Phelan-McDermid syndrome is a rare genetic disorder characterized by various neurodevelopmental, medical, and psychiatric issues. Although bipolar disorder-like presentations and catatonia are particularly common, psychosis has also been reported but is less well described. As such, this systematic review sought to characterize the phenomenology of psychosis in Phelan-McDermid syndrome, clarify the association of psychotic symptoms with other neuropsychiatric features of the disorder, and describe antipsychotic treatment response.

A literature search was completed in July 2024 using PubMed and Scopus. Only English-language articles that reported the occurrence of psychotic symptoms in Phelan-McDermid syndrome were eligible for inclusion. 18 articles describing 35 individuals were included in the main analyses. Three additional articles of relevance are discussed separately, as they either provided limited clinical information or did not present data in a patient-specific manner.

The average age of psychosis onset was ∼17 years, and 65% of individuals developed symptoms at or before age 15. ∼69% of individuals also experienced catatonia, ∼81% experienced mood symptoms, and 50% experienced both. Visual hallucinations were the most commonly reported psychotic symptom. Where reported, ∼76% (13/17) of individuals exhibited at least a partial and/or temporary response to antipsychotic therapy.

Psychotic presentations in Phelan-McDermid syndrome may qualitatively differ from schizophrenia. Although numerous antipsychotics may be efficacious in the treatment of Phelan-McDermid syndrome-associated psychosis, this review most importantly highlights the paucity of available high-quality evidence to guide treatment decisions in this respect, and as such indicates the need for more reports to be published.

Delirium is a severe neuropsychiatric syndrome caused by physical illness, associated with high mortality. Understanding risk factors for delirium is key to targeting prevention and screening. Whether severe mental illness (SMI) predisposes people to delirium is not known. We aimed to establish whether pre-existing SMI diagnosis is associated with higher risk of delirium diagnosis and mortality following delirium diagnosis.

A retrospective cohort and nested case–control study using linked primary and secondary healthcare databases from 2000–2017. We identified people diagnosed with SMI, matched to non-SMI comparators. We compared incidence of delirium diagnoses between people with SMI diagnoses and comparators, and between SMI subtypes; schizophrenia, bipolar disorder and ‘other psychosis’. We compared 30-day mortality following a hospitalisation involving delirium between people with SMI diagnoses and comparators, and between SMI subtypes.

We identified 20 566 people with SMI diagnoses, matched to 71 374 comparators. Risk of delirium diagnosis was higher for all SMI subtypes, with a higher risk conferred by SMI in the under 65-year group, (aHR:7.65, 95% CI 5.45–10.7, ⩾65-year group: aHR:3.35, 95% CI 2.77–4.05). Compared to people without SMI, people with an SMI diagnosis overall had no difference in 30-day mortality following a hospitalisation involving delirium (OR:0.66, 95% CI 0.38–1.14).

We found an association between SMI and delirium diagnoses. People with SMI may be more vulnerable to delirium when in hospital than people without SMI. There are limitations to using electronic healthcare records and further prospective study is needed to confirm these findings.

Nearly two-thirds of individuals with a mental disorder start experiencing symptoms during adolescence or early adulthood, and the onset of a mental disorder during this critical life stage strongly predicts adverse socioeconomic and health outcomes. Subthreshold manifestations of autism spectrum disorders (ASDs), also called autistic traits (ATs), are known to be associated with a higher vulnerability to the development of other psychiatric disorders. This study aimed to assess the presence of ATs in a population of young adults seeking specialist assistance and to evaluate the study population across various psychopathological domains in order to determine their links with ATs.

We recruited a sample of 263 adolescents and young adults referring to a specialized outpatient clinic, and we administered them several self-report questionnaires for the evaluation of various psychopathological domains. We conducted a cluster analysis based on the prevalence of ATs, empathy, and sensory sensitivity scores.

The cluster analysis identified three distinct groups in the sample: an AT cluster (22.43%), an intermediate cluster (45.25%), and a no-AT cluster (32.32%). Moreover, subjects with higher ATs exhibited greater symptomatology across multiple domains, including mood, anxiety, eating disorder severity, psychotic symptoms, and personality traits such as detachment and vulnerable narcissism.

This study highlights the importance of identifying ATs in young individuals struggling with mental health concerns. Additionally, our findings underscore the necessity of adopting a dimensional approach to psychopathology to better understand the complex interplay of symptoms and facilitate tailored interventions.

