Manon H J Hillegers

• MD, PhD
• Head of Department at Erasmus MC

Background Fetal life and infancy might be critical periods for brain development leading to increased risks of neurocognitive disorders and psychopathology later in life. We examined the associations of fetal and infant weight growth patterns and birth characteristics with behavior and cognitive outcomes at the age of 13 years. Methods Population...

Introduction. Adolescent psychology is embracing intensive longitudinal methods, such as diaries and experience sampling techniques, to investigate real-life experiences. However, participants might perceive the repetitive self-reporting in these data collection techniques as burdensome and demotivating, resulting in decreased compliance rates. In...

Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers a...

This systematic review primarily aims to provide a summary of the game mechanics implemented in eHealth tools supporting young people's self-management of their chronic diseases. This review secondarily investigates the rationale for implementing game mechanics and the effects of these tools. A systematic search was conducted in Embase, Medline, Ps...

Objectives To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. Methods Data from the Generation R Study were used, a...

Mobile Health (mHealth) interventions have the potential to improve early identification, prevention, and treatment of mental health problems. Grow It! is a multiplayer smartphone app designed for youth aged 12–25, allowing them to monitor their emotions and engage in daily challenges based on Cognitive Behavioral Therapy (CBT) principles. Recently...

Background Anorexia nervosa is a severe psychiatric disorder with a heterogeneous course with one of the highest rates of morbidity and mortality of all psychiatric disorders. Little is known about factors that predict both course and treatment outcomes of this disorder. The BRAVE Study is a longitudinal first-onset anorexia nervosa cohort study fo...

Background Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at elevated risk of developing psychiatric illness owing to both genetic predisposition and increased burden of environmental stress. Emerging evidence indicates a disruption of brain network connectivity in young offspring of patients with bipo...

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one’s children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to del...

Resilience, the dynamic process of adapting to or recovering from stress, predicts well-being and mental health. While most studies have investigated resilience after major life events, less is known about resilience in everyday life. To understand how individuals cope with everyday stress, and the associations with other psychosocial variables, we...

Background One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of interge...

Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning w...

Purpose To examine implications of the COVID-19 pandemic on eating disorder (ED) features and psychopathology in female adolescents with anorexia nervosa (AN). Method In total 79 females with first-onset AN (aged 12–22 years) were included and were followed up across a period of 1 year. We assessed AN participants recruited pre-pandemic (n = 49) t...

Background A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accountin...

Objectives To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if we had intervened on eliminating postnatal depression and increasing social support within 6 months after birth. Methods Data from the Generation R Stud...

Background With the Experience Sampling Method (ESM) participants are asked to provide self-reports of their symptoms, feelings, thoughts and behaviours in daily life. This preregistered systematic review assessed how ESM is being used to monitor emotional well-being, somatic health, fatigue and pain in children and adolescents with a chronic somat...

Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterised by severe intellectual disability, movement disorder, epilepsy, sleeping problems, and behavioural issues. Little is known on child health‐related quality of life (HRQoL) in AS. AS family studies have reported elevated parenting stress and a high impact of the chi...

Background Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study w...

Background Clinicians in Child and Adolescent Mental Healthcare Services (CAMHS) face the challenge to determine who is at risk of persistence of depressive problems into adulthood and requires continued treatment after reaching the CAMHS upper age limit of care-provision. We assessed whether risk factors for persistence were related to CAMHS clini...

There is convincing evidence from rodent studies suggesting that prenatal infections affect the offspring’s brain, but evidence in humans is limited. Here, we assessed the occurrence of common infections during each trimester of pregnancy and examined associations with brain outcomes in adolescent offspring. Our study was embedded in the Generation...

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive...

Importance: Clinical decision-making on antidepressant treatment during pregnancy, particularly selective serotonin reuptake inhibitors (SSRIs), is challenging, as both prenatal SSRI exposure and maternal depressive symptoms may be associated with negative outcomes in offspring. Objective: To investigate the association between intrauterine SSRI...

