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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.

BACKGROUND: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients three months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTS: Individuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE=.03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r=.44;pFWE=.041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes. CONCLUSIONS: Brain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.

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.

INTRODUCTION: Borderline personality disorder (BPD) is common among people diagnosed with first episode of psychosis (FEP), but is often under-recognized and under-researched. This study aimed to determine: (i) the prevalence of borderline personality pathology (subthreshold features and categorical disorder) in a FEP cohort (termed FEP + BPP); (ii) demographic and clinical factors associated with FEP + BPP; (iii) the symptomatic and functional outcomes. METHODS: This study was conducted within the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen over the 30-month period between 2014 and 2016. BPP was evaluated by using the Structured Clinical Interview for DSM-IV Axis II Personality Questionnaire BPD criteria. RESULTS: In a cohort of 457 young people with a FEP (mean age 19.5 years, 56% male), 18.4% had borderline personality pathology (BPP). Compared with FEP alone, young people with FEP + BPP were more likely to be female, younger, Australian-born. In addition, young people with FEP + BPP were more likely to be diagnosed with Psychosis NOS, present with more severe hallucinations, and have alcohol abuse. Young people with FEP + BPP had more relationship difficulties at presentation and they were more likely to suffer of depression and to engage in self-harm throughout the follow-up. In relation to outcome, FEP + BPP was not associated with different rates of remission or relapse, however they were less likely to be admitted to hospital at presentation or involuntarily during their episode of care. CONCLUSION: BPP is a common occurrence in psychotic disorders and is associated with more severe hallucinations and depression with higher risks of self-harm. Specific interventions need to be developed.

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

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.

AIM: The sexual health of adults with schizophrenia is poorer than the general population; however, less is known about young people experiencing a first episode of psychosis (FEP). The aim of this study was to explore the high-risk sexual behaviours and sexual well-being indicators of a cohort of young people with FEP. METHODS: Data collected from young people (15-24 years) with FEP attending the EPPIC service in Melbourne and participating in a physical health intervention were analysed. Baseline trial data collected on sexual health and high-risk behaviours, psychiatric symptomology, functioning, and substance use are presented by gender. Associations between symptomology and functioning with sexual behaviour are explored. RESULTS: A total of 69 young people were included in this study; mean age was 19.6 years (SD±2.8), 53.6% were male, 59.6% identified as heterosexual, and 21.7% were currently in a relationship. Within the cohort, 78.3% had ever been sexually active. Of these, 44.2% consistently used a condom at last sex act and 35.7% used barrier contraception consistently, 22.5% had previously been pregnant, and 18.6% had tested positive for an STI. Finally, young people were more likely to have been sexually active if they were currently using substances. CONCLUSIONS: These findings suggest that high rates of high-risk sexual behaviour remain an issue for young people experiencing a first episode of psychosis. Promoting sexual well-being and communication skills between sexual partners should be targeted to ensure that high-risk sexual health outcomes are mitigated as early as possible.

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.

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 signaling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia patients 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 fMRI and positron emission tomography. 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 signaling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors

AIMS: The COVID-19 pandemic forced the rapid move of mental health services to being delivered online. This included the delivery of a psychosocial recovery program (PRP) delivered in youth mental health services in Melbourne, Australia which consists of groups that address functional recovery. At the time, there was limited evidence about how this switch in service provision would be received by service users or what impact the pandemic was having on their mental health. METHODS: Young people engaged with the PRP between March and May 2020 were sent a link to complete an online survey that was co-developed by young people and clinicians. Attendance data at groups were extracted as a proximal measure of feasibility and acceptability. RESULTS: A total of 44 young people undertook the survey with the domains of wellbeing most impacted by lockdown being work/study, motivation and social connection. Groups provided online were generally well attended during lockdown, particularly those that had a focus on therapeutic content. Young people indicated little preference for continuing to attend groups run purely online when restrictions eased, with many expressing a preference for these to be offered face-to-face or in a combined format. CONCLUSIONS: These findings suggest that implementation of online psychosocial groups during periods of lockdown is both feasible and acceptable. Whilst young people found accessing groups online to be of benefit at the time, they felt that continued substitution of face-to-face groups would not necessarily be preferable and clinical services should consider these preferences in their long-term service delivery.

BACKGROUND: Anxiety is common in young people with early psychosis and treatment options for this co-morbidity remain limited. Yoga is a promising adjunct intervention that has been shown to reduce anxiety for adults with schizophrenia, therefore this pilot study evaluated the acceptability and potential effectiveness of yoga for anxiety in early psychosis. METHODS: A prospective single arm pilot study of a yoga intervention was conducted within an Early Intervention for psychosis service. Rates of attendance, as well as symptoms of anxiety pre and post yoga session were measured. RESULTS: A total of 14 young people participated in the study and over 70% attended half or more of the yoga sessions offered. Significant transient reduction in state anxiety after a single session of yoga was observed (p < 0.01). CONCLUSIONS: Yoga was found to be an acceptable and potentially effective adjunctive treatment for anxiety in early psychosis and the results warrant further clinical trials.

