Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis.

Background: Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. Method: We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Results: Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Conclusion: Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

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.

Identifying and managing treatment resistance early with the integration of a clozapine clinic within an early intervention for psychosis service.

BACKGROUND: Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. AIMS: This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to initiation of clozapine, the number of trials of different antipsychotic medications prior to clozapine, community initiation and discontinuation rates. METHODS: A clozapine clinic was established in the Early Psychosis Prevention and Intervention Centre in Melbourne. This was a pre- and post-evaluation study design. The 'clozapine clinic' cohort included those who commenced on clozapine from 01 January 2016 to 30 June 2018. RESULTS: Prior to the clozapine clinic, 24 young people commenced clozapine over the 30-month period compared to 36 in the clozapine clinic cohort (RR = 1.30, 95% CI: 0.75-2.28, p = .32). In the pre-clozapine clinic cohort, 4.6% of all those with a first episode of psychosis were commenced on clozapine compared to 6% in the clozapine clinic cohort. Prior to the clozapine clinic, the median time to the commencement of clozapine was 72 weeks (IQR: 38, 87), compared to 53.5 weeks (IQR: 38, 81.5) in the clozapine clinic (Z = -0.86, p = .393). The mean number of different antipsychotic medications prior to commencing clozapine remained stable at 3.2 (SD ± 1.1) in both cohorts (t = -0.20, p = .841). There was a lower rate of discontinuation in the clozapine clinic (43.5% vs. 14.7%, HR = 0.30, 95% CI: 0.09-0.98, p = .046). CONCLUSIONS: While this study was underpowered and there are limitations to the naturalistic study design, the findings lend support to the integration of a clozapine clinic within early intervention for psychosis services.

Response rates to sequential trials of antipsychotic medications according to algorithms or treatment guidelines in psychotic disorders. A systematic review and meta-analysis.

BACKGROUND: There is a relative lack of research evaluating the outcomes when treatment guidelines or algorithms for psychotic disorders are followed. This systematic review and meta-analysis determined the response rates to antipsychotic medications at different stages of these algorithms and whether these response rates differ in first episode cohorts. METHODS: Data sources: A systematic search strategy was conducted across four databases PubMed, EMBASE, PsycINFO (Ovid) and CINAHL. Studies that had sequential trials of different antipsychotic medications were included. A meta-analysis of proportions was performed using random effects models and sub-group analysis in first episode psychosis studies. RESULTS: Of the 4078 unique articles screened, fourteen articles, from nine unique studies, were eligible and included 2522 participants. The proportion who experienced a response to any antipsychotic in the first stage of an algorithm was 0.53 (95 % C.I.:0.38,0.68) and this decreased to 0.26 (95 % C.I.:0.15,0.39) in the second stage. When clozapine was used in the third stage, the proportion that achieved a response was 0.43 (95 % C.I. 0.19, 0.69) compared to 0.26 (95 % C.I.:0.05,0.54) if a different antipsychotic was used. Four studies included 907 participants with a first episode of psychosis and the proportions that achieved a response were: 1st stage: 0.63 (95 % C.I.: 0.45, 0.79); 2nd stage: 0.34 (95 % C.I.:0.16,0.55); clozapine 3rd stage: 0.45 (95 % C.I.:0.0,0.97), different antipsychotic 3rd stage: 0.15 (95 % C.I.,0.01,0.37). DISCUSSION: These findings support the recommendation to have a trial of clozapine after two other antipsychotic medications have been found to be ineffective.

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.

The prevalence of vitamin D deficiency and associated factors in first-episode psychosis.

AIM: Vitamin D deficiency is prevalent in people with established psychotic disorders, but less is known about vitamin D levels in people with first-episode psychosis (FEP). This study aimed to determine the prevalence of vitamin D deficiency in people with FEP and identify the factors associated with vitamin D status. METHODS: This was a prospective cohort study nested within a randomized controlled trial, which included 37 young people with an FEP with minimal antipsychotic medication exposure. RESULTS: Twenty-four percent of participants were vitamin D deficient, and a further 30% were vitamin D insufficient. There was no association between vitamin D and demographic factors or clinical symptoms (positive, negative, general psychopathology and depressive symptoms) or cognition and functioning. However, vitamin D levels were associated with season of sampling. CONCLUSIONS: Considering the longer-term adverse effects associated with vitamin D deficiency, it is warranted to ensure this clinical population receives supplementation if indicated.

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.

Social disadvantage in early psychosis and its effect on clinical presentation and service access, engagement and use.

