GDNF and miRNA-29a as biomarkers in the first episode of psychosis: uncovering associations with psychosocial factors.

Aim: Schizophrenia involves complex interactions between biological and environmental factors, including childhood trauma, cognitive impairments, and premorbid adjustment. Predicting its severity and progression remains challenging. Biomarkers like glial cell line-derived neurotrophic factor (GDNF) and miRNA-29a may bridge biological and environmental aspects. The goal was to explore the connections between miRNAs and neural proteins and cognitive functioning, childhood trauma, and premorbid adjustment in the first episode of psychosis (FEP). Method: This study included 19 FEP patients who underwent clinical evaluation with: the Childhood Trauma Questionnaire (CTQ), the Premorbid Adjustment Scale (PAS), the Positive and Negative Syndrome Scale (PANSS), and the Montreal Cognitive Assessment Scale (MoCA). Multiplex assays for plasma proteins were conducted with Luminex xMAP technology. Additionally, miRNA levels were quantitatively determined through RNA extraction, cDNA synthesis, and RT-qPCR on a 7500 Fast Real-Time PCR System. Results: Among miRNAs, only miR-29a-3p exhibited a significant correlation with PAS-C scores (r = -0.513, p = 0.025) and cognitive improvement (r = -0.505, p = 0.033). Among the analyzed proteins, only GDNF showed correlations with MoCA scores at the baseline and after 3 months (r = 0.533, p = 0.0189 and r = 0.598, p = 0.007), cognitive improvement (r = 0.511, p = 0.025), and CTQ subtests. MIF concentrations correlated with the PAS-C subscale (r = -0.5670, p = 0.011). Conclusion: GDNF and miR-29a-3p are promising as biomarkers for understanding and addressing cognitive deficits in psychosis. This study links miRNA and MIF to premorbid adjustment and reveals GDNF's unique role in connection with childhood trauma.

Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Tracking Needs-Based Community and Specialized Services of Young Adults and Their Parents Before and During a First Episode of Psychosis (FEP): Highlighting Intervention Trajectories in FEP.

Aim: This article aims to document 10 service trajectories of young adults (YA) and their parents, informed by healthcare professionals (HP), before and during a first episode of psychosis (FEP). Design: Based on a crisis model perspective of the Life Course Theory (Elder; Elder and Shanahan) developed by Carpentier and White, and adapted to the current context to track community and specialized services trajectories. Thematic analysis was used to code responses to open-ended questions around the need for help and accessing services by young adults affected by a psychotic disorder, and their parents. Setting: In collaboration with FEP clinics, setting of choice by YA and their parents. Participants: 5 YA, 12 parents, and 6 HP. Results: 10 individual service trajectories grouped into 3 distinct types of trajectories (optimal, typical, and complex) based on grouping 5 similar characteristics, highlighting service access complexity and early intervention in FEP. Conclusion: This study is the first of its kind to examine the experiences of those who seek needs-based community and specialized services leading up to and during a FEP. Findings provide key insights related to early intervention in FEP and recommendations on improving access to such services in Quebec.

Executively-mediated language skills are related to performance-based social functioning in the early psychosis spectrum.

Social impairment is a core deficit in psychotic spectrum disorders (PSDs). Prior work shows that language abnormalities can predict psychosis onset and are related to social outcomes in PSDs. Few studies have investigated nuanced relationships between language/verbal abilities and social functioning in the early psychosis spectrum, including at-risk (schizotypy) and first episode of psychosis (FEP) individuals. This study aimed to examine the relationship to between language/verbal performance and performance-based and examiner-rated social functioning. We also aimed to replicate prior models that demonstrate neurocognition is related to social functioning through negative symptoms and social cognition. Low schizotypy (n = 42), high schizotypy (n = 44), and FEP (n = 15) participants completed a battery of language/verbal, social cognition, and social functioning measures. Regression analyses revealed that Proverb Test performance was uniquely and significantly associated with performance-based but not examiner-rated social functioning. Other language/verbal measures were not significantly related to social functioning. In mediational analyses, language/verbal performance was indirectly related to social functioning through negative traits, and also through social cognition. Findings extend support for negative symptom and social cognitive intervention in the early psychosis spectrum, and uniquely suggest that executively-mediated language skills may be an additional target to improve social functioning.

