Speech Illusions in People at Clinical High Risk for Psychosis Linked to Clinical Outcome

Background and hypothesis Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes. Study design At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning. Study results CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029). Conclusions In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes.The European Network of National Schizophrenia Networks Studying Gene Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2- 2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. Additional support was provided by a Medical Research Council Fellowship to M Kempton (grant MR/J008915/1), and by the Ministerio de Ciencia, Innovación e Universidades to N Barrantes-Vidal (project PSI2017-87512-C2-1-R)

Impact of adverse childhood experiences on educational achievements in young people at clinical high risk of developing psychosis

BACKGROUND: Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). METHODS: In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community'sSeventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview. RESULTS: At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment. CONCLUSIONS: ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.The European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2–2010–241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. Additional support was provided by a Medical Research Council Fellowship to M. Kempton (grant MR/J008915/1). S. Tognin is supported by a Maudsley Charity Grant (1510). B. Nelson was supported by an NHMRC Senior Research Fellowship (1137687)

Neurocognition and functioning in adolescents at clinical high risk for psychosis

BACKGROUND: Once psychosis has set in, it is difficult for patients to achieve full recovery. Prevention of psychosis and early intervention are promising for improving the outcomes of this disorder. In the last two decades, neurocognition has been studied as a biomarker for clinical-high risk for psychosis (CHR-P). However, neurocognitive functioning has been under-investigated in adolescents. METHODS: We enrolled 116 adolescents from 12 to 17years old (mean=15.27, SD=1.56; 76 females). This 3-year cohort study aimed to identify differences in neurocognitive and overall functioning in three groups of adolescent patients divided according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): adolescents with established psychosis, adolescents with CHR-P, and adolescents not meeting either criteria (non-CHR-P). To differentiate the profiles, clinicians administered cognitive evaluation and neuropsychological tasks. Moreover, they filled in scales to assess their global, social, and role functioning and a questionnaire to assess the severity of the disease. RESULTS: We made a between-group comparison on neurocognitive measures and found that the CHR-P and the psychosis groups differed in processing speed (TMT-A; p=.002 in BVN categorial fluency (p=.018), and Rey-Osterrieth complex figure drawing from memory task (p=.014), with psychosis group showing worse performance. No differences emerged between non-CHR-P and CHR-P (p=.014) individuals. CHR-P had better functioning than the psychosis group but worse than the non-CHR-P one. CONCLUSIONS: These results confirm that neurocognition can be a helpful biomarker in identifying specific subgroups of adolescents with emerging psychopathology and help clinicians develop stratified preventive approaches.The present study was supported by the Italian Ministry of Health (Ricerca Corrente)

Can an Experimental White Noise Task Assess Psychosis Vulnerability in Adult Healthy Controls?

Background This is an extension of a paper published earlier. We investigated the association between the tendency to detect speech illusion in random noise and levels of positive schizotypy in a sample of 185 adult healthy controls. Materials and methods Subclinical positive, negative and depressive symptoms were assessed with the Community Assessment of Psychic Experiences (CAPE); positive and negative schizotypy was assessed with the Structured Interview for Schizotypy-Revised (SIS-R). Results Speech illusions were associated with positive schizotypy (OR: 4.139, 95% CI: 1.074-15.938; p = 0.039) but not with negative schizotypy (OR: 1.151, 95% CI: 0.183-7.244; p = 0.881). However, the association of positive schizotypy with speech illusions was no longer significant after adjusting for age, sex and WAIS-III (OR: 2.577, 95% CI: 0.620-10.700; p = 0.192). Speech illusions were not associated with self-reported CAPE measures. Conclusions The association between schizotypy and the tendency to assign meaning in random noise in healthy controls may be mediated by cognitive ability and not constitute an independent trait

The Long-Term Neuroprotective Effect of the Endocannabinoid 2-AG and Modulation of the SGZ’s Neurogenic Response after Neonatal Hypoxia-Ischemia

Neonatal hypoxia-ischemia (HI) often causes hypoxic-ischemic encephalopathy (HIE), a neurological condition that can lead to overall disability in newborns. The only treatment available for affected neonates is therapeutic hypothermia; however, cooling is not always effective to prevent the deleterious effects of HI, so compounds such as cannabinoids are currently under research as new therapies. Modulating the endocannabinoid system (ECS) may reduce brain damage and/or stimulate cell proliferation at the neurogenic niches. Further, the long-term effects of cannabinoid treatment are not so clear. Here, we studied the middle- and long-term effects of 2-AG, the most abundant endocannabinoid in the perinatal period after HI in neonatal rats. At middle-term (postnatal day 14), 2-AG reduced brain injury and increased SGZ’s cell proliferation and the number of neuroblasts. At post-natal day 90, the treatment with the endocannabinoid showed global and local protection, suggesting long-lasting neuroprotective effects of 2-AG after neonatal HI in rats.This research was funded by EITB Maratoia-BIOEF, grant BIO18/IC/003, by MCIN/AEI/10.13039/501100011033, grant MINECOR20/P66 and by the “Programa Investigo” by the European Union-Next Generation EU, grant PIFINVE22/15

A qualitative research of adolescents with behavioral problems about their experience in a dialectical behavior therapy skills training group

BACKGROUND: Several quantitative studies support the effectiveness of the Dialectical Behavior Therapy (DBT) psychosocial skills training group component for adolescents with impulse-control disorder and/or emotional dysregulation. However, qualitative research to assess this psychotherapeutic tool in the adolescent population is sparse. This study aims to examine the subjective experience of adolescents with behavioral issues who have completed DBT skills training group, as well as using this experience to extract hypotheses regarding its usefulness which can then be verified at a later time by means of quantitative instruments. METHODS: We developed a qualitative study by using focus groups with adolescents (N=20) whose diagnosis includes symptoms such as behavior disorder, impulse-control disorder and/or emotional dysregulation, and good informants, who have completed DBT skills training. Three focus groups were created. RESULTS: The subjective experience of adolescents who have completed a DBT skills training group is collected in four main categories: experience of illness, motivation for therapy, experience of therapy and results of the therapy. CONCLUSIONS: Adolescents with behavioral problems assess their participation in the DBT skills training group positively, even recommending its usefulness to healthy population. Beyond learning skills, they emphasize the intrapsychic changes (as improvement in reflective activity) that they objectify after the group experience.This study was partially funded by the Spanish Association of Child and Adolescent Psychiatry (AEPNYA) by awarding the research team the 2015 AEPNYA research prize. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Implementing Precision Psychiatry: a Systematic Review of Individualized Prediction Models for Clinical Practice

BACKGROUND: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders. METHODS: PRISMA/RIGHT/CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models. FINDINGS: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (beta = .29, P = .03) and diagnostic compared to prognostic (beta = .84, p < .0001) and predictive (beta = .87, P = .002) models were associated with increased accuracy. INTERPRETATION: To date, several validated prediction models are available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gapThis study was supported by the King’s College London Confidence in Concept award from the Medical Research Council (MC_PC_16048) to Dr Fusar-Poli. Dr Salazar de Pablo and Dr Vaquerizo-Serrano are supported by the Alicia Koplowitz Foundation. Dr Danese was funded by the Medical Research Council (grant no. P005918) and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King’s College Londo

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis

[EN] Background To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). Methods A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I-2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. Results One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Conclusions Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years