Background Prenatal alcohol exposure (PAE) is a worldwide public health concern. While PAE is known to be associated with low birth weight, little is known about timing and quantity of PAE on fetal growth. This study investigated the association between periconceptional and prenatal alcohol exposure and longitudinal fetal growth, focusing on timing...

Magnetic resonance imaging (MRI) procedures often evoke anxiety in children. Further, anxious children may be less likely to participate in MRI research, leading to a possible selection bias, and may be more likely to move during image acquisition, resulting in lower image quality and possible information bias. Therefore, state anxiety is problemat...

Physical symptoms, also known as somatic symptoms, are those for which medical examinations do not reveal a sufficient underlying root cause (e.g., pain and fatigue). The extant literature of the neurobiological underpinnings of physical symptoms is largely inconsistent and primarily comprises of (clinical) case-control studies with small sample si...

Objective: Whereas the risk and course of psychopathology in offspring of parents with bipolar disorder (BD) have been the primary focus of high-risk offspring studies to date, functional outcomes have not been given much attention. We present a systematic review of functional outcomes and quality of life (QoL) across development in offspring of p...

Objectives: Offspring of parents with bipolar disorder (BDo) and schizophrenia (SZo) are at increased risk for these disorders and general psychopathology. Little is known about their (dis)similarities in risk and developmental trajectories during adolescence. A clinical staging approach may help define the developmental course of illness. Method...

Aims Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side‐effects, including weight gain. This study assessed the population pharmacokinetics of aripiprazole and its active metabolite and investigated the relationship between pharmacokinetic parameters...

Background: Prior studies have shown that psychotic experiences are prospectively associated with an increased risk of suicidality. However, it is unclear whether this association is causal or arises from shared risk factors. Furthermore, little is known about the association between psychotic experiences and non-suicidal self-injury (NSSI). Meth...

Objective: Exposure to infection during pregnancy may be a potential risk factor for later psychopathology, but large-scale epidemiological studies investigating associations between prenatal infection and long-term offspring behavioral problems in the general population are scarce. In our study, we aimed to investigate the following: (1) the asso...

Background: A history of childhood maltreatment often has a negative and long-lasting impact across different domains in life. A childhood maltreatment experience in parents may even affect the next generation. So far, the effects of family factors have been considered in the intergenerational transmission of adversity across the childhood years,...

Eating problems, such as food selectivity or picky eating, are thought to be an epiphenomenon of autism spectrum disorders (ASD). Yet eating problems are also common in the general pediatric population and overlap with ASD symptoms. However, the temporal association between ASD symptoms and eating problems is poorly understood. This study examines...

Background: Alterations in stress regulation and function of the hypothalamic-pituitary-adrenal (HPA) axis during infancy may be a risk factor for the development of psychopathology later in life. Maternal childhood trauma, depression, anxiety and stressful life events are individually associated with HPA axis dysregulation. Less is known about th...

Importance: Gender-diverse youths have higher rates of mental health problems compared with the general population, as shown in both clinical and nonclinical populations. Brain correlates of gender diversity, however, have been reported only among youths with gender dysphoria or in transgender individuals. Objective: To examine brain morphologic...

BACKGROUND Mobile Health (mHealth) may improve early identification, prevention, and treatment of mental health problems. The multiplayer smartphone app Grow It!, lets 12-25 years old adolescents monitor their emotions and provides them with daily challenges based on Cognitive Behavioral Therapy (CBT). OBJECTIVE This preregistered study evaluates...

Background Cognitive and brain reserve refer to individual differences that allow some people to better withstand brain pathology than others. Although early life stress has been recognized as a risk factor for low reserve in late life, no research yet has studied this across midlife. Objective To examine the associations of life stress with brain...

Objective: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. Methods: Eight cohorts were combined to create a sample of 1,884 participants ages 2-36 years, includ...