Gradual Increase in Inflammation-Linked Glycoproteins and a Proatherogenic Lipoprotein Profile in the Early Stages of Psychosis as Characterized by 1H NMR Blood Analysis.

Minimally invasive prognostic markers of inflammation and dyslipidemia in individuals with a risk of psychosis, also called "at-risk mental state" (ARMS), or in the first episode of psychosis (FEP) are of utmost clinical importance to prevent cardiovascular disorders. We analyzed the plasma concentration of inflammation-linked glycoproteins (Glycs) and lipoprotein subclasses by proton nuclear magnetic resonance (1H NMR) in a single acquisition. Study participants were healthy controls (HCs, N = 67) and patients with ARMS (N = 58), FEP (N = 110), or early psychosis diagnosis with ≥2 episodes (critical period (CP), N = 53). Clinical biomarkers such as high-sensitivity C-reactive protein, interleukin 6, fibrinogen, insulin, and lipoproteins were also measured. Although all participants had normal lipoprotein profiles and no inflammation according to conventional biomarkers, a gradual increase in the Glyc 1H NMR levels was observed from HCs to CP patients; this increase was statistically significant for GlycA (CP vs HC). In parallel, a progressive and significant proatherogenic 1H NMR lipoprotein profile was also identified across stages of psychosis (ARMS and CP vs HC). These findings highlight the potential of using 1H NMR Glyc and lipoprotein profiling to identify blood changes in individuals with ARMS or FEP and pave the way for applications using this technology to monitor metabolic and cardiovascular risks in clinical psychiatry.

The Role of the Microbiome in First Episode of Psychosis.

The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.

Sleep Disturbances in At-Risk Mental States and First Episode of Psychosis: A Narrative Review on Interventions.

Sleep disturbances are a common yet often overlooked symptom of psychosis that can drastically affect the quality of life and well-being of those living with the condition. Sleep disorders are common in people diagnosed with schizophrenia and have significant negative effects on the clinical course of the illness and the functional outcomes and quality of life of patients. There is a limited number of studies addressing this question in first-episode psychosis (FEP). In this narrative review, we aimed to provide an overview of sleep disorders in populations with FEP and at-risk mental states (ARMS). The review was focused on the various treatments currently used for sleep disorders, including both non-pharmacological and pharmacological treatments. A total of 48 studies were included. We found that sleep disturbances are associated with attenuated psychotic symptoms and other psychopathological symptoms in ARMSs. The association of sleep disturbances with the transition to psychosis has been poorly investigated. Sleep disturbances have an impact on the quality of life and the psychopathological symptoms of people suffering from FEP. The non-pharmacological treatments include cognitive behavioral therapy for insomnia, bright light therapy, cognitive restructuring techniques, sleep restriction therapy, basic sleep hygiene education, and the provision of portable sleep trackers. Other treatments include antipsychotics in acute phases and melatonin. The early intervention in sleep disturbances may improve overall prognosis in emerging psychosis populations.

Cannabis Use and Endocannabinoid Receptor Genes: A Pilot Study on Their Interaction on Brain Activity in First-Episode Psychosis.

The role of both cannabis use and genetic background has been shown in the risk for psychosis. However, the effect of the interplay between cannabis and variability at the endocannabinoid receptor genes on the neurobiological underpinnings of psychosis remains inconclusive. Through a case-only design, including patients with a first-episode of psychosis (n = 40) classified as cannabis users (50%) and non-users (50%), we aimed to evaluate the interaction between cannabis use and common genetic variants at the endocannabinoid receptor genes on brain activity. Genetic variability was assessed by genotyping two Single Nucleotide Polymorphisms (SNP) at the cannabinoid receptor type 1 gene (CNR1; rs1049353) and cannabinoid receptor type 2 gene (CNR2; rs2501431). Functional Magnetic Resonance Imaging (fMRI) data were obtained while performing the n-back task. Gene × cannabis interaction models evidenced a combined effect of CNR1 and CNR2 genotypes and cannabis use on brain activity in different brain areas, such as the caudate nucleus, the cingulate cortex and the orbitofrontal cortex. These findings suggest a joint role of cannabis use and cannabinoid receptor genetic background on brain function in first-episode psychosis, possibly through the impact on brain areas relevant to the reward circuit.

Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis.

