Papers by Antonella Trotta
Psychological Medicine, Jul 6, 2020
The association between childhood adversity (CA) and psychosis has been extensively investigated ... more The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.
Alcuni studi in letteratura supportano l\u2019associazione tra consumo di cannabis, et\ue0 di eso... more Alcuni studi in letteratura supportano l\u2019associazione tra consumo di cannabis, et\ue0 di esordio ed espressivit\ue0 psicopatologica nei pazienti al primo episodio psicotico (Orlandi, 2001). Questo lavoro si propone di analizzare la gravit\ue0 della sintomatologia psicotica in relazione al consumo di cannabis, confrontando due campioni di pazienti all'esordio psicotico (FEP) reclutati a Palermo e a Londra
Brain, Behavior, and Immunity, 2021
Exposure to victimization in childhood has been linked to the development of psychosis. However, ... more Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR=3.34, 95% CI 1.69-6.59, p=0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR=1.94, 95% CI 0.94-4.04, p=0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p's>0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors.
Psychiatry Research, 2020
Background Up to 35% of first-episode schizophrenia patients are estimated to meet criteria for t... more Background Up to 35% of first-episode schizophrenia patients are estimated to meet criteria for treatment resistant schizophrenia (TRS) over the five years after illness onset (Lally et al., 2016). Emerging evidence demonstrates that around 70% of TRS patients did not respond to antipsychotic medications from the start of first treatment (i.e., early treatment resistant (E-TR) schizophrenia); whereas, the remaining 30% of TRS patients, broadly defined as latetreatment resistant (L-TR) schizophrenia, gradually transition to treatment resistance during the 5-year period, having initially responded to antipsychotic medications (Lally et al., 2016). Given TRS is a major cause of disability and is associated with high social and economic costs (Kennedy et al., 2014), having reliable prediction models for estimating an individual risk for E-TR and L-TR would advance our understanding of patients' risk of developing treatment resistance, especially after a period of favourable response to the ongoing treatment with antipsychotic medications. Development of accurate prediction models for estimating individual, rather than average, risk for a disorder outcome during the illness (Steyerberg et al., 2010), based on available patient characteristics and clinical findings, is generally thought to require large datasets (Califf et al., 1997), mainly when the outcome of interest is a rare event. As they are often unavailable in schizophrenia research, stepwise selection techniques, particularly with the traditional p-value of 0.05, are frequently employed, which tend to provide readily interpretable models (Steyerberg et al., 2000). However, these stepwise selection techniques increase the risk of biased regression coefficients and overfitting (Derksen and Keselman, 1992) potentially leading to development of a prediction model with inaccurate predictions in new cases (Osborne et al., 2012; Steyerberg et al., 1999). Computer intensive statistical learning methods, particularly regularised regression methods (RRMs), have been suggested as optimal methods for clinical and personalised risk prediction (Steyerberg, 2019), especially for small datasets (Steyerberg et al., 2000). Through an 2 introduction of penalty, RRMs produce a model with good interpretability and overcome problems of overfitting, multicollinearity and poor prediction of new cases (Hastie et al., 2009). As RRMs have not been applied to small datasets for estimating an individual risk of TRS subtypes, their usefulness for these important outcomes is unknown. Therefore, in this study, employing RRMs, we aimed to develop robust prediction models for estimating an individual risk for E-TR and L-TR in a sample of first-episode schizophrenia patients who were followedup during the first 5 years of their illness (Ajnakina et al., 2017; Lally et al., 2016). 2.Methods 2.1.Sample The study comprised 282 participants aged 18-65 meeting criteria for schizophrenia spectrum (FES) disorders (International Classification of Diseases, 10th-Revision (ICD-10) diagnoses: F20.0, F25.0, F28.0, F29.0)(World Health Organization, 1992), validated by administration of the Schedules for Clinical Assessment in Neuropsychiatry (WHO, 1994). All cases had been admitted to psychiatric inpatient units or seen by community-based mental health teams within the South London and Maudsley (SLaM) NHS Foundation Trust between December 2005 and October 2010(Di Forti et al., 2013). The study exclusion criteria were evidence of 1) psychotic symptoms precipitated by an organic cause; 2) evidence of transient psychotic symptoms resulting from acute intoxication as defined by ICD-10; 3) moderate or severe learning disabilities as defined by ICD-10; or 4) head injury causing clinically significant loss of consciousness. 2.2.Baseline predictors Overall, 13 predictors were included in the models as described below. These predictors were chosen because they have consistently been implicated in the risk for schizophrenia onset and development of TRS (
European Neuropsychopharmacology, 2019
heightened expression in the late prenatal period (the third trimester of pregnancy). We will als... more heightened expression in the late prenatal period (the third trimester of pregnancy). We will also seek to correlate GREX in SCZ and BD cases with specific endophenotypes and clinical measures that are both shared and distinct between the two disorders.
