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McGorry, Patrick D., and Cristina Mei. "Ultra-high-risk paradigm: lessons learnt and new directions." Evidence Based Mental Health 21, no. 4 (October 24, 2018): 131–33. http://dx.doi.org/10.1136/ebmental-2018-300061.
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Within the embryonic early psychosis field in the early 1990s, the conceptualisation and definition of an at-risk or ultra-high-risk (UHR) mental state for psychosis was a breakthrough which transformed the clinical and research landscape in psychiatry. Twenty-five years later, we have a new evidence base that has illuminated the neurobiology of the onset phase of psychotic disorder, delivered Cochrane level 1 evidence showing that the onset of full-threshold sustained psychotic disorder can be at least delayed, and is paving the way to a new generation of transdiagnostic research. Here, we document the contribution of the UHR approach to understanding the underlying mechanisms of psychosis onset as well as the long-term outcomes. Particularly, we highlight that psychosis onset can be delayed in those meeting UHR criteria and that these criteria have a higher valence for subsequent psychotic disorders and some valence for persistent non-psychotic syndromes. Critiques have helped to identify some of the limitations of this paradigm, which are acknowledged. These include evidence that psychotic disorders can emerge more acutely and from other, as yet undefined, precursor states. Rather than defending, or alternatively questioning the value of, the UHR approach, we propose a broader, transdiagnostic staging model that is consistent with the pluripotent and variably comorbid trajectories for mental disorders. This approach moves beyond psychosis to capture a wider range of subthreshold symptoms and full-threshold disorders, thus enhancing prediction for the emergence and progression of a range of mental disorders, as well as providing new avenues for early intervention and prevention.
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Demjaha, Arsime, Sara Weinstein, Daniel Stahl, Fern Day, Lucia Valmaggia, Grazia Rutigliano, Andrea De Micheli, Paolo Fusar-Poli, and Philip McGuire. "Formal thought disorder in people at ultra-high risk of psychosis." BJPsych Open 3, no. 4 (July 2017): 165–70. http://dx.doi.org/10.1192/bjpo.bp.116.004408.
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BackgroundFormal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear.AimsExamine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis.MethodThe Thought and Language Index (TLI) was used to assess 24 ultra-high-risk participants, 16 people with first-episode psychosis and 13 healthy controls. Ultra-high-risk individuals were followed up for a mean duration of 7 years (s.d.=1.5) to determine the relationship between formal thought disorder at baseline and transition to psychosis.ResultsTLI scores were significantly greater in the ultra-high-risk group compared with the healthy control group (effect size (ES)=1.2), but lower than in people with first-episode psychosis (ES=0.8). Total and negative TLI scores were higher in ultra-high-risk individuals who developed psychosis, but this was not significant. Combining negative TLI scores with attenuated psychotic symptoms and basic symptoms predicted transition to psychosis (P=0.04; ES=1.04).ConclusionsTLI is beneficial in evaluating formal thought disorder in ultra-high-risk participants, and complements existing instruments for the evaluation of psychopathology in this group.
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McGuire, Philip, Sudhakar Selvaraj, and Oliver Howes. "Is clinical intervention in the ultra high risk phase effective?" Revista Brasileira de Psiquiatria 33, suppl 2 (October 2011): s161—s174. http://dx.doi.org/10.1590/s1516-44462011000600004.
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Recent research suggests that early intervention in psychosis might improve the chances of recovery and may even be able to prevent the onset of psychotic disorders. Clinical intervention in subjects at ultra high risk (UHR) of psychosis can have three different objectives. The first aim is to improve the 'prodromal' symptoms and problems that subjects usually present with. The second is to reduce the risk of the subsequent onset of frank psychosis. The third objective is to minimize the delay before the initiation of antipsychotic treatment in the subgroup of UHR subjects that go on to develop a first episode of psychosis. Both pharmacological and psychological interventions appear to be effective in reducing the severity of presenting symptoms in UHR subjects. Clinical trials of the impact of these interventions on the risk of subsequent transition to psychosis have been positive, but have involved small samples, and thus the issue of whether the effects persist in the long term remains to be determined. The monitoring of UHR subjects for the first signs of frank psychosis is an effective means of reducing the delay between the onset of the first episode and the start of antipsychotic treatment. Follow-up studies are required to test whether the reduction in this delay leads to an improved long term outcome. To date, the majority of the interventions that have been used in UHR subjects, such as case management, antipsychotic medication, and cognitive behavior therapy have previously been employed in patients with established psychosis. However, it is possible that treatments that are not normally used in patients with psychotic disorders may prove effective when applied at this stage.
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Yun, Yang, Lisa J. Phillips, Sue Cotton, Alison R. Yung, Shona M. Francey, Hok Pan Yuen, and Patrick D. Mcgorry. "Obstetric Complications and Transition to Psychosis in an ‘Ultra’ High Risk Sample." Australian & New Zealand Journal of Psychiatry 39, no. 6 (June 2005): 460–66. http://dx.doi.org/10.1080/j.1440-1614.2005.01604.x.
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Objective: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. Method: The ‘ultra’ high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. Results: Obstetric complicationswere not associated with the later development of psychosis in the UHR group included in this study. Conclusions: This study does not suppor t a role for OCs as a risk factorfor the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.
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Schultze-Lutter, Frauke, Chantal Michel, Stephan Ruhrmann, and Benno G. Schimmelmann. "Prevalence and clinical relevance of interview-assessed psychosis-risk symptoms in the young adult community." Psychological Medicine 48, no. 7 (September 11, 2017): 1167–78. http://dx.doi.org/10.1017/s0033291717002586.
