Centre for Youth Mental Health - Research Publications
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ItemResearch and practice for ultra-high risk for psychosis: A national survey of early intervention in psychosis services in England(WILEY, 2019-02)BACKGROUND: Evidence from meta-analyses of randomized clinical trials show interventions for young people at ultra-high risk (UHR) of developing psychosis are effective both clinically and economically. While research evidence has begun to be integrated into clinical guidelines, there is a lack of research on the implementation of these guidelines. This paper examines service provision for UHR individuals in accordance with current clinical guidelines within the National Health Service (NHS) in England. METHOD: A self-report online survey was completed by clinical leaders of early intervention in psychosis (EIP) teams (N = 50) within the NHS across England. RESULTS: Of the 50 EIP teams responding (from 30 NHS trusts), 53% reported inclusion of the UHR group in their service mandate, with age range predominantly 14 to 35 years (81%) and service provided for at least 12 months (53%). Provision of services according to NICE clinical guidelines showed 50% of services offered cognitive behavioural therapy (CBT) for psychosis, and 42% offered family intervention. Contrary to guidelines, 50% of services offered antipsychotic medication. Around half of services provided training in assessment by Comprehensive Assessment of At Risk Mental States, psycho-education, CBT for psychosis, family work and treatment for anxiety and depression. CONCLUSIONS: Despite clear evidence for the benefit of early intervention in this population, current provision for UHR within EIP services in England does not match clinical guidelines. While some argue this is due to a lack of allocated funding, it is important to note the similar variable adherence to clinical guidelines in the treatment of people with established schizophrenia.
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ItemPerceptual abnormalities in an ultra-high risk for psychosis population relationship to trauma and co-morbid disorder(WILEY, 2019-04)AIMS: The aims of this study were 3-fold. We wished to investigate whether at baseline entry to an ultra-high risk (UHR) clinic whether: (1) perceptual abnormalities are more prevalent in those young people with co-morbid psychiatric diagnoses, (2) perceptual abnormalities are more prevalent in those young people with histories of childhood adversity (childhood trauma, bullying) and (3) perceptual abnormality type is associated with co-morbid psychiatric diagnoses or histories of childhood adversity. METHODS: In a sample of 118 UHR patients we investigated the relationship between perceptual abnormalities and non-psychotic diagnoses and adverse life events at entry to a UHR clinic. RESULTS: Depressive disorder at baseline was associated with increased odds of experiencing perceptual abnormalities (OR 3.59, P = .004), particularly visual perceptual abnormalities (OR 2.36, P = .02). Borderline personality disorder at baseline was associated with increased odds of any auditory perceptual abnormalities (OR 3.44, P = .04) and specifically second person perceptual abnormalities (OR 2.69, P = .04). A history of childhood trauma and childhood bullying were both associated with increased odds of experiencing perceptual abnormalities at baseline (trauma OR 6.30, P < .001; bullying OR 5.00, P = .01). CONCLUSIONS: Our findings suggest that in the UHR population, certain types of perceptual abnormalities index risk for co-morbid non-psychotic disorder and indicate prior experience of childhood trauma. The use of detailed phenomenology of psychotic symptoms can help to shape our understanding of risk in UHR patients.
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ItemShort-term outcome of substance-induced psychotic disorder in a large UK first episode psychosis cohort(WILEY, 2016-10)OBJECTIVE: The incidence and outcome of first-episode substance-induced psychotic disorder (SIPD) are unclear. The study aimed to compare the 1-year outcomes of those given a SIPD diagnosis by clinicians compared to other psychosis diagnoses in a first-episode cohort. METHOD: Data were from a large (n = 1027) cohort of first-episode psychosis (FEP) patients admitted to early intervention services in the UK (National EDEN). Diagnosis, including that of SIPD, was made by treating psychiatrists at baseline using ICD10 criteria. Details on symptoms, functioning, quality of life, relapse and recovery were available at baseline and 12 months. RESULTS: There were 67 cases of SIPD (6.5% of the cohort). At baseline, SIPD patients were no different to other psychoses on symptoms, functioning and quality of life. At 12 months, there was no difference in SIPD and other psychoses on functioning, quality of life or relapse and recovery rates. Levels of psychotic and general symptomatology were similar but depressive symptoms were higher in the SIPD group. CONCLUSIONS: First-episode psychosis patients with a diagnosis of SIPD do not appear to have better outcomes than those with other primary psychotic diagnoses. The higher levels of depressive symptoms may be a specific marker in these patients.
