Ultra-high Risk Research Articles

The association between aberrant salience and psychotic experiences in general population twins, and genetic vulnerability as a modifier

BackgroundPrevious studies assessing the hypothesis that the construct of ‘aberrant salience’ is associated with psychosis and psychotic symptoms showed conflicting results. For this reason, the association between measures to index aberrant salience and subclinical psychotic symptoms in a general population sample was analysed. In addition, genetic vulnerability was added to the analysis as a modifier to test the hypothesis that modification by genetic vulnerability may explain variability in the results.MethodsThe TwinssCan project obtained data from general population twins (N = 887). CAPE (Community Assessment of Psychic Experience) scores were used to index psychotic experiences. Aberrant salience was assessed with white noise task and ambiguous situations task.ResultsMeasures of aberrant salience were not associated with psychotic experiences, nor was there evidence for an interaction with genetic predisposition in this association (Z = 1.08, p = 0.282).ConclusionsVarious studies including the present could not replicate the association between aberrant salience and psychotic experiences in general population samples. The conflicting findings might be explained by moderation by genetic vulnerability, but results are inconsistent. If there was evidence for a main effect or interaction, this was in the positive symptom scale only. On the other hand, the association was more robust in so-called ‘ultra-high risk’ patients and first episode psychosis patients. Thus, this association may represent a state-dependent association, present only at the more severe end of the psychosis spectrum.

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial.

In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing. A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel. There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups. This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up. This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).

A generalisability theory approach to quantifying changes in psychopathology among ultra-high-risk individuals for psychosis

Distinguishing stable and fluctuating psychopathological features in young individuals at Ultra High Risk (UHR) for psychosis is challenging, but critical for building robust, accurate, early clinical detection and prevention capabilities. Over a 24-month period, 159 UHR individuals were assessed using the Positive and Negative Symptom Scale (PANSS). Generalisability Theory was used to validate the PANSS with this population and to investigate stable and fluctuating features, by estimating the reliability and generalisability of three factor (Positive, Negative, and General) and five factor (Positive, Negative, Cognitive, Depression, and Hostility) symptom models. Acceptable reliability and generalisability of scores across occasions and sample population were demonstrated by the total PANSS scale (Gr = 0.85). Fluctuating symptoms (delusions, hallucinatory behaviour, lack of spontaneity, flow in conversation, emotional withdrawal, and somatic concern) showed high variability over time, with 50–68% of the variance explained by individual transient states. In contrast, more stable symptoms included excitement, poor rapport, anxiety, guilt feeling, uncooperativeness, and poor impulse control. The 3-factor model of PANSS and its subscales showed robust reliability and generalisability of their assessment scores across the UHR population and evaluation periods (G = 0.77–0.93), offering a suitable means to assess psychosis risk. Certain subscales within the 5-factor PANSS model showed comparatively lower reliability and generalisability (G = 0.33–0.66). The identified and investigated fluctuating symptoms in UHR individuals are more amendable by means of intervention, which could have significant implications for preventing and addressing psychosis. Prioritising the treatment of fluctuating symptoms could enhance intervention efficacy, offering a sharper focus in clinical trials. At the same time, using more reliable total scale and 3 subscales can contribute to more accurate assessment of enduring psychosis patterns in clinical and experimental settings.

Service users perspectives on psychosis-risk terminology: An Italian study on labeling terms preferences and stigma

AimsThe current range of labeling terms—at-risk mental state (ARMS), ultra-high risk for psychosis (UHR), and attenuated psychotic syndrome (APS)—used to refer to the psychosis-risk concept is varied, and their acceptability and potential stigma are not well understood. By involving Italian youth with lived experience of mental ill-health, we aimed to generate new labeling terms for psychosis-risk, and to evaluate literacy, attitudes, and preferences regarding these and the existing terms. Additionally, we investigated opinions of disclosure of the at-risk concept in clinical practice. MethodsThrough a dual-moderator focus group, novel diagnostic terms were coined for the at-risk concept: psychosis proneness (PP), change of personal reality (CPR), and hints of subjectivity dysregulation (HSD). A specifically designed questionnaire was then completed by 47 help-seeking youths, 60 relatives, and 61 clinicians to test newly generated and already established at-risk terms. ResultsLiteracy on already established terms was significantly lower among youth (mean= 42 %) and relatives (mean= 38 %). ARMS was the preferred and least stigmatizing term among young people and clinicians. UHR was considered the most stigmatizing label. Among newly generated terms, CPR was the least stigmatizing and most informative. Disclosure of at-risk terminology was generally preferred after establishing a trusting clinician-patient relationship. ConclusionsFindings support ARMS as a useful and acceptable term in clinical practice with young people, while UHR is associated with the highest stigma. CPR is promising and should be tested in cross-cultural studies. In Italy, there is an urgent need for improving literacy on prevention in mental health.