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AbstractBackgroundAn efficient indicated prevention of psychotic disorders requires valid risk criteria that work in both clinical and community samples. Yet, ultra-high risk and basic symptom criteria were recently recommended for use in clinical samples only. Their use in the community was discouraged for lack of knowledge about their prevalence, clinical relevance and risk factors in non-clinical, community settings when validly assessed with the same instruments used in the clinic.MethodsUsing semi-structured telephone interviews with established psychosis-risk instruments, we studied the prevalence of psychosis-risk symptoms and criteria, their clinical relevance (using presence of a non-psychotic mental disorder or of functional deficits as proxy measures) and their risk factors in a random, representative young adult community sample (N=2683; age 16–40 years; response rate: 63.4%).ResultsThe point-prevalence of psychosis-risk symptoms was 13.8%. As these mostly occurred too infrequent to meet frequency requirements of psychosis-risk criteria, only 2.4% of participants met psychosis-risk criteria. A stepwise relationship underlay the association of ultra-high risk and basic symptoms with proxy measures of clinical relevance, this being most significant when both occurred together. In line with models of their formation, basic symptoms were selectively associated with age, ultra-high risk symptoms with traumatic events and lifetime substance misuse.ConclusionsPsychosis-risk criteria were uncommon, indicating little risk of falsely labelling individuals from the community at-risk for psychosis. Besides, both psychosis-risk symptoms and criteria seem to possess sufficient clinical relevance to warrant their broader attention in clinical practice, especially if ultra-high risk and basic symptoms occur together.
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Bartholomeusz, Cali F., Vanessa L. Cropley, Cassandra Wannan, Maria Di Biase, Patrick D. McGorry, and Christos Pantelis. "Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model." Australian & New Zealand Journal of Psychiatry 51, no. 5 (October 12, 2016): 455–76. http://dx.doi.org/10.1177/0004867416670522.
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Objective: This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. Methods: A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. Results: In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). Conclusion: We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.
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Yücel, Murat, Stephen J. Wood, Lisa J. Phillips, Geoffrey W. Stuart, Deidre J. Smith, Alison Yung, Dennis Velakoulis, Patrick D. Mcgorry, and Christos Pantelis. "Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness." British Journal of Psychiatry 182, no. 6 (June 2003): 518–24. http://dx.doi.org/10.1192/bjp.182.6.518.
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BackgroundThe anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder.AimsTo examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness.MethodMagnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features.ResultsCompared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness.ConclusionsAlthough ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.
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Valmaggia, L. R., F. L. Day, C. Jones, S. Bissoli, C. Pugh, D. Hall, S. Bhattacharyya, et al. "Cannabis use and transition to psychosis in people at ultra-high risk." Psychological Medicine 44, no. 12 (February 6, 2014): 2503–12. http://dx.doi.org/10.1017/s0033291714000117.
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BackgroundCannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.MethodLifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.ResultsLifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).ConclusionsIn people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.
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Palmier-Claus, J. E., G. Dunn, and S. W. Lewis. "Emotional and symptomatic reactivity to stress in individuals at ultra-high risk of developing psychosis." Psychological Medicine 42, no. 5 (November 9, 2011): 1003–12. http://dx.doi.org/10.1017/s0033291711001929.
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BackgroundThe stress–vulnerability model of psychosis continues to be influential. The aim of this study was to compare emotional and symptomatic responses to stress in individuals at ultra-high risk (UHR) of developing psychosis, in age- and gender-matched healthy controls, and in patients with non-affective psychosis.MethodA total of 27 UHR, 27 psychotic and 27 healthy individuals completed the experience sampling method, an ambulant diary technique, where they were required to fill in self-assessment questions about their emotions, symptoms and perceived stress at semi-random times of the day for 6 days. Quesionnaire and interview assessments were also completed.ResultsMultilevel regression analyses showed that individuals at UHR of developing psychosis reported greater negative emotions in response to stress than the healthy individuals. Against the initial hypotheses, the UHR individuals also experienced greater emotional reactivity to stress when compared with the patient group. No significant differences were observed between the patients and the non-clinical sample. Stress measures significantly predicted the intensity of psychotic symptoms in UHR individuals and patients, but the extent of this did not significantly differ between the groups.ConclusionsIndividuals at UHR of developing psychosis may be particularly sensitive to everyday stressors. This effect may diminish after transition to psychosis is made and in periods of stability. Subtle increases in psychotic phenomena occur in response to stressful events across the continuum of psychosis.
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Morrison, Anthony P., Paul French, Lara Walford, Shôn W. Lewis, Aoiffe Kilcommons, Joanne Green, Sophie Parker, and Richard P. Bentall. "Cognitive therapy for the prevention of psychosis in people at ultra-high risk." British Journal of Psychiatry 185, no. 4 (October 2004): 291–97. http://dx.doi.org/10.1192/bjp.185.4.291.
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BackgroundAdvances in the ability to identify people at high risk of developing psychosis have generated interest in the possibility of preventing psychosis.AimsTo evaluate the efficacy of cognitive therapy for the prevention of transition to psychosis.MethodA randomised controlled trial compared cognitive therapy with treatment as usual in 58 patients at ultra-high risk of developing a first episode of psychosis. Therapy was provided over 6 months, and all patients were monitored on a monthly basis for 12 months.ResultsLogistic regression demonstrated that cognitive therapy significantly reduced the likelihood of making progression to psychosis as defined on the Positive and Negative Syndrome Scale over 12 months. In addition, it significantly reduced the likelihood of being prescribed antipsychotic medication and of meeting criteria for a DSM – IV diagnosis of a psychotic disorder. Analysis of covariance showed that the intervention also significantly improved positive symptoms of psychosis in this population over the 12-month period.ConclusionsCognitive therapy appears to be an acceptable and efficacious intervention for people at high risk of developing psychosis.
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Armando, M., M. Schneider, M. Pontillo, S. Vicari, M. Debbane, F. Schultze-Lutter, and S. Eliez. "Ultra High Risk Status and Transition to Psychosis in 22q11.2 Deletion Syndrome." European Psychiatry 41, S1 (April 2017): S81—S82. http://dx.doi.org/10.1016/j.eurpsy.2017.01.258.
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The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high-risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of sociodemographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.56176 months after initial assessment. Eighty-nine participants with 22q11DS (age range: 8–30 years; mean: 16.1647) were assessed using the structured interview for psychosis-risk syndromes. Information on axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non-UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high-risk samples. Nevertheless, the relatively high transition rate in non-UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Jarrett, M., L. Valmaggia, J. Parrott, A. Forrester, T. Winton-Brown, H. Maguire, D. Ndegwa, P. McGuire, and T. K. J. Craig. "Prisoners at ultra-high-risk for psychosis: a cross-sectional study." Epidemiology and Psychiatric Sciences 25, no. 2 (March 3, 2015): 150–59. http://dx.doi.org/10.1017/s2045796015000062.
