Luis Alameda

• MD-PhD
• PhD Student at King's College London

Individuals at clinical high risk for psychosis (CHR) have variable clinical outcomes and low conversion rates, limiting development of novel and personalized treatments. Moreover, given risks of antipsychotic drugs, safer effective medications for CHR individuals are needed. The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Program...

Studies on schizophrenia feature diffusion magnetic resonance imaging (dMRI) to investigate white matter (WM) anomalies. The heterogeneity in the possible interpretations of typical Diffusion Tensor Imaging (DTI) metrics highlights the importance of increasing their specificity. Here, we characterize WM pathology in early psychosis (EP) and schizop...

Background Childhood trauma (CT), in the form of abuse and neglect, and altered social cognition (SC) are both linked to poorer clinical and functional outcomes in psychosis. The impact of CT and its subtypes on SC in early psychosis has been underexplored, with mixed findings from previous studies. The current study investigated the effects of CT...

Aims Characterising the association between childhood maltreatment (CM) and cognitive functioning in bipolar disorder (BD) is crucial for improving the understanding of how early environmental risk factors impact the presentation of the disorder. We conducted a systematic review and meta-analysis to estimate associations between overall and subtype...

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and...

Neuroimaging with MRI has been a frequent component of studies of individuals at clinical high risk (CHR) for developing psychosis, with goals of understanding potential brain regions and systems impacted in the CHR state and identifying prognostic or predictive biomarkers that can enhance our ability to forecast clinical outcomes. To date, most st...

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating...

Onyeama et al have examined the clinical profile of individuals with psychosis and childhood trauma using a stringent approach that yielded selective evidence, affecting power and insight into the specific and differential roles of abuse and neglect in the clinical profile. This commentary puts the findings into a broader meta-analytical context.

Background Complex post-traumatic stress disorder (cPTSD) is a newly recognized condition characterized by core PTSD symptoms and disturbances in self-organization (DSO) that has been associated with psychotic-like experiences (PLEs). This study employs two psychopathology network approaches to identify which post-traumatic symptoms are related to...

Background Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified. Methods We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of...

Background and Hypothesis: Duration of untreated psy-chosis (DUP) has been linked to worse mental health outcomes in psychotic disorders. We meta-analytically studied the relationship between "long" vs. "short" DUP and mental health outcomes. Study Design: This PRISMA/MOOSE-compliant meta-analysis searched for nonoverlapping individual studies fr...

The COVID-19 pandemic brought unprecedented global challenges. Amid the crisis, the potential impact of COVID-19 exposure on the neurodevelopment of offspring born to infected mothers emerged as a critical concern. This is a prospective cohort study of offspring exposed to mild or severe COVID-19 during pregnancy. Pregnant women who acquired SARS-C...

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive...

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study...

Schizophrenia (SZ) is a severe mental health condition involving gene-environment interactions, with obstetric complications (OCs) conferring an elevated risk for the disease. Current research suggests that OCs may exacerbate SZ symptoms. This study conducted a systematic review and meta-analysis to comprehensively evaluate differences in psychopat...

Introduction: Clinical High Risk for Psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution throug...

Background Patients can respond differently to intervention in the early phase of psychosis. Diverse symptomatic and functional outcomes can be distinguished and achieving one outcome may mean achieving another, but not necessarily the other way round, which is difficult to disentangle with cross-sectional data. The present study's goal was to eval...

In groups of patients suffering from psychosis, redox dysregulation was reported in both peripheral fluids and brain. It has been hypothesized that such dysregulation, including alterations of the glutathione (GSH) cycle could participate in the brain white matter (WM) abnormalities in schizophrenia (SZ) due to the oligodendrocytes’ susceptibility...

Introduction: Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender...

The COVID-19 pandemic brought unprecedented global challenges. Amid the crisis, the potential impact of SARS-CoV-2 on the neurodevelopment of offspring born to infected mothers emerged as a critical concern. This is a prospective cohort study of offspring exposed to maternal SARS-CoV-2 mild or severe infection during pregnancy. Pregnant women who a...

IntroductionTraditional classification systems based on broad nosological categories do not adequately capture the high heterogeneity of mental illness. One possible solution to this is to move to a multi-dimensional model of mental illness, as has been proposed by the Research Domain Criteria and Hierarchical Taxonomy of Psychopathology frameworks...