Identification and validation of a novel five-gene signature in high-risk MYCN-not-amplified neuroblastoma

ObjectiveHigh-risk neuroblastoma patients often have poor outcomes despite multi-treatment options. The risk stratification of high-risk MYCN-not-amplified (HR-MYCN-NA) patients remains difficult. This study aims to identify a gene set signature that can help further stratify HR-MYCN-NA patients for a potential personalized therapeutic strategy.MethodsThree microarrays and one single-cell RNA sequence dataset were acquired and analyzed. Firstly, the prognostic-related genes (PRGs) in HR-MYCN-NA tumor cells were identified using TARGET-NB and GSE137804 datasets. Then, the prognostic model was established by LASSO-Cox regression, and verified in external cohort (GSE49710, GSE45547). Moreover, a time-dependent receiver operating characteristic curve (ROC) and area under the ROC (AUC) was used to assess survival prediction. A nomogram was established to predict the 1-, 3- and 5-year overall survival (OS) of HR-MYCN-NA patients.ResultsIn the training set, a five-PRGs signature, which include GAL, GFRA3, MARCKS, PSMD13, and ZNHIT3 genes, was identified and successfully stratified HR-MYCN-NA patients into ultra-high risk (UHR) and high-risk (HR) subtypes (HR = 4.29, P < 0.001). ROC curve analysis confirmed its predictive power (AUC = 0.74–0.82), suggesting a good predictive efficacy. Consistently, high-risk scores also predicted worse OS (HR = 2, P = 0.033) in the external validation dataset (AUC = 0.67–0.71). Moreover, the overall C-index of the nomogram was 0.75 (P < 0.001), which indicated good agreement between the observed and predicted survival rates. Further integrating the five PRGs signature with clinical factors, these 5 gene signature (HR = 4.45, P < 0.001) and tumor grade (HR = 4.15, P = 0.02) were found to be independent prognostic factors for HR-MYCN-NA patients.ConclusionThe novel five PRGs signature could well predict the survival of HR-MYCN-NA patients, which may provide constructive information for these subsets.

Development and temporal validation of a clinical prediction model of transition to psychosis in individuals at ultra-high risk in the UHR 1000+ cohort.

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets have now been integrated into the UHR 1000+ cohort, consisting of a sample of 1,245 UHR individuals with a follow-up period ranging from 1 to 16.7 years. This paper describes the cohort, presents a clinical prediction model of transition to psychosis in this cohort, and examines how predictive performance is affected by changes in UHR samples over time. We analyzed transition to psychosis using a Cox proportional hazards model. Clinical predictors for transition to psychosis were investigated in the entire cohort using multiple imputation and Rubin's rule. To assess performance drift over time, data from 1995-2016 were used for initial model fitting, and models were subsequently validated on data from 2017-2020. Over the follow-up period, 220 cases (17.7%) developed a psychotic disorder. Pooled hazard ratio (HR) estimates showed that the Comprehensive Assessment of At-Risk Mental States (CAARMS) Disorganized Speech subscale severity score (HR=1.12, 95% CI: 1.02-1.24, p=0.024), the CAARMS Unusual Thought Content subscale severity score (HR=1.13, 95% CI: 1.03-1.24, p=0.009), the Scale for the Assessment of Negative Symptoms (SANS) total score (HR=1.02, 95% CI: 1.00-1.03, p=0.022), the Social and Occupational Functioning Assessment Scale (SOFAS) score (HR=0.98, 95% CI: 0.97-1.00, p=0.036), and time between onset of symptoms and entry to UHR service (log transformed) (HR=1.10, 95% CI: 1.02-1.19, p=0.013) were predictive of transition to psychosis. UHR individuals who met the brief limited intermittent psychotic symptoms (BLIPS) criteria had a higher probability of transitioning to psychosis than those who met the attenuated psychotic symptoms (APS) criteria (HR=0.48, 95% CI: 0.32-0.73, p=0.001) and those who met the Trait risk criteria (a first-degree relative with a psychotic disorder or a schizotypal personality disorder plus a significant decrease in functioning during the previous year) (HR=0.43, 95% CI: 0.22-0.83, p=0.013). Models based on data from 1995-2016 displayed good calibration at initial model fitting, but showed a drift of 20.2-35.4% in calibration when validated on data from 2017-2020. Large-scale longitudinal data such as those from the UHR 1000+ cohort are required to develop accurate psychosis prediction models. It is critical to assess existing and future risk calculators for temporal drift, that may reduce their utility in clinical practice over time.