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ItemSchool mobility during childhood predicts psychotic symptoms in late adolescence(WILEY, 2016-08)BACKGROUND: Recently, school mobility was identified as a risk factor for psychotic symptoms in early adolescence. The extent to which this risk continues into late adolescence and the trajectories via which this risk manifests remain unexplored. METHODS: Psychotic symptoms in 4,720 adolescents aged 18 were ascertained by trained psychologists using the Psychosis-Like Symptoms Interview. Mothers reported on sociodemographic factors (i.e., family adversity, ethnicity and urbanicity) from pregnancy to 4 years; child's involvement in bullying at age 6-7 years; residential mobility at 11 years and school mobility at 11-12 years. Young people reported on their friendships at 8 years, and antisocial behaviour and cannabis use at 15 years. RESULTS: School mobility across childhood significantly predicted psychotic symptoms at 18 years (adjusted odds ratio = 2.15; 95% confidence intervals = 1.06, 4.40). Within path analysis, school mobility (β = .183, p = .035), involvement in bullying (β = .133, p = .013), antisocial behaviour (β = .052, p = .004), cannabis use (β = .254, p = .020) and female sex (β = .420, p < .001) significantly predicted psychotic symptoms. Residential mobility (β = .375, p < .001), involvement in bullying (β = .120, p = .022) and poor friendships (β = .038, p = .014) significantly predicted school mobility. Residential mobility indirectly increased the risk of psychotic symptoms via school mobility (β = .069, p = .041). CONCLUSIONS: Children who move schools often are more likely to have experienced peer problems. School mobility, in turn, appears to be a robust marker for psychotic symptoms in late adolescence. Clinicians and teachers should consider school mobility as an important risk indicator for both peer problems and psychopathology.
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ItemStaged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants(WILEY, 2019-08)AIM: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. METHODS: This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. RESULTS: Ninety participants have been recruited and baseline characteristics are presented. CONCLUSIONS: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.
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ItemDoes reason for referral to an ultra-high risk clinic predict transition to psychosis?(WILEY, 2019-04)AIM: To examine reasons for referral to a specialist ultra-high risk (UHR) for psychosis clinic and whether these reasons are associated with risk for subsequent transition to psychosis. METHODS: Data for 127 patients referred to the Personal Assessment and Crisis Evaluation clinic were collected by medical record audit. Time to transition to psychosis was calculated from date of referral to time at which the young person was judged by their treating team to be experiencing onset of first episode psychosis. RESULTS: Patients were primarily referred due to attenuated psychotic symptoms and depression (40.2%). There was an association with transition, with those in the attenuated psychotic-symptom-only category being more likely to transition. CONCLUSION: As well as attenuated psychotic symptoms, depression and anxiety were also important reasons for referral indicating that there is a broad clinical phenotype of young people presenting to UHR clinics. Clinical reason for referral may index level of risk for subsequent transition to psychosis.
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ItemExperiences and satisfaction of children, young people and their parents with alternative mental health models to inpatient settings: a systematic review(SPRINGER, 2020-12)Community-based mental health services for children and young people (CYP) can offer alternatives to inpatient settings and treat CYP in less restrictive environments. However, there has been limited implementation of such alternative models, and their efficacy is still inconclusive. Notably, little is known of the experiences of CYP and their parents with these alternative models and their level of satisfaction with the care provided. Therefore, the main aim of this review was to understand those experiences of the accessibility of alternative models to inpatient care, as well as overall CYP/parental satisfaction. A searching strategy of peer-reviewed articles was conducted from January 1990 to December 2018, with updated searches conducted in June 2019. The initial search resulted in 495 articles, of which 19 were included in this review. A narrative synthesis grouped the studies according to emerging themes: alternative models, tele-psychiatry and interventions applied to crisis, and experiences and satisfaction with crisis provision. The identified articles highlighted increased satisfaction in CYP with alternative models in comparison with care as usual. However, the parental experiential data identified high levels of parental burden and a range of complex emotional reactions associated with engagement with crisis services. Furthermore, we identified a number of interventions, telepsychiatric and mobile solutions that may be effective when applied to urgent and emergency care for CYP experiencing a mental health crisis. Lastly, both parental and CYP experiences highlighted a number of perceived barriers associated with help-seeking from crisis services.
