[The influence of maternal choline supplementation on fetal brain development and the risk of psychotic symptoms]. / De invloed van maternale cholinesuppletie op foetale hersenontwikkeling en het risico op psychose.

BACKGROUND: Choline is an essential micronutrient important for fetal brain development. Research suggests that maternal choline supplementation during pregnancy may reduce the risk of developing neuropsychiatric disorders such as psychosis in offspring. AIM: To provide a narrative review of evidence from the literature for the possible prevention of neuropsychiatric problems such as psychosis by maternal choline supplementation. METHOD: A narrative review of the literature obtained after searches in PubMed, Embase and PsycINFO. RESULTS: Nutritional studies indicate that most pregnant women do not receive sufficient dietary choline. This may have adverse effects on fetal brain development. A total of 8 studies were identified; 4 animal and 4 clinical studies. Beneficial effects of maternal choline supplementation were found on fetal brain development, including cognitive and psychosocial functioning of children. No evidence of (serious) side effects was found. Due to the relatively short duration and limited size of the studies, no conclusions could be drawn about the role of maternal choline supplementation in the prevention of neuropsychiatric problems such as psychosis. CONCLUSION: Maternal choline supplementation and/or a choline-rich diet during pregnancy should be further investigated because of evidence of beneficial effects on infant mental functioning, low cost and few side effects. There is no evidence that maternal choline supplementation can prevent psychotic symptoms in offspring.

Complementary/Integrative Medicine Treatment and Prevention of Youth Psychosis.

The rationale for CIM treatments in youth psychoses is to optimize treatment by targeting symptoms not resolved by antipsychotics, such as negative symptoms (major drivers of disability). Adjunctive omega-3 fatty acids (ω-3 FA) or N-acetyl cystine (NAC usage for > 24-week) can potentially reduce negative symptoms and improve function. ω-3 FA or exercise may prevent progression to psychosis in youth (in prodromal stage). Weekly 90-minute moderate to vigorous physical activity or aerobic exercise can reduce positive and negative symptoms. Awaiting better research, CIM agents are also recommended because they are devoid of any serious side-effects.

Pretreatment with Carpolobia lutea ethanol extract prevents schizophrenia-like behavior in mice models of psychosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Carpolobia lutea decoction is widely used as a phytotherapeutic against central nervous system-related disorders including insomnia, migraine headache, and mental illness in West and Central Tropical Africa. AIM: This study was designed to investigate the antipsychotic activity of Carpolobia lutea (EECL) in mice models of psychosis. METHODS: Male Swiss mice (n = 5/group) were given EECL (100, 200, 400, and 800 mg/kg), haloperidol (1 mg/kg), clozapine (5 mg/kg) and vehicle (10 mL/kg) orally before amphetamine (5 mg/kg)-induced hyperlocomotion and stereotypy, apomorphine (2 mg/kg)-induced stereotypy, or ketamine (10, 30, and 100 mg/kg)-induced hyperlocomotion, enhancement of immobility and cognitive impairment. RESULTS: EECL (200, 400, and 800 mg/kg) prevented amphetamine- and apomorphine-induced stereotypies, as well as reduced hyperlocomotion induced by amphetamine and ketamine, all of which are predictors of positive symptoms. Regardless of the dose administered, EECL prevented the index of negative symptoms induced by ketamine. Furthermore, higher doses of EECL (400 and 800 mg/kg) also prevented ketamine-induced cognitive impairment, a behavioral phenotype of cognitive symptoms. CONCLUSION: Pretreatment with EECL demonstrated antipsychotic activity in mice, preventing amphetamine-, apomorphine-, and ketamine-induced schizophrenia-like symptoms, with 800 mg/kg being the most effective dose.

Results of a prospective, mixed methods study to assess feasibility, acceptability and effectiveness of TRIumPH (Treatment and Recovery In PsycHosis): an integrated care pathway for psychosis, compared to usual treatment.

