Paolo Fusar-Poli

King's College London (primary) and University of Pavia (secondary) · Psychosis Studies (KCL) and Brain and Behavioral Sciences (Pavia)

Psychosocial stress is a well-established risk factor for psychosis, yet the neurobiological mechanisms underlying this relationship have yet to be fully elucidated. Much of the research in this field has investigated hypothalamic-pituitary-adrenal (HPA) axis function and immuno-inflammatory processes among individuals with established psychotic di...

Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven...

IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subg...

Objective Umbrella reviews are a new form of literature review that summarises the strength and/or quality of the evidence from all systematic reviews and meta-analyses conducted on a broad topic. This type of review thus provides an exhaustive examination of a vast body of information, providing the highest synthesis of knowledge. A critical stren...

Introduction: People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental hea...

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 functioni...

Empirical evidence indicates a significant bidirectional association between mental disorders and physical diseases, but the prospective impact of men­tal disorders on clinical outcomes of physical diseases has not been comprehensively outlined. In this PRISMA‐ and COSMOS‐E‐compliant umbrella review, we searched PubMed, PsycINFO, Embase, and Joanna...

Importance: Alterations in prolactin and cortisol levels have been reported in antipsychotic naïve patients with first episode psychosis (FEP). However, it has been studied in very small samples, and inter-group variability has never been studied before. Objective: To provide estimates of standardized mean differences (SMD) and inter-group variabi...

To study mental illness and health, in the past researchers have often broken down their complexity into individual subsystems (e.g., genomics, transcriptomics, proteomics, clinical data) and explored the components independently. Technological advancements and decreasing costs of high throughput sequencing has led to an unprecedented increase in d...

Informal caregivers of individuals affected by psychotic disorder can play a key role in the recovery process. However, little research has been conducted on the lived experiences of carers and family members. We conducted a bottom-up (from lived experience to theory) review of first-person accounts, co-written between academics and experts by expe...

Importance Abnormal sleep is frequent in psychosis; however, sleep abnormalities in different stages (ie, clinical high risk for psychosis [CHR-P], early psychosis [EP], and chronic psychosis [CP]) have not been characterized. Objective To identify sleep abnormalities across psychosis stages. Data Sources Web of Science and PubMed were searched b...

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from...

Introduction: No systematic review has estimated the consistency and the magnitude of the risk of developing bipolar disorder I-II (BD-I/II) in individuals at clinical high risk for bipolar disorder (CHR-BD). Methods: PubMed and Web of Science databases were searched until April 2022 in this pre-registered (PROSPERO CRD42022346515) PRISMA-compli...

The two most used semi‐structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Structured Interview for Psychosis‐Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Dev...

The randomised controlled trial of antipsychotic reduction and discontinuation addresses essential questions with regard to continued use of antipsychotics in schizophrenia, pertaining to social functioning and continued antipsychotic use. However, significant methodological issues stated in the trial protocol have the potential to confound interpr...

Background: The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories. Methods: We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of...

Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is currently lacking. Voxel-Mirrored Homotopic Connectivity (VMHC) was evaluated in a sample of 85 neurotypical individuals aged 7–18 years. VMHC associations...

Introduction Indicated primary prevention of psychosis is recommended by NICE clinical guidelines, but implementation research on Clinical High Risk for Psychosis (CHR-P) services is limited. Methods Electronic audit of CHR-P services in England, conducted between June and September 2021, addressing core implementation domains: service configurati...

Improving outcomes in psychosis is reliant on efficient early detection of individuals at risk; however, current strategies are suboptimal. Electronic health records (EHRs) contain detailed individual-level data that are routinely collected as part of clinical care, providing a unique opportunity for personalised prognostication. This chapter explo...

Objetivo: Graduar as evidências sobre fatores de risco de transtornos alimentares (anorexia nervosa, bulimia nervosa e transtorno de compulsão alimentar periódica) com o método de revisão guarda-chuva. Métodos: Trata-se de revisão sistemática de estudos observacionais sobre fatores de risco de transtornos alimentares publicados no PubMed, PsycInfo,...

