Valeria Mondelli

King's College London | KCL · Department of Psychological Medicine

In adolescence, parental care is associated with lower depression symptoms whereas parental overprotection is associated with greater depression symptoms, effects which may be mediated by adolescent brain activity and connectivity. The present study examined associations between perceived parenting, brain activity and connectivity, and depression s...

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC ab...

Digital mental health is becoming increasingly common. This includes use of smartphones and wearables to collect data in real time during day-to-day life (remote measurement technologies, RMT). Such data could capture changes relevant to depression for use in objective screening, symptom management and relapse prevention. This approach may be parti...

Background: Mental health status assessment is mostly limited to clinical or research settings, but recent technological advances provide new opportunities for measurement using more ecological approaches. Leveraging apps already in use by individuals on their smartphones, such as chatbots, could be a useful approach to capture subjective reports o...

Objective To present the protocol and methods for the prospective longitudinal assessments—including clinical and digital phenotyping approaches—of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) study, which comprises Brazilian adolescents stratified at baseline by risk of developing depression or presence of d...

Sommario Lo stress rappresenta la risposta di adattamento dell’organismo a una minaccia all’equilibrio (omeostasi) dell’organismo da parte di eventi o stressor di natura intrinseca o estrinseca, reali o percepiti. Gli stressor attivano un variegato e intricato repertorio di risposte fisiologiche biologiche e comportamentali (allostasi) volte a rist...

Background Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigate...

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...

Evidence suggests affective disorders such as depression and bipolar disorder are characterised by dysregulated autonomic nervous system (ANS) activity. These findings suggest ANS dysregulation may be involved in the pathogenesis of affective disorders. Different affective states are characterised by different ANS activity patterns (i.e., an increa...

Background: Associations between inflammatory markers and depression are reported among adults; however, less is known in adolescent depression in particular whether these associations are sex-specific. We aimed to identify inflammatory markers of increased risk and presence of depression in adolescence and their association with severity of depre...

Objective: To explore differences in regional cortical morphometric structure between adolescents at risk for depression or with current depression. Methods: We analyzed cross-sectional structural neuroimaging data from a sample of 150 Brazilian adolescents classified as low-risk (n=50) or high-risk for depression (n=50) or with current depressi...

Background and aims: We investigated kynurenine pathway (KP) metabolites levels and their association with suicidal ideation in patients with treatment-resistant depression (TRD) and elevated peripheral inflammation. The effect of antidepressant augmentation with minocycline on KP metabolites was tested. Methods: We analysed data from MINocyclin...

Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international p...

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia...

Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four...

Background There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. Aims To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders. Method MEDLINE, Emba...

Neuroinflammation is an important component of many neurodegenerative diseases, whether as a primary cause or a secondary outcome. For that reason, either as diagnostic tools or to monitor progression and/or pharmacological interventions, there is a need for robust biomarkers of neuroinflammation in the brain. Mitochondrial TSPO (18 kDa Translocato...

Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy to improve treatment efficacy, par...

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n=269 CHR, n=56 healthy controls) using multiplex immunoassays, and then follow...

Introduction: Although there is a general perception that adolescent social media use is a global phenomenon, there is a scarcity of data on patterns and preferences of social media use among youth in low- and middle-income countries. We here describe self-reported prevalences and perceived effects of social media use in a school-based sample of B...

BACKGROUND Assessment of mental health status is mostly limited to clinical or research settings, but recent technological advances provide new opportunities for measurement using more ecological approaches. Leveraging apps already in use by individuals on their smartphones, such as chatbots, could represent useful tools to capture subjective repor...

Background Mental health status assessment is mostly limited to clinical or research settings, but recent technological advances provide new opportunities for measurement using more ecological approaches. Leveraging apps already in use by individuals on their smartphones, such as chatbots, could be a useful approach to capture subjective reports of...