Patients with Schizophrenia may show different clinical presentations, not only regarding inter-individual comparisons but also in one specific subject over time. In fMRI studies, functional connectomes have been shown to carry valuable individual level information, which can be associated with cognitive and behavioral variables. Moreover, functional connectomes have been used to identify subjects within a group, as if they were fingerprints. For the particular case of Schizophrenia, it has been shown that there is reduced connectome stability as well as higher inter-individual variability. Here, we studied inter and intra-individual heterogeneity by exploring functional connectomes' variability and related it with clinical variables (PANSS Total scores and antipsychotic's doses). Our sample consisted of 30 patients with First Episode of Psychosis and 32 Healthy Controls, with a test-retest approach of two resting-state fMRI scanning sessions. In our patients' group, we found increased deviation from healthy functional connectomes and increased intragroup inter-subject variability, which was positively correlated to symptoms' levels in six subnetworks (visual, somatomotor, dorsal attention, ventral attention, frontoparietal and DMN). Moreover, changes in symptom severity were positively related to changes in deviation from healthy functional connectomes. Regarding intra-subject variability, we were unable to replicate previous findings of reduced connectome stability (i.e., increased intra-subject variability), but we found a trend suggesting that result. Our findings highlight the relevance of variability characterization in Schizophrenia, and they can be related to evidence of Schizophrenia patients having a noisy functional connectome.

The Placentas of Women Who Suffer an Episode of Psychosis during Pregnancy Have Increased Lipid Peroxidation with Evidence of Ferroptosis.

Psychosis is a complex entity characterized by psychological, behavioral, and motor alterations resulting in a loss of contact with reality. Although it is not common, pregnancy can be a period in which a first episode of psychosis can manifest, entailing detrimental consequences for both the fetus and the mother. The pathophysiological basis and study of maternofetal wellbeing need to be further elucidated. Lipid peroxidation and ferroptosis are two phenomena that are tightly linked to the placental dysfunction commonly observed in different complications of pregnancy. In the present study, we aim to explore the histopathological and gene expression of different markers of lipid peroxidation and ferroptosis in the placentas of women who underwent a first episode of psychosis during their pregnancy (n = 22). The aim is to then compare them with healthy pregnant women (n = 20). In order to achieve this goal, iron deposits were studied using Prussian Blue staining. In addition, the protein/gene expression of a transferrin receptor (TFRC), as well as an acyl-CoA synthetase long-chain family member 4 (ACSL-4), arachidonate lipoxygenase-5 (ALOX-5), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4) were all analyzed through gene expression (RT-qPCR) and immunohistochemical procedures. Our results demonstrate an increased presence of iron deposits that are accompanied by a further expression of TFRC, ACSL-4, ALOX-5, MDA, and GPX4-all of which are observed in the placenta tissue of women who have suffered from a first episode of psychosis. Therefore, in our study, a histopathological increase in lipid peroxidation and ferroptosis markers in the affected women is suggested. However, further studies are needed in order to validate our results and to establish possible consequences for the reported alterations.

Exploring the efficacy of a low intensity psychological intervention for family members and carers of individuals with a first episode of psychosis in early intervention services.

AIM: The study aimed to evaluate the efficacy, and explore carers' experience, of a brief carer focussed intervention in an Early Intervention in Psychosis (EIP) service using a mixed methods approach. METHODS: Carers within EIP services were invited to have the intervention, comprising a psychoeducation and wellbeing component, and 153 carers completed routine outcome measures including the Brief Experience of Caregiving Inventory (BECI), The Warwick-Edinburgh Mental Well-being Scale (WEMWEBS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and after the completion of the intervention. Separately, nine carers took part in semi-structured interviews about their experience of the intervention. RESULTS: The intervention resulted in improvement of overall well-being, a reduction in self-reported anxiety and caregiving experience relating to difficult behaviours and stigma/effects on the family. Overall, the carers' subjective experiences of the intervention were positive. Thematic analysis indicated epistemic trust indexed by the connection carers achieved with the service, an experience of being valued and of experiencing change through the intervention. CONCLUSION: A short, 8 weeks intervention delivered by assistant psychologists, may offer an effective method for facilitating understanding of the illness and acclimatizing to new challenges. Exploring the effectiveness of psychoeducation and capturing this with specific measures may allow the service to make meaningful adaptations to their intervention.

Sustained specialized and family treatment in first-episode schizophrenia or related disorders: a 5-year randomized controlled trial.