Incidence of psychosis varies geographically due to factors such as social disadvantage. Whether this influences the clinical presentation and/or engagement of those experiencing psychosis remains relatively understudied. This study analysed data from young people across Australia accessing ultra-high risk (UHR) or first episode psychosis (FEP) services delivered through the headspace Early Psychosis (hEP) program between June 2017 and March 2021. The cohort was categorised into low, middle, and high tertiles of social disadvantage using the Index of Relative Socioeconomic Disadvantage (IRSD). Data from 3089 participants aged 15-25 were included (1515 UHR, 1574 FEP). The low and middle tertiles for both cohorts had greater percentages of those not in education or employment (NEET), with First Nations or culturally and linguistically diverse backgrounds. Clinical presentations to services were similar across all tertiles in both cohorts, however, functioning at presentation varied significantly within the FEP cohort. Significantly lower numbers of direct services were provided in the low tertile of both cohorts, with significantly poorer engagement in the initial three-months also occurring for these young people. This variation in early psychosis service patterns associated with geographical variation in social deprivation demonstrates the need for further research and fine tuning of national early psychosis services.

Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis.

Importance: Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. Objective: To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads. Design, Settings, and Participants: This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023. Main Outcomes and Measures: Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated and empirical spatial patterns of GMV alterations were used to quantify model performance. Results: Of 534 included individuals, 354 (66.3%) were men, and the mean (SD) age was 28.4 (7.4) years. In both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately estimated by coordinated deformation models constrained by structural, rather than functional, network architecture (r range, >0.46 to <0.57; P < .01). The same model also robustly estimated longitudinal volume changes related to illness (r ≥ 0.52; P < .001) and antipsychotic exposure (r ≥ 0.50; P < .004). Network diffusion modeling consistently identified, across all 4 data sets, the anterior hippocampus as a putative epicenter of pathological spread in psychosis. Epicenters of longitudinal GMV loss were apparent in posterior cortex early in the illness and shifted to the prefrontal cortex with illness progression. Conclusion and Relevance: These findings highlight a central role for white matter fibers as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicenter of early brain pathology from which dysfunction may spread to affect connected areas.

Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial.

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460).

Outcomes 1 year after a first episode of psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is a robust risk factor for developing a psychotic disorder, yet there is a paucity of research on the outcomes of migrants who develop a psychotic disorder. Identifying sub-groups within FEP cohorts who have a poorer outcome, could assist in the development and delivery of more targeted interventions. AIMS: There is a paucity of research on the outcomes of migrants who develop a psychotic disorder. This study aimed to evaluate a broad range of outcomes for those with a FEP who migrated to the Republic of Ireland, including: (i) symptomatic; (ii) functional; (iii) hospitalisation and (iv) engagement with psychosocial services. METHODS: All individuals with a FEP aged 18 to 65 who presented between 01.02.2006 and 01.07.2014 were included. Structured and validated instruments were used to measure positive, negative, depressive symptoms and insight. RESULTS: Of the 573 individuals with a FEP, 22.3% were first-generation migrants and 63.4% (n = 363) were followed up at 1 year. At this time, 72.4% of migrants were in remission of positive psychotic symptoms compared to 78.5% of the Irish born (OR = 0.84, 95% CI [0.50-1.41], p = .51). In relation to negative symptoms, 60.5% of migrants were in remission compared to 67.2% of the Irish born (OR = 0.75, 95% CI [0.44-1.27], p = .283). There was no difference in the severity of positive, negative or depressive symptoms between groups and there was a trend for the Irish born to have better insight (p = .056). The functional outcomes were similar across groups. One third of migrants were admitted to hospital compared to 28.7% of the Irish born (OR = 1.24, 95% CI [0.73-2.13], p = .426). Just over half of both groups attended CBT and 46.2% of caregivers for migrants attended the psychoeducation programme, compared to 39.7% for the Irish born (OR = 1.30, 95% CI [0.79-2.16], p = .306). CONCLUSIONS: These findings demonstrate that migrants have broadly similar outcomes to the native-born populations, however there is still considerable scope for the outcomes for all individuals affected by psychotic disorders to be improved.

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.

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.

Gradients of striatal function in antipsychotic-free first-episode psychosis and schizotypy.

Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e., modes) of functional organization. Here, we investigated two of these functional connectivity modes, previously associated with variations in the topographic patterning of cortico-striatal connectivity (first-order gradient), and dopaminergic innervation of the striatum (second-order gradient), and assessed continuities in striatal function from subclinical to clinical domains. We applied connectopic mapping to resting-state fMRI data to obtain the first-order and second-order striatal connectivity modes in two distinct samples: (1) 56 antipsychotic-free patients (26 females) with first-episode psychosis (FEP) and 27 healthy controls (17 females); and (2) a community-based cohort of 377 healthy individuals (213 females) comprehensively assessed for subclinical PLEs and schizotypy. The first-order "cortico-striatal" and second-order "dopaminergic" connectivity gradients were significantly different in FEP patients compared to controls bilaterally. In the independent sample of healthy individuals, variations in the left first-order "cortico-striatal" connectivity gradient were associated with inter-individual differences in a factor capturing general schizotypy and PLE severity. The presumed cortico-striatal connectivity gradient was implicated in both subclinical and clinical cohorts, suggesting that variations in its organization may represent a neurobiological trait marker across the psychosis continuum. Disruption of the presumed dopaminergic gradient was only noticeable in patients, suggesting that neurotransmitter dysfunction may be more apparent to clinical illness.

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.

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.