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Background.The definition of ultra-high risk (UHR) for psychosis was derived from community-based help-seeking populations. Prisoners have high rates of psychosis and other severe mental health (MH) problems. They also have high rates of risk factors for psychiatric morbidity and yet they are among the populations who are less likely to seek help in the community. Despite a policy of equivalence of care for individuals in prison there are no early intervention services for psychosis in prisons in the UK. This was a study exploring feasibility of introducing such a service into a local London prison. This paper discusses the differences in MH profile of prisoners who met criteria for at-risk mental state compared with those who did not.Method.A two-stage procedure was used. Participants in a local London prison were routinely screened in the first week of arrival in prison with the Prodrome Questionnaire – Brief Version (PQ-B; Loewyet al.2011). Those that screened positive as well as a small sample of those who screened negative underwent a further semi-structured assessment to see whether they met criteria for UHR state. Data on self-harm and suicide attempt, family psychiatric history, and anxiety and depression was also collected.Results.A total of 891 prisoners were screened, 44% of whom screened positive. A total of 354 underwent second stage assessment, 60 of whom had screened negative. Four groups were identified: those that had no MH problems, a group experiencing First Episode Psychosis, those at UHR of psychosis and a group with other MH problems. The UHR state and Psychotic groups had very similar MH profiles of symptoms and distress. Prisoners with no MH problems were at the other end of the spectrum with few symptoms and little distress. The Other group fell in between this group and the psychotic spectrum group in terms of symptomology and distress.Conclusions.This study is the first to examine risk for psychosis in an adult male prison population. We identified a broad spectrum of MH disorder for which there is little current service provision in prisons. Screening early in the custodial process has the potential to identify unmet MH need and has implications for keeping individuals safe in custody. A long-term strategic approach is required to address MH need in prisons.
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Phillips, Lisa J., Christina Curry, Alison R. Yung, Hok Pan Yuen, Steven Adlard, and Patrick D. Mcgorry. "Cannabis Use is Not Associated With the Development of Psychosis in an ‘Ultra’ High-Risk Group." Australian & New Zealand Journal of Psychiatry 36, no. 6 (December 2002): 800–806. http://dx.doi.org/10.1046/j.1440-1614.2002.01089.x.
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Background: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. Method: The ‘ultra’ high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrolment in the study was assessed at intake. Results: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. Conclusion: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area.
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Santayana, G. Pardo de, R. Landera, M. Juncal, O. Porta, M. Gómez, N. Núñez, and L. Sánchez. "Ultra-high risk psychosis. A case report." European Psychiatry 41, S1 (April 2017): S730—S731. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1335.
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IntroductionThere is much debate on whether patients who are at high risk of developing a psychotic disorder in the near future (such as patients suffering of attenuated psychotic symptoms, brief limited intermittent psychotic symptoms or personality trait vulnerability) should be treated with antipsychotic drugs to prevent possible psychotic breaks from happening.AimTo review articles from the existing medical literature about treatment of patients in ultra-high risk of developing psychosis.MethodsWe describe the case of a 19-year-old male who was hospitalized after a suicide attempt in April 2015. He had been diagnosed of different psychiatric disorders such as mixed anxiety-depressive disorder, adjustment disorder and probable borderline personality disorder. During his stay at the hospital, we observed that he had schizoid personality traits. In the initial anamnesis, he denied ever having psychotic symptoms, but a few days later he admitted that the previous year he suffered throw a period of brief self-limiting psychotic symptoms.ResultsProphylactic treatment was started with oral aripiprazole 15 mg/day, which was well tolerated by the patient. He has been free of psychotic symptoms for the last 17 months (from April 2015 to September 2016). No relevant side effects were detected.ConclusionsOral aripiprazole 15 mg/day can be a good therapeutic option in patients at ultra-high risk of developing a psychotic episode.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Ising, H. K., F. Smit, W. Veling, J. Rietdijk, S. Dragt, R. M. C. Klaassen, N. S. P. Savelsberg, et al. "Cost-effectiveness of preventing first-episode psychosis in ultra-high-risk subjects: multi-centre randomized controlled trial." Psychological Medicine 45, no. 7 (October 21, 2014): 1435–46. http://dx.doi.org/10.1017/s0033291714002530.
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BackgroundAlthough there is evidence for the effectiveness of interventions for psychosis among ultra-high-risk (UHR) groups, health economic evaluations are lacking. This study aimed to determine the cost effectiveness and cost–utility of cognitive–behavioural therapy (CBT) to prevent first-episode psychosis.MethodThe Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients with an 18-month follow-up. All participants were treated with routine care (RC) for non-psychotic disorders. The experimental group (n = 95) received add-on CBT to prevent first-episode psychosis. We report the intervention, medical and travel costs, as well as costs arising from loss of productivity. Treatment response was defined as psychosis-free survival and quality-adjusted life years (QALYs) gained.ResultsIn the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition (89.5% v. 76.2%). CBT showed a 63.7% probability of being more cost effective, because it was less costly than RC by US$844 (£551) per prevented psychosis. In the cost–utility analysis, QALY health gains were slightly higher for CBT than for RC (0.60 v. 0.57) and the CBT intervention had a 52.3% probability of being the superior treatment because, for equal or better QALY gains, the costs of CBT were lower than those of RC.ConclusionsAdd-on preventive CBT for UHR resulted in a significant reduction in the incidence of first psychosis. QALY gains show little difference between the two conditions. The CBT intervention proved to be cost saving.
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Bradley, Jonathan, Daniel Freeman, Eleanor Chadwick, Allison G. Harvey, Bradley Mullins, Louise Johns, Bryony Sheaves, Belinda Lennox, Matthew Broome, and Felicity Waite. "Treating Sleep Problems in Young People at Ultra-High Risk of Psychosis: A Feasibility Case Series." Behavioural and Cognitive Psychotherapy 46, no. 3 (October 30, 2017): 276–91. http://dx.doi.org/10.1017/s1352465817000601.
