Paolo Brambilla

University of Milan | UNIMI · Department of Pathophysiology and Transplantation

The brain’s intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows complex inter-individual variability, consolidated during development. Nevertheless, the role of gene and environment on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an optimal platform...

Background: Across a range of age, educational and clinical characteristics, adults experiencing depression and anxiety already use digital technology to manage their symptoms. Although several reviews and meta-analyses indicated feasibility and efficacy for adults with depression and anxiety, digital treatments are poorly accessed and disseminate...

An influence of the Covid-19 pandemic on First Episode Psychosis (FEP) has been hypothesized. We previously reported an increase of FEP during the early stages of the pandemic in Milan, Italy. Here we report a 1-year follow-up of the same cohort and comparison with a FEP cohort from 2019. The higher proportion of non-chronic psychoses observed duri...

In recent years, machine learning (ML) has been a promising approach in the research of treatment outcome prediction in psychosis. In this study, we reviewed ML studies using different neuroimaging, neurophysiological, genetic, and clinical features to predict antipsychotic treatment outcomes in patients at different stages of schizophrenia. Litera...

Background: The SARS-CoV-2 pandemic compromised the mental health of COVID-19 patients and their family members. Due to social distancing and lockdown measures, a remote, tele-psychotherapy program for former or current COVID-19 patients and their relatives was implemented. Objective: The primary goal of this project was to evaluate intervention...

Background Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. Aims To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. Metho...

Introduction: Estimating the risk of manic relapse could help the psychiatrist individually adjust the treatment to the risk. Some authors have attempted to estimate this risk from baseline clinical data. Still, no studies have assessed whether the estimation could improve by adding structural magnetic resonance imaging (MRI) data. We aimed to eval...

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of pati...

Background: Analyzing cortical folding may provide insight into the biological underpinnings of neurodevelopmental diseases. A neurodevelopmental subtype of bipolar disorders (BD-ND) has been characterized by the combination of early age of onset and psychotic features. We investigate potential cortical morphology differences associated with this...

Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder...

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,...

Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with disorders affecting the peripheral and the central nervous system. A high number of patients develop post-COVID-19 syndrome with the persistence of a large spectrum of symptoms, including neurological, beyond 4 weeks after infection. Several potential m...

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level infere...

Background: Although it has been proposed that childhood adversities (CAs) may affect the hypothal- amic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP pati...

Background Major Depressive Disorder (MDD) is a psychiatric disorder characterized by functional brain deficits, as documented by resting-state functional magnetic resonance imaging (rs-fMRI) studies. Aims In recent years, some studies used machine learning (ML) approaches, based on rs-fMRI features, for classifying MDD from healthy controls (HC)....

Background Bipolar disorder (BD) is a psychiatric condition characterized by alternating episodes of mania and depression frequently associated with cognitive impairments. BD is associated with brain alterations in fronto-temporal and limbic networks. Recent conceptualizations view BD as a neurodegenerative disorder characterized by progressive det...

Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding inte...

Cognitive deficits are prevalent in bipolar disorder even during the euthymic phase, having a negative impact on global functioning and quality of life. As such, more and more mental health professionals agree that neuropsychological assessment should be considered an essential component of the clinical management of bipolar patients. However, no g...

Infant-caregiver dyads show high heterogeneity in terms of compatibility. Several lines of evidence indicate that the modalities by which areas of good and poor fit were emotionally recognized and managed by caregivers influence the infant's personality development, the integration of their personality traits, the overall sense of authenticity, as...

Major Depressive Disorder (MDD) and Bipolar Disorder Depression (BDD) are common psychiatric illnesses characterized by structural and functional brain alterations and signs of neuroinflammation. In line with the neuroinflammatory pathogenesis of depressive syndromes (1), recent studies have demonstrated how white matter (WM) microstructural impair...

Background: Coronavirus disease 2019 (COVID-19) leads to peripheral and central disorders, frequently with neurological implications. Blood-brain barrier disruption (BBBd) has been hypothesized as a mechanisms in the acute phase. We tested whether markers of BBBd, brain injury and inflammation could help identify a blood signature for disease sever...

The brain intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows a complex inter-individual variability, consolidated during development. Nevertheless, the role of genetic and environmental factors on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an opt...

Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by lack of self-regulation and deficits in organizing behaviors in response to emotional stimuli. Methylphenidate (MPH) is one of the most effective psychostimulant drugs for ADHD, however, a possible predictive utility of brain hemodynamic d...

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension...

Background Bipolar Disorder (BD) is a severe chronic psychiatric disorder whose aetiology is still largely unknown. However, increasing literature reported the involvement of neurovascular factors in the pathophysiology of BD, suggesting that a measure of Cerebral Blood Flow (CBF) could be an important biomarker of the illness. To date, Magnetic Re...

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive int...

Clozapine-induced myocarditis and pericarditis are uncommon adverse effects of clozapine treatment. However, in most cases, they lead to clozapine discontinuation. Here, we describe a case of successful clozapine rechallenge after clozapine-induced myopericarditis. The patient, a 31-year-old male with treatment-resistant schizophrenia (TRS), develo...

Background Patients with post-infective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often show both short- and long-term cognitive deficits within the dysexecutive/inattentive spectrum. However, little is known about which cognitive alterations are commonly found in patients recovered from SARS-CoV-2, and which psychometric tools c...