BACKGROUND: The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning. METHODS: A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15-28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA. RESULTS: We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning. CONCLUSION: Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Co-occurring first-episode psychosis and borderline personality pathology in an early intervention for psychosis cohort.

INTRODUCTION: Borderline personality disorder (BPD) is common among people diagnosed with first episode of psychosis (FEP), but is often under-recognized and under-researched. This study aimed to determine: (i) the prevalence of borderline personality pathology (subthreshold features and categorical disorder) in a FEP cohort (termed FEP + BPP); (ii) demographic and clinical factors associated with FEP + BPP; (iii) the symptomatic and functional outcomes. METHODS: This study was conducted within the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen over the 30-month period between 2014 and 2016. BPP was evaluated by using the Structured Clinical Interview for DSM-IV Axis II Personality Questionnaire BPD criteria. RESULTS: In a cohort of 457 young people with a FEP (mean age 19.5 years, 56% male), 18.4% had borderline personality pathology (BPP). Compared with FEP alone, young people with FEP + BPP were more likely to be female, younger, Australian-born. In addition, young people with FEP + BPP were more likely to be diagnosed with Psychosis NOS, present with more severe hallucinations, and have alcohol abuse. Young people with FEP + BPP had more relationship difficulties at presentation and they were more likely to suffer of depression and to engage in self-harm throughout the follow-up. In relation to outcome, FEP + BPP was not associated with different rates of remission or relapse, however they were less likely to be admitted to hospital at presentation or involuntarily during their episode of care. CONCLUSION: BPP is a common occurrence in psychotic disorders and is associated with more severe hallucinations and depression with higher risks of self-harm. Specific interventions need to be developed.

Negative symptoms and sex differences in first episode schizophrenia: What's their role in the functional outcome? A longitudinal study.

INTRODUCTION: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. MATERIAL AND METHODS: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. RESULTS: Females showed fewer NS (p=0.031; Cohen's d=-0.312), especially those related to EXP (p=0.024; Cohen's d=-0.326) rather than MAP (p=0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R2=0.494; p<0.001), while only higher deficits in MAP predicted worse functioning in males (R2=0.088; p=0.012). CONCLUSIONS: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes.

Theory of Mind as an endophenotype for schizophrenia spectrum disorder: Study in first episode of psychosis patients and first-degree relatives.

BACKGROUND: Deficits in Theory of Mind (ToM) had been suggested as a possible endophenotype for unaffected relatives of first episode of psychosis (FEP) patients. There are a limited number of studies which have evaluated ToM deficits among the siblings and parents of FEP patients. AIM: This study aimed to explore ToM deficits and its correlates among FEP patients, their siblings, parents, and controls. METHODOLOGY: FEP patients (N=102), their parents (N=135), siblings (N=97), and controls (N=167) were evaluated on ToM performance with the Reading the Mind in the Eyes Test (Eyes Test). Interview for sociodemographic variables of age, sex, years of education, and IQ estimation and neurocognitive tests were administered to all groups. RESULTS: FEP patients had a significantly lower performance on the Eyes Test compared to their siblings and controls. However, no significant differences were found between siblings and parents or siblings and controls. CONCLUSION: Attending our results, we found no evidence for ToM deficits as an endophenotype of SSDs. Furthermore, ToM accuracy may be mediated by interaction with other cognitive domains and play a protective role against psychosis in unaffected siblings.

Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.

Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.

A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.

We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.

Metabolic syndrome following a first episode of psychosis: results of a 1-year longitudinal study conducted in metropolitan Lisbon, Portugal.

OBJECTIVE: We aimed to assess the prevalence and course of metabolic syndrome (MetS) and the associated metabolic parameters during the year following a first episode pf psychosis (FEP). METHODS: We performed a 1-year longitudinal observation of 60 patients who experienced FEP. MetS was defined using the modified definition of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the metabolic parameters and socio-demographic and psychopathological data for the participants. RESULTS: The mean age of the participants was 27.1 years, and 33.3% of them were women. There was an increase in the prevalence of MetS from 6.7% to 11.7% during the year following the baseline assessment during the year following the baseline assessment (p = 0.250). There were also significant increases in the prevalences of abnormal triglyceride concentration, waist circumference, and high-density lipoprotein (HDL)-cholesterol concentration during this period. In addition, there was a considerable worsening of the metabolic profile of the participants. No baseline parameters were identified to be predictors of MetS over the 1-year follow-up period. CONCLUSIONS: We can conclude that metabolic abnormalities are common in patients with FEP and that these rapidly worsen during the first year following the diagnosis of FEP. Studies on interventions are needed to reduce metabolic risk to cardiovascular diseases following the FEP.

