to estimate causal effects. Analyses were conducted using two-stage least squares modelling. Sensitivity analyses examined effects stratified by confounders and effects of specific SSRIs.
Results
Our final sample included 22,666 individuals diagnosed with depression in adolescence, of whom 60.2% (n = 13,650) had used SSRIs. 10.7% of adolescents with depression went on to be diagnosed with a non-affective psychotic disorder. SSRI treatment for adolescent depression was not associated with a reduced risk of developing a psychotic disorder (one-year β = 0.04,CI:−0.01 to 0.09; two-years β = 0.02,CI:−0.06 to 0.09; three-years β = −0.02,CI:−0.08 to 0.05).
Conclusions
Our quasi-experimental investigation does not support the hypothesis that treatment of adolescent depression reduces the subsequent risk of psychosis. Our findings question the assumption that treatment of common mental health disorders in youth may impact the risk of developing severe mental illnesses in adulthood.
Jennifer tells us the story of her mother who received ECT. She was a very resilient person, kept a job and looked after the children. Three bereavements during her life -- her husband, her sister, and later on, her son -- made her brain finally break down and she developed a severe depression in her old age. The final bereavement occurred during lockdown. They were one of the first families to experience trying to grieve and bury a loved one, whilst not being allowed to be together. Her mother’s depression worsened, and she became psychotic, believing that she will become financially destitute and also grossly obese. After four months in hospital, there was no improvement and she continued to decline. After the initial shock of hearing the suggestion about ECT, Jennifer researched the topic and the family agreed on the treatment. After eight sessions, her mother improved. This was not the end, as after a year, towards the anniversary of her son’s death, the depression came back. More treatments, including cold water therapy in Scottish lochs, but made no difference to her, and ECT was prescribed again. This time it took twelve sessions for it to work, but she is still well at the time of writing.
The story is told through the experience of the patient, Paul, as well as through his partner and carer during that time, Sally. Their accounts feature next to each other, to provide a contrast for the different experiences of the patient and his wife. Following the decision to take early retirement from a high-powered job in business, Paul suffered a severe mental breakdown, which gradually led him into a world of fear, paranoia, catastrophic thinking and a desire to take his own life. For his own safety he was sectioned and spent four months in a psychiatric hospital. After various antidepressants and antipsychotics had no effect, Paul was persuaded to undergo ECT and, after only six sessions of treatment, had what his partner describes as ‘a complete and miraculous cure’. Four years after the event he is still fit and well and has had no relapses. This story explores the thoughts and feelings of someone who is suffering with acute anxiety/depression, as well as presenting the fears and desperation experienced by his partner.
Depression and psychosis came out of the blue for Berlinda, who found herself in A&E after trying to kill herself with various means. She is lucky to be alive, probably due to the excellent reflexes of a driver whose car should have driven into her. Admission to hospital was proving impossible due to lack of beds. Recollections from the hospital stay are patchy and are supplemented by the accounts of friends and relatives. More self-inflicted injuries followed, and the situation was getting out of control. When ECT was mentioned after a long time, Berlinda was sceptical of it as she thought that nothing would help her. And then everybody noticed an almost immediate relief of her symptoms. Berlinda has remained completely well since and started taking part in inspections of ECT clinics for the ECT Accreditation Service.
Sue was living a charmed life: financially secure, a stable marriage, a holiday home, and lots of holidays made possible as a result of early retirement. In March 2020 she and her husband became locked down in different countries for several months. Sue contracted Covid, and symptoms of long Covid followed. Symptoms of depression developed, and Sue started carefully planning how to end her life. Then she became psychotic, believing that she would become destitute and homeless, that she had infected the country’s Child Protection system with computer viruses and that her husband would cheat her out of her money. Three hospital admissions and a lot of medication later, she was still suicidal. At that point her psychiatrist suggested ECT. Sue’s first reaction was horror. She had always thought of ECT as throwing the furniture of a doll’s house in the air and hoping it lands in the right places in the right rooms – an unlikely outcome. She decided to go ahead and ‘getting all the furniture in the right place’ has given her life back. Her husband finishes the story with recollections of Sue’s psychotic ideas and his inability to do anything about them.
Liz remembers experiencing episodes of depression since an early age but completed her university degree and worked as a medical doctor for many years. The story starts with the description of a psychotic episode that she experienced for the duration of one summer. Diaries kept from that time were used for the story, giving the episode detail, helped by a poem also written at the time. The depression gradually got worse over the years, despite trying more than twenty different antidepressants and mood stabilisers, regular exercises and prolonged courses of psychotherapy, causing an early retirement and eventually hospital admissions. Finally, ECT was recommended, and it worked despite the very long and resistant type of depression. The improvement was incomplete, though; it required maintenance treatment and caused marked memory problems, which are also described in detail.