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Background: Our view is that sleep disturbance may be a contributory causal factor in the development and maintenance of psychotic experiences. A recent series of randomized controlled intervention studies has shown that cognitive-behavioural approaches can improve sleep in people with psychotic experiences. However, the effects of psychological intervention for improving sleep have not been evaluated in young people at ultra-high risk of psychosis. Improving sleep might prevent later transition to a mental health disorder. Aims: To assess the feasibility and acceptability of an intervention targeting sleep disturbance in young people at ultra-high risk of psychosis. Method: Patients were sought from NHS mental health services. Twelve young people at ultra-high risk of psychosis with sleep problems were offered an eight-session adapted CBT intervention for sleep problems. The core treatment techniques were stimulus control, circadian realignment, and regulating day-time activity. Participants were assessed before and after treatment and at a one month follow-up. Results: All eligible patients referred to the study agreed to take part. Eleven patients completed the intervention, and one patient withdrew after two sessions. Of those who completed treatment, the attendance rate was 89% and an average of 7.6 sessions (SD = 0.5) were attended. There were large effect size improvements in sleep. Post-treatment, six patients fell below the recommended cut-off for clinical insomnia. There were also improvements in negative affect and psychotic experiences. Conclusion: This uncontrolled feasibility study indicates that treating sleep problems in young people at ultra-high of psychosis is feasible, acceptable, and may be associated with clinical benefits.
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Korkeila, J., R. K. R. Salokangas, M. Heinimaaa, T. Svirskis, T. Laine, S. Ruhrmann, H. von Reventlow, et al. "Physical illnesses, developmental risk factors and psychiatric diagnoses among subjects at risk of psychosis." European Psychiatry 28, no. 3 (September 9, 2011): 135–40. http://dx.doi.org/10.1016/j.eurpsy.2011.06.005.
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AbstractBackgroundSubjects with psychoses have significantly increased rates of physical illnesses, but the nature of the relationship remains largely unknown.Material and methodsThe present study is part of the European Prediction of Psychosis Study (EPOS). Data were collected from 245 help-seeking individuals from six European centers (age 16–35) who met criteria for ultra-high risk of psychosis criteria. This paper seeks to investigate self-reported physical ill health and its associations with psychiatric symptoms and disorders, risk factors, and onset of psychosis during 48 months of follow-up.ResultsIn multivariate analysis, lifetime panic disorder (OR = 2.43, 95%CI: 1.03–5.73), known complications during pregnancy and delivery (OR = 2.81, 95%CI: 1.10–7.15), female gender (OR = 2.88, 95%CI: 1.16–7.17), family history of psychosis (OR = 3.08, 95%CI: 1.18–8.07), and having a relationship (OR = 3.44, 95%CI: 1.33–8.94) were significantly associated with self-reported physician-diagnosed illness. In the Cox proportional hazard model we found no significant differences between those who had undergone a transition to psychosis and those who had not.ConclusionsThe physical health of patients defined to be at ultra-high risk of psychosis seems to be commonly impaired and associated with female gender, marital status, complications during pregnancy and birth, lifetime panic disorder, and genetic risk of psychosis.
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R. Yung, Alison, Paolo Fusar-Poli, and Barnaby Nelson. "The Ultra High Risk Approach to Define Psychosis Risk." Current Pharmaceutical Design 18, no. 4 (February 1, 2012): 346–50. http://dx.doi.org/10.2174/138161212799316299.
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O'Connor, K. "Research in young people at ultra-high risk for psychosis: a review of the current evidence." Irish Journal of Psychological Medicine 30, no. 1 (March 2013): 77–89. http://dx.doi.org/10.1017/ipm.2012.9.
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BackgroundThe past 15 years have seen a growing interest in early intervention and detection of psychosis before the onset of the first episode. Recent proposals to include a psychosis risk syndrome (PRS) in DSM 5 have focused attention on the evidence base achieved to date in this field.AimsThis article aims to (1) review the underlying principles of early identification and intervention during the pre-psychotic phase, (2) summarise the naturalistic follow-up studies conducted to date in this ‘at-risk’ population, (3) discuss the identified clinical risk factors for transition to psychosis, (4) summarise the interventional studies both psychological and pharmacological completed to date and (5) briefly discuss the controversy around the proposed inclusion of the PRS in DSM 5.MethodsElectronic databases EmBase, MedLine and PsychInfo were searched using the keywords ultra-high risk/at-risk mental state/risk syndrome/pre-psychotic/prodrome/prodromal and psychosis/schizophrenia.ResultsThe evidence suggests that it is possible to identify individuals who may be at risk of developing psychosis. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioural therapy, are currently insufficient to make treatment recommendations for this group. The emerging research with regard to possible neuroprotective factors such as omega fatty acids is promising, but will require replication in larger cohorts before it can be recommended.
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Kawakami, Karina Mayumi, Sonia Maria Motta Palma Sonia Maria Motta Palma, Rayssa Nailla Santos Duarte, Heloisa Rocha Falcão, and Barbara Modesto. "Adolescente com alto risco para Psicose (“Ultra High Risk”): uma revisão integrativa." Brazilian Journal of Global Health 1, no. 4 (August 27, 2021): 30–33. http://dx.doi.org/10.56242/globalhealth;1;4;30-33.
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OBJECTIVE: Many psychotic disorders such as schizophrenia can start with attenuated psychotic symptoms and / or declining social and occupational functions. People who present with these “prodromal” characteristics are described as being at Ultra High Risk (UHR) for psychosis. Due to the impact that these disorders have on their quality of life, it is important to review the existing literature. The aim was to conduct an integrative review on UHR and its impact on the quality of life in children and adolescents. METHODS: Searched for articles in the Pubmed database in the period 2010-2019 with the following descriptors: "Psychotic Disorders", "Risk Factors", "Schizophrenia", "Clinical Diagnosis". RESULTS: The search selected 10 articles and an Australian guideline Orygen, of which seven were selected for the present review after analysis. According to the results found, several psychotic disorders may have prodromal characteristics that are the same as Ultra High Risk (UHR). CONCLUSION: Patients with psychosis have worsened quality of life and more unfavorable prognosis, therefore, UHR present an opportunity for intervention to prevent the onset of the first psychotic episode. In clinical trials conducted with UHR patients, both the duration and periods of intervention have been relatively short. Thus, the question remains whether this intervention in the productive phase is effective over time. There should be more discussion about the cost benefit of treatments in UHR patients.