Aim: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung. Methods: A qualitative survey derived and adapted from Kotlicka‐Antczak et al. (...

Background The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown. Study Design PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both gro...

Background Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity associated psychopathological signature is yet to be clarified. Methods Using data from the EU-GEI study, in 376 First Episode Psychosis (FEP) cases, we evaluated the interaction between polygenic risk...

Background and Hypothesis: Studies on schizophrenia feature diffusion magnetic resonance imaging (dMRI) to investigate white matter (WM) anomalies. The heterogeneity in the possible interpretations of these metrics highlights the importance of increasing their specificity. Here, we characterize WM pathology in early psychosis (EP) and schizophrenia...

Background There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research. Aims This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scal...

Background: Bipolar disorder (BD) is among the leading causes of disability worldwide [1]. Childhood maltreatment (CM) is associated with the onset and course of BD. CM is further related to clinical and neurobiological characteristics that could be relevant to cognitive functioning [2]. However, whether different types of CM (physical/emotional/se...

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, r...

Both interpersonal trauma (IPT) and substance use are linked to mental health problems, however their interplay is understudied. This study will investigate the relationship between IPT, substance use and mental health in a large population-based sample. Participants included 3756 individuals, mainly young university students using a snowball sampl...

Background Alterations in brain connectivity occur early during psychosis and underlie the clinical manifestations of the illness as well as patient functioning and outcome. After a first episode of psychosis (FEP), different trajectories are possible and best described by the clinical-staging model that places the patient along a continuum of cond...

Purpose Recovery in people with first-episode psychosis (FEP) remains a major issue. When risk factors are studied in relation to the disorder, potential protective factors should also be considered since they can modulate this relationship. This study is aimed at exploring which premorbid and baseline characteristics are associated with a good and...

Background and Objectives: The COVID-19 pandemic and its associated factors have been shown to affect anxiety levels of young people. We meta-analytically assessed the prevalence of anxiety symptoms and anxiety disorders in children and adolescents during the pandemic, and the predictors and moderating factors influencing anxiety. Methods: Multiple...

As psychoses can have a long-term impact, they need to be diagnosed as quickly as possible in order to provide appropriate care and avoid the onset of comorbid complications. As general practitioners are often the first to be approached, it is important that they think about this diagnosis in young patients, even if the manifestations are often aty...

Background: Childhood trauma (CT) has been shown to impact depressive symptoms measured broadly in early psychosis patients. Beyond the broad intensity of such impact, less is known about which depressive features are more impacted. Methods: Patients of a specialized early intervention programme were evaluated after the first two and six months...

The rising prevalence and legalization of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study...

Aims: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments. It investigates the eff...

Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (...

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, int...

Background: Frequently associated with early psychosis, depressive and manic dimensions may play an important role in its course and outcome. While manic and depressive symptoms can alternate and co-occur, most of the studies in early intervention investigated these symptoms independently. The aim of this study was therefore to explore the co-occu...

Background: Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research f...

Background Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adve...

Background: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. Methods: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-...

Abtract Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood...

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders....

Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome-wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue f...

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised p...

Traumatic events during childhood/early adolescence can cause long-lasting physiological and behavioral changes with increasing risk for psychiatric conditions including psychosis. Genetic factors and trauma (and their type, degree of repetition, time of occurrence) are believed to influence how traumatic experiences affect an individual. Here, we...

Background and Hypothesis Despite the accepted link between childhood adversity (CA) and psychotic disorders, evidence on the relationship between CA and poor functional outcome remains less consistent and has never been reviewed quantitatively. The aim of this meta-analysis was to systematically examine the association between CA and functional ou...

Background Few investigations have been carried out on metabolic syndrome in antipsychotic- naïve patients with schizophrenia. Methods Our primary objective was to compare the prevalence of Metabolic Syndrome (MetS), as defined by the National Cholesterol Education Program, Adult Treatment Panel III in 2001 (NCEP-ATP III), between a Spanish cohort...

A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the deve...

Background Prevention of violent behaviors (VB) in the early phase of psychosis (EPP) is a real challenge. Impulsivity was shown to be strongly related to VB, and different evolutions of impulsivity were noticed along treatments. One possible variable involved in the relationship between VB and the evolution of impulsivity is cannabis use (CU). The...

Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the associatio...

Background: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network...

Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizo...

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schiz...

