Associations between soluble urokinase plasminogen activator receptor (suPAR) concentration and psychiatric disorders - A systematic review and meta-analysis.

BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. METHOD: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). DISCUSSION: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.

Frontostriatothalamic effective connectivity and dopaminergic function in the psychosis continuum.

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.

The development of a novel sexual health promotion intervention for young people with mental ill-health: the PROSPEct project.

BACKGROUND: Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. This study aimed to co-design a novel intervention to address the sexual health needs of young people with mental ill-health to test its effectiveness in a future trial undertaken in youth mental health services in Melbourne, Australia. METHODS: We followed the 2022 Medical Research Council (MRC) guidelines for developing and evaluating complex interventions. This involved synthesising evidence from the 'top down' (published evidence) and 'bottom up' (stakeholder views). We combined systematic review findings with data elicited from qualitative interviews and focus groups with young people, carers, and clinicians and identified critical cultural issues to inform the development of our intervention. RESULTS: Existing evidence in the field of sexual health in youth mental health was limited but suggested the need to address sexual wellbeing as a concept broader than an absence of negative health outcomes. The Information-Motivation-Belief (IMB) model was chosen as the theoretical Framework on which to base the intervention. Interviews/focus groups were conducted with 29 stakeholders (18 clinicians, three carers, and eight young people). Synthesis of the evidence gathered resulted in the co-design of a novel intervention consisting of an initial consultation and four 60-90-minute sessions delivered individually by a young 'sex-positive' clinician with additional training in sexual health. Barriers and supports to intervention success were also identified. CONCLUSIONS: Using the MRC Framework has guided the co-design of a potentially promising intervention that addresses the sexual health needs of young people with mental ill-health. The next step is to test the intervention in a one-arm feasibility trial.

Psychosocial and behavioural interventions for the negative symptoms of schizophrenia: a systematic review of efficacy meta-analyses.

BACKGROUND: Currently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit. AIM: To review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia. METHOD: A systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality. RESULTS: In total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from -0.59 to -0.24 and psychological interventions ranging from -0.65 to -0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0-100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches. CONCLUSIONS: Most of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.

Risk of first-episode psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland. METHODS: We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18-65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios. RESULTS: The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11-3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16-0.81, p = 0.01). CONCLUSIONS: Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.

Discharge destinations for young people with a first episode of psychosis after attending an early intervention for psychosis service.

OBJECTIVE: Early intervention for psychosis services result in superior outcomes in the domains of symptomatic and functional recovery, hospitalisation and employment compared to standard services; however, the optimal duration of care with these services is unknown. Knowledge on the discharge destinations, specifically the proportion discharged to high- and low-intensity services, could provide insights into the proportion of who may require a longer tenure of care. This study aimed to determine (1) the discharge destinations from early intervention for psychosis services and (2) baseline and intra-episode factors associated with discharge to the secondary care/adult mental health service. METHODOLOGY: This study was conducted at the Early Psychosis Prevention and Intervention Centre in Melbourne and included all young people treated by the service with a first episode of psychosis over a 6-year period. Discharge destinations were categorised according to high-intensity services, namely, secondary mental health care, or lower intensity services, such as private practitioners or primary care. RESULTS: A total of 1101 young people with a first episode of psychosis were included in the study, of whom 58.8% were male and the median age was 20.0 years (interquartile range: 17-22). After a median of 95.4 weeks (interquartile range: 66.7-105.7), 36.6% were discharged to the adult mental health services, which was associated with being not in employment, education or training at presentation (odds ratio = 1.71, 95% confidence interval [1.23, 2.37]); experiencing a relapse (odds ratio = 1.76, 95% confidence interval [1.24, 2.49]); and being admitted to a mental health unit (odds ratio = 3.98, 95% confidence interval [2.61, 6.09]). Young people who lived with their parents were less likely to be discharged to secondary care services (odds ratio = 0.52, 95% confidence interval [0.37, 0.73]), as were those who were achieving symptomatic remission within 12 weeks (odds ratio = 0.60, 95% confidence interval [0.43, 0.83]). Migrant status and the duration of untreated psychosis were not associated with discharge destination. CONCLUSION: These findings indicate that there is a sizable, identifiable minority who may benefit from a longer episode of care with early intervention for psychosis services.

Neighbourhood characteristics and the treated incidence rate of borderline personality pathology among young people.