BACKGROUND: No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group. METHODS: Three-arm randomized controlled trial of 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. The study includes a 6-week lead-in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At-Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6 months post baseline to evaluate if treatment effects are sustained. CONCLUSION: This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder.

INTRODUCTION: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to care and clinical presentation of migrants attending an At-Risk Mental State clinic. METHODOLOGY: This study included consecutive UHR cases identified over five years attending the PACE clinic in Melbourne, Australia. The CAARMS was used to assess the severity of attenuated psychotic symptoms. Depressive symptoms and functioning were measured using the PHQ9 and GAF, respectively. RESULTS: Over the five-year study period, 461 UHR young people attended the PACE clinic and 13.7% were first-generation migrants. A higher proportion of migrants were referred by community health services, such as general practitioners, than other referral sources. Australian born UHR patients were more likely to be referred via another mental health service. There was no difference in the type or severity of attenuated psychotic symptoms based on migrant status, except that there was a trend for young African migrants to have more severe unusual thought content. Depressive symptoms and poor functioning were highly prevalent across the total cohort and did not differ according to migrant status. CONCLUSIONS: It is not yet understood why migrants are under-represented in UHR cohorts. Qualitative interviews of migrants, who are not typically identified in the UHR stage, could provide insights into the barriers to accessing care.

BACKGROUND: Factors that contribute to the early mortality observed in psychotic disorders, specifically obesity, smoking and sedentary behaviour, occur early in the disorder. AIMS: We aimed to determine whether the integration of a physical health nurse in the care of young people with first-episode psychosis could prevent clinically significant weight gain (≥7% body weight). Secondary outcomes included rates of smoking, metabolic syndrome and sedentary behaviour. METHOD: In this single-blind, randomised controlled trial, participants who had received under 4 weeks of antipsychotic medication were randomly allocated to either the intervention (addition of a physical health nurse to their care) or treatment as usual (TAU) for 12 weeks. RESULTS: Of the 77 participants, there were follow-up data for 86.8% (n = 33) of the intervention group and 82.1% (n = 32) of the TAU group. After 12 weeks, 27.3% of the intervention group experienced clinically significant weight gain compared with 34.4% of the TAU group (odds ratio 0.72, 95% CI 0.25-2.06, P = 0.54). After 6 months, 40.7% of the intervention group gained clinically significant weight compared with 44.1% of the TAU group (P = 0.79). There was no difference in mean change in weight between groups after 12 weeks (2.6 kg v. 2.9 kg, P = 0.87) or 6 months (3.6 kg v. 4.3 kg, P = 0.64). There were no differences in the rates of tobacco smoking cessation, prevalence of metabolic syndrome or physical activity levels. CONCLUSIONS: This intervention failed to prevent the metabolic complications that are highly prevalent in psychotic disorders in the short to medium term, indicating that more intensive interventions are required.

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 < 0.0

OBJECTIVE: Early intervention for psychosis services have been established worldwide and consist of specialist services for those with the At-Risk Mental State (ARMS) and a first episode of psychosis (FEP). This systematic review identified the literature on the outcomes of people who initially presented via an ARMS clinic and later transitioned to a psychotic disorder (UHR-T), compared to those who presented directly to an EI service with a FEP (FEP-D). The outcomes examined were (i) symptomatic (ii) functional, (iii) morbidity and mortality (including physical health) and (iv) service-usage. METHOD: A systematic search strategy was employed using three databases: MEDLINE, PsycInfo, and EMBASE. Studies published in English and that compared any of the above outcomes in a cohort of people with a first episode of psychosis who initially presented via an ARMS clinic to those who presented directly to a FEP service were included. Meta-analysis was performed for any outcome data from at least two studies. RESULTS: A total of 988 unique articles were identified and of these, three studies fulfilled the inclusion criteria and these included a total of 78 UHR-T and 253 FEP-D individuals. In the one study examining remission rates, there was no difference observed after one year in the UHR-T and FEP-D groups. In the one study that examined neurocognition, no differences were observed in any of the neurocognitive domains between groups after one year. Two studies examined psychiatric admission rates within one year and one of these found that UHR-T individuals were less likely to have any psychiatric admission (46% vs 68%) and admissions were less likely to be involuntary (30% vs 74%), while the other study found no difference in admission rates. In the meta-analysis, UHR-T individuals had lower odds for any psychiatric hospital admission within one year compared to FEP-D individuals (OR = 0.54, 95% C.I. 0.32 - 0.94, p = .03). No studies examined functional outcomes or morta