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Wood, Stephen J., Warrick J. Brewer, Penny Koutsouradis, Lisa J. Phillips, Shona M. Francey, Tina M. Proffitt, Alison R. Yung, Henry J. Jackson, Patrick D. McGorry, and Christos Pantelis. "Cognitive decline following psychosis onset." British Journal of Psychiatry 191, S51 (December 2007): s52—s57. http://dx.doi.org/10.1192/bjp.191.51.s52.
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BackgroundThe origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progressAimsTo investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individualsMethodParticipants consisted of two groups: controls (n = 17) and individuals at ultra-high risk for development of psychosis (n = 16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month intervalResultsBoth the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over timeConclusionsThese preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication
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Rasskazova, E., M. Omel’chenko, and V. Kaleda. "The role of cognitive insight in reduction of positive symptoms in youth with ultra-high risk for psychosis." European Psychiatry 41, S1 (April 2017): S182. http://dx.doi.org/10.1016/j.eurpsy.2017.01.2095.
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IntroductionCognitive insight was shown to be impaired in schizophrenia while its high level predicts improvement of psychotic symptoms. However, later studies demonstrated that in other mental disorders and healthy subjects cognitive insight might play ambiguous role being related to anxiety and lack of self-confidence.ObjectivesDevelopment of clinical criteria for high and ultra-high risk for psychosis allows to study the role of cognitive insight in these patients.AimsThe aim was to examine the role of cognitive insight in different clinical groups of youth with ultra-high risk for psychosis.MethodsSeventy-six male patients 16–25 years old with non-psychotic mental disorders (with preliminary diagnoses of mood disorders – 30, personality disorders – 25, schizotypal disorder – 21 patients) meeting criteria of ultra-high risk for psychosis and 55 healthy male controls filled Beck Cognitive Insight Scale, Symptom Checklist 90-R. The Scale of Prodromal Symptoms was used twice upon hospitalization and after 1-month period.ResultsModeration analysis reveals that in patients with preliminary diagnoses of mood disorders and schizotypal disorder cognitive insight is related to higher anxiety and obsessiveness and to poorer improvement on SOPS and positive symptoms. In patients with symptoms of personality disorders, it predicts better symptoms improvement.ConclusionsResults demonstrate importance of differentiation of the functions of cognitive insight in different patients with ultra-high risk for psychosis both in clinical psychological assessments and CBT.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Pyle, Melissa, and Anthony P. Morrison. "Internalised stereotypes across ultra-high risk of psychosis and psychosis populations." Psychosis 9, no. 2 (April 3, 2017): 110–18. http://dx.doi.org/10.1080/17522439.2017.1295097.
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Chaumette, B., C. Jiao, and Q. He. "Resilience Factors Preventing Schizophrenia in Ultra-high Risk Patients: Lessons from Genetics." European Psychiatry 65, S1 (June 2022): S9—S10. http://dx.doi.org/10.1192/j.eurpsy.2022.49.
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Over the past decades, researchers and psychiatrists in the field of psychosis have moved from a conception of a chronic presentation to a more dynamic paradigm. Accordingly, schizophrenia is now conceptualized as a progressive illness that typically emerges during late adolescence and follows different stages: early vulnerability, ultra-high risk state, first episode of psychosis, and chronic disease. Only one-quarter of the ultra-high risk patients will convert to a full-blown psychotic episode within 3 years while the others, called non-converters, will remain at-risk, develop other psychiatric disorders, or fully recover. The reasons for this differential outcome are not yet understood but this concept opens the way to scientific research to determine the protective factors involved in resilience for non-converters. Based on the Gene X Environment interaction model, schizophrenia results from genetic vulnerability and environmental aggressions which can have an impact on the epigenome and gene expression. Recent studies have shown that genetic variants play a role in the resilience of psychosis. Polygenic risk scores, computed as the addition of genetic polymorphisms, can modulate the effects of genetic at-risk deletions (i.e. del22q11) that predispose to psychosis and may also influence the cognitive symptoms of ultra-high risk patients. Resilience, defined as the ability to withstand adversity, is not only related to external skills or psychotherapeutic care but could also be explained by internal molecular factors. Identifying the genetic factors of resilience might help to stratify the risk and to develop precision medicine in psychiatry. Disclosure No significant relationships.
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Berger, Maximus, Eva Burkhardt, Alison Yung, Barnaby Nelson, Shona Francey, Ashleigh Lin, Stephen Wood, et al. "M22. IGG ANTIBODIES TO TOXOPLASMA GONDII ARE ASSOCIATED WITH INCREASED LONG-TERM RISK FOR PSYCHOSIS IN INDIVIDUALS AT ULTRA-HIGH RISK FOR PSYCHOSIS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S141—S142. http://dx.doi.org/10.1093/schbul/sbaa030.334.
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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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Phillips, Lisa J., Alison R. Yung, and Patrick D. McGorry. "Identification of Young People at Risk of Psychosis: Validation of Personal Assessment and Crisis Evaluation Clinic Intake Criteria." Australian & New Zealand Journal of Psychiatry 34, no. 1_suppl (February 2000): A164—A169. http://dx.doi.org/10.1177/000486740003401s25.
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Objective To describe the development and validation of the criteria used at the Personal Assessment and Crisis Evaluation (PACE) Clinic to identify young people at ‘ultra-high’ risk of developing a psychotic disorder within a short follow-up period. Method The PACE Clinic criteria initially grew out of clinical observations and retrospective research describing the prodromal phase of first-episode psychosis. Early prospective research refined the criteria into the three intake groups for the Clinic. These criteria combine putative state and trait risk factors for psychosis. Whether or not a person meets criteria for one or more of these groups can usually be determined by a thorough psychological assessment interview. Two early studies are described that assess the validity of this screening protocol. Results The transition rate to acute psychosis of the ‘ultra-high’ risk group identified in the second study was 41%. Conclusions These results suggest that it is possible to accurately identify young people at imminent risk of psychosis. The PACE criteria have now been adopted (or adapted) by a number of other clinical research programs both in Australia (i.e. Psychological Assistance Service in Newcastle) and other programs in the United States and elsewhere. This research may lead the way to the development of preventive interventions for the ultra-high risk group.
