Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

Borderline personality disorder vs. mood disorders: clinical comparisons in young people treated within an “Early Intervention” service for first episode psychosis

Background and Objective Borderline Personality Disorder (BPD) is under-investigated in First Episode Psychosis (FEP). BPD psychotic manifestations and mood changes are also difficult to differentiate from first episode affective psychosis. The aim of this study was to compare sociodemographic and clinical features between FEP patients with BPD vs. Bipolar Disorder (BD) or Major Depressive Disorder (MDD) both at baseline and across a 2-year follow-up period. Methods 224 FEP participants (49 with BPD, 93 with BD and 82 with MDD) completed the Health of the Nation Outcome Scale (HoNOS), the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Psychiatric diagnosis was reformulated at the end of our follow-up. Inter-group comparisons were analyzed using the Kruskal-Wallis or the Chi-square test. A mixed-design ANOVA model was also performed to assess the temporal stability of clinical scores within and between the 3 subgroups. Results Compared to FEP/BD subjects at baseline, FEP/BPD patients showed higher depressive symptom severity and lower excitement severity. Compared to FEP/MDD at entry, they had a higher prevalence rate of substance abuse, a lower interpersonal impairment and a shorter DUP. Finally, they had a lower treatment response on HoNOS “Psychiatric Symptoms” subscale scores across the follow-up in comparison with both FEP/BD and FEP/MDD individuals. Conclusion BPD as categorical entity represents a FEP subgroup with specific clinical features and treatment response. Appropriate treatment guidelines for this FEP subgroup are thus needed. (AU)

Postpartum Psychosis: A Review of Risk Factors, Clinical Picture, Management, Prevention, and Psychosocial Determinants.

Postpartum psychosis is rare, but is a serious clinical and social problem. On its own, it is not included in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) or ICD-10 (International Statistical Classification of Diseases and Related Health Problems) as a disease entity, and current diagnostic criteria equate it with other psychoses. This poses a serious legal problem and makes it difficult to classify. The disorder is caused by a complex combination of biological, environmental, and cultural factors. The exact pathophysiological mechanisms of postpartum psychosis remain very poorly understood. There is a need for further research and increased knowledge of the medical sector in the prevention and early detection of psychosis to prevent stigmatization of female patients during a psychiatric episode. It is necessary to regulate its position in the DSM5 and ICD-10. Attention should be paid to the social education of expectant mothers and their families. This article aims to review the current status of risk factors, prevention, and management of postpartum psychosis.

The Promotion of Mental Health and Prevention of First-Episode Psychosis: A Pilot and Feasibility Non-Randomised Clinical Trial.

BACKGROUND: Mental-health-related stigma prevents active help seeking and therefore early therapeutic approaches and the recovery of functionality. National and international agencies recommend the implementation of prevention and mental health promotion programs that support the elimination of stigma in the classroom, since most mental health problems usually start in the adolescent stage. In view of the evidence that teachers present stigmatizing attitudes towards mental health, it has been considered as convenient to carry out an anti-stigma program with the main objective of evaluating the impact of an intervention based on the education and promotion of mental health, aimed at teachers and counsellors of a secondary school. The specific objectives were to get to know which were the most stigmatising attitudes that prevailed in the sample before and after the intervention; to evaluate the knowledge of the teaching staff and counsellors on psychosis before the intervention; to analyse correlations between clinically relevant variables; and assess whether this programme was beneficial and feasible for alphabetising counsellors/teachers of educational centres on stigma and FEP. METHODS: This was a non-randomised clinical trial in which a nursing intervention was performed. TOOLS: a psychosis test (pre), Stigma Attribution Questionnaire (AQ-27) (pre-post), and satisfaction survey (post) were used. The inferential analysis included the Wilcoxon and the Pearson Correlation Test. RESULTS: In the sample (n = 22), the predominant stigmatising attitude was "Help". The p-values obtained in the Wilcoxon Test were statistically significant, except for "Responsibility" and "Pity". The following constructs of interest were faced: "Fear"-"Age" and "Professional experience"; and "Help"-"Psychosis test". CONCLUSIONS: Despite the scores obtained in "Responsibility" and "Pity", the intervention was useful for reducing stigma in the sample. Implications for the profession: There are adolescents who have suffered stigma from their teachers, and consequently have minimized their symptoms and not asked for help. For this reason, we implemented a nursing intervention based on the education and promotion of mental health, with the aim of expanding knowledge and reducing stigma. In fact, this intervention, which we carried out on high school teachers, managed to reduce the majority of stigmatizing attitudes measured on the stigma attribution scale.