Family members of people experiencing a first-episode psychosis (FEP) can experience high levels of carer burden, stigma, emotional challenges, and uncertainty. This indicates the need for support and psychoeducation. To address these needs during the COVID-19 pandemic, we developed a multidisciplinary, blended, telehealth intervention, incorporating psychoeducation and peer support, for family members of FEP service users: PERCEPTION (PsychoEducation for Relatives of people Currently Experiencing Psychosis using Telehealth, an In-person meeting, and ONline peer support). The aim of the study was to explore the acceptability of PERCEPTION for family members of people who have experienced an FEP.

Ten semi-structured interviews were conducted online via Zoom and audio recorded. Maximum variation sampling was used to recruit a sample balanced across age, gender, relatives’ prior mental health service use experience, and participants’ relationship with the family member experiencing psychosis. Data were analysed by hand using reflexive thematic analysis.

Four themes were produced: ‘Developing confidence in understanding and responding to psychosis’; ‘Navigating the small challenges of a broadly acceptable and desirable intervention’; ‘Timely support enriches the intervention’s meaning’; and ‘Dealing with the realities of carer burden’.

Broadly speaking, PERCEPTION was experienced as acceptable, with the convenient, safe, and supportive environment, and challenges in engagement being highlighted by participants. Data point to a gap in service provision for long-term self-care support for relatives to reduce carer burden. Providing both in-person and online interventions, depending on individuals’ preference and needs, may help remove barriers for family members accessing help.

Epidemiologic research suggests that youth cannabis use is associated with psychotic disorders. However, current evidence is based heavily on 20th-century data when cannabis was substantially less potent than today.

We linked population-based survey data from 2009 to 2012 with records of health services covered under universal healthcare in Ontario, Canada, up to 2018. The cohort included respondents aged 12–24 years at baseline with no prior psychotic disorder (N = 11 363). The primary outcome was days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder according to validated diagnostic codes. Due to non-proportional hazards, we estimated age-specific hazard ratios during adolescence (12–19 years) and young adulthood (20–33 years). Sensitivity analyses explored alternative model conditions including restricting the outcome to hospitalizations and ED visits to increase specificity.

Compared to no cannabis use, cannabis use was significantly associated with psychotic disorders during adolescence (aHR = 11.2; 95% CI 4.6–27.3), but not during young adulthood (aHR = 1.3; 95% CI 0.6–2.6). When we restricted the outcome to hospitalizations and ED visits only, the strength of association increased markedly during adolescence (aHR = 26.7; 95% CI 7.7–92.8) but did not change meaningfully during young adulthood (aHR = 1.8; 95% CI 0.6–5.4).

This study provides new evidence of a strong but age-dependent association between cannabis use and risk of psychotic disorder, consistent with the neurodevelopmental theory that adolescence is a vulnerable time to use cannabis. The strength of association during adolescence was notably greater than in previous studies, possibly reflecting the recent rise in cannabis potency.

Migration is a well-established risk factor for psychotic disorders, and migrant language has been proposed as a novel factor that may improve our understanding of this relationship. Our objective was to explore the association between indicators of linguistic distance and the risk of psychotic disorders among first-generation migrant groups.

Using linked health administrative data, we constructed a retrospective cohort of first-generation migrants to Ontario over a 20-year period (1992–2011). Linguistic distance of the first language was categorized using several approaches, including language family classifications, estimated acquisition time, syntax-based distance scores, and lexical-based distance scores. Incident cases of non-affective psychotic disorder were identified over a 5- to 25-year period. We used Poisson regression to estimate incidence rate ratios (IRR) for each language variable, after adjustment for knowledge of English at arrival and other factors.

Our cohort included 1 863 803 first-generation migrants. Migrants whose first language was in a different language family than English had higher rates of psychotic disorders (IRR = 1.08, 95% CI 1.01–1.16), relative to those whose first language was English. Similarly, migrants in the highest quintile of linguistic distance based on lexical similarity had an elevated risk of psychotic disorder (IRR = 1.15, 95% CI 1.06–1.24). Adjustment for knowledge of English at arrival had minimal effect on observed estimates.

We found some evidence that linguistic factors that impair comprehension may play a role in the excess risk of psychosis among migrant groups; however, the magnitude of effect is small and unlikely to fully explain the elevated rates of psychotic disorder across migrant groups.

Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms.

Patients with SCZ (n = 64; mean age = 30.4 years, s.d. = 9.8), BPD (n = 91; mean age 31.0 years, s.d. = 10.2), and CTR (n = 155; mean age = 31.9 years, s.d. = 9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3 T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms.

No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses.

While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.

The role of adolescent loneliness in adult mental health and prescriptions of psychotropic drugs remains underexplored.

We aim to determine whether (a) experiencing loneliness in adolescence and (b) changes in loneliness from adolescence to adulthood are prospectively associated with prescriptions for a variety of psychotropic drugs in adulthood.

We used data from a Norwegian population-based sample with 2602 participants, collected across four waves between 1992 and 2006. Loneliness was assessed at each wave, with survey data linked to medicinal drug prescription records from the Norwegian Prescription Database. We identified prescription histories of antipsychotics, mood stabilisers, antidepressants and benzodiazepines from 2007 to 2015, for each participant. We use latent growth curve analyses to model the relationship of adolescent loneliness and loneliness change from adolescence to adulthood, with subsequent psychotropic drugs prescription.

Adolescents with heightened loneliness, and adolescents whose loneliness increased into young adulthood, had a greater likelihood of being prescribed antipsychotics, mood stabilisers and antidepressants in adulthood. These associations remained significant after adjustment for confounders such as sociodemographic characteristics, conduct problems, substance use and mental health problems.

Loneliness in adolescence and its adverse development over a span of 15 years was linked to higher risk of receiving prescriptions for antipsychotics, mood stabilisers and antidepressants later in life. The findings may indicate that loneliness increases the risk for developing psychotic disorders, bipolar disorders and major depression.

An average of 1300 adults develop First Episode Psychosis (FEP) in Ireland each year. Early Intervention in Psychosis (EIP) is now widely accepted as best practice in the treatment of conditions such as schizophrenia. A local EIP programme was established in the Dublin South Central Mental Health Service in 2012.

This is a cross-sectional study of service users presenting to the Dublin South Central Mental Health Service with FEP from 2016 to 2022 following the introduction of the EIP programme. We compared this to a previously published retrospective study of treatment as usual from 2002 to 2012.

Most service users in this study were male, single, unemployed and living with their partner or spouse across both time periods. Cognitive Behavioural Therapy for psychosis was provided to 12% (n = 8) of service users pre-EIP as compared to 52% (n = 30) post-programme introduction (p < 0.001), and 3% (n = 2) of service users engaged with behavioural family therapy pre-EIP as opposed to 15% (n = 9) after (p < 0.01). Rates of composite baseline physical healthcare monitoring improved significantly (p < 0.001).

Exclusive allocation of multidisciplinary team staff to EIP leads to improved compliance with recommended guidelines, particularly CBT-p, formal family therapy and physical health monitoring.

Early intervention programmes (EIPs) in psychosis have gained attention as specialised interventions to improve health-related and societal impacts for people with psychotic disorders. Previous studies have presented evidence in favour of EIPs over the first year of intervention, despite none considering the critical period before psychosis onset (5 years).

To compare the associated costs of the First Episode Psychosis Intervention Program (CRUPEP) and treatment as usual (TAU) in a real-world cohort in a non-specialised psychiatric community setting.

Direct and indirect mental health-related costs were calculated over 1 year and up to 7 years. Healthcare and societal costs were calculated from economic data related to the consumption of all healthcare resources, including emergency department attendances, hospital admissions, psychotropic medication prescriptions and societal costs.

From a healthcare perspective, the intervention (CRUPEP) group initially showed a marginally higher cost per patient than the TAU group (€7621 TAU group v. €11 904 CRUPEP group) over the first year of follow-up. However, this difference was reversed between the groups on considering the entire follow-up, with the TAU group showing considerably higher associated costs per patient (€77 026 TAU v. €25 247 CRUPEP).

The EIP (CRUPEP) showed clinical benefits and minimised the direct and indirect health-related costs of the management of psychosis. Although the CRUPEP intervention initially reported increased costs over 1 year, TAU surpassed the global costs over the entire follow-up.

We previously reported that dual injections of lipopolysaccharide (LPS) in mice constitute a valuable tool for investigating the contribution of inflammation to psychotic disorders. The present study investigated how immune activation affects the kynurenine pathway and rat behaviour of relevance for psychotic disorders.