OBJECTIVE: The impact of the wider social environment, such as neighbourhood characteristics, has not been examined in the development of borderline personality disorder. This study aimed to determine whether the treated incidence rate of full-threshold borderline personality disorder and sub-threshold borderline personality disorder, collectively termed borderline personality pathology, was associated with the specific neighbourhood characteristics of social deprivation and social fragmentation. METHOD: This study included young people, aged 15-24 years, who attended Orygen's Helping Young People Early programme, a specialist early intervention service for young people with borderline personality pathology, from 1 August 2000-1 February 2008. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Personality Disorders, and census data from 2006 were used to determine the at-risk population and to obtain measures of social deprivation and fragmentation. RESULTS: The study included 282 young people, of these 78.0% (n = 220) were female and the mean age was 18.3 years (SD = ±2.7). A total of 42.9% (n = 121) met criteria for full-threshold borderline personality disorder, and 57.1% (n = 161) had sub-threshold borderline personality disorder, defined as having three or four of the nine Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) borderline personality disorder criteria. There was more than a sixfold increase in the treated incidence rate of borderline personality pathology in the neighbourhoods of above average deprivation (Quartile 3) (incidence rate ratio = 6.45, 95% confidence interval: [4.62, 8.98], p < 0.001), and this was consistent in the borderline personality disorder sub-groups. This association was also present in the most socially deprived neighbourhood (Quartile 4) (incidence rate ratio = 1.63, 95% confidence interval: [1.10, 2.44]), however, only for those with sub-threshold borderline personality disorder. The treated incidence of borderline personality pathology increased incrementally with the level of social fragmentation (Quartile 3: incidence rate ratio = 1.93, 95% confidence interval: [1.37, 2.72], Quartile 4: incidence rate ratio = 2.38, 95% confidence interval: [1.77, 3.21]). CONCLUSION: Borderline personality pathology has a higher treated incidence in the more socially deprived and fragmented neighbourhoods. These findings have implications for funding and location of clinical services for young people with borderline personality pathology. Prospective, longitudinal studies should examine neighbourhood characteristics as potential aetiological factors for borderline personality pathology.

Prevalence and predictors of admission at the time of presentation in first episode psychosis.

BACKGROUND: Individuals presenting with first episode psychosis (FEP) constitute a population with high admission rates. Across psychiatric services, community based treatment is aimed for where appropriate. Therefore, further knowledge on predictors of admission is required. PURPOSE: The objectives were to: (i) determine the proportion of individuals with FEP admitted at time of presentation (voluntarily and involuntarily) (ii) identify associated demographic and clinical factors. METHODS: This study included all young people (aged 15-24) who presented with FEP to the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia from 01.01.11 to 31.12.16. Binary logistic regression was used to determine unadjusted and adjusted odds ratios. RESULTS: Of 1208 participants, 58.6% were male and the median age was 20 years (I.Q.R.17-22). At time of presentation, 50.2% were admitted. On multivariate analysis, the following factors predicted admission: being a migrant (OR = 1.75, 95% CI [1.17, 2.62]), aggression (OR = 1.42, 95% CI [1.02, 1.99]), and more severe psychotic symptoms. Longer duration of untreated psychosis was associated with lower admission rates. 70.1% of admissions were involuntary (33.7% of the cohort). Risk factors for involuntary admission were consistent with any admission, other than aggression, and with the addition of older age and male sex. CONCLUSION: There remains a high admission rate for FEP, even in an established early intervention service, with severity of psychopathology being the strongest predictive factor. There is an independent association between migrancy and admission. Potential reasons for these findings are discussed, and initiatives to reduce admission rates including (i) interventions to prevent admission and (ii) alternative care pathways.

The Australian Early Psychosis Collaborative Consortium (AEPCC): Improving Clinical Care in Early Psychosis.

OBJECTIVES: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical research infrastructure is urgently required to enable the sector to deliver the highest quality care and expand and translate evidence more quickly and efficiently. This paper describes the establishment of the Australian Early Psychosis Collaborative Consortium (AEPCC) that aims to achieve this. CONCLUSION: AEPCC is the first of its kind in Australia (and internationally). It will deliver the required clinical research infrastructure through the implementation of a clinical quality registry, clinical trials and translation network, and lived experience network. AEPCC will provide a critical resource to better understand the state of early psychosis care, and trial new interventions on a scale that has not previously been possible in Australia.

Pathways to care for first-generation migrants with first episode psychosis in northwestern metropolitan Melbourne.