Assessing biological stress markers in the hair of individuals at ultra-high risk for psychosis using a novel method of extraction

Assessing biological stress markers in the hair of individuals at ultra-high risk for psychosis using a novel method of extraction

Cognitive profiles across the psychosis continuum

Cognitive impairments are core features in individuals across the psychosis continuum and predict functional outcomes. Nevertheless, substantial variability in cognitive functioning within diagnostic groups, along with considerable overlap with healthy controls, hampers the translation of research findings into personalized treatment planning.Aligned with precision medicine, we employed a data driven machine learning method, self-organizing maps, to conduct transdiagnostic clustering based on cognitive functions in a sample comprising 228 healthy controls, 200 individuals at ultra-high risk for psychosis, and 98 antipsychotic-naïve patients with first-episode psychosis.The self-organizing maps revealed six clinically distinct cognitive profiles that significantly predicted baseline functional level and changes in functional level after one year. Cognitive flexibility in particular, as well as specific executive functions emerged as cardinal in differentiating the profiles. The application of self-organizing maps appears to be a promising approach to inform clinical decision-making based on individualized cognitive profiles, including patient allocation to different interventions. Moreover, this method has the potential to enable cross-diagnostic stratification in research trials, utilizing data-driven subgrouping informed by categories from underlying dimensions of cognition rather than from clinical diagnoses. Finally, the method enables cross-diagnostic profiling across other data modalities, such as brain networks or metabolic subtypes.

Efficacy of the unified protocol for transdiagnostic treatment of comorbid emotional disorders in patients with ultra high risk for psychosis: Results of a randomized controlled trial

BackgroundThe most common reason for help-seeking in ultra-high risk (UHR) for psychosis patients is comorbid symptoms, mainly anxiety and depression. However, psychological interventions are mainly focused on subthreshold psychotic symptoms. There is a growing push to include transdiagnostic therapies in specialized intervention teams for psychosis in young people. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy in emotional disorders, and its application has recently expanded to other pathologies such as borderline personality disorder (BPD) and bipolar disorder (BD). MethodsThis pilot study was conducted with 36 patients with UHR for psychosis and symptoms of comorbid emotional disorders who were receiving treatment in an early intervention programme for psychosis. This is a randomised control trial (RCT) with two conditions: treatment as usual (TAU) with the group and online application of the UP (UP+TAU) (n = 18) and TAU (n = 18). Evaluations were conducted at baseline, after treatment, and at the three-month follow-up. ResultsComorbid anxiety and depression symptoms improved significantly in patients in the UP+TAU group compared to those in the TAU. Significant improvements in negative affect, emotional dysregulation, neuroticism, extraversion, functioning, and quality of life were also observed, and satisfaction with the intervention was high. ConclusionsUP may be an acceptable and effective intervention for the treatment of symptoms of comorbid emotional disorders in patients with UHR for psychosis. LimitationsThe sample size was small, and further studies are needed to test this intervention with larger samples of patients with UHR for psychosis with emotional comorbidities.

Oméga-3 et psychiatrie : que dit la littérature ?