OBJECTIVES: To evaluate whether a newly developed care pathway, Treatment and Recovery In PsycHosis (TRIumPH), is feasible, acceptable and effective in meeting National Institute of Health and Care Excellence (NICE) quality standards in a timely manner. METHODS: This is a pragmatic, non-randomised, prospective, mixed methods study comparing an implementation (TRIumPH) and comparator site (not implementing TRIumPH) across three cohorts to assess feasibility, acceptability and effectiveness of the integrated pathway. SETTING: Early intervention in psychosis (EIP) services at two National Health Service organisations in South of England. PARTICIPANTS: All patients accepted into EIP services between 1 June 2014 and 31 May 2017 were each followed up for 1 year within their respective cohorts. METHODOLOGY: Quantitative data consisted of routinely collected clinical data retrieved from patient records to assess whether the implementation of TRIumPH achieved better concordance to NICE standards. These included time to access services, physical health assessments, clinical outcomes based timeliness of delivery and acute data. The controlled trial has evaluated the effect of TRIumPH (Intervention) with Care As Usual (Comparator). Qualitative measures consisted of questionnaires, interviews and focus groups to assess acceptability and satisfaction. Outcome measures were compared within the baseline, year 1 and year 2 cohorts and between the two sites. Quantitative data were statistically analysed by comparing means and proportions. RESULTS: Time to assessment improved in the implementation site and remained within the target in comparator site. Meeting of quality standards increased substantially in the implementation site but was more variable and reached lower levels in the comparator site especially for physical health standards. Cognitive therapy for psychosis, family intervention and carer and employment support were all offered to a greater extent in the implementation site and uptake increased over the period. CONCLUSIONS: Pathway implementation generally led to greater improvements in achievement of access and quality standards compared with comparator site. TRIAL REGISTRATION NUMBER: UK Clinical Research Network Portfolio (19187).

Diet and Psychosis: A Scoping Review.

INTRODUCTION: Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD. OBJECTIVE: This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research. METHODS: This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed. RESULTS: Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan). DISCUSSION: Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes.

Supporting the intimate relationship needs of service users with psychosis: what are the barriers and facilitators?

Background: Mental health services aim to provide holistic care, but the intimacy needs of clients are neglected. Currently there is limited understanding of the challenges mental health professionals (MHPs) face when considering supporting the relationship needs of people with psychosis.Aim: This study investigated the views of community-based MHPs from a range of disciplines regarding the barriers and facilitators to supporting clients with their romantic relationship needs.Method: Semi-structured interviews were conducted with 20 professionals and analysed from a realist perspective using thematic analysis.Results: Barriers identified were: (1) "They will never be able to form close attachments." (2) "Modern social care teaches us reduce risk, reduce risk, reduce risk." (3) "You're only relying on what you've picked up over the years". Facilitators were: (1) "If they could find a partner they would progress a lot more". (2) "It's all to do with the relationship you've got between you and your client". (3) "It's having the resources".Conclusions: Results highlight areas for service improvement and will help inform the development of future interventions.

Applying intervention mapping approach to a program for early intervention in first-episode mental crisis of a psychotic type

Abstract The holotropic mind perspective, an integral part of the framework of transpersonal psychology, has been considered a revolutionary approach to a certain spectrum of experiences in Non-ordinary states of consciousness (NOSC) which conventional approaches tend to treat indiscriminately as pathological processes, because PHM recognizes in these experiences their healing and evolutionary potential. This article describes the needs assessment, implementation, and evaluation of an experiential and educational program on the holotropic mind perspective and its praxis, Holotropic Breathwork® (HB), with students and professionals from the Group for Early Intervention in First-Episode Mental Crisis of a Psychotic Type of the University of Brasilia. The intervention aimed to establish change goals and objectives that would promote the adoption of the holotropic mind perspective's elements, such as a framework to broaden and strengthen mental health programs that assist people experiencing NOSC. The stages developed, inspired by the Intervention Mapping protocol, included a needs assessment; elaboration of change objective matrices; selection and description of methods based on theory and their applications; conception, planning, and implementation of the intervention; and results evaluation. Participants reported that the intervention allowed the expansion of their theoretical-conceptual and technical frameworks, giving them a less pathologizing understanding of and approach to NOSC and allowing them to perceive and manage such states, not as indiscriminately pathological expressions, but as phenomena inherent to the human condition that can be accepted and cared for without the exclusionary and exhaustive bias of mental disorders. Limitations and practical implications are discussed.