Background Inflammation is a well-known risk factor for depression. Specifically, patients who do not respond to antidepressant treatment show higher levels of inflammatory biomarkers compared with responders. Thus, several studies have investigated the efficacy of anti-inflammatory add-on treatment in this population. However, major depressive dis...

The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) has been externally assessed in samples from four continents, but North America is lacking. Our aim here was to evaluate the performance of the IDEA-RS in predicting future onset of Major Depressive Disorder (MDD) in an adolescent population-based sample in the United States of Am...

Background There is a lack of research on the adolescent experience of depression in low- and middle-income countries. Criteria derived from research conducted primarily among adult Western populations inform current diagnostic standards for depression. These clinical categories are often used without exploration of their relevance to adolescent ex...

Background Remote measurement technologies (RMT), such as smartphones and wearables, allow data collection from an individual in real-time during their day-to-day life, from which their mood, physiology, behaviour, and environment can be inferred. As such, RMT could monitor and detect changes relevant to depression for objective screening, symptom...

Study Objectives Major Depressive Disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rh...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Background Inflammation-related proteins constitute a promising avenue in studying biological correlates of major depressive disorder (MDD). However, MDD is a heterogeneous condition – a crucial aspect to be considered in association studies. We examined whether inflammatory proteins are associated with categorical diagnosis, a dimensional total su...

Background/Purpose Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-fre...

Aim: Identifying predictors for future onset of depression is crucial to effectively developing preventive interventions. We conducted a systematic review and meta-analysis to identify risk factors for first-onset depression among adolescents and young people. Methods: We searched MEDLINE (Ovid), PsycINFO, Cochrane Database, Web of Science, Lila...

A handling procedure of off-wrist episodes in actimetry time series of motor activity is presented using two records (regular vs. irregular sleep-wake cycle and daytime activity) of 14 consecutive days sampled in 1-minute epochs. We generated single missing value (NA) intervals of 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h as well as random NA episodes fol...

Importance: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. Objective: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcri...

Background There have been significant challenges in understanding functional brain connectivity associated with adolescent depression, including the need for a more comprehensive approach to defining risk, the lack of representation of participants from low- and middle-income countries, and the need for network-based approaches to model connectivi...

Objective: To explore associations between self-reported weekly physical activity and depressive symptomatology among adolescents in a school-based sample from Brazil. Methods: We surveyed 7,405 adolescents aged 14 to 16 years in 101 public schools in Porto Alegre, Brazil. We assessed physical activity using an adapted version of the Patient-Cen...

Current lines of research into mood disorders indicate that immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions, even when these mediators are produced in peripheral tissues. Elevated levels of circulating immune molecules have been consistently associated with depressive symp...

There is growing policy, practice, and research interest in reducing the treatment gap for adolescent depression in low- and middle-income countries, where 90% of the world's adolescents live. Despite increased efforts for adolescent depression services in these settings, there is a risk that services will not be utilized if initiatives are not cul...

Receiving a diagnosis of depression can have an important impact on the lives of adolescents. However, there is limited information about how youth tackle, attribute meaning to and understand mental health diagnoses. The aim of this study was to explore adolescents’ initial reactions after receiving a clinical diagnosis of Major Depressive Disorder...

Aim: Depression is one of the most common mental illnesses globally and a leading cause of disability. It is often established by late adolescence and thus identifying which adolescents are most at risk is crucial to enable early intervention to prevent depression onset. We have previously developed a risk calculator to stratify which adolescents...

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity – a risk factor for MDD – becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigatio...

Calls for refining the understanding of depression beyond diagnostic criteria have been growing in recent years. We examined the prevalence and relevance of DSM and non-DSM depressive symptoms in two Brazilian school-based adolescent samples with two commonly used scales, the Patient Health Questionnaire (PHQ-A) and the Mood and Feelings Questionna...

Several studies reported abnormal cortisol and inflammatory biomarker levels in youths with attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. We conducted a systematic review followed by a meta-analysis of case-control studies assessing blood or saliva cortisol levels and blood levels of inflammatory biomark...