To explore associations between autism traits and family functioning over time, we studied longitudinal data of a mixed group of 168 clinically referred autistic and non-autistic children. Cross-lagged models showed a significant association between fewer autism traits at the diagnostic assessment and better family functioning 1 year later for the...

Background: To study clinicians' and parents' awareness of suicidal behaviour in adolescents reaching the upper age limit of their Child and Adolescent Mental Health Service (CAMHS) and its association with mental health indicators, transition recommendations and mental health service (MHS) use. Methods: 763 CAMHS users from eight European count...

Background Given the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness course. We conducted a systematic review of the effectiveness of interventions in the early course of BD I or II. Methods We completed a systematic search on MEDLINE, P...

Background: Antipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both...

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies with modest sample...

Maternal sensitivity has been implicated in various aspects of child health and development, including overweight. However, long-term effects, the role of paternal sensitivity and the explanatory pathways are unclear. This study examined whether maternal sensitivity in early childhood is prospectively associated with adolescent body mass index and...

Depressive symptoms differ in severity and stability over time. Trajectories depicting these changes, particularly those with high late-life depressive symptoms, have been associated with poor brain health at old age. To better understand these associations across the lifespan, we examined depressive symptoms trajectories in relation to brain healt...

Background Unplanned or unintended pregnancies form a major public health concern because they are associated with unfavorable birth outcomes as well as social adversity, stress and depression among parents-to-be. Several risk factors for unplanned pregnancies in women have previously been identified, but studies usually take a unidimensional appro...

Introduction Young people (aged 10–25 years) with chronic diseases are vulnerable to have reduced social participation and quality of life. It is important to empower young people to engage in their chronic diseases self-management. In comparison with traditional face-to-face care, interventions delivered through the internet and related technologi...

Introduction Higher thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population (Boedhoe et al. 2017, Weeland et al. 2021a). Functionally distinct thalamic nuclei are an integral part of OCD-relevant brain circuitry. Objectives We aimed to study the tha...

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies in small sample siz...

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies in small sample siz...

Adolescents are at increased risk for developing mental health problems. The Grow It! app is an mHealth intervention aimed at preventing mental health problems through improving coping by cognitive behavioral therapy (CBT)-inspired challenges as well as self-monitoring of emotions through Experience Sampling Methods (ESM). Yet, little is known abou...

Early life stress (ELS) is associated with lower IQ and academic achievement; however, it remains unclear whether it additionally explains their discrepancy. In 2,401 children (54% girls, 30.2% migration background) from the population‐based study Generation R Study, latent factors of prenatal and postnatal (age 0–10) ELS were estimated, and IQ‐ach...

Adolescents are at increased risk for developing mental health problems. The Grow It! app is an mHealth intervention aimed at preventing mental health problems through improving coping by cognitive behavioral therapy (CBT)-inspired challenges as well as self-monitoring of emotions through Experience Sampling Methods (ESM). Yet, little is known abou...

Knowledge on determinants of children’s psychosocial care use is important to improve their access to care. This study examined the independent contributions of need and predisposing factors to psychosocial care use in 9-year-old children, guided by the Gateway Provider Model. Data of the Generation R Study, a prospective cohort of children born in...

Adolescents with a visible difference can experience difficult social situations, (e.g., people staring or making unwanted comments) and are at risk for mental health problems. Unfortunately, interventions for adolescents with a visible difference experiencing appearance-related distress are scarce and lack an evidence-base. This study tests the ac...

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar a...

Objective The etiology of autism spectrum disorder (ASD) remains unclear, due to genetic heterogeneity and heterogeneity in symptoms across individuals. This study compares ASD symptomatology between monogenetic syndromes with a high ASD prevalence, in order to reveal syndrome specific vulnerabilities and to clarify how genetic variations affect AS...

Adolescent mental health and well-being have been adversely impacted by the COVID-19 pandemic. In this preregistered longitudinal study, we evaluated whether adolescents’ well-being improved after playing the multiplayer serious game app Grow It! During the first lockdown (May–June 2020), 1282 Dutch adolescents played the Grow It! app (age = 16.67,...