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Pinho, M., D. Martins, and S. Carvalho. "Cognitive-behavioural therapy role in the prevention of psychosis." European Psychiatry 64, S1 (April 2021): S498. http://dx.doi.org/10.1192/j.eurpsy.2021.1333.
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IntroductionAbout 30% of individuals in ultra-high risk (UHR) of psychosis develop overt psychosis within 3 years, and about 40% of those who don’t will keep experiencing ongoing attenuated psychotic symptoms and persistent functional disability. During this prodromal period, it’s possible to prevent the transition to a first-episode psychosis.ObjectivesTo conduct a short review of literature on the role of cognitive-behavioural therapy (CBT) in preventing psychosis in ultra-high risk patients.MethodsWe performed a literature search on PUBMED, using the query: “Cognitive Behavioral Therapy” [Mesh] AND “psychosis” AND “prevention”. We focused on data from systematic reviews, clinical trials and meta-analysis published on last 5 years, either in English or Portuguese.ResultsSome authors claim cognitive-behavioural therapy (CBT) as first-choice treatment in clients with ultra-high risk (UHR) for psychosis. CBT aims to normalize extraordinary experiences with education and to prevent delusional explanations. On a Japanese study, the total score of Positive and Negative Syndrome Scale (PANSS) significantly improved on post-intervention and follow-up assessments, with large effect sizes observed. Teaching families to apply CBT with their offspring may bolster therapeutic gains made in time-limited treatment. CBT showed an 83% probability of being more effective and less costly than routine care.ConclusionsPatients with UHR for psychosis can be treated successfully with CBT to postpone and prevent the transition to a first-episode psychosis. CBT for UHR has been included in the European guidelines and awaits dissemination and implementation in mental health services.
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Yung, Alison R., and Barnaby Nelson. "Young people at ultra high risk for psychosis: research from the PACE clinic." Revista Brasileira de Psiquiatria 33, suppl 2 (October 2011): s143—s160. http://dx.doi.org/10.1590/s1516-44462011000600003.
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Over the last fifteen years, attempts have been made to prospectively identify individuals in the prodromal phase of schizophrenia and other psychotic disorders. The ultra high risk approach, based on a combination of known trait and state risk factors, has been the main strategy used. The validation of the ultra high risk criteria allowed for predictive research in this population in an attempt to identify clinical, neurocognitive and neurobiological risk factors for psychosis onset. It also led to a series of intervention studies in this population, which have included the use of low dose antipsychotic medication, cognitive therapy, and omega-3 fatty acids. Although there is moderate evidence for the effectiveness of specific intervention strategies in this population, the most effective type and duration of intervention is yet to be determined. A current controversy in the field is whether to include an adaption of the ultra high risk criteria (the attenuated psychosis syndrome) in the next version of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).
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Kraan, T., E. Velthorst, L. Koenders, K. Zwaart, H. K. Ising, D. van den Berg, L. de Haan, and M. van der Gaag. "Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis." Psychological Medicine 46, no. 4 (November 16, 2015): 673–81. http://dx.doi.org/10.1017/s0033291715002329.
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BackgroundPrevious research has established the relationship between cannabis use and psychotic disorders. Whether cannabis use is related to transition to psychosis in patients at ultra-high risk (UHR) for psychosis remains unclear. The present study aimed to review the existing evidence on the association between cannabis use and transition to psychosis in UHR samples.MethodA search of PsychInfo, Embase and Medline was conducted from 1996 to August 2015. The search yielded 5559 potentially relevant articles that were selected on title and abstract. Subsequently 36 articles were screened on full text for eligibility. Two random-effects meta-analyses were performed. First, we compared transition rates to psychosis of UHR individuals with lifetime cannabis use with non-cannabis-using UHR individuals. Second, we compared transition rates of UHR individuals with a current DSM-IV cannabis abuse or dependence diagnosis with lifetime users and non-using UHR individuals.ResultsWe found seven prospective studies reporting on lifetime cannabis use in UHR subjects (n = 1171). Of these studies, five also examined current cannabis abuse or dependence. Lifetime cannabis use was not significantly associated with transition to psychosis [odds ratio (OR) 1.14, 95% confidence interval (CI) 0.856–1.524, p = 0.37]. A second meta-analysis yielded an OR of 1.75 (95% CI 1.135–2.710, p = 0.01), indicating a significant association between current cannabis abuse or dependence and transition to psychosis.ConclusionsOur results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose–response relationship between current cannabis use and transition to psychosis.
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Freitas, Elder Lanzani, Alexandre Andrade Loch, Camille Chianca, Julio Cesar Andrade, Mauricio Henriques Serpa, Tania Maria Alves, Lucas Hortêncio, et al. "Childhood maltreatment in individuals at risk of psychosis: Results from the Brazilian SSAPP cohort." International Journal of Social Psychiatry 66, no. 6 (May 21, 2020): 566–75. http://dx.doi.org/10.1177/0020764020922252.
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Background: Childhood maltreatment is a known risk factor for the development of mental disorders, such as psychotic symptoms. An extensive body of literature about childhood maltreatment and mental health has been developed in wealthy countries, but information about this connection is lacking in developing countries. Aims: To explore a possible relationship between childhood maltreatment and ultra-high risk of psychosis in a non-help-seeking population in a low- and middle-income country. Methods: A household survey was conducted in Sao Paulo, Brazil, involving over 2,500 individuals aged 18–30 years who were randomly selected from the general population. The participants underwent screening with the Prodromal Questionnaire. Ultra-high risk status was assessed using the Structured Interview for Prodromal Syndromes, and childhood maltreatment was assessed using the Childhood Trauma Questionnaire. The final sample comprised 87 ultra-high risk individuals and 115 controls. Results: Childhood maltreatment was significantly more present among ultra-high risk individuals. In ultra-high risk individuals, physical and emotional neglect were inversely related to grandiosity symptoms, physical abuse was related to perceptual abnormalities and physical neglect was related to disorganized speech and thought. Conclusion: This is the first study to investigate the relationship between childhood maltreatment and ultra-high risk status and psychopathological features in a large Latin American sample. Further studies in this field are necessary to better understand the specific influence of various early life adversities on psychosis risk.