Background: Aberrant dopaminergic activity within fronto-striato-thalamic (FST) circuits is thought to contribute to psychosis onset. It remains unclear whether primary abnormality arises from bottom-up subcortical signaling or impaired top-down cortical regulation. We mapped causal interactions (effective connectivity) of dorsal and ventral FST circuits across the psychosis continuum and identified connections associated with striatal dopamine synthesis. Method(s): Spectral dynamic causal modelling (DCM) for resting-state functional magnetic resonance imaging (fMRI) modelled FST effective connectivity in: (1) 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls; (2) 36 established schizophrenia (SCZ) patients and 100 controls; and (3) 33 healthy individuals assessed for psychosis-like experiences (PLEs) with concurrent [18F]DOPA positron emission tomography. DCM estimated FST connectivity in patients and their respective controls, associations with symptom severity in all cohorts, and with striatal [18F]DOPA uptake in the PLE group. Result(s): Patients commonly showed midbrain disinhibition and reduced top-down influence of thalamus on nucleus accumbens. Cortical dysfunction was only apparent in the SCZ group. Positive symptoms were primarily associated with bottom-up connectivity in FEP and a mixture of bottom-up and top-down connectivity in SCZ and PLE groups, with disinhibition of ventromedial prefrontal cortex and extrinsic connectivity of the midbrain implicated across all cohorts. Thalamic and midbrain connectivity were associated with striatal [18F]DOPA uptake. Conclusion(s): We identified a primary role for subcortical dysconnectivity in psychosis, with cortical dysfunction emerging in established illness. Effective connectivity of the midbrain and thalamus are robustly linked to positive symptom severity and striatal dopamine synthesis capacity, suggesting a central role in the emergence of psychotic symptoms. Supported By: Nationa

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.

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.

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.

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.

IMPORTANCE: Altered functional connectivity (FC) is a common finding in resting-state functional magnetic resonance imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotic treatment influences these disturbances, remains unknown. OBJECTIVE: To investigate longitudinal FC changes in antipsychotic-naive and antipsychotic-treated patients with first-episode psychosis (FEP). DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a triple-blind, randomized clinical trial was conducted over a 5-year recruitment period between April 2008 and December 2016 with 59 antipsychotic-naive patients with FEP receiving either a second-generation antipsychotic or a placebo pill over a treatment period of 6 months. Participants were required to have low suicidality and aggression, to have a duration of untreated psychosis of less than 6 months, and to be living in stable accommodations with social support. Both FEP groups received intensive psychosocial therapy. A healthy control group was also recruited. Participants completed rs-fMRI scans at baseline, 3 months, and 12 months. Data were analyzed from May 2019 to August 2020. INTERVENTIONS: Resting-state functional MRI was used to probe brain FC. Patients received either a second-generation antipsychotic or a matched placebo tablet. Both patient groups received a manualized psychosocial intervention. MAIN OUTCOMES AND MEASURES: The primary outcomes of this analysis were to investigate (1) FC differences between patients and controls at baseline; (2) FC changes in medicated and unmedicated patients between baseline and 3 months; and (3) associations between longitudinal FC changes and clinical outcomes. An additional aim was to investigate long-term FC changes at 12 months after baseline. These outcomes were not preregistered. RESULTS: Data were analyzed for 59 patients (antipsychotic medication plus psychosocial treatment: 28 [47.5%]; mean [SD] a

Background: Ensuring young people experience good sexual health is a key public health concern, yet some vulnerable groups of young people remain at higher risk of poor sexual health. These individuals require additional support to achieve good sexual health but the best way to provide this remains needs to be better understood. Methods: We searched for randomised controlled trials of behavioural and psychosocial interventions aimed at promoting sexual health in high-risk young populations. Outcomes of interest were indicators of sexual health (e.g., condom use, attitudes to contraception, knowledge of risk). Participants were under 25 years old and in one of the following high-risk groups: alcohol and other drug use; ethnic minority; homeless; justice-involved; LGBTQI+; mental ill-health; or out-of-home care. Results: Twenty-eight papers from 26 trials met our inclusion criteria, with all but one conducted in North America. Condom use was the most frequently reported outcome measure along with knowledge and attitudes towards sexual health but considerable differences in measures used made comparisons across studies difficult. Change in knowledge and attitudes did not consistently result in long-term change in behaviours. Conclusions: There remains a dearth of research undertaken outside of North America across all high-risk groups of young people. Future interventions should address sexual health more broadly than just the absence of negative biological outcomes, with LGBTQI+, homeless and mental ill-health populations targeted for such work. An international consensus on outcome measures would support the research field going forward, making future meta-analyses possible.

