Publications by authors named "Dimitri Papadopoulos Orfanos"

Background And Aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design And Setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures.

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  • The study utilized machine learning models to identify reliable diagnostic markers for eating disorders, major depressive disorder, and alcohol use disorder, targeting young adults aged 18-25.
  • The classification models showed high accuracy rates (AUC-ROC ranging from 0.80 to 0.92) even without considering body mass index and highlighted shared predictors like neuroticism and hopelessness.
  • Additionally, the models were moderately successful in predicting future symptoms related to eating disorders, depression, and alcohol use in a longitudinal sample of adolescents, indicating the potential for improved diagnosis and risk assessment in mental health.
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Introduction: A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e.

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  • This study uses multi-modal MRI to investigate neurobiological differences between anorexia nervosa (AN) and bulimia nervosa (BN), revealing structural and functional brain changes linked to these eating disorders.
  • Key findings include reduced gray matter volume in specific brain regions (like the orbitofrontal cortex) and decreased cortical thickness, particularly in anorexia patients, which are associated with impulsivity and cognitive restraint regarding eating behaviors.
  • The results suggest that these brain changes affect reward processing and contribute to the persistence of eating disorder symptoms, highlighting potential targets for future treatment interventions.
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  • * A study utilizing the Adolescent Brain Cognitive Development cohort revealed seven genomic regions where gene-environment interactions affect gray matter volume, tied to metabolic and inflammatory processes, as well as synaptic plasticity.
  • * The analysis highlighted that socioeconomic status, rather than family environment, plays a crucial role in how maternal education influences genetic effects on neurodevelopment, offering insights into the biological and social mechanisms involved.
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Background: Psychotic symptoms in adolescence are associated with social adversity and genetic risk for schizophrenia. This gene-environment interplay may be mediated by personality, which also develops during adolescence. We hypothesized that (i) personality development predicts later Psychosis Proneness Signs (PPS), and (ii) personality traits mediate the association between genetic risk for schizophrenia, social adversities, and psychosis.

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  • This study investigates structural brain aging by analyzing both cross-sectional and longitudinal data from over 37,000 healthy individuals in the UK Biobank, identifying two distinct patterns of brain aging.
  • Participants showing signs of accelerated brain aging also experienced faster biological aging, cognitive decline, and higher genetic risks for neuropsychiatric disorders.
  • The research supports the 'last in, first out' hypothesis linking brain aging to brain development, and includes genomic analysis to uncover genetic factors influencing both accelerated brain aging and delayed development.
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  • Resilience to emotional disorders in adolescents, particularly after childhood abuse, is influenced by brain responses to environmental stressors, but the specific brain signatures of resilience are still being studied.
  • Research identified two brain networks linked to resilience, with a notable finding that girls with greater activation in a specific orbitofrontal network experienced fewer emotional symptoms after childhood abuse when they had a higher genetic risk for depression.
  • The study suggests these genetic influences on brain activity can predict emotional disorders in late adolescence, highlighting the potential for developing resilience-based interventions to improve adolescent mental health.
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Neural variability, or variation in brain signals, facilitates dynamic brain responses to ongoing demands. This flexibility is important during development from childhood to young adulthood, a period characterized by rapid changes in experience. However, little is known about how variability in the engagement of recurring brain states changes during development.

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Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories.

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  • * It analyzed over 1000 participants from ages 14 to 23 to determine if issues with sustained attention predict future substance use rather than being just a side effect.
  • * The results showed that strong brain connections related to sustained attention at age 14 can predict an increase in cannabis and cigarette use later, highlighting sustained attention as a key indicator of vulnerability to substance use.
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Importance: The development of an alcohol use disorder in adolescence is associated with increased risk of future alcohol dependence. The differential associations of risk factors with alcohol use over the course of 8 years are important for preventive measures.

Objective: To determine the differential associations of risk-taking aspects of personality, social factors, brain functioning, and familial risk with hazardous alcohol use in adolescents over the course of 8 years.

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Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV).

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Perseverative negative thoughts, known as rumination, might arise from emotional challenges and preclude mental health when transitioning into adulthood. Due to its multifaceted nature, rumination can take several ruminative response styles, that diverge in manifestations, severity, and mental health outcomes. Still, prospective ruminative phenotypes remain elusive insofar.

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  • - The study investigates how the balance between excitation and inhibition in brain cortex microcircuits changes during adolescence, a critical period for brain maturation.
  • - Using advanced simulations and resting-state fMRI data from two large groups, researchers found an increase in inhibition in certain brain regions (association cortices) as adolescents age, while sensorimotor areas showed more stable excitation levels.
  • - The findings suggest that there’s a consistent developmental pattern in the excitation-inhibition balance that can vary among individuals, providing a new computational method to study brain maturation at a personal level.
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Background: Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers.

Methods: We explored associations between personality and ED-related mental health symptoms using canonical correlation analyses.

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Current psychiatric diagnoses are not defined by neurobiological measures which hinders the development of therapies targeting mechanisms underlying mental illness . Research confined to diagnostic boundaries yields heterogeneous biological results, whereas transdiagnostic studies often investigate individual symptoms in isolation. There is currently no paradigm available to comprehensively investigate the relationship between different clinical symptoms, individual disorders, and the underlying neurobiological mechanisms.

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Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample.

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Background: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively.

Methods: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank).

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Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance-use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants.

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  • Cannabis has been the most commonly used illicit drug, especially among young people, with research indicating links to mental health issues due to its impact on brain functions related to reward and cognition, though these findings are often inconsistent.
  • A study classified participants based on their cannabis use from ages 19 to 22, examining predictive factors like psychopathological symptoms, cognitive performance, and brain activity through tasks designed to measure incentives.
  • Results showed that conduct problems at age 14 were a strong predictor of later cannabis use, and while light cannabis users displayed more behavioral issues than non-users at age 19, there were no significant differences in emotional or cognitive functioning, suggesting that executive function impairments aren't factors that lead to or follow cannabis use.
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Background: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development.

Methods: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort ( = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects).

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Background: Early negative life events (NLE) have long-lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist.

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Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences.

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This study uses machine learning models to uncover diagnostic and risk prediction markers for eating disorders (EDs), major depressive disorder (MDD), and alcohol use disorder (AUD). Utilizing case-control samples (ages 18-25 years) and a longitudinal population-based sample (n=1,851), the models, incorporating diverse data domains, achieved high accuracy in classifying EDs, MDD, and AUD from healthy controls. The area under the receiver operating characteristic curves (AUC-ROC [95% CI]) reached 0.

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