Ruth starts with details from her childhood, when she tended to be a perfectionist and had obsessions around contamination. Ruth suffered with episodes of depression herself, but they were short lived and didn’t require treatment. Her severe depression started while on a long travel in two continents. She developed delusions of guilt and was receiving messages, resulting in an admission to a hospital in Canada, and then permitted to fly back home under sedation. Several years later, after severe social stressors, she relapsed and remained depressed for several years. She was again psychotic, believing that she had ‘killed the world’ and eventually became almost mute. Her sister, aware that their grandfather had received ECT, researched the topic and felt that it should be tried, especially after listening to a talk by Dr Sherwin Nuland, who had ECT himself. It was him who used the phrase ‘rising like a phoenix’, which was chosen as the title of this chapter. Ruth had twenty-three sessions before she felt better. She describes in detail her memory problems. She has since followed Sherwin Nuland’s lead by talking about her ECT experience publicly.
Previous studies have estimated the lifetime incidence, age of onset and prevalence of mental disorders, but none have used nationwide data covering both primary and secondary care, even though mental disorders are commonly treated in primary care. We aimed to determine lifetime incidence, age-specific incidence, age of onset and service utilization for diagnosed mental disorders.
Methods
This register-based cohort study followed the entire population of Finland from 2000 to 2020. We estimated the cumulative incidence of diagnosed mental disorders with the Aalen–Johansen estimator, accounting for competing risks such as death and emigration. We also calculated age-specific incidence and 12-month service utilization as of 31 December 2019, providing diagnosis-, age- and gender-specific estimates.
Results
We followed 6.4 million individuals for 98.5 million person-years. By age 100, lifetime incidence of any diagnosed mental disorder was 76.7% (95% CI, 76.6–76.7) in women and 69.7% (69.6–69.8) in men; in psychiatric secondary care, it was 39.7% (39.6–39.8) and 31.5% (31.4–31.6). At age 75, stricter estimates for non-organic disorders (ICD-10: F10–F99) were 65.6% (65.5–65.7) for women and 60.0% (59.9–60.1). Anxiety disorders (F40–F48) had the highest cumulative incidence. Median age of onset of non-organic mental disorders was 24.1 (interquartile range, 14.8–43.3 years) in women and 20.0 (interquartile range, 7.3–42.2 years) in men. Service utilization within 12 months was 9.0% for women and 7.7% for men.
Conclusions
Most, though not all, individuals experience at least one type of mental disorder, often during youth. Capturing the overall occurrence of mental disorders requires including both primary and secondary care data.
Insight in nonverbal correlates of paranoid ideation can potentially help improve diagnostic procedures and guide interventions. The aim was to systematically evaluate the scientific evidence investigating nonverbal correlates of paranoid ideation.
Methods
The review follows the PRISMA guidelines. Databases PsycINFO, PubMed, Web of Science, and Cinahl were searched for studies concerning the use of standardized instruments for both verbal and nonverbal measurements of paranoid ideation in adult participants. Quality of studies was evaluated using the Effective Public Health Practice Project tool. Data were systematically extracted and summarized thematically and narratively. This review was registered with PROSPERO (CRD42022288001).
Results
The search strategy yielded 3962 results of which 22 papers met inclusion criteria. Half (n = 11) of the included articles included patients with a diagnosis on the psychosis spectrum, the other articles (n = 11) studied healthy populations. Identified nonverbal categories were spatial behavior (n = 6), brain region activity (n = 5), visual perception (n = 5), stress physiology (n = 4), information processing (n = 3), and aggression (n = 1). Some studies investigated multiple nonverbal categories.
Conclusions
Evidence was strongest for spatial behavior and brain region activity as nonverbal correlates of paranoid ideation. Evidence for stress physiology, information processing, and aggression as potential nonverbal correlates was less robust, due to inconsistent findings and small numbers of publications. Using nonverbal methods to assess paranoid ideation requires more investigation and evaluation. The integration of nonverbal assessments might offer new diagnostic possibilities that move beyond traditional verbal methods.
Past meta-analyses have confirmed robust associations between childhood traumatic experiences and the risk of psychosis. However, the dose–response relationship between cumulative adversity exposure and psychosis risk observed in some, but not all, previous studies in this area has not been specifically scrutinized or substantiated via recommended meta-analytic methods. This meta-analysis aimed to synthesize the available evidence on dose–response effects between childhood trauma and psychosis outcomes.
Methods
PsycINFO, PubMed, EMBASE, Web of Science, CNKI, and WANFANG were searched from inception to July 2024 to identify observational studies reporting odds ratios for psychosis outcomes across multiple levels of childhood trauma exposure. Dose–response effects were extracted from eligible studies and synthesized via robust error meta-regression analyses.
Results
Twenty-one studies comprising 59,975 participants were included in the meta-analysis. A significant nonlinear relationship was observed between the number of childhood adversities and the risk of future psychosis experiences (p for nonlinearity = .021). The pooled odds ratio for psychosis increased from 1.76 (95% confidence interval [CI]: 1.39–2.22) for 1 exposure to 6.46 (95% CI: 4.37–9.53) for 5+ exposures compared to no traumatic experience.
Conclusions
This meta-analysis provides robust evidence for a dose–response relationship between cumulative childhood adversity and psychosis risk, with nonlinear patterns suggestive of an accelerating, more pronounced, risk at higher levels of trauma exposure. These findings underscore the importance of considering childhood traumatic experiences as a putative and potentially causative risk factor for psychotic experiences, as well as early prevention and intervention efforts targeting childhood adversity to reduce the risk of psychosis.