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Bloemen, O. J. N., M. B. de Koning, N. Schmitz, D. H. Nieman, H. E. Becker, L. de Haan, P. Dingemans, D. H. Linszen, and T. A. M. J. van Amelsvoort. "White-matter markers for psychosis in a prospective ultra-high-risk cohort." Psychological Medicine 40, no. 8 (November 9, 2009): 1297–304. http://dx.doi.org/10.1017/s0033291709991711.
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BackgroundSubjects at ‘ultra high risk’ (UHR) for developing psychosis have differences in white matter (WM) compared with healthy controls. WM integrity has not yet been investigated in UHR subjects in relation to the development of subsequent psychosis. Hence, we investigated a prospective cohort of UHR subjects comparing whole brain fractional anisotropy (FA) of those later developing psychosis (UHR-P) to those who did not (UHR-NP).MethodWe recruited 37 subjects fulfilling UHR criteria and 10 healthy controls. Baseline 3 Tesla magnetic resonance imaging (MRI) scans and Positive and Negative Syndrome Scale (PANSS) ratings were obtained. UHR subjects were assessed at 9, 18 and 24 months for development of frank psychosis. We compared baseline FA of UHR-P to controls and UHR-NP subjects. Furthermore, we related clinical data to MRI outcome in the patient population.ResultsOf the 37 UHR subjects, 10 had transition to psychosis. UHR-P subjects showed significantly lower FA values than control subjects in medial frontal lobes bilaterally. UHR-P subjects had lower FA values than UHR-NP subjects, lateral to the right putamen and in the left superior temporal lobe. UHR-P subjects showed higher FA values, compared with UHR-NP, in the left medial temporal lobe. In UHR-P, positive PANSS negatively correlated to FA in the left middle temporal lobe. In the total UHR group positive PANSS negatively correlated to FA in the right superior temporal lobe.ConclusionsUHR subjects who later develop psychosis have differences in WM integrity, compared with UHR subjects who do not develop psychosis and to healthy controls, in brain areas associated with schizophrenia.
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Thompson, Andrew, Steven Marwaha, and Matthew R. Broome. "At-risk mental state for psychosis: identification and current treatment approaches." BJPsych Advances 22, no. 3 (May 2016): 186–93. http://dx.doi.org/10.1192/apt.bp.115.015487.
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SummaryThe concept of an ‘at-risk mental state’ for psychosis arose from previous work attempting to identify a putative psychosis prodrome. In this article we summarise the current criteria used to identify ‘at-risk’ individuals, such as the ultra-high-risk (UHR) criteria, and the further identification of important clinical risk factors or biomarkers to improve prediction of who might develop a psychotic disorder. We also discuss important ethical issues in classifying and treating at-risk individuals, current treatment trials in this area and what treatment current services can offer.
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McHugh, M. J., P. D. McGorry, A. R. Yung, A. Lin, S. J. Wood, J. A. Hartmann, and B. Nelson. "Cannabis-induced attenuated psychotic symptoms: implications for prognosis in young people at ultra-high risk for psychosis." Psychological Medicine 47, no. 4 (November 8, 2016): 616–26. http://dx.doi.org/10.1017/s0033291716002671.
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BackgroundCannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).MethodParticipants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).ResultsA history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.ConclusionsFindings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
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Schmidt, A., M. Antoniades, P. Allen, A. Egerton, C. A. Chaddock, S. Borgwardt, P. Fusar-Poli, J. P. Roiser, O. Howes, and P. McGuire. "Longitudinal alterations in motivational salience processing in ultra-high-risk subjects for psychosis." Psychological Medicine 47, no. 2 (October 4, 2016): 243–54. http://dx.doi.org/10.1017/s0033291716002439.
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BackgroundImpairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis.MethodA total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features.ResultsAt presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features.ConclusionsThese findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing.
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An, Suk Kyoon. "Ultra-High Risk for Psychosis : Clinical Characteristics and Diagnosis." Journal of Korean Neuropsychiatric Association 57, no. 3 (2018): 210. http://dx.doi.org/10.4306/jknpa.2018.57.3.210.
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McGorry, Patrick D., Barnaby Nelson, G. Paul Amminger, Andreas Bechdolf, Shona M. Francey, Gregor Berger, Anita Riecher-Rössler, et al. "Intervention in Individuals at Ultra-High Risk for Psychosis." Journal of Clinical Psychiatry 70, no. 9 (June 30, 2009): 1206–12. http://dx.doi.org/10.4088/jcp.08r04472.
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Yung, Alison R. "Treatment of people at ultra-high risk for psychosis." World Psychiatry 16, no. 2 (May 12, 2017): 207–8. http://dx.doi.org/10.1002/wps.20424.
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Guloksuz, S., and J. van Os. "The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum." Psychological Medicine 48, no. 2 (July 10, 2017): 229–44. http://dx.doi.org/10.1017/s0033291717001775.
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The concept of schizophrenia only covers the 30% poor outcome fraction of a much broader multidimensional psychotic syndrome, yet paradoxically has become the dominant prism through which everything ‘psychotic’ is observed, even affective states with mild psychosis labelled ‘ultra-high risk’ (for schizophrenia). The inability of psychiatry to frame psychosis as multidimensional syndromal variation of largely unpredictable course and outcome – within and between individuals – hampers research and recovery-oriented practice. ‘Psychosis’ remains firmly associated with ‘schizophrenia’, as evidenced by a vigorous stream of high-impact but non-replicable attempts to ‘reverse-engineer’ the hypothesized biological disease entity, using case–control paradigms that cannot distinguish between risk for illness onset and risk for poor outcome. In this paper, the main issues surrounding the concept of schizophrenia are described. We tentatively conclude that with the advent of broad spectrum phenotypes covering autism and addiction in DSM5, the prospect for introducing a psychosis spectrum disorder – and modernizing psychiatry – appears to be within reach.
