Biomedical subjects

Albertine J Oldehinkel

Publications and source records attributed to Albertine J Oldehinkel.

18 recordsLinked to original sources

PubMed2026

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗

PubMed2026

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans↗

PubMed2026

Genetics of major depressive disorder in a homogeneous population with uniform phenotyping.

Harmonized phenotyping and diverse population-specific studies are crucial for advancing gene discovery in psychiatric genetics. We conducted a genome-wide association (GWAS) mega-analysis of DSM-defined lifetime major depressive disorder (MDD) in 64 941 participants (25.7% cases) from the Dutch BIObanks Netherlands Internet Collaboration (BIONIC) consortium. Liability-scale SNP-based heritability was 12.0% (SE = 1.4%) as estimated by LDSC (assuming a lifetime prevalence of 15%) and 26.6% (SE = 1.1%) when estimated by LDAK-REML on individual-level genotype data, indicating substantial common-variant signal in this clinically harmonized sample. The genetic correlation with the latest major depression GWAS from the Psychiatric Genomics Consortium (PGC-MD) was high (rG = 0.89, SE = 0.048). Polygenic scores (PGSs) based on BIONIC predicted depression in UK Biobank, and PGSs derived from PGC-MD predicted MDD in BIONIC, supporting transferability of depression polygenic signal across cohorts and phenotype definitions. Within-family PGS analyses in twins suggested that the observed prediction was not primarily driven by detectable family-level confounding, and twin concordance for MDD increased with polygenic burden. We identified one genome-wide significant locus, indexed by rs3818852 in PALMD, but this finding currently lacks independent replication and should be interpreted cautiously. Finally, genetic correlation and latent causal variable analyses identified multiple traits showing shared or directionally consistent genetic associations with MDD. Together, these findings underscore the value of clinically harmonized phenotyping in regional biobank collaborations for studying the genetic architecture of MDD.

Humans↗

PubMed2025

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article↗

PubMed2007

Are the vulnerability effects of personality and psychosocial functioning on depression accounted for by subthreshold symptoms?

Previous studies could not evaluate adequately the extent to which deviant levels of personality measures and psychosocial functioning found before and after a major depressive episode (MDE) should be attributed to subthreshold depressive symptoms. Our aim is to investigate whether pre- and post-MDE personality alterations and psychosocial disability truly reflect vulnerability, or whether they can be accounted for by the presence of subthreshold depressive symptoms. Data were derived from the Netherlands Mental Health and Incidence Study, a prospective general population study with three waves. Psychopathology was measured with the Composite International Diagnostic Interview (CIDI). Course of depressive symptoms was assessed with the Life Chart Instrument in a cohort of 195 respondents with a new or recurrent MDE between waves 2 and 3. Personality and psychosocial functioning were assessed with, respectively, four and two different measures. Alterations in measurements of personality and psychosocial functioning were present before onset and after remission of an MDE. Most pre- and postonset alterations occurred in the presence of subthreshold depressive symptoms. But even without these subthreshold symptoms, some alterations in measurements of personality and psychosocial functioning were found before and after an MDE. Depressive complaints between waves 2 and 3 were retrospectively assessed, and only a limited set of brief questionnaires was used to assess personality styles and psychosocial functioning. It is unlikely that the pre- and post-MDE alterations in personality and psychosocial functioning observed in earlier studies are entirely due to subthreshold depressive symptoms. This suggests that a depressive episode is interwoven in a long-standing and enduring pattern of mild personality deviance and limitations in psychosocial functioning.

Activities of Daily Living↗

PubMed2006

The genetic relationship between neuroticism and autonomic function in female twins.

BACKGROUND: Neuroticism is widely used as an explanatory concept in etiological research of psychopathology. In order to clarify what neuroticism actually represents, we investigated the genetic association between neuroticism and cardiovascular measures. METHOD: In 125 female twin pairs (18-30 years), electrocardiogram and continuous finger blood pressure were assessed during two rest and two mental stress conditions. Mean values for baroreflex sensitivity (BRS), heart rate variability (HRV) and inter-beat interval (IBI) were calculated for each condition. Neuroticism was assessed by multiple questionnaires. Multivariate genetic model-fitting analyses were used to investigate the genetic correlation between latent neuroticism and the cardiovascular autonomic nervous system (ANS) measures. RESULTS: Neuroticism was negatively correlated to BRS and HRV. Neuroticism was not correlated to IBI. For BRS, this phenotypical relation was entirely determined by shared genetic influences. For HRV, the genetic contribution to the phenotypical correlation was not significant, but the proportions of explained covariance showed a trend of more genetic than environmental influences on the phenotypical relationship. CONCLUSIONS: High neuroticism is associated with a deregulated ANS. Pleiotropic genetic effects may be partly responsible for this effect.

Autonomic Nervous System↗

PubMed2006

Disruptive behaviors and HPA-axis activity in young adolescent boys and girls from the general population.