Interventions for prodromal stage of psychosis.

BACKGROUND: Psychosis is a serious mental condition characterised by a loss of contact with reality. There may be a prodromal period or stage of psychosis, where early signs of symptoms indicating onset of first episode psychosis (FEP) occur. A number of services, incorporating multimodal treatment approaches (pharmacotherapy, psychotherapy and psychosocial interventions), developed worldwide, now focus on this prodromal period with the aim of preventing psychosis in people at risk of developing FEP. OBJECTIVES: The primary objective is to assess the safety and efficacy of early interventions for people in the prodromal stage of psychosis. The secondary objective is, if possible, to compare the effectiveness of the various different interventions. SEARCH METHODS: We searched Cochrane Schizophrenia's study-based Register of studies (including trials registers) on 8 June 2016 and 4 August 2017. SELECTION CRITERIA: All randomised controlled trials (RCTs) evaluating interventions for participants older than 12 years, who had developed a prodromal stage of psychosis. DATA COLLECTION AND ANALYSIS: Review authors independently inspected citations, selected studies, extracted data, and assessed study quality. MAIN RESULTS: We included 20 studies with 2151 participants. The studies analysed 13 different comparisons. Group A comparisons explored the absolute effects of the experimental intervention. Group B were comparisons within which we could not be clear whether differential interactive effects were also ongoing. Group C comparisons explored differential effects between clearly distinct treatments. A key outcome for this review was 'transition to psychosis'. For details of other main outcomes please see 'Summary of findings' tables. In Group A (comparisons of absolute effects) we found no clear difference between amino acids and placebo (risk ratio (RR) 0.48 95% confidence interval (CI) 0.08 to 2.98; 2 RCTs, 52 participants; very low-quality evidence). When omega-3 fatty acids were compared to placebo, fewer participants given the omega-3 (10%) transitioned to psychosis compared to the placebo group (33%) during long-term follow-up of seven years (RR 0.24 95% CI 0.09 to 0.67; 1 RCT, 81 participants; low-quality evidence). In Group B (comparisons where complex interactions are probable) and in the subgroup focusing on antipsychotic drugs added to specific care packages, the amisulpiride + needs-focused intervention (NFI) compared to NFI comparison (no reporting of transition to psychosis; 1 RCT, 102 participants; very low-quality evidence) and the olanzapine + supportive intervention compared to supportive intervention alone comparison (RR 0.58 95% CI 0.28 to 1.18; 1 RCT, 60 participants; very low-quality evidence) showed no clear differences between groups. In the second Group B subgroup (cognitive behavioural therapies (CBT)), when CBT + supportive therapy was compared with supportive therapy alone around 8% of participants allocated to the combination of CBT and supportive therapy group transitioned to psychosis during follow-up by 18 months, compared with double that percentage in the supportive therapy alone group (RR 0.45 95% CI 0.23 to 0.89; 2 RCTs, 252 participants; very low-quality evidence). The CBT + risperidone versus CBT + placebo comparison identified no clear difference between treatments (RR 1.02 95% CI 0.39 to 2.67; 1 RCT, 87 participants; very low-quality evidence) and this also applies to the CBT + needs-based intervention (NBI) + risperidone versus NBI comparison (RR 0.75 95% CI 0.39 to 1.46; 1 RCT, 59 participants; very low-quality evidence). Group C (differential effects) also involved six comparisons. The first compared CBT with supportive therapy. No clear difference was found for the 'transition to psychosis' outcome (RR 0.74 95% CI 0.28 to 1.98; 1 RCT, 72 participants; very low-quality evidence). The second subgroup compared CBT + supportive intervention was compared with a NBI + supportive intervention, again, data were equivocal, few and of very low quality (RR 6.32 95% CI 0.34 to 117.09; 1 RCT, 57 participants). In the CBT + risperidone versus supportive therapy comparison, again there was no clear difference between groups (RR 0.76 95% CI 0.28 to 2.03; 1 RCT, 71 participants; very low-quality evidence). The three other comparisons in Group C demonstrated no clear differences between treatment groups. When cognitive training was compared to active control (tablet games) (no reporting of transition to psychosis; 1 RCT, 62 participants; very low quality data), family treatment compared with enhanced care comparison (RR 0.54 95% CI 0.18 to 1.59; 2 RCTs, 229 participants; very low-quality evidence) and integrated treatment compared to standard treatment comparison (RR 0.57 95% CI 0.28 to 1.15; 1 RCT, 79 participants; very low-quality evidence) no effects of any of these approaches was evident. AUTHORS' CONCLUSIONS: There has been considerable research effort in this area and several interventions have been trialled. The evidence available suggests that omega-3 fatty acids may prevent transition to psychosis but this evidence is low quality and more research is needed to confirm this finding. Other comparisons did not show any clear differences in effect for preventing transition to psychosis but again, the quality of this evidence is very low or low and not strong enough to make firm conclusions.