Psychiatry is faced with a lack of new treatments despite a great deal of research and is re-exploring the use of old molecules and dietary supplements. Our aim here is to present a narrative review of the indications for omega-3 supplementation in various psychiatric disorders. Omega-3s belong to the family of polyunsaturated fatty acids (PUFAs). The 3 important omega-3 PUFAs in psychiatry are α-linolenic acid (ALA): C18:3n-3, eicosapentaenoic acid (EPA) C20:5n-3 and docosahexaenoic acid (DHA) C22:6n-3. In psychosis, a distinction must be made between 3 categories of patients: patients who have chronic schizophrenia (SCZ), patients with a first psychotic episode (FEP) and patients at ultra-high risk of psychosis (UHR).The data in the literature indicate that omega-3 supplementation is well tolerated. However, there is an increased risk of atrial fibrillation at doses over 4g/d, mainly in people over the age of 65.Omega-3 supplementation is not recommended for eating disorders, attention deficit hyperactivity disorder or autism spectrum disorders. Omega-3 supplementation could be beneficial in borderline personality disorder and psychotic disorders, particularly in patients at ultra-high risk of psychotic transition (UHR) to prevent psychotic transition and FEP to improve remission, and in bipolar disorder. It is now recommended for unipolar depression by the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. There are a large number of clinical trials of omega-3 supplementation. However, these trials use different types of supplementation (EPA alone, DHA alone, EPA+DHA, etc.) with different dosages and EPA/DHA ratios and over variable durations. In addition, the origin of the omega-3s may vary, although most of the studies used omega-3s of marine origin (fish). Finally, it has not been studied whether the time of day (fasting, during a meal, morning, evening, etc.) impacts the efficacy of the treatment.Confounding factors are often not taken into account. For example, some studies suggest a link between the response to omega-3 supplementation and the inflammation or oxidative stress level. Omega-3 supplementation acts on numerous biological pathways: inflammation, oxidative stress, monocarbon metabolism (vitamin B9, B12, homocysteine), myelination,... For psychotic disorders, meta-analyses tend not to distinguish between UHR, PEP and schizophrenic patients.There have not been enough studies to validate the doses and duration of supplementation. The doses and durations in the recommendations are based solely on incomplete data from published studies. Further studies are needed to optimize these recommendations. Except for UHR patients and those with borderline personality disorder, omega-3 supplementation is always used as a complement to psychotropic treatment.In conclusion, the results of clinical trials, meta-analyses and recommendations are heterogeneous and may be divergent. Omega-3 supplementation in psychiatry is still extensively studied, with numerous studies and meta-analyses published recently. Omega-3 supplementation could be part of the goal of personalized medicine, as some studies are already suggesting. In the future, the efficacy of omega-3 supplementation could be improved by targeting sub-groups of patients: patients with inflammatory profiles, high levels of oxidative stress and low blood omega-3 concentrations. Due to the increasing number of studies published on omega-3 supplementation in psychiatric disorders, the conclusions of this review are provisional and will need to be updated.

What impact did the COVID-19 pandemic have on psychosis and the delivery of early intervention psychosis services?

BackgroundIn Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. MethodsThis prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment ‘pre-COVID-19’ (between 16th August 2018 and 15th August 2019), and ‘during-COVID-19’ (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders. ResultsOf 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001). ConclusionsEarly intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.

The full spectrum of clinical stages of psychosis at prison entry: prevalence and concurrent validity of symptom screening.

Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening. Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed. Amongst men and women entering prison, almost one quarter (24.1%) met UHR criteria, 5.1% met the FEP threshold and 10.6% had an established psychosis. Those on the psychosis spectrum reported greater disadvantage across sociodemographic and justice factors. The presence of perceptual disturbance and paranoid beliefs emerged as the two best screening items for identifying those with an underlying psychosis spectrum illness. The prevalence of psychosis spectrum illness, including the UHR state, amongst those entering prison is high. Current prison mental health approaches should include screening for the presence of perceptual disturbances and paranoid beliefs to improve the detection of psychosis spectrum illness.

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

Functional and structural abnormalities of thalamus in individuals at early stage of schizophrenia

BackgroundThalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. Methods75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. ResultsNo significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. ConclusionsOur findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. Trial registrationClinicalTrials.govNCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.

Impulsivity as a predictor of clinical and psychological outcomes in a naturalistic prospective cohort of subjects at ultra-high risk (UHR) for psychosis from Tunisia

BackgroundImpulsivity is associated with serious detrimental consequences on physical, mental, behavioral and social aspects of health among patients with psychosis. The present prospective 12-month follow-up study aimed to determine the prevalence of highly impulsive individuals among Ultra High Risk (UHR) patients, how impulsivity evolves over the follow-up period, and whether impulsivity impacts clinical, psychological and functional outcomes in this population. MethodUHR patients were invited to complete a battery of measurements at three-time points: at baseline, and at 6 and 12 months of follow-up. Impulsivity was assessed using both behavioral (the Wisconsin Card Sorting Test, WCST) and self-report (the Barratt Impulsiveness Scale, BIS-11) measures. ResultsFindings showed that at 6 months of follow-up, higher 6-month BIS-11 attentional and motor impulsivity were significantly associated with lower quality of life and greater general psychological distress. In addition, higher baseline BIS-11 motor impulsivity significantly predicted more severe positive psychotic symptoms at 12 months of follow-up. However, WCST scores did not show any significant associations with study variables at the different times of follow-up. ConclusionInterventions targeting impulsivity in UHR individuals could help decrease psychological distress and positive psychotic symptoms’ severity, as well as improve quality of life in UHR individuals.