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome,...

Clinical High Risk for Psychosis (CHR-P) services have been primarily developed to support young people with attenuated symptoms (indicated prevention). No evidence-based appraisal has systematically investigated to what extent these clinics may implement other preventive approaches. PRISMA 2020-compliant systematic review of Web of Science, Cochra...

The purpose of this article is to narratively review the empirical literature on clinicians’ emotional, cognitive, and behavioral responses (i.e., countertransference) to depressive and other symptoms of patients with mood disorders. Therapist subjective responses (countertransference) can negatively affect both diagnostic and therapeutic processes...

As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-sub...

Precision psychiatry is an emerging field with transformative opportunities for mental health. However, the use of clinical prediction models carries unprecedented ethical challenges, which must be addressed before accessing the potential benefits of precision psychiatry. This critical review covers multidisciplinary areas, including psychiatry, et...

The impact of timing of antipsychotics and benzodiazepine treatment during a first episode of psychosis on clinical outcomes is unknown. We present a RECORD-compliant electronic health record cohort study including patients ( n = 4,483, aged 14–35) with a primary diagnosis of any non-organic ICD-10 first episode of psychosis at SLAM-NHS between 200...

p>Objective: People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population. Methods: Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for phy...

22q11.2 deletion syndrome (22q.11.2DS) might be one of the strongest genetic risk factors for psychosis, but robust estimates of prevalence and incidence of psychotic disorders in this condition are not available. To address this gap, we performed a multistep systematic PRISMA/MOOSE-compliant literature search of articles reporting prevalence (prim...

Measuring interhemispheric connectivity on a regional and network level may help to clarify how homotopic asymmetry is related to late neurodevelopment. Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is cur...

Hüfner, Katharina, Fabio Caramazza, Evelyn R. Pircher Nöckler, Agnieszka E. Stawinoga, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Ken Zafren, Hermann Brugger, and Barbara Sperner-Unterweger. Association of pre-existing mental health conditions with acute mountain sickness at Eve...

Introduction There is limited research in adolescent at risk for psychosis. The new criteria of Attenuated Psychosis Syndrome (APS) of Diagnostic and Statistical Manual of Mental Disorders- 5 (DSM-5) have not been validated. Objectives The aims of this study were to: 1) characterize adolescent’s profile with APS (DSM-5 APS) compared to adolescents...

State-dependent reallocation of cognitive resources is impaired in schizophrenia and may be underlined by alterations in brain local-connectivity. Increasing evidence suggests local connectivity reductions from rest to task in healthy individuals, while insufficient information is available for schizophrenia spectrum. Resting-state and stop-signal...

Psychosocial interventions are recommended in schizophrenia and first-episode psychosis/early psychosis (EP). Nevertheless, literature is heterogeneous and often contradictory. We conducted an umbrella review of (network) meta-analyses of randomized controlled trials (RCTs) comparing psychosocial interventions vs treatment as usual (TAU)/active int...

As COVID-19 becomes endemic, identifying vulnerable population groups for severe infection outcomes and defining rapid and effective preventive and therapeutic strategies remains a public health priority. We performed an umbrella review, including comprehensive studies (meta-analyses and systematic reviews) investigating COVID-19 risk for infection...

Objective To develop a reporting guideline for overviews of reviews of healthcare interventions. Design Development of the preferred reporting items for overviews of reviews (PRIOR) statement. Participants Core team (seven individuals) led day-to-day operations, and an expert advisory group (three individuals) provided methodological advice. A pa...

Background: Despite significant research progress surrounding precision medicine in psychiatry, there has been little tangible impact upon real-world clinical care. Objective: To identify barriers and facilitators affecting the real-world implementation of precision psychiatry. Method: A PRISMA-compliant systematic literature search of primary...