Marijuana and Psychosis: Policy Implications for Treatment Providers.

In 2017, the annual prevalence of marijuana use rose to 24% among 8th to 12th graders, despite decreases in rates of other illicit substance use.1 This is of concern, as increasing use is coupled with declining perception of harm among adolescents,1 increasing potency of cannabis,2 ease of adolescents' access to marijuana,1 and progressive medicalization and legalization of marijuana. Exposure to high levels of Δ-9-tetrahydrocannabinol through cannabis use triggers repeated activation of the endogenous mesolimbic dopaminergic system, desensitization, and progressive enhancement of acquired susceptibility to psychosis.3.

Mindfulness and psychotic experiences in college students / Mindfulness y experiencias psicóticas en estudiantes universitarios

The study of the relation between psychotic experiences and mindfulness in the general population is linked to research into factors of risk and protection against the development of a psychotic disorder. This study looks into the presence of psychotic experiences in a sample of university students and whether there is any variation according to gender. It also analyzes the predictive and discriminant relation of mindfulness with these experiences. The sample consisted of 526 university students (72.8% women) with a mean age of 21.39 years (SD = 3.53). The results showed the presence of psychotic experiences with differing levels of intensity, with variations according to gender, and an inverse relationship between mindfulness and psychotic experiences. Results indicated that students with high scores in psychotic experiences had lower scores in mindfulness. Our findings imply that mindfulness may be a factor of protection against psychotic experiences and its training may have a role to play in the development and implementation of preventive and early intervention programs in risk groups in the general and clinical population

El estudio de la relación entre experiencias psicóticas y mindfulness en la población general se asocia con la investigación de factores de riesgo y protección frente al desarrollo de un trastorno psicótico. Con este estudio se pretende examinar la presencia de experiencias psicóticas en una muestra de estudiantes universitarios y sus diferencias según el sexo, así como analizar la relación predictiva y discriminante de mindfulness con estas experiencias. Los participantes fueron 526 estudiantes universitarios (72.8% mujeres) con una media de edad de 21.39 años (DT = 3.53). Los resultados mostraron la presencia de experiencias psicóticas con diferentes niveles de intensidad, diferencias según el sexo en las mismas, y una relación inversa entre mindfulness y las experiencias psicóticas, y se encontró que las personas con altas puntuaciones en experiencias psicóticas contaron con menores puntuaciones en mindfulness. Estos resultados suponen que mindfulness puede ser un factor de protección en la experimentación de experiencias psicóticas y su entrenamiento puede ser útil para implementación y desarrollo de programas preventivos y de intervención precoz en grupos de riesgo en población general y clínica

Biofeedback to treat anxiety in young people at clinical high risk for developing psychosis.