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ItemS134. INCIDENCE, IMPACT AND TRAJECTORIES OF PSYCHOTIC EXPERIENCES FROM CHILDHOOD TO ADULTHOOD, AND PREDICTION OF PSYCHOTIC DISORDER(Oxford University Press (OUP), 2020-05-18)Abstract Background Given the global burden of disease of psychotic disorders and the promise of benefit from early intervention, there is an imperative to understand the developmental trajectories from onset of psychotic experiences to clinical disorder and to improve identification of individuals at greatest risk. The aims of this study therefore were: 1) to describe, for the first time, the change in incidence of psychotic experiences in the general population from childhood through early adulthood; 2) to describe the prevalence and burden of unmet clinical need of at-risk mental states and psychotic disorder among young adults in the general population; 3) to examine the predictive ability of both self-reported and interviewer-rated measures of psychotic experiences during childhood and adolescence in identifying psychotic disorder by early adulthood; and 4) to describe longitudinal profiles of psychotic experiences from childhood through early adulthood and investigate a comprehensive range of childhood determinants of symptom persistence. Methods We used data from the ALSPAC birth cohort study. Psychotic experiences and disorder were assessed using semi-structured interviews at ages 12, 18, and 24 (N=7,900 with any data). Incidence rates were estimated using flexible parametric modeling, and positive predictive values (PPVs), sensitivity, specificity, and area under the curve were estimated for prediction. Longitudinal profiles were constructed based on interviewer ratings and frequency of experiences, with profiles describing no experiences (62.5%), episodic experiences (26.5%), persistent/recurrent low frequency (9.1%), and persistent/recurrent high frequency (1.9%) groups. Multinomial regression was used to examine risk factors for persistence, covering socio-demographic, genetic, behavioural, cognitive, and psychological characteristics during childhood. Results The incidence rate of psychotic experiences increased between ages 12 and 24, peaking during late adolescence. A total of 109 individuals (2.8%) met criteria for a psychotic disorder up to age 24, of whom 70% had sought professional help. Prediction of current psychotic disorder at age 24 (N=47, 1.2%), by both self-report and interviewer-rated measures of psychotic experiences at age 18 (PPVs, 2.9% and 10.0%, respectively), was improved by incorporating information on frequency and distress (PPVs, 13.3% and 20.0%, respectively), although sensitivities were low. The PPV of an at-risk mental state at age 18 predicting incident disorder at ages 18–24 was 21.1% (95%CI 6.1, 45.6), and the sensitivity was 14.3% (95%CI 4.0, 32.7). Longitudinal profile analysis showed that persistence was highest in those with higher levels of emotional instability and borderline personality traits in childhood, whilst persistence was strongly related to concurrent and increasing levels of social isolation, anxiety, self-harm, and substance use over time. Discussion Our study results show a peak in incidence of psychotic experience during late adolescence just prior to the peak incidence rate for schizophrenia, and an unmet need for care in young people with psychotic disorders. Although we show the potential efficiency of self-report measures for prediction, because of the low sensitivity, targeting individuals in non-help-seeking samples based only on more severe symptom cutoff thresholds will likely have little impact on population levels of first-episode psychosis. The primary characteristics indexing whether psychotic experiences are likely to persist over time is the presence of emotion regulation difficulties in childhood, providing evidence of a potentially modifiable target for prevention.
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ItemT34. THE IMPACT OF ANTIDEPRESSANT USE ON THE TRANSITION TO PSYCHOSIS RATE IN THE NEURAPRO TRIAL(Oxford University Press (OUP), 2020-05-18)Abstract Background Over the last two decades, several randomised controlled trials (RCTs) have indicated that preventive psychosocial, pharmacologic (Van der Gaag et al. 2013), and nutritional interventions (Amminger et al. 2010) are likely to be beneficial in people at ultra-high risk (UHR) of psychosis, in terms of delaying or preventing a transition to psychosis. Antidepressant medication is commonly prescribed in young people at UHR for psychosis; however, the evidence regarding its efficacy for psychosis prevention is limited (Fusar-Poli et al. 2007; Cornblatt et al. 2007; Fusar-Poli et al. 2015). The main aim of the present study is to investigate the impact of concomitant AD medication on the transition to psychosis rate in young people at ultra-high risk of psychosis who participated in the NEURAPRO trial (McGorry et al. 2017). Methods In this secondary analysis, data from 304 participants of a multicenter, double-blind, placebo-controlled, randomized clinical trial (NEURAPRO) of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) were included. During the trial, concomitant antidepressant medication was permitted for treatment of moderate to severe major depressive disorder (a score of ≥ 21 on the Montgomery-Asberg Depression Rating Scale, MADRS) in all participants. Results Of 304 participants, 189 (62.2%) were treated with ADs. 98 (64.1%) of those were in the omega-3 group and 91 (60.3%) in the placebo group. The transition rate to psychosis was higher in individuals who received AD treatment (13.2%; 25 of 189) as in individuals without ADs (6.1%; 7 of 115). The Kaplan-Meier survival curve estimated a group difference of X2 = 3.237, P = .072 (log rank test). Discussion Antidepressants are widely used in early psychosis. This analysis does not support the view that antidepressants may have reduced the transition to psychosis rate in this cohort. The findings are limited by the fact that antidepressants were prescribed based on clinical discretion. A randomised controlled trial is needed to determine whether antidepressants have a role in prevention of transition to psychosis.