We performed an umbrella review on environmental risk/protective factors and biomarkers for postpartum depressive symptoms to establish a hierarchy of evidence. We systematically searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception until 12 January 2021. We included systematic reviews providing meta-analyses relat...

We aim to assess how functioning, depressive symptoms, and psychotic symptoms are associated with different numbers of Clinical High At-Risk Mental State (CHARMS) categories. In this cross-sectional study, we assessed 62 help-seeking subjects aged 15-24 with a drop in functioning, with Structured Clinical Interview for DSM-5, Social and Occupationa...

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface are...

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and...

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 20...

Psychosis is the most ineffable experience of mental disorder. We provide here the first co‐written bottom‐up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically‐informed perspectives. First‐person accounts within and outside the m...

[This corrects the article DOI: 10.3389/fpsyt.2022.861201.].

This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central R...

Objective: To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression. Design: A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical ou...

Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol:...

Background: The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders. Methods: We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in...

Background: Individuals at Clinical High Risk for Psychosis (CHR) present with either Attenuated Psychotic Symptoms (APS), Brief Limited Intermittent Psychotic Symptoms (BLIPS), and/or genetic vulnerability (GRD), and demonstrate a heightened risk for transition to a first episode of psychosis compared with the general population. However, the CHR...

Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progre...

We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions va...

The presence of a positive family relationship has been suggested as a protective factor from parental stress and from the development of full-blown psychosis. However, to date, there is limited research on family functioning in adolescents with psychosis and at clinical high risk for psychosis (CHR-P). This study is aimed at comparing family funct...

Introduction Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response. Method Following a pre-registered protocol...

The Preferred Reporting Items for Overviews of Reviews (PRIOR) statement provides an evidence-based reporting guideline developed using established, rigorous methods that involved a four-stage process (project launch, evidence reviews, modified Delphi exercise, development of the reporting guideline) and an international stakeholder group represent...

Background: The clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated...

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection ser...

Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced in...

Neuroimaging findings in people at either genetic risk or at clinical high-risk for psychosis (CHR-P) or bipolar disorder (CHR-B) remain unclear. A meta-analytic review of whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies in individuals with genetic risk or CHR-P or CHR-B and controls identified 94 d...

Background : Few studies have investigated the protective role of higher levels of wellbeing in relation to common mental disorders (CMDs). The objective was to explore the protective role of mental wellbeing at baseline on CMDs during a 12-16 months follow-up period in the Danish general population. Methods : Data stem from a Danish nationally-re...

Background: The current conceptualization of schizophrenia as neurodevelopmental disorder should lead to innovative public health policies in terms of a reorganization of the mental health care systems, particularly in the transition from adolescence to adulthood, to reduce personal, familiar, and social costs and burdens. The purpose of the proje...

Objective: Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from he...

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/re...

Variation in the expression level and activity of genes involved in drug disposition and action in tissues of pharmacological importance have been increasingly investigated in patients treated with psychotropic drugs. Findings are promising, but reliable predictive biomarkers of response have yet to be identified. Here we conducted a PRISMA-complia...

Aims: Source Monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy...

Purpose: Although first-episode psychosis (FEP) in youth, particularly early-onset schizophrenia (EOS), is managed similarly to adult-onset schizophrenia, few antipsychotics are approved for people aged 13-18 years. We aimed to explore areas of uncertainty in EOS management and provide evidence-based recommendations to mental health specialists. W...

Importance: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an effi...

Aims The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods “Preferred Reporting Items for Systematic reviews...

Background In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. Objectives We describe and validate a...

The COVID-19 pandemic and related restrictions can impact mental health. In order to quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and meta-analysis, searching World Health Organization COVID-19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in a...

Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search...

Objective The clinical high risk for psychosis (CHR-P) holds the potential to improve outcomes through primary indicated prevention. Its impact is determined by efficient detection, prognostication and prophylactic interventions. Specifically, ascertaining the likelihood of psychosis onset from a CHR-P state is of paramount relevance to inform clin...