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WOOD, S. J., C. PANTELIS, T. PROFFITT, L. J. PHILLIPS, G. W. STUART, J. A. BUCHANAN, K. MAHONY, W. BREWER, D. J. SMITH, and P. D. McGORRY. "Spatial working memory ability is a marker of risk-for-psychosis." Psychological Medicine 33, no. 7 (September 25, 2003): 1239–47. http://dx.doi.org/10.1017/s0033291703008067.
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Background. Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients.Method. Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS).Results. Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P=0·02).Conclusions. Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.
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Lim, Keane, Max Lam, Jian-Jun Liu, and Jimmy Lee. "SA124POLYGENIC RISK ASSOCIATION IN INDIVIDUALS AT ULTRA-HIGH RISK FOR PSYCHOSIS." European Neuropsychopharmacology 29 (2019): S1256—S1257. http://dx.doi.org/10.1016/j.euroneuro.2018.08.346.
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Amminger, P., N. Mossaheb, M. Schlögelhofer, and M. Schäfer. "Fatty acid metabolism and the onset of psychotic disorder." European Psychiatry 26, S2 (March 2011): 2089. http://dx.doi.org/10.1016/s0924-9338(11)73792-0.
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IntroductionPotentially chronic diseases often have a critical point in their course beyond which treatment becomes less effective. In support of this, early treatment in schizophrenia and other psychoses has been linked to better outcome.ObjectivesThe emergence of simultaneous brain volume changes in those ultra-high-risk individuals who develop psychosis indicate an active biological process, and underline the importance of pre-onset treatment. However, pre-psychotic intervention has also been questioned as, using current criteria, only 20–50% of individuals classified as prodromal develop a psychotic disorder within a 1–2 years period.AimsTreatment agents in the pre-psychotic phase should, therefore, not have major side effects. Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression.MethodsLong-chain omega-3 polyunsaturated fatty acids (PUFAs) have been shown effective for both, mood and psychotic symptoms, and they have neuroprotective properties. Because of the controversy concerned with the extent to which an intervention may produce harm which outweighs its benefits, omega-3 PUFAs are prime candidates for evaluation in putatively prodromal individuals.ResultsWe report on the first randomized, placebo-controlled trial on the preventive use of omega-3 fatty acids in 81 ultra-high-risk individuals.ConclusionsSupplementation with long-chain omega-3 PUFAs reduces the risk of progression to psychotic disorder, and offers a safe and efficacious strategy for indicated prevention in individuals at ultra-high-risk of developing a psychotic illness.
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Valmaggia, L., D. Stahl, A. Yung, B. Nelson, P. McGorry, and P. McGuire. "The structure of the ultra high risk mental state for psychosis. A latent class cluster analysis study." European Psychiatry 26, S2 (March 2011): 2087. http://dx.doi.org/10.1016/s0924-9338(11)73790-7.
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IntroductionIndividuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms.The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis.MethodPsychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis.A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne.ResultsLatent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%).ConclusionsDifferent constellations of symptomatology are associates with varying levels of risk to of transition to psychosis.
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Falkenberg, Irina, Huai-Hsuan Tseng, Gemma Modinos, Barbara Wild, Philip McGuire, and Paul Allen. "S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S93. http://dx.doi.org/10.1093/schbul/sbaa031.216.
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Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.
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Padula, Maria Carmela, Marie Schaer, Marco Armando, Corrado Sandini, Daniela Zöller, Elisa Scariati, Maude Schneider, and Stephan Eliez. "Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis." Psychological Medicine 48, no. 14 (January 17, 2018): 2375–83. http://dx.doi.org/10.1017/s0033291717003920.
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AbstractBackgroundPatients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile.MethodsIn this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach.ResultsOur results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS.ConclusionsThese results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.
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Bakker, G., M. W. A. Caan, R. S. Schluter, O. J. N. Bloemen, F. da Silva- Alves, M. B. de Koning, E. Boot, et al. "Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis." Psychological Medicine 46, no. 11 (May 19, 2016): 2299–311. http://dx.doi.org/10.1017/s0033291716000970.
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BackgroundPatients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.MethodFractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.ResultsCompared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.ConclusionsUHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.
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de la Fuente-Sandoval, Camilo, Pablo León-Ortiz, Mariana Azcárraga, Rafael Favila, Sylvana Stephano, and Ariel Graff-Guerrero. "Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study." International Journal of Neuropsychopharmacology 16, no. 2 (April 17, 2012): 471–75. http://dx.doi.org/10.1017/s1461145712000314.
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Abstract Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.
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Tognin, S., A. Riecher-Rössler, E. M. Meisenzahl, S. J. Wood, C. Hutton, S. J. Borgwardt, N. Koutsouleris, et al. "Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis." Psychological Medicine 44, no. 3 (May 10, 2013): 489–98. http://dx.doi.org/10.1017/s0033291713000998.
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BackgroundGrey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.MethodWe examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.ResultsAt baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.ConclusionsThese data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
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Lee, Ju-Yeon, Young-Chul Chung, Jae-Min Kim, Il-Seon Shin, Jin-Sang Yoon, and Sung-Wan Kim. "School Counselors’ Recognition of the Ultra-High Risk for Psychosis." Psychiatry Investigation 15, no. 3 (March 25, 2018): 320–24. http://dx.doi.org/10.30773/pi.2017.06.19.
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Nelson, Barnaby, and Alison R. Yung. "Can Clinicians Predict Psychosis in an Ultra High Risk Group?" Australian & New Zealand Journal of Psychiatry 44, no. 7 (July 2010): 625–30. http://dx.doi.org/10.3109/00048671003620210.
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Moran, Mark. "CBT for Ultra-High-Risk Patients Lowers Incidence of Psychosis." Psychiatric News 51, no. 19 (October 7, 2016): 1. http://dx.doi.org/10.1176/appi.pn.2016.10a1.
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