Introduction Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has focused on the role of the HPA axis in depression in adolescence and young adulthood globally. The aim of this study was to conduct a systematic review and meta-analysis of...

Background Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods 51 depressed participants (HDRS score >13) an...

Extensive research suggests a role for the innate immune system in the pathogenesis of depression, but most of the studies are conducted in adult populations, in high-income countries and mainly focus on the study of inflammatory proteins alone, which provides only a limited understanding of the immune pathways involved in the development of depres...

Background Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods 51 depressed participants (HDRS score >13) an...

Inflammatory processes in the Central Nervous System (CNS) have been proposed to mediate the association between peripheral inflammation and the development of psychiatric disorders, but we currently lack sensitive measures of CNS inflammation for human studies in vivo. Here we used quantitative MRI (qMRI) to explore the in vivo central response to...

Background Considering the rapid antidepressant action of ketamine, we aimed to investigate its anti-inflammatory effect. Methods As part of a randomised double-blind placebo-controlled study plasma samples from 31 healthy remitted depressed were collected before and 1.5 hours after ketamine (0.5 mg/kg) and saline (placebo) administration in a two...

Background The Minocycline in Depression (MINDEP) study is a 4-weeks double-blind, placebo-controlled clinical trial, investigating the efficacy of minocycline in treatment resistant depressed (TRD) patients with major depressive disorder, and C-reactive protein (CRP) ≥ 1 mg/L. Methods We explored sex differences in the effects of study arms and C...

To understand how systemic immune changes affect central pathophysiological mechanisms of depression, we investigated the effects of peripheral inflammatory response on human neurogenesis in vitro, using serum from healthy participants challenged with interferon-alpha (IFNa) to model of inflammation-induced depression. Human hippocampal progenitor...

Background In youth at clinical high-risk for psychosis, cortisol elevations predict transition to psychosis, but it is unclear whether cortisol alterations are evident at an earlier clinical stage. We investigated whether cortisol levels and stressors in childhood were associated with later attenuated psychotic (AP) symptoms. Methods A sample of...

Background While the role of inflammation in adult depression is well documented, less is known in the context of adolescent depression. Our study aims to identify inflammatory markers associated with increased risk and presence of adolescent depression Methods We recruited 150 adolescents stratified into 3 groups based on the depression risk scor...

Background Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is suggested to play a role in the association between depression and obesity. We investigated differences in cortisol levels in individuals with obesity with and without depression, and the effects of perceived stress and binge eating on cortisol levels. Methods Saliva samples wer...

Introduction Major Depressive Disorder (MDD) has a prevalence of 11% by the end of adolescence and 90% of adolescents live in low and middle income countries (LMIC). Hence, identifying biomarkers to early identify adolescents at risk of developing the disorder is of paramount importance. Methods A risk-stratified cohort of 150 adolescents was recr...

Background: Neuroimaging studies on adolescents at risk for depression have relied on a single risk factor and focused on adolescents in high-income countries. Using a composite risk score, this study aims to examine neural activity and connectivity associated with risk and presence of depression in adolescents in Brazil. Methods: Depression ris...

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 (PE...

Background In youth at clinical high-risk for psychosis, elevated cortisol levels predict subsequent onset of psychotic disorder. However, it is unclear whether cortisol alterations are evident at an earlier clinical stage and promote progression of psychosis expression. The present study aimed to address this issue by investigating whether cortiso...

Neuroimmunology in the broadest sense is the study of interactions between the nervous and the immune systems. These interactions play important roles in health from supporting neural development, homeostasis and plasticity to modifying behaviour. Neuroimmunology is increasingly recognised as a field with the potential to deliver a significant posi...

p>Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate c...

Background Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim This systematic review...

Background: The characterization of adolescents at high risk for developing depression has traditionally relied on the presence or absence of single risk factors. More recently, the use of composite risk scores combining information from multiple variables has gained attention in prognostic research in the field of mental health. We previously deve...