Psychological medicine, 2015
Evidence suggests that childhood adversity is associated with the development of psychotic experi... more Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time. A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup. A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine stu...
Schizophrenia Research, 2012
Background: Recent studies suggest that Schizophrenia (SZ) and Bipolar disorder (BD) share a numb... more Background: Recent studies suggest that Schizophrenia (SZ) and Bipolar disorder (BD) share a number ofpathophysiological and phenomenological similarities, but other research supports a model whereby SZ is associated with additional risks factors which impair neurodevelopment (Demjaha, MacCabe and Murray, 2011). SZ is characterised by a broadly global cognitive impairment, and this impairment precedes the onset of the disease at least in part. In contrast, some studies suggest that these premorbid deficits appear to be absent, or even reversed, in BD (MacCabe et al, 2010). However, studies of both disorders following the onset of illness, show that partients suffer impairments in cognitive functioning, regardless of diagnosis (Demjaha, 2011). The purpose of this study was to compare premorbid and current IQ between diagnoses. The hypotheses were that (a) only schizophrenia will show deficits in premorbid IQ but (b) both disorders will show similar declines after illness onset. Methods: Studies were identified through searches of Medline (PubMed), Embase, and PsychINFO databases using as keywords: "Schizophrenia AND Bipolar Disorder" combined with "cognitive function", "neuropsychological function", "intellectual functioning", "premorbid IQ", "current IQ". Additional studies were identified by reviewing the references of each article found. In total, 222 studies were obtained and assessed manually. Of these, only 31 studies met the criteria and were included in the meta-analysis. Meta-analyses were performed with STATA, version 10.1, using the Metan and Meta programs. Effect Sizes for each original study were expressed as the standardized mean difference (SMD) between SZ, BD and control group means, divided by their pooled standard deviation (Cohen, 1969). Standardized effect sizes were analysed using random effects meta-analysis for the presence of statistically significant heterogeneity between studies. Results: Premorbid IQ. SZ patients show a significant cognitive impairment compared to controls (CT), (SMD:-0.619; 95%
Schizophrenia Research, 2014
Schizophrenia Research, 2014
Schizophrenia Research, 2014
Schizophrenia Research, 2020
The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psych... more The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.
Mediterranean Journal of Clinical Psychology, 2018
The Oedipus complex represents a key concept of psychoanalytic theory and is one of Freud’s most ... more The Oedipus complex represents a key concept of psychoanalytic theory and is one of Freud’s most significant ideas. It constitutes a basic conflict in all humans’ psyche and it defines the structure of individual’s sexual identity. Despite Freud fully recognizing its crucial role in the organization of mental life, he never dedicated to it an entire writing. The Oedipus complex was, in fact, developed in multiple steps and its development cannot be disentangled from events in Freud’s personal and professional life. The aim of this paper is to describe the development of Freud’s concept of the Oedipus complex throughout his writings. Objectives of the study were, first, to provide a description of the theoretical mechanisms and, second, to focus on the Oedipus complex on three of Freud’s clinical cases: Dora, Little Hans and the Wolf-Man.
CHAPTER 1-Literature review of association between childhood adversity, onset and outcome of psyc... more CHAPTER 1-Literature review of association between childhood adversity, onset and outcome of psychotic disorder ..
Clinical Psychological Science, 2020
More than 10% of the general population regularly experience paranoid thoughts. Persecutory delus... more More than 10% of the general population regularly experience paranoid thoughts. Persecutory delusions occur in one third of psychiatric patients in the United Kingdom and are associated with severe clinical and social impairment. Furthermore, individuals with elevated vulnerability to paranoia interpret ambiguous environmental information more negatively than those with low vulnerability, a cognitive phenomenon called interpretation bias. We conducted a systematic review and meta-analysis of the association between interpretation bias and paranoia. Twenty studies were included, and our meta-analysis indicated that a negative interpretation bias was associated with paranoia both in clinical (standardized mean difference, or SMD = 1.01; 95% confidence interval [CI] = [0.51, 1.52], p < .001) and nonclinical populations ( SMD = 1.06; 95% CI = [0.28, 1.85], p = .008). Our results also showed that higher negative interpretation bias was positively correlated with the severity of parano...