Male Sprague Dawley rats were treated with either dual injections of LPS (0.5 mg/kg + 0.5 mg/kg, i.p.) or dual injections of saline. Twenty-four hours after the second injection, behavioural tests were carried out, including locomotor activity test, fear conditioning test, spontaneous alternation Y-maze test, and novel object recognition test. In a separate batch of animals, in vivo striatal microdialysis was performed, and tryptophan, kynurenine, quinolinic acid, and kynurenic acid (KYNA) in the dialysate were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Dual-LPS treatment decreased spontaneous locomotion, exaggerated d-amphetamine-induced locomotor activity, and impaired recognition memory in male Sprague-Dawley rats. In vivo microdialysis showed that dual-LPS treatment elicited metabolic disturbances in the kynurenine pathway with increased extracellular levels of kynurenine and KYNA in the striatum.

The present study further supports the feasibility of using the dual-LPS model to investigate inflammation-related psychotic disorders and cognitive impairments.

Despite a substantial epidemiological literature on the incidence of psychotic disorders in Ireland, no systematic review has previously been undertaken. Such evidence can help inform understanding of need for psychosis care.

We conducted a prospectively registered systematic review (PROSPERO: CRD42021245891) following PRISMA guidelines. We searched four databases (Medline, PsycInfo, Web of Science, Embase) for papers containing incidence data on non-organic psychotic disorders, in people 16–64 years, published between 1950 and 2021 in the general adult population. We conducted duplicate screening, risk of bias assessments, and extracted data to a standardised template. We undertook a narrative synthesis for each major diagnostic outcome. Random effects meta-analyses were conducted for comparisons with ≥5 incidence rates.

Our search yielded 1975 non-duplicate citations, of which 23 met inclusion criteria, containing incidence data ascertained between 1974 and 2016 (median study quality: 5/8; interquartile range: 4–6). Incidence of all psychotic disorders (N = 4 studies) varied from 22.0 (95%CI: 17.3–28.0) in Dublin to 34.1 per 100,000 person-years (95%CI: 31.0–37.5) in Cavan and Monaghan. The pooled incidence of schizophrenia (N = 6 studies, N = 8 settings) was 20.0 per 100,000 person-years, though with imprecision around this estimate (95%CI: 10.6–37.5; I2: 97.6%). Higher rates of most outcomes were observed in men. There was consistent evidence of raised rates in more deprived and fragmented social environments, but no clear pattern by rural-urban status.

Patterns of incidence of psychotic disorders in Ireland are broadly consistent with the wider literature from the Global North. Findings could help identify populations at higher risk of psychosis in Ireland.

Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited.

To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P.

PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle–Ottawa Scale.

Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%–75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3–92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication.

Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.

Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.

Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.

The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.

Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.

We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.

Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.

Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.

Previous studies suggest that migrants tend to utilise antipsychotics less often than their native-born peers. However, studies examining antipsychotic use among refugees with psychosis are lacking.

To compare the prevalence of antipsychotic drug use during the first 5 years of illness among refugees and Swedish-born individuals with a newly diagnosed non-affective psychotic disorder, and to identify sociodemographic and clinical factors associated with antipsychotic use.

The study population included refugees (n = 1656) and Swedish-born persons (n = 8908) aged 18–35 years during 2007–2018, with incident diagnosis of non-affective psychotic disorder recorded in the Swedish in-patient or specialised out-patient care register. Two-week point prevalence of antipsychotics use was assessed every 6 months in the 5 years following first diagnosis. Factors associated with antipsychotic use (versus non-use) at 1 year after diagnosis were examined with modified Poisson regression.

Refugees were somewhat less likely to use antipsychotics at 1 year after first diagnosis compared with Swedish-born persons (37.1% v. 42.2%, age- and gender-adjusted risk ratio 0.88, 95% CI 0.82–0.95). However, at the 5-year follow-up, refugees and Swedish-born individuals showed similar patterns of antipsychotic use (41.1% v. 40.4%). Among refugees, higher educational level (>12 years), previous antidepressant use and being diagnosed with schizophrenia/schizoaffective disorder at baseline were associated with an increased risk of antipsychotics use, whereas being born in Afghanistan or Iraq (compared with former Yugoslavia) was associated with decreased risk.

Our findings suggest that refugees with non-affective psychotic disorders may need targeted interventions to ensure antipsychotic use during the early phase of illness.