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ItemM22. IGG ANTIBODIES TO TOXOPLASMA GONDII ARE ASSOCIATED WITH INCREASED LONG-TERM RISK FOR PSYCHOSIS IN INDIVIDUALS AT ULTRA-HIGH RISK FOR PSYCHOSIS(Oxford University Press (OUP), 2020-05-18)Abstract Background The prevalence of antibodies to Toxoplasma gondii, a ubiquitous parasitic protozoan causing the infectious disease toxoplasmosis, is increased in patients with psychotic disorders compared to the general population. We have previously shown that antibody titers for T.gondii correlate with the severity of positive symptoms in young people at ultra-high risk (UHR) for psychosis, suggesting that infection with T. gondii may be relevant to the manifestation of psychosis. However, it is unclear if T. gondii antibodies represent a risk factor for psychosis onset or non-psychotic outcome in UHR individuals. The aim of the present study was to examine whether seropositivity for T.gondii is associated with transition to psychosis and other outcomes in young people at UHR for psychosis. Methods The study sample consisted of 96 individuals at UHR for psychosis who were referred to the Personal Assistance and Crisis Evaluation (PACE) clinic in Melbourne, Australia, between 2001 and 2004, consented to optional blood tests for infectious agents and were followed up for up to 10 years after baseline (median (interquartile range) duration of follow-up: 7.15 (3.14 – 7.72) years). Serum IgG antibodies to six viral and parasitic pathogens (Toxoplasma gondii, Herpes Simplex Virus Type 1 and 2, Cytomegalovirus, Epstein Barr Virus, Varicella-Zoster Virus) were measured at baseline. Outcome measures included transition to psychosis, general psychiatric symptomatology and positive psychotic symptoms (BPRS), negative symptoms (SANS), depressive symptoms (HAM-D), anxiety symptoms (HAM-A) and functioning (SOFAS and GAF). Cox proportional hazards regression and linear regression models were used to examine the associations of seropositivity and antibody titers at baseline and transition to psychosis and other outcomes at follow-up. Results A total of 17 individuals (17.7%) were seropositive for Toxoplasma gondii at baseline. The rate of transition to psychosis was higher among seropositive (35.7%) compared to seronegative participants (14.6%), although this was not statistically significant (p=0.101). Antibody titers (IgG) for Toxoplasma gondii were significantly higher at baseline in participants who later transitioned to psychosis (1.34 ± 1.36 vs. 0.79 ± 0.73, p=0.027). Seropositivity for T.gondii IgG at baseline significantly predicted transition to psychosis within the follow-up duration (hazard ratio [HR]=3.61, 95%CI 1.08 – 12.00, p=0.036). Toxoplasma IgG at baseline were significantly associated with higher BPRS scores at follow-up in participants who were seropositive at baseline (Beta=6.38, 95%CI 0.43 – 12.34, p=0.038). No significant associations were found between antibodies to other pathogens and outcome, or between antibodies to Toxoplasma gondii and any other outcomes. Discussion Our findings suggest that the presence of IgG class antibodies for Toxoplasma gondii is associated with a higher risk for psychosis transition in individuals at UHR for psychosis, but not with risk for other long-term outcomes. These observations provide support for the hypothesis that infection with Toxoplasma gondii may be an environmental risk factor for psychosis and suggest that IgG antibodies for Toxoplasma gondii in individuals at UHR for psychosis have prognostic relevance.
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