A systematic review of factors prolonging or reducing the duration of untreated psychosis for people with psychosis in low- and middle-income countries.

AIM: This review aims to identify factors that may prolong or reduce the duration of untreated psychosis for people with psychosis in low- and middle-income countries. METHODS: Electronic searches of six databases were conducted, to find studies from low- and middle-income countries on people with psychotic disorders provided they statistically measured an association between factors that may prolong or reduce the duration of untreated psychosis. Studies were critically appraised and a narrative synthesis exploring differences between and within studies is presented. A socio-ecological model is used to convey the main findings. RESULTS: Thirty studies of 16 473 participants in total were included in this review. Taken together participants were 51.5% male and 48.5% female. Various factors potentially associated with longer duration of untreated psychosis for people with psychosis in low- and middle-income countries were found. Examples of these factors are an insidious mode of onset, greater family stigma and low social class. Other factors, such as marital status, educational level, diagnostic type, predominant symptoms and employment status, yielded inconsistent results. CONCLUSIONS: The methodological quality of the included studies limits the conclusions of this review. The results indicate an urgent need for further high-quality research in these countries. The socio-ecological model is a helpful framework for clinicians, scholars, and decision-makers to conceptualize factors that may affect the duration of untreated psychosis, highlight gaps in the literature as well as reflect on potential prevention strategies that may ultimately support early intervention services for people with psychosis in developing countries.

[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.

Factor neurotrófico derivado del cerebro y primeros episodios psicóticos. Estudio pronóstico de un año / Brain-derived neurotrophic factor (bdnf) and first-episode psychosis. a longitudinal one-year prognosis study

Introducción. El factor neurotrófico derivado del cerebro(BDNF) es una neurotrofina que se ha relacionado con la hipótesis del neurodesarrollo de la esquizofrenia. Varios estudios confirman que los niveles de BDNF en el primer episodio psicótico (PEP) son más bajos que en los controles sanos. Sin embargo, los datos al respecto de la evolución de los niveles tras un PEP y el valor pronóstico de dichos niveles son controvertidos. Método. Se compararon los niveles séricos de BDNF al ingreso de 28 pacientes hospitalizados con PEP con 28controles sanos. También se midió el BDNF al momento del alta, a los tres, seis, nueve y doce meses. Los niveles de BDNF se presentan en ng/ml. Se buscó correlación con la sintomatología psicótica medida con la Escala de Síndrome Positivo y Negativo (PANSS) y se evaluó en valor pronóstico de los niveles basales para predecir mala funcionalidad (medida por la Evaluación Global del Funcionamiento) y/o recaída, así como el diagnóstico ulterior de un trastorno psicótico crónico. Resultados. Al ingreso, los niveles de BDNF de los pacientes fueron significativamente más bajos que los niveles de los controles sanos (18,52±4,51 vs. 26,55±3,22, p<0,001). Al altalos niveles de PEP aumentaron hasta niveles de los controles sanos (25,95±3,96 vs. 26,55±3,22, p=0,539). En las siguientes determinaciones, los niveles de BDNF en PEP disminuyeron, alcanzando los valores de ingreso y siendo significativamente más bajos que los controles sanos y los niveles al alta(pacientes: tres meses: 19,68±3,88; seis meses: 19,02±4,13;nueve meses: 17,64±5,24; doce meses:17,51±3,45 vs. controles sanos: 26,55±3,22, todos p<0,001). Se encontró una correlación negativa entre el BDNF al ingreso y las puntuaciones de la subescala de síntomas negativos de la PANSS con una tendencia hacia la significación (r=-0,303, p=0,093). ... (AU)

Introduction. The brain-derived neurotrophic factor(BDNF) is a neurotrophin that has been linked to the schizophrenia neurodevelopmental hypothesis. Several studiesconfirm that the BDNF levels in first-episode psychosis (FEP)are lower than in healthy controls (HC). However, data aboutevolution of BDNF levels after a FEP and about the prognostic value of these levels are controversial. Method. Serum BDNF levels at admission of 28 inpatients with FEP were compared with 28 HC. BDNF was also measured at discharge, three, six, nine and twelve months. BDNF levels are presented in ng/ml. We looked for correlation of BDNF levels with the psychotic symptomatology measuredwith the Positive and Negative Syndrome Scale (PANSS) andalso the prognostic value of basal levels was evaluated topredict poor functionality (measured by the Global Assessment of Functioning) and/or relapse, as well as the subsequent diagnosis of a chronic psychotic disorder. Results. At admission, patients BDNF levels were significantly lower than HC levels (18.52±4.51 vs. 26.55±3.22,p<0.001). At discharge FEP levels increase until HC levels(25.95±3.96 vs. 26.55±3.22, p=0,539). Upon the following determinations, BDNF FEP levels decreased, reaching the admission values, and being significantly lower than the HC andthe levels at discharge (patients: three months: 19.68±3.88;six months: 19.02±4.13; nine months: 17.64±5.24; twelve months: 17.51±3.45 vs. HC: 26.55±3.22, all p<0.001). A negative correlation was found between admission BDNF levels and the PANSS negative symptoms subscale score with a trend towards significance (r=-0.303, p=0.093). BDNF levels at admission of patients with por functionality and/orrelapse at 12 months were lower than BDNF levels of patients with goof functionality and without relapse, this difference had a trend towards significance. (15.38±4.72 vs.19.57±4.06; p=0.071). (AU)