OBJECTIVE: Understanding the pathways to care for migrants experiencing a first episode of psychosis is important, as they are more likely to experience longer delays to treatment and negative experiences, such as involuntary treatment. Despite the increased risk of developing a psychotic illness and barriers associated with pathways to care, there are limited studies exploring pathways to care in migrants in Australia. This study seeks to examine pathways to care for young people with a first episode of psychosis to a publicly funded youth mental health service. METHODS: This study included all young people aged 15-24 years who presented with a first episode of psychosis to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 February 2011 and 31 December 2016. Referral sources and place of birth were recorded at the time of presentation. The severity of psychotic symptoms was rated at baseline. RESULTS: A total of 1220 young people presented with a first episode of psychosis during the study period, including 293 (24.5%) first-generation migrants. First-generation migrants with a first episode of psychosis were more likely to be admitted to hospital than Australian-born youth (odds ratio = 1.67, 95% confidence interval = [1.27, 2.18], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.41, 95% confidence interval = [1.07, 1.88], p = 0.016) and clinical factors (adjusted odds ratio = 1.38,95% confidence interval = [1.01, 1.89], p = 0.044). First-generation migrants were also more likely to have an involuntary admission (odds ratio = 1.67, 95% confidence interval = [1.26, 2.21], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.42, 95% confidence interval = [1.05, 1.91], p = 0.022) and clinical factors (adjusted odds ratio = 1.50, 95% confidence interval = [1.08, 2.09], p = 0.017). Migrants had more severe delusions (p = 0.005), bizarre behavior (p < 0.001) and positive formal thought disorder (p = 0.003) at the time of presentation. Migrants were also more likely to attend the emergency department during their presentation with first episode of psychosis (odds ratio = 1.76, 95% confidence interval = [1.31, 2.36], p < 0.001). CONCLUSION: First-generation migrants who develop a psychotic disorder are at greater risk of experiencing negative pathways to care than the Australian-born population. Further research is needed to identify the factors that lead to migrants being involuntarily admitted to hospital for first episode of psychosis.

The incidence and admission rate for first-episode psychosis in young people before and during the COVID-19 pandemic in Melbourne, Australia.

OBJECTIVE: The COVID-19 pandemic has had a profound effect on global mental health, with one-third of infected individuals developing a psychiatric or neurological disorder 6 months after infection. The risk of infection and the associated restrictions introduced to reduce the spread of the virus have also impacted help-seeking behaviours. Therefore, this study aimed to determine whether there was a difference during the COVID-19 pandemic in the treated incidence of psychotic disorders and rates of admission to hospital for psychosis (including involuntary admission). METHODS: Incident cases of first-episode psychosis in young people, aged 15 to 24, at an early intervention service in Melbourne from an 8-month period before the pandemic were compared with rates during the pandemic. Hospital admission rates for these periods were also compared. RESULTS: Before the pandemic, the annual incidence of first-episode psychosis was 104.5 cases per 100,000 at-risk population, and during the pandemic it was 121.9 (incidence rate ratio = 1.14, 95% confidence interval = [0.92, 1.42], p = 0.24). Immediately after the implementation of restrictions, there was a non-significant reduction in the treated incidence (incidence rate ratio = 0.80, 95% confidence interval = [0.58, 1.09]), which was followed by a significant increase in the treated incidence in later months (incidence rate ratio = 1.94, 95% confidence interval = [1.52, 2.49]; incidence rate ratio = 1.64, 95% confidence interval = [1.25, 2.16]). Before the pandemic, 37.3% of young people with first-episode psychosis were admitted to hospital, compared to 61.7% during the pandemic (odds ratio = 2.71, 95% confidence interval = [1.73, 4.24]). Concerning the legal status of the admissions, before the pandemic, 27.3% were admitted involuntarily to hospital, compared to 42.5% during the pandemic (odds ratio = 1.97, 95% confidence interval = [1.23, 3.14]). CONCLUSION: There was a mild increase, which did not reach statistical significance, in the overall incidence of first-episode psychosis; however, the pattern of presentations changed significantly, with nearly twice as many cases presenting in the later months of the restrictions. There was a significant increase in both voluntary and involuntary admissions, and the possible explanations for these findings are discussed.

What impact does illness severity have on the sexual health of young people affected by mental health disorders? A comparison of inpatients and outpatients.