Objectives Cognitive deficits in Bipolar Disorder (BD) are significant enough to have an impact on daily functioning. Therefore, appropriate cognitive tools must be used to improve our understanding of the nature and severity of cognitive deficits in BD. In this study, we aimed to compare the cognitive profiles of patients with BD and healthy contr...

Brain incidental findings (IFs) are unexpected brain abnormalities detected by a structural magnetic resonance (MRI) examination. We conducted a study to assess whether brain IFs are associated with first-episode psychosis (FEP) and chronic psychosis (affective vs. non-affective) compared to healthy controls (HC). Chi-squared analyses were run to c...

Background Despite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to: 1. Identify current treatment gaps along...

Importance: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective: To use machine learning techniques to cluster, compare, and comb...

Background Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SCZ) share clinical features and genetic bases. Magnetic Resonance Imaging (MRI) studies assessing the effect of polygenic risk score (PRS), a measure of genetic susceptibility, for psychiatric disorders on brain structure show heterogeneous results. Therefore, we...

Background Social Anxiety Disorder (SAD) or Social Phobia is characterized by fear and anxiety of social circumstances that negatively impact an individuals' occupational and relational life. There are several treatment options for this disorder ranging from pharmacological therapy to psychotherapies. In particular, the Acceptance and Commitment Th...

Mental imagery is part of people's own internal processing and plays an important role in everyday life, cognition and pathology. The neural network supporting mental imagery is bottom‐up modulated by the imagery content. Here, we examined the complex associations of gender and age with the neural mechanisms underlying emotion imagery. We assessed...

Background Early-onset bipolar disorder (BD) is a complex psychiatric illness characterized by mood swings, irritability and functional impairments. To improve our understanding of the pathophysiology of the disorder, we collected the existing resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies exploring resting-state functional c...

Cognitive alterations are core features of psychotic disorders and severe psychiatric conditions significantly affecting patients’ quality of life and socio-occupational outcomes. Considering that these alterations respond only mildly to pharmacological interventions, in the last 30 years research has focused on the development of behavioural inter...

Background: The COVID-19 pandemic is negatively impacting the mental health of both COVID-19 patients and the general population. As current guidelines are limiting in-person contacts to reduce the spread of the virus, the development of a digital approach to implement in psychiatric and psychological consultation is needed. In this paper we prese...

BACKGROUND The COVID-19 pandemic is negatively impacting the mental health of both COVID-19 patients and the general population. Given the current guidelines limiting in person contact to reduce the spread of the virus, a digital approach is needed to tackle the psychological aftermath of the pandemic. Here, we present DigiCOVID, a digital mental h...

Background: Deficits in processing speed and verbal learning, manifest in psychotic illness (Mesholam-Gately et al., 2009) and mood disorder (Snyder, 2013) whilst predicting transitioning to psychosis at clinical high risk (CHR; Cannon, 2016). Recent studies including our own identified cognitive subgroups in psychosis spectrum (Wenzel et al., 2020...

Objective Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the l...

Background Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This stu...

Bipolar disorder is a psychiatric condition associated with shifts in mood, energy, and activity levels severely altering the quality of life of affected individuals. Although widely accepted, the neurobiological bases of the disorder are still incompletely described. This chapter offers an in-depth description of the brain alterations characterist...

Background Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity, and provide better candidates for predictive modelling. We aimed to identify clusters across patients with recent onset depression (ROD) and recent onset psychosis (ROP) based on structural neuroimaging data. We hypothe...

Background Borderline personality disorder (BPD) is a serious mental condition characterized by instability in identity, interpersonal relationships, emotion regulation and impulsivity. These symptoms seem to be associated to specific brain alterations, which have been largely investigated. In particular, positron emission tomography (PET) and func...

Background Current screening options in the setting of postpartum depression (PPD) are firmly rooted in self-report symptom-based tools. The implementation of the modern machine learning (ML) approaches might, in this context, represent a way to refine patient screening by precisely identifying possible PPD predictors and, subsequently, a populatio...

The clinical outcome of the disease provoked by the SARS-CoV-2 infection, COVID-19, is largely due to the development of interstitial pneumonia accompanied by an Acute Respiratory Distress Syndrome (ARDS), often requiring ventilatory support therapy in Intensive Care Units (ICUs). Current epidemiologic evidence is demonstrating that the COVID-19 pr...

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and heal...

Background Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal...

Background Cognitive Remediation (CR) is designed to halt the pathological neural systems that characterize major psychotic disorders (MPD), and its main objective is to improve cognitive functioning. The magnitude of CR-induced cognitive gains greatly varies across patients with MPD, with up to 40% of patients not showing gains in global cognitive...

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...

Background Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to...

Early-life adverse events or childhood adversities (CAs) are stressors and harmful experiences severely impacting on a child's wellbeing and development. Examples of CAs include parental neglect, emotional and physical abuse and bullying. Even though the prevalence of CAs and their psychological effects in both healthy and psychiatric populations i...

Background Major Depressive Disorder (MDD) is a severe psychiatric condition characterized by selective cognitive dysfunctions. In this regard, functional Magnetic Resonance Imaging (fMRI) studies showed, both at resting state and during tasks, alterations in the brain functional networks involved in cognitive processes in MDD patients compared to...

Objective Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational f...