Cognitive complaint inversely associated to UHR transition

The aim of this study was to identify the impact of staging on a six-months transition in Ultra-High Risk (UHR) youth.Subjects were enrolled at assessment; evolution was monitored for six months. Clinical determinants (unusual thought content, perceptual abnormalities, cognitive complaint, etc.) were collected.37 non-psychotic and 39 UHR subjects were included. 13 UHR (35.2 %) experienced psychotic transition, while none of non-psychotic subjects did log-rank p < 0.001. Self-reported cognitive complaint was inversely associated to transition OR 0.13 95 % IC [0.03–0.64]. Unusual Thought Content was associated to psychotic transition 0R 8.57 95 % IC [1.17–63]. Self-reported cognitive complaint could be a protective transition marker in UHR.

Comparison of two multivalent modified live viral/bacterial combination vaccines in feedlot calves at ultra-high risk of developing undifferentiated fever/bovine respiratory disease

Vaccine 1 (VAC1 group) and Vaccine 2 (VAC2 group) are com­mercially available vaccines labeled for the control of bovine respiratory disease (BRD) in beef cattle. There are limited data from large-scale commercial feedlot trials comparing VAC1 and VAC2 arrival processing vaccination pro­grams. The objective of this study was to evaluate the relative effects of VAC1 and VAC2 arrival processing vacci­nation programs on animal health, feedlot performance and carcass characteristic outcomes in feedlot calves at ultra-high risk of developing undifferentiated fever/BRD under large-scale commercial production conditions. Animals were randomly allocated at feedlot arrival to 1 of 2 experimental groups: VAC1 or VAC2. Animals in the VAC1 group (6 multi-pen lots; 3,001 animals) received a bovine rhinotracheitis-virus diarrhea-parainfluenza 3-respiratory syncytial virus-Mannheimia hae­molytica-Pasteurella multocida vaccine per animal once at allocation. Animals in the VAC2 group (6 multi-pen lots; 3,005 animals) received a bovine rhinotracheitis-virus diarrhea-parainfluenza 3-respiratory syncytial virus vaccine with a Mannheimia haemolytica toxoid per animal once at allocation. Vaccines differed regarding viral strains, bacterial protection, means for providing bacterial immunity, and adjuvant use. Animals were housed by experi­mental group in commercial feedlot pens and followed from allocation until slaughter. Although histophilosis mortality was higher in the VAC1 group compared to the VAC2 group (P = 0.040), no statistical differences were detected in overall mor­tality or any of the other outcome variables (P ≥ 0.050). The relative cost effectiveness of each arrival processing vaccina­tion program in the study population is therefore dependent on relative program cost.

Compensatory thickening of cortical thickness in early stage of schizophrenia.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

Genome-wide association exploratory studies in individuals with ultra-high risk for schizophrenia in Chinese Han nationality in two years follow-up: A subpopulation study

BackgroundAlthough ultra-high risk for schizophrenia (UHR) is related to both genetic and environment factors, the precise pathogenesis is still unknow. To date, few studies have explored the Genome-Wide Association Studies (GWAS) in UHR or HR individuals especially in Han population in China. MethodsIn this study, a GWAS analysis for 36 participants with UHR and 43 with HR were performed, and all deletion variations in 22q11 region were also compared. Results: Sixteen individuals with UHR (44.4%) and none with HR converted into schizophrenia in follow-up after two years. Six loci including neurexin-1(NRXN1) (rs1045881), dopamine D1 receptor (DRD1) (rs686, rs4532), chitinase-3-like protein 1 (CHI3L1) (rs4950928), velocardiofacial syndrome (ARVCF) (rs165815), dopamine D2 receptor (DRD2) (rs1076560) were identified higher expression with significant difference in individuals converted into schizophrenia after two years. The Family with Sequence Similarity 230 Member H (FAM230H) gene in the 22q11 region were also found high expression in UHR group. ConclusionsFurther expansion of sample size and validation studies are needed to explore the pathogenesis of these risk loci in UHR conversion into schizophrenia in the future.

Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.