OBJECTIVE: Young people affected by mental health disorders have greater sexual health needs compared to their peers. Less is known about this need across illness severity. METHOD: A cross-sectional survey of the sexual health of those attending outpatients or inpatients within a youth mental health service was conducted. Statistical differences between groups were explored. RESULTS: One hundred and seven young people (18-25 years) participated and of these, 37.7% were inpatients who had more severe psychiatric symptoms than outpatients. While inpatients were as likely to be sexually active as outpatients, they were significantly less likely to have a regular sexual partner (25% vs 64.5%). Additionally, they used amphetamines more frequently during sex (28.6% vs 5.8%). Sexual dysfunction was experienced by 55.6% of inpatients and 37.9% of outpatients. CONCLUSIONS: High-risk sexual behaviours and sexual dysfunction were highly prevalent in both groups. For some behaviours and dysfunction, this prevalence was higher in the inpatient population. Holistic clinical services that address the mental, physical and sexual health needs of consumers are needed both within inpatient and outpatient settings.

Risk of psychotic disorders in migrants to Australia.

BACKGROUND: Certain migrant groups are at an increased risk of psychotic disorders compared to the native-born population; however, research to date has mainly been conducted in Europe. Less is known about whether migrants to other countries, with different histories and patterns of migration, such as Australia, are at an increased risk for developing a psychotic disorder. We tested this for first-generation migrants in Melbourne, Victoria. METHODS: This study included all young people aged 15-24 years, residing in a geographically-defined catchment area of north western Melbourne who presented with a first episode of psychosis (FEP) to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 January 2011 and 31 December 2016. Data pertaining to the at-risk population were obtained from the Australian 2011 Census and incidence rate ratios were calculated and adjusted for age, sex and social deprivation. RESULTS: In total, 1220 young people presented with an FEP during the 6-year study period, of whom 24.5% were first-generation migrants. We found an increased risk for developing psychotic disorder in migrants from the following regions: Central and West Africa (adjusted incidence rate ratio [aIRR] = 3.53, 95% CI 1.58-7.92), Southern and Eastern Africa (aIRR = 3.06, 95% CI 1.99-4.70) and North Africa (aIRR = 5.03, 95% CI 3.26-7.76). Migrants from maritime South East Asia (aIRR = 0.39, 95% CI 0.23-0.65), China (aIRR = 0.25, 95% CI 0.13-0.48) and Southern Asia (aIRR = 0.44, 95% CI 0.26-0.76) had a decreased risk for developing a psychotic disorder. CONCLUSION: This clear health inequality needs to be addressed by sufficient funding and accessible mental health services for more vulnerable groups. Further research is needed to determine why migrants have an increased risk for developing psychotic disorders.

Symptomatic, functional and service utilization outcomes of migrants with a first episode of psychosis.

BACKGROUND: Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement). METHODS: Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms. RESULTS: A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up. DISCUSSION: The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.

The associations between migrant status and ethnicity and the identification of individuals at ultra-high risk for psychosis and transition to psychosis: a systematic review.

PURPOSE: Migrant and ethnic minority populations exhibit a higher incidence of psychotic disorders. The Ultra-High Risk for psychosis (UHR) paradigm provides an opportunity to explore the stage at which such factors influence the development of psychosis. In this systematic review, we collate and appraise the literature on the association between ethnicity and migrant status and the rate of identification of individuals at UHR, as well as their rate of transition to psychosis. METHODS: We conducted a systematic review in the Ovid Medline, PsychINFO, Pubmed, CINAHL and EMBASE databases according to PRISMA guidelines. We included studies written in English that included an UHR cohort, provided a measure of ethnicity or migrant status, and examined the incidence, rate, or risk of UHR identification or transition to psychosis. RESULTS: Of 2182 unique articles identified, seven fulfilled the criteria. One study found overrepresentation of UHR individuals from black ethnic groups, while another found underrepresentation. Two studies found increased rates of transition among certain ethnic groups and a further two found no association. Regarding migrant status, one study found that first-generation migrants were underrepresented in an UHR sample. Lastly, a lower transition rate in migrant populations was identified in one study, while two found no association. CONCLUSION: Rates of UHR identification and transition according to ethnic and migrant status were inconsistent and insufficient to conclusively explain higher incidences of psychotic disorders among these groups. We discuss the clinical implications and avenues for future research, which is required to clarify the nature of the associations.

The association between migrant status and transition in an ultra-high risk for psychosis population.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

Early intervention in psychosis: health economic evaluation using the net benefit approach in a real-world setting.

BACKGROUND: Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice. AIMS: To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions. METHOD: Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18-65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment. RESULTS: From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI - €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI -€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI - €2075 to €41 931). CONCLUSIONS: Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.

Terminology and assessment tools of psychosis: A systematic narrative review.