Background Psychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here the authors investigated longitudinal associations...

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...

Psychopathology and cognitive development are closely related. Assessing the relationship between multiple domains of psychopathology and cognitive performance can elucidate which cognitive tasks are related to specific domains of psychopathology. This can help build theory and improve clinical decision-making in the future. In this study, we inclu...

A visible difference to the face or body may challenge adolescents’ adjustment and engagement in life activities, where some require psychosocial support. However, evidence is limited for whether existing interventions for this adolescent group reduce social or appearance-related distress. We therefore conducted a parallel-group, randomised control...

Objective: To investigate whether child mental health problems prospectively associate with IQ-achievement discrepancy (i.e. academic under- and overachievement) in emerging adolescence. Secondary aims were to test whether these associations are specific to certain mental health problems, to assess potential sex differences, and to examine whether...

Background Sleep problems, altered sleep patterns and mental health difficulties often co-occur in the pediatric population. Different assessment methods for sleep exist, however, many studies only use one measure of sleep or focus on one specific mental health problem. In this population-based study, we assessed different aspects of sleep and moth...

Background & Aims: Disorganized speech (DS) refers to the failure to communicate coherently. Children with autism spectrum disorder (ASD) show disorganized speech, such as abrupt topic changes. Disorganized speech can be explained by 1) social pragmatic communication difficulties (SPCD) or 2) social cognition problems (SCP). Methods: We tested whet...

Background Gender diversity in young adolescents is understudied outside of referral clinics. We investigated gender diversity in an urban, ethnically diverse sample of adolescents from the general population and examined predictors and associated mental health outcomes. Methods The study was embedded in Generation R, a population‐based cohort of...

Objective The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the government’s aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsych...

Background: Anxiety and mood problems in adolescents often go unnoticed and may therefore remain untreated. Identifying and preventing the development of emotional problems requires monitoring and effective tools to strengthen adolescents' resilience, for example, by enhancing coping skills. Objective: The current study describes the developmental...

Children of parents with anxiety or mood disorders have an increased risk of developing an anxiety or mood disorder themselves. A qualitative review of different components of well-studied prevention programs shows that all programs use elements of psychoeducation. Programs that primarily target children often use elements of cognitive behavioral t...

Approximately, 15% of children in Western countries suffer from emotional and behavioural problems. However, not all children receive the psychosocial care they need, especially children with a non-Western background experience an unmet need for care. This might be because parents of non-Western children report a lower need for care than parents of...

Background: Antipsychotic drugs are associated with serious side effects in children and adolescents including weight gain. It is still unknown whether therapeutic drug monitoring (TDM) can improve patient outcomes. Aim: To test whether the dried blood spot method is a valid and feasible method to measure antipsychotic drug concentrations with a...

Objective Cardiac surgery patients are at risk for psychopathology. Symptoms of post-traumatic stress disorder (PTSD) and depression occur in 10–20% of these patients and affect their quality of life. The aim of this study was to assess factors associated with psychopathology after cardiac surgery. Methods We followed participants of the multi-cen...

This study investigated the association of child, caregiver, and caregiving measurements with the quality of life (QoL) in 81 caregivers (mostly parents) of clinically referred children with autism spectrum disorder (ASD). We used the EuroQol five-dimensional (EQ-5D) questionnaire and the care-related QoL questionnaire (CarerQol) to respectively as...

Background The prevalence of mental health problems in Europe is higher among children with a non-Western than a Western background. Nevertheless, non-Western children use less psychosocial care. A possible explanation is the differences in parents' perceived need for care. Non-Western parents generally have a lower perceived need, which calls for...

Background Individuals with anorexia nervosa (AN) tend to have rigid thoughts and behaviors regarding their body weight, body image, and eating habits. While a diagnosis of AN implies severe levels of impairment, AN traits can vary on a continuum within the population. However, little is known about how early markers of AN relate to rigid thought p...