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.

Prevention of First-Episode Psychosis in People at Clinical High Risk: A Randomized Controlled, Multicentre Trial Comparing Cognitive-Behavioral Therapy and Clinical Management Plus Low-Dose Aripiprazole or Placebo (PREVENT).

BACKGROUND: There is limited knowledge of whether cognitive-behavioral therapy (CBT) or second-generation antipsychotics (SGAs) should be recommended as the first-line treatment in individuals at clinical high risk for psychosis (CHRp). HYPOTHESIS: To examine whether individual treatment arms are superior to placebo and whether CBT is non-inferior to SGAs in preventing psychosis over 12 months of treatment. STUDY DESIGN: PREVENT was a blinded, 3-armed, randomized controlled trial comparing CBT to clinical management plus aripiprazole (CM + ARI) or plus placebo (CM + PLC) at 11 CHRp services. The primary outcome was transition to psychosis at 12 months. Analyses were by intention-to-treat. STUDY RESULTS: Two hundred eighty CHRp individuals were randomized: 129 in CBT, 96 in CM + ARI, and 55 in CM + PLC. In week 52, 21 patients in CBT, 19 in CM + ARI, and 7 in CM + PLC had transitioned to psychosis, with no significant differences between treatment arms (P = .342). Psychopathology and psychosocial functioning levels improved in all treatment arms, with no significant differences. CONCLUSIONS: The analysis of the primary outcome transition to psychosis at 12 months and secondary outcomes symptoms and functioning did not demonstrate significant advantages of the active treatments over placebo. The conclusion is that within this trial, neither low-dose aripiprazole nor CBT offered additional benefits over clinical management and placebo.

Psychosis prediction 2.0: why child and adolescent mental health services should be a key focus for schizophrenia and bipolar disorder prevention research.

Existing approaches to psychosis prediction capture only a small minority of future cases. Recent research shows that specialist child and adolescent mental health services (CAMHS) offer a (previously unrecognised) high-risk and high-capacity approach for psychosis early identification, prediction and, ultimately, prevention.

Relapse prevention through health technology program reduces hospitalization in schizophrenia.

BACKGROUND: Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge. METHODS: The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge. RESULTS: The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = -4.58, 95% CI -9.03 to -0.13, p = 0.044) in the intervention condition compared to control. CONCLUSIONS: These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.

A principle-based framework for disclosing a psychosis risk diagnosis.

In recent decades, researchers have attempted to prospectively identify individuals at high risk of developing psychosis in the hope of delaying or preventing psychosis onset. These psychosis risk individuals are identified as being in an 'At-Risk Mental State' (ARMS) through a standardised psychometric interview. However, disclosure of ARMS status has attracted criticism due to concerns about the risk-benefit ratio of disclosure to patients. Only approximately one quarter of ARMS patients develop psychosis after three years, raising concerns about the unnecessary harm associated with such 'false-positive' results. These harms are especially pertinent when identifying psychosis risk individuals due to potential stigma and discrimination in a young clinical population. A dearth of high-quality evidence supporting interventions for ARMS patients raises further doubts about the benefit accompanying an ARMS disclosure. Despite ongoing discussion in the bioethical literature, these concerns over the ethical justification of disclosure to ARMS patients are not directly addressed in clinical guidelines. In this paper, we aim to provide a unified disclosure strategy grounded in principle-based analysis for ARMS clinicians. After considering the ethical values at stake in ARMS disclosure, and their normative significance, we argue that full disclosure of the ARMS label is favoured in the vast majority of clinical situations due to the strong normative significance of enhancing patients' understanding. We then compare our framework with other approaches to ARMS disclosure and outline its limitations.