In the last three decades, early intervention for psychosis (EIP) services have been established worldwide and have resulted in superior symptomatic and functional outcomes for people affected by psychotic disorders. These improved outcomes are a result of reducing delays to treatment and the provision of specialised, holistic interventions. The COVID-19 pandemic poses significant challenges to the delivery of these services, such as undetected cases or long delays to treatment. Furthermore, the COVID-19 pandemic will likely increase the mental health needs of communities, including the incidence of psychotic disorders. In this perspective piece, we provide suggestions as to how EIP services can adapt within this environment, such as utilising novel technologies. Finally, we argue that despite the economic consequences of the pandemic, the funding for mental health services, including EI services, should be increased in line with the need for these services during and beyond the pandemic.

This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP.

Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down

Background Clinical and functional recovery is usually achieved after treatment for a first episode of psychosis (FEP). Unfortunately, subsequent relapse remains common, occurring within a year for approximately 30% of individuals and within five years for 80%. What makes someone more likely to relapse remains poorly understood. Methods This study is a naturalistic cohort study of young people (15–25 years old) accessing an early intervention in psychosis service in Melbourne, Australia between 1st January 2011 and 31st December 2016. Demographic and clinical predictors of relapse were collected from patient records and analysed using Cox regression analysis. Results A total of 1220 young people presented with a FEP during the study period and 37.7% (N=460) experienced at least one relapse during their episode of care. Over half of all relapses resulted in an admission to hospital. Non-adherence to medication, substance use and psychosocial stressors precipitated relapses. Significant predictors of relapse in this sample were a diagnosis of a schizophrenia spectrum disorder or an affective psychotic disorder, amphetamine use, and substance use during treatment. Discussion These findings suggest that relapse occurs frequently for young people who have experienced FEP. This is one of the first studies to find that amphetamine use increases the risk of relapse. Clinical services, especially in Australasia, need to consider how best to manage this co-morbidity in young people with FEP.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress - with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.

AIM: Young people with psychotic disorders have poorer physical health compared to their healthy peers, a state compounded by the metabolic side-effects of antipsychotic medications. To address this, Orygen Youth Health has introduced physical health services including exercise physiologists and dieticians. These services are typically coordinated by the case manager and doctor. It is not yet known whether a treating team member dedicated to physical health will improve engagement, adherence and outcomes with these services. Hence, the protocol is presented here for a trial to evaluate the effect of including a physical health nurse in the care of young people with first-episode psychosis. METHODS: This will be a single-blind randomized controlled trial that includes 15- to 24-year-olds with first-episode psychosis who have just commenced (within 30 days) antipsychotic medication. The primary outcome will be the event of clinically significant weight gain (≥7% body weight). Participants will be assigned either a physical health nurse in their treating team (in addition to the case manager and doctor) for a 12-week period, or treatment as usual (case manager and doctor). Research assessments will be conducted at baseline, 12 and 26 weeks. Activity trackers worn by participants for the study's duration will measure sleep and physical activity. CONCLUSION: The present study will determine whether a physical health nurse will facilitate participants in attending and engaging in physical health interventions and whether this will be associated with physical health improvements or the prevention of worsening physical health.

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

The COVID-19 outbreak may profoundly impact population mental health because of exposure to substantial psychosocial stress. An increase in incident cases of psychosis may be predicted. Clinical advice on the management of psychosis during the outbreak needs to be based on the best available evidence. We undertook a rapid review of the impact of epidemic and pandemics on psychosis. Fourteen papers met inclusion criteria. Included studies reported incident cases of psychosis in people infected with a virus of a range of 0.9% to 4%. Psychosis diagnosis was associated with viral exposure, treatments used to manage the infection, and psychosocial stress. Clinical management of these patients, where adherence with infection control procedures is paramount, was challenging. Increased vigilance for psychosis symptoms in patients with COVID-19 is warranted. How to support adherence to physical distancing requirements and engagement with services in patients with existing psychosis requires careful consideration. Registration details: https://osf.io/29pm4.

BACKGROUND: Certain migrant groups are more likely to develop a psychotic disorder compared to the native-born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra-high risk for psychosis (UHR) compared to native-born young people and whether migrant status was associated with the risk of transition to a full-threshold psychotic disorder. METHODS: The cohort included all young people aged 15-24 who were identified as UHR at a specialist clinic over a five-year period (2012-16). Australian census data were used to obtain the at-risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. RESULTS: 467 young people were identified as UHR, of which 13.5% (n = 63) were born overseas. First-generation migrants were 2.6-fold less likely to be identified as UHR compared to Australian-born young people (IRR = 0.39, 95% CI [0.30, 0.51], P < 0.001). There was no difference between migrant and native-born young people in their risk of transitioning to a psychotic disorder (HR = 0.90, 95% CI [0.39, 2.08], P = 0.81). CONCLUSIONS: UHR first-generation migrants may be under-accessing mental health services.