AIM: Phenomena within the psychosis continuum that varies in frequency/duration/intensity have been increasingly identified. Different terms describe these phenomena, however there is no standardization within the terminology. This review evaluated the definitions and assessment tools of seven terms - (i) 'psychotic experiences'; (ii) 'psychotic-like experiences'; (iii) 'psychotic-like symptoms'; (iv) 'attenuated psychotic symptoms'; (v) 'prodromal psychotic symptoms'; (vi) 'psychotic symptomatology'; and (vii) 'psychotic symptoms'. METHODS: EMBASE, MEDLINE, and CINAHL were searched during February-March 2019. Inclusion criteria included 1989-2019, full text, human, and English. Papers with no explicit definition or assessment tool, duplicates, conference abstracts, systematic reviews, meta-analyses, or no access were excluded. RESULTS: A total of 2238 papers were identified and of these, 627 were included. Definitions and assessment tools varied, but some trends were found. Psychotic experiences and psychotic-like experiences were transient and mild, found in the general population and those at-risk. Psychotic-like symptoms were subthreshold and among at-risk populations and non-psychotic mental disorders. Attenuated psychotic symptoms were subthreshold but associated with distress, risk, and help-seeking. Prodromal psychotic symptoms referred to the prodrome of psychotic disorders. Psychotic symptomatology included delusions and hallucinations within psychotic disorders. Psychotic symptoms was the broadest term, encompassing a range of populations but most commonly involving hallucinations, delusions, thought disorder, and disorganization. DISCUSSION: A model for conceptualizing the required terms is proposed and future directions needed to advance this field of research are discussed.

Defining disengagement from mental health services for individuals experiencing first episode psychosis: a systematic review.

BACKGROUND: Individuals affected by psychotic disorders frequently disengage from mental health services, although reports of this rate in the literature have ranged from 6 to 60%. One of the potential explanations for the large variation is that studies have adopted different definitions. Without a universal definition it is challenging to compare rates and factors leading to disengagement across studies. This systematic review aims to identify and compare how disengagement from psychosis services has been defined, measured and operationalised in the literature to date. METHODS: A systemic literature search of the PubMed, PsycINFO and CINAHL databases was completed following the PRISMA guidelines for systematic reviews. RESULTS: 1506 Studies were identified, of which 30 were eligible to be included. It was found that disengagement was operationalized as either a categorical or continuous variable across studies, with 18 studies classifying it as a categorical, binary variable. Only four studies applied a time period over which disengagement was said to occur, and only four studies used an instrument to measure or predict disengagement. Few studies considered similar factors in their definition, when this occurred it was because the papers came from the same research group. DISCUSSION: To truly understand the phenomenon of disengagement, studies need to have a comparable outcome variable. The need for consensus on a gold standard definition of disengagement that considers the full breadth of its complexity remains. A potential process for establishing a definition that includes set parameters, agreed upon terminology and time periods of assessment is discussed.

The rates and determinants of disengagement and subsequent re-engagement in young people with first-episode psychosis.

BACKGROUND: A core component of treatment provided by early intervention for psychosis (EI) services is ensuring individuals remain successfully engaged with the service. This ensures they can receive the care they may need at this critical early stage of illness. Unfortunately, rates of disengagement are high in individuals with a first episode of psychosis (FEP), representing a major barrier to effective treatment. This study aimed to ascertain the rates and determinants of disengagement and subsequent re-engagement of young people with FEP in a well-established EI service in Melbourne, Australia. METHOD: This cohort study involved all young people, aged 15-24, who presented to the Early Psychosis Prevention and Intervention Centre (EPPIC) service with FEP between 1st January 2011 and 1st September 2014. Data were collected retrospectively from clinical files and electronic records. Cox regression analysis was used to identify determinants of disengagement and re-engagement. RESULTS: A total of 707 young people presented with FEP during the study period, of which complete data were available for 700. Over half of the cohort (56.3%, N = 394) disengaged at least once during their treatment period, however, the majority of these individuals (85.5%, N = 337) subsequently re-engaged following the initial episode of disengagement. Of those who disengaged from the service, 54 never re-engaged, representing 7.6% of the total cohort. Not being in employment, education or training, not having a family history of psychosis in second degree relatives and using cannabis were found to be significant predictors of disengagement. No significant predictors of re-engagement were identified. CONCLUSION: In this study, the rate of disengagement in young people with first-episode psychosis was higher than found previously. Encouragingly, rates of re-engagement were also high. The concept of disengagement from services might be more complex than previously thought with individuals disengaging and re-engaging a number of times during their episode of care. What prompts individuals to re-engage with services needs to be better understood.