Schizophrenia Bulletin, 2018
Discussion: Neurocognitive deficits are numerous in 7-year-old children of parents with schizophr... more Discussion: Neurocognitive deficits are numerous in 7-year-old children of parents with schizophrenia, which supports the neurodevelopmental model of schizophrenia. Unimpaired neurocognitive abilities in children of parents with bipolar disorder indicate different neurodevelopmental manifestations in these high risk populations at this early age. Our results call for early identification of schizophrenia offspring with cognitive dysfunctions.
Schizophrenia Bulletin, 2018
Background: Childhood psychotic symptoms, such as hallucinations and delusions, are relatively co... more Background: Childhood psychotic symptoms, such as hallucinations and delusions, are relatively common and have been shown to increase risk of psychotic disorders in adulthood. However, less is known about their association with other forms of psychopathology and more broadly with social and occupational functioning during the crucial transition to adulthood. Using a prospective genetically-sensitive birth cohort we investigated associations between age-12 psychotic symptoms and a range of mental health problems and functional outcomes at age 18. Methods: Data from utilized from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 twins born in 1994-1995 in England and Wales, followed to age 18 with 93% retention. Childhood psychotic symptoms were assessed in private interviews at age 12. At age 18, interviews were conducted to assess psychopathology, social and occupational functioning, physical health, quality of life, risky and offending behaviors. Results: Children with psychotic symptoms were at greater risk of psychotic phenomena, depression, anxiety, and suicide attempts or self-harm in young adulthood than children without such symptoms. They were also more likely to be obese, smoke cigarettes, be lonely, already have children, and report a lower quality of life at age 18 compared with their unaffected peers. These associations held when controlling for sex, age-5 IQ, other psychopathology at age 12, and family environment. Discussion: In our genetically sensitive cohort, we showed strong evidence of continuity between early psychotic symptoms in childhood and persistence of psychotic phenomena to young adulthood. Psychotic symptoms in childhood are also important risk markers for a wide range of non-psychotic disorders and poor functional outcomes and therefore should be carefully assessed and treated to prevent adverse consequences in adulthood.
Schizophrenia Bulletin, 2018
characterized with more serious medical or psychiatric conditions, experience of loss and instabi... more characterized with more serious medical or psychiatric conditions, experience of loss and instability, as well as family disruption and violence. Their personality traits were characterized by low interpersonal skills, while controls were described as more "high-functioning". Discussion: The current study partially replicated previously published findings and provided detailed description of the characteristics of environment, functioning and personal traits of people who experienced first outbreak of psychotic disorder, in the years before the outcome. Unlike most of the studies that focused on premorbid period, the current study used unique premorbid data and a combination of in-depth qualitative analyses, performed blinded to outcome, and novel machine learning techniques.
Risk prediction algorithms have long been used in health research and practice (e.g., in predicti... more Risk prediction algorithms have long been used in health research and practice (e.g., in prediction of cardiovascular disease, diabetes, etc.) However, similar tools have not been developed for mental health problems, despite extensive research on risk factors. For example, for psychotic disorders, attempts to sum environmental risk are rare, usually unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the total environmental risk for psychotic disorders, which can be used in research and clinical practice.We first reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis and, then, used the largest available meta-analyses to derive current best estimates of risk. We devised a method of scoring individuals based on the level of exposure to each risk factor, using odds ratios from the meta-analyses, to produce an Environmental Risk Score (ERS).Six risk factors (ethnic minor...
Schizophrenia Bulletin, 2019
Background Childhood psychotic symptoms have been associated with various psychiatric disorders i... more Background Childhood psychotic symptoms have been associated with various psychiatric disorders in adulthood but their role as early markers of poor outcomes during the crucial transition to adulthood is largely unknown. Therefore, we investigated associations between age-12 psychotic symptoms and a range of mental health problems and functional outcomes at age 18. Methods Data were used from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in 1994–1995 in England and Wales, followed to age 18 with 93% retention. Childhood psychotic symptoms were assessed in structured interviews at age 12. At age 18, study members’ mental health problems, functional outcomes, risky behaviors, and offending were measured using self-reports and official records. Results Children with psychotic symptoms (N = 125, 5.9%) were more likely to experience a range of mental health problems in young adulthood than children without such symptoms. They ...
Psychological Medicine, 2018
BackgroundJumping to conclusions (JTC), which is the proneness to require less information before... more BackgroundJumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case–control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.MethodsOne-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning ‘Beads’ Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) – and inpatient days).ResultsFEP who presented ...
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Papers by Antonella Trotta