AIM: Anxiety is a common presenting concern for individuals at clinical high risk (CHR) for psychosis. Treatment for CHR is still in the early stages and has focused on transition to psychosis and positive symptom reduction, but little is known about what may be effective in reducing anxiety for these young people. One treatment that may be effective for anxiety is heart rate variability (HRV) biofeedback. The aim of this study was to test the efficacy and feasibility of using HRV biofeedback to reduce anxiety and distress in those at CHR. METHODS: Twenty participants who met minimum scores for anxiety and distress completed 4 weeks of an HRV biofeedback intervention and received pre- and post-intervention assessments. Repeated measures were used to examine changes in scores over time. RESULTS: There was a significant decrease in impaired ability to tolerate normal stressors (P ≤ 0.001) and dysphoric mood (P ≤ 0.001) over time. There was no change on self-reported measures of anxiety and distress. However, when two outliers were removed there was a trend towards improvement in self-reported anxiety (P = 0.07). These results were not impacted by including usage time as a covariate. Feedback and adherence were significant. CONCLUSIONS: HRV biofeedback may be a feasible treatment option for individuals at CHR who have concerns with impaired stress tolerance and dysphoric mood. Future studies with a randomized controlled trial design will be necessary to further determine efficacy.

A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol.

BACKGROUND: The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries. METHODS/DESIGN: A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis. DISCUSSION: The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015.

Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study.

Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.

Indicated prevention with long-chain polyunsaturated omega-3 fatty acids in patients with 22q11DS genetically at high risk for psychosis. Protocol of a randomized, double-blind, placebo-controlled treatment trial.

AIM: It has been found that long-chain omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of progression to first episode of psychosis (FEP) and may offer a safe and efficacious strategy for selective and indicated prevention in young people with ultra-high-risk (UHR) states. An opportunity for exploring the trajectory of FEP and for investigating the efficacy of preventive treatments exists in 22q11.2 deletion syndrome (22q11DS), which has a 30% psychotic transition rate. The fact that 22q11DS patients are more homogeneous than other UHR groups and are characterized by high level of negative symptoms provides a strong rationale for the use of PUFAs. The principal aim of the present trial is to investigate the effects of PUFAs in individuals with 22q11DS who are at UHR for developing FEP. METHODS: A prospective, randomized, double-blind, placebo-controlled, single-centre study design will be used. Eighty individuals aged 12-26 will be randomly assigned to two treatment conditions. RESULTS: The experimental group will receive PUFAs. The placebo group will receive paraffin oil. Standard clinical assessments and neuropsychological tests will be performed at baseline and at 8-, 12-, 26- and 52-week follow-up. Blood samples will be collected at baseline and after 12 weeks. This study is registered as an International Standard RCT, number 02070211. The corresponding author is supported by a NARSAD Young Investigator Award. CONCLUSIONS: This is the protocol of a planned study that aims to test the efficacy of PUFAs in the prodromal phase of FEP, in a specific syndrome where there is strong evidence that a high genetic load is involved in the disorder.

Primary prevention of psychosis through interventions in the symptomatic prodromal phase, a pragmatic Norwegian Ultra High Risk study.

BACKGROUND: Evidence has been accumulating that it may be possible to achieve prevention in psychotic disorders. The aim of the Prevention Of Psychosis (POP) study is to reduce the annual incidence of psychotic disorders in a catchment area population through detection and intervention in the prodromal phase of disorder. Prodromal patients will be recruited through information campaigns modelled on the Scandinavian early Treatment and Intervention in Psychosis (TIPS) study and assessed by low-threshold detection teams. METHODS/DESIGN: The study will use a parallel control design comparing the incidence of first episode psychotic disorders between two Norwegian catchment areas with prodromal detection and treatment (Stavanger and Fonna) with two catchment areas without a prodromal intervention program (Bergen and Østfold). The primary aim of the current study is to test the effect of a Prodromal Detection and Treatment program at the health care systems level. The study will investigate: 1) If the combination of information campaigns and detection teams modelled will help in identifying individuals (age 13-65, fulfilling study inclusion criteria) at high risk of developing psychosis early, and 2) If a graded, multi-modal treatment program will reduce rates of conversion compared to the rates seen in follow-along assessments. DISCUSSION: Positive results could potentially revolutionize therapy by treating risk earlier rather than disorder later and could open a new era of early detection and intervention in psychosis. Negative results will suggest that the potential for psychosis is determined early in life and that research should focus more on genetically linked neurodevelopmental processes. If we can identify people about to become psychotic with high accuracy, we can track them to understand more about how psychosis unfolds. Appropriate intervention at this stage could also prevent or delay the onset of psychosis and/or subsequent deterioration, i.e., social and instrumental disability, suicide, aggressive behavior, affective- and cognitive deficits. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20328848 . Registered 02 November 2014.

Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial.

OBJECTIVE: To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis. METHODS: We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery-Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography. RESULTS: At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups. CONCLUSIONS: Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00396643).

Objectif : Rechercher si les acides gras polyinsaturés à longue chaîne (AGPLC) oméga-3 (n-3) améliorent le fonctionnement et les symptômes psychiatriques chez les jeunes personnes souffrant du trouble de la personnalité limite (TPL) qui satisfont aussi aux critères du risque ultra-élevé de psychose. Méthodes : Nous avons mené une analyse a posteriori d'un sous-groupe d'un essai randomisé contrôlé à double insu. Quinze adolescents souffrant du TPL (âge moyen 16,2 ans, [ET 2,1]) ont été assignés au hasard à 1,2 g/jour AGPLC n-3, ou à un placebo. La période d'intervention était de 12 semaines. Les mesures de l'étude étaient notamment l'Échelle des symptômes positifs et négatifs, l'échelle de dépression Montgomery­Åsberg, et l'évaluation globale du fonctionnement. Les effets secondaires ont été documentés à l'aide de l'échelle Udvalg for Kliniske Undersøgelser. Les acides gras des érythrocytes ont été analysés par chromatographie capillaire gazeuse. Résultats : Au départ, les taux d'AGPLC n-3 des érythrocytes corrélaient positivement avec le fonctionnement psychosocial et négativement avec la psychopathologie. À la fin de l'intervention, les AGPLC n-3 amélioraient significativement le fonctionnement et réduisaient les symptômes psychiatriques, comparativement au placebo. Les effets secondaires ne différaient pas entre les groupes. Conclusions : Les AGP à longue chaîne n-3 devraient être davantage explorés comme stratégie de traitement viable comportant un risque associé minimal chez les jeunes personnes souffrant du TPL. (Numéro d'enregistrement d'essai clinique : NCT00396643).

Early interventions to prevent psychosis: systematic review and meta-analysis.

OBJECTIVE: To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. REVIEW METHODS: Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results. RESULTS: 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference -0.07 (-0.14 to -0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months. CONCLUSIONS: Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.

Glycine treatment of the risk syndrome for psychosis: report of two pilot studies.

Patients meeting criteria for the risk syndrome for psychosis have treatment needs including positive and negative symptoms and cognitive impairment. These features could potentially respond to NMDA glycine-site agonists. The present objective was to determine which symptoms or domains of cognition promise to show the greatest response to glycine in risk syndrome patients. We conducted two short-term pilot studies of glycine used without adjunctive antipsychotic medication. In the first trial, 10 risk syndrome subjects received open-label glycine at doses titrated to 0.8 g/kg/d for 8 weeks, followed by discontinuation and 16 weeks of evaluation for durability of effects. In the second, 8 subjects were randomized to double-blind glycine vs. placebo for 12 weeks, followed by open-label glycine for another 12 weeks. Patients were evaluated every 1-2 weeks with the Scale Of Psychosis-risk Symptoms (SOPS) and before and after treatment with a neurocognitive battery. Within-group and between-group effect sizes were calculated. Effect sizes were large for positive (open-label within-group -1.10, double-blind between-group -1.11) and total (-1.39 and -1.15) symptoms and medium-to-large (-0.74 and -0.79) for negative symptoms. Medium or large effect sizes were also observed for several neurocognitive measures in the open-label study, although data were sparse. No safety concerns were identified. We conclude that glycine was associated with reduced symptoms with promising effect sizes in two pilot studies and a possibility of improvement in cognitive function. Further studies of agents that facilitate NMDA receptor function in risk syndrome patients are supported by these preliminary findings.