Outcomes for first-episode psychosis after entry via an at-risk mental state clinic compared to direct entry to a first episode of psychosis service: A systematic review and meta-analysis.

OBJECTIVE: Early intervention for psychosis services have been established worldwide and consist of specialist services for those with the At-Risk Mental State (ARMS) and a first episode of psychosis (FEP). This systematic review identified the literature on the outcomes of people who initially presented via an ARMS clinic and later transitioned to a psychotic disorder (UHR-T), compared to those who presented directly to an EI service with a FEP (FEP-D). The outcomes examined were (i) symptomatic (ii) functional, (iii) morbidity and mortality (including physical health) and (iv) service-usage. METHOD: A systematic search strategy was employed using three databases: MEDLINE, PsycInfo, and EMBASE. Studies published in English and that compared any of the above outcomes in a cohort of people with a first episode of psychosis who initially presented via an ARMS clinic to those who presented directly to a FEP service were included. Meta-analysis was performed for any outcome data from at least two studies. RESULTS: A total of 988 unique articles were identified and of these, three studies fulfilled the inclusion criteria and these included a total of 78 UHR-T and 253 FEP-D individuals. In the one study examining remission rates, there was no difference observed after one year in the UHR-T and FEP-D groups. In the one study that examined neurocognition, no differences were observed in any of the neurocognitive domains between groups after one year. Two studies examined psychiatric admission rates within one year and one of these found that UHR-T individuals were less likely to have any psychiatric admission (46% vs 68%) and admissions were less likely to be involuntary (30% vs 74%), while the other study found no difference in admission rates. In the meta-analysis, UHR-T individuals had lower odds for any psychiatric hospital admission within one year compared to FEP-D individuals (OR = 0.54, 95% C.I. 0.32 - 0.94, p = .03). No studies examined functional outcomes or mortality and morbidity between the groups. CONCLUSION: The limited research indicates similar or superior outcomes for people with a FEP who present initially via an ARMS clinic. The reduced psychiatric admission rate is an important potential benefit of ARMS clinics that requires replication.

Psychotic symptoms prior or concomitant to diagnosis of multiple sclerosis: a systematic review of case reports and case series.

OBJECTIVE: We aimed to examine the clinical features of psychotic symptoms preceding or concomitant to multiple sclerosis (MS) diagnosis. METHOD: From the 1st to 10th of January 2020 a systematic review was conducted through an electronic search of different databases. Results were limited to English, French, German, Italian and Spanish language articles. RESULTS: We identified 599 titles, and included 32 cases from case-report and case series. One case report from our department was added. The mean age of first psychiatric symptoms was 25.8 ± 10.2 years, the mean age of MS diagnosis was 31.2 ± 10.7 years and the mean delay until MS diagnosis was 2.7 ± 3 years. Most reported symptoms were delusions (81%), auditory hallucinations (59%) and visual hallucinations (50%). Upon the MS diagnosis, immunosuppressive therapy was significantly more effective for psychotic symptoms than antipsychotics (OR = 9.0; 95%CI: 2.15-37; p = 0.002). Diffuse periventricular lesions were found in 95.6% of cases, with mostly temporal or frontal predominant lesions. In cases affected by predominant temporal lesions, 83% of cases presented visual hallucinations (p < 0.05). CONCLUSION: Poor response or resistance to antipsychotics treatment should alert clinicians on the need to consider a differential diagnosis. Considering the impact of delay in MS diagnosis further research regarding this subject is warranted.KEY POINTSInsight into the occurrence of psychotic symptoms in multiple sclerosis (MS) is mainly limited to case reports and case series.Delay in MS management between initial psychotic symptoms and the MS diagnosis is 2.73 ± 3 years and 0.8 ± 1.2 years for patients presenting a first episode of psychosis.The resistance and poor response to antipsychotics found in most cases (75%) were associated with an excellent improvement (95%) of both psychiatric and neurologic symptoms with corticosteroids.Prospective studies are needed to investigate the spectrum of psychosis in MS.