We present data on the incidence of admissions for first episode psychosis in a region of southern Spain. All consecutive cases of admissions to the psychiatric hospitalization unit due to psychosis were selected. The incidence rates for first episode psychosis among immigrants and non-immigrants between two years were calculated. Incidence rate ra...

The main aim of this study is to examine the association between psychosis and immigration, independent of the language barrier, drug consumption, and the social support index. The second aim is to explore the clinical and demographic characteristics of the immigrants in the catchment area, compared with the native Spanish population suffering from...

Background Considerable evidence on general population suggests that an “Affective pathway to psychosis”, involving depression and anxiety dimensions, mediates the abuse-psychosis association. However, this has never been tested in Early Psychosis (EP) patients. We aim at testing whether severity of depressive and anxiety mediates the abuse-positiv...

Objective: The influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder was systematically reviewed. Methods: Randomised and non-randomised studies of interventions for bipolar disorder that included an assessment of childhood trauma were eligible....

Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episod...

Background It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general populat...

Despite the accepted link between childhood abuse and positive psychotic symptoms, findings between other adversities, such as neglect, and the remaining dimensions in people with psychosis have been inconsistent, with evidence not yet reviewed quantitatively. The aim of this study was to systematically examine quantitatively the association betwee...

Schizophrenia (SZ), Bipolar Disorder (BD) and Depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUGEI case-control study, we...

History of adversity is associated with subsequent psychosis, and with a spectrum of cognitive alterations in individuals with psychosis. These cognitive features go from neurocognitive aspects as working memory and attention, to complex social cognitive processes as theory of mind and emotional perception. Difficulties in these domains impact pati...

Objective The aim of this systematic review and meta-analysis was to study the association between specific environmental risk factors (ERF) and later development of Bipolar disorder and Psychotic depression. Methods A systematic search of prospective studies was conducted in MEDLINE, EMBASE and PsycINFO databases, and supplemented by hand searchi...

Diabetes is the fourth cause of death globally. To date, there is not a practical, as well as an accurate sample for reflecting chronic glucose levels. We measured earwax glucose in 37 controls. Participants provided standard serum, glycated hemoglobin (HbA1c) and earwax samples at two time-points, one month apart. The specimens measured baseline f...

Background It has been suggested that exposure to Childhood Trauma [CT] may play a role in the risk of obesity in Early Psychosis [EP] patients; however, whether this is independently of age at exposure to CT and the medication profile has yet to be investigated. Methods 113 EP-patients aged 18–35 were recruited from the Treatment and Early Interv...

Increased chronic glucose is associated with pandemic diseases. To date, there is not a practical, as well as accurate sample for reflecting that level. We measured earwax glucose in 37 controls. They provided standard serum samples, Glycated Haemoglobin (HbA1c) and earwax samples on two time-points, one month a part. The specimens measured baselin...

Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review fol...

Background: Although evidence from psychosis patients demonstrates the adverse effects of cannabis use (CU) at a young age and that the rate of CU is high in subgroups of young violent patients with psychotic disorders, little is known about the possible effect of the age of onset of CU on later violent behaviors (VB). So, we aimed to explore the...

Background There is replicated evidence of a shared genetic load between affective and non-affective psychosis, but much less is known of whether affective psychosis is affected by the same environmental risk factors as well. The aim of this review and meta-analysis is to study the association between specific environmental risk factors of interest...

Background Various psychological and biological pathways have been proposed as mediators between childhood adverse events (CA) and psychosis. A systematic review of the evidence in this domain is needed; open new venues for treatment interventions in traumatized patients with psychosis. The aim of the current work is to systematically review the ev...

Background Current clinical utility of diagnostic categories in patients with psychosis is in debate. Alternatively, symptom-based dimensional approaches are suggested, but research on their utility and longitudinal stability is at its early phases, showing lack of consistencies. The aims of this prospective study are: 1) to test the stability of s...

Background The importance of inherited factors in the development of affective psychosis, which includes bipolar disorder and major depression disorder, is widely accepted, but the fact that monozygotic twin concordance is substantially less than 100% suggests that environmental factors (ERF) are likely to play an important role as well. While the...

Background: Increased systemic glucose level over long-term is associated with several chronic illnesses, such as diabetes. To date, no single sample is affordable, harmless and predictable, as a whole, at reflecting this level. We tested earwax or cerumen, as a practical choice to measure acute and chronic glucose levels in comparison with Glycate...