It is important to investigate associations between biological factors and disruptive behaviors in children and adolescents. Antisocial, aggressive, and criminal behaviors in adults often begin early in life. Disruptive behaviors are often thought to be associated with low activity of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol, the end-product of this axis, can be measured to investigate HPA-axis activity. Previous studies on this topic concerned clinical or high risk samples. The aim of the present study was to investigate to which extent HPA-axis functioning plays a role in disruptive behaviors in pre-adolescents from the general population. One thousand seven hundred and sixty eight 10- to 12-year-olds from the Dutch general population were investigated. Disruptive behaviors were assessed with the Child Behavior Checklist, the Youth Self-Report, and the Antisocial Behavior Questionnaire. Baseline morning and evening salivary cortisol levels were assessed. Unexpectedly, small associations were found between disruptive behaviors, including attention problems, and higher cortisol levels. However, all effect sizes of significant effects were very small. Our study indicated that HPA-axis functioning may be more relevant in clinical or high risk samples than at the general population level. The association between HPA-axis functioning and attention problems, that has gotten less attention than that with aggressive or delinquent behaviors, requires further research. Furthermore, because effect sizes were relatively small, it can be concluded that, in pre-adolescence, the measures of baseline HPA-axis functioning that were used for the present study can not be used as biological markers for disruptive behaviors.

Adolescent↗

PubMed2006

Temperament, parenting, and depressive symptoms in a population sample of preadolescents.

BACKGROUND: Depressive symptoms can be triggered by negative social experiences and individuals' processing of these experiences. This study focuses on the interaction between temperament, perceived parenting, and gender in relation to depressive problems in a Dutch population sample of preadolescents. METHODS: The sample consisted of 2230 ten-to-twelve-year-olds from the North of The Netherlands. Perceived parenting (overprotection, rejection, emotional warmth) was assessed by the EMBU (a Swedish acronym for My Memories of Upbringing) for Children, temperament (fearfulness and frustration) by the parent version of the Early Adolescent Temperament Questionnaire-Revised, and depressive problems by the Child Behavior Checklist (parent report) and the Youth Self-Report (child report). RESULTS: All parenting and temperament factors were significantly associated with depressive problems. Frustration increased the depressogenic effect of parental overprotection and lack of emotional warmth. Fearfulness increased the effect of rejection in girls, but not in boys. Furthermore, the association between frustration and depression was stronger in boys. CONCLUSIONS: These findings support the hypothesis that the effect of specific parenting behaviors depends on the temperament and gender of the child.

Child↗

PubMed2005

Classes of adolescents with disruptive behaviors in a general population sample.

BACKGROUND: To study disruptive behaviors adequately, we need to distinguish between individuals with different types of problems that may have a different etiology. The availability of a taxonomic system that helps in identifying homogeneous groups of individuals, with similar patterns of disruptive behaviors, is crucial to achieve this goal. Therefore, we examine which classes of preadolescents with symptoms of Attention Deficit/Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) can be identified in the general population. METHODS: Disruptive behaviors of 2,230 10-12 year olds from the Dutch general population were assessed with the Child Behavior Checklist and Youth Self-Report. RESULTS: Latent class analysis revealed three classes of preadolescents: the first characterized by high scores on ADHD, ODD, and CD items; a second by high probabilities of ADHD and ODD symptoms; a third with low scores on all items. CONCLUSIONS: Because classes of preadolescents with symptoms of only one type of disruptive behavior problems could not be identified, it can be questioned how useful separate diagnostic distinctions are in general population studies.

Adolescent↗

PubMed2005

Concurrent validity of the DSM-IV scales Affective Problems and Anxiety Problems of the Youth Self-Report.

This study investigated the concurrent validity of the DSM-IV scales Anxiety Problems and Affective Problems of the Youth Self-Report (YSR) in a community sample of Dutch young adolescents aged 10-12 years. We first examined the extent to which the YSR/DSM-IV scales reflect symptoms of DSM-IV anxiety disorders and DSM-IV Major Depressive Disorder, assessed with the Revised Child Anxiety and Depression Scale (RCADS). Second, we examined whether the association between the YSR/DSM-IV scales and the RCADS scales was stronger than the association between the empirically derived YSR narrow-band scales Anxious/Depressed and Withdrawn and the same RCADS scales. Results showed that the YSR/DSM-IV scale Affective Problems had a stronger association with symptoms of DSM-IV Major Depressive Disorder than the YSR narrow-band scales Withdrawn and Anxious/Depressed. However, the YSR/DSM-IV scale Anxiety Problems had a weaker association with symptoms of DSM-IV anxiety disorders, compared to the YSR narrow-band scale Anxious/Depressed. It was concluded that the construction of the DSM-IV scales improved the correspondence with DSM-IV Major Depressive Disorder, but not with DSM-IV anxiety disorders.

Adolescent↗

PubMed2005

Evaluation of non-response bias in mental health determinants and outcomes in a large sample of pre-adolescents.

Since non-response may jeopardize the validity of studies, comprehensive assessment of non-response is a prerequisite for proper interpretation of study findings. Recently, the baseline assessment of the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective cohort study among Dutch pre-adolescents, was completed. The aim of this report is to examine non-response bias by comparing responders and non-responders regarding mental health determinants (e.g., demographics and cognitive performance) and outcomes, as well as associations between the two. Furthermore, we examine whether extended efforts to recruit participants contribute to the prevention or reduction of non-response bias. Thanks to various recruitment procedures, the initial response rate of 66% increased to a final rate of 76%. The extended efforts to recruit participants prevented non-response bias in the prevalence rates of psychopathology. Although non-responders differed from responders with respect to several individual characteristics, no significant differences were found regarding associations between these characteristics and psychopathology. We conclude that TRAILS provides a solid basis to improve our understanding of the development of mental health during adolescence.

Adolescent↗

PubMed2005

Bullying and victimization in elementary schools: a comparison of bullies, victims, bully/victims, and uninvolved preadolescents.

Research on bullying and victimization largely rests on univariate analyses and on reports from a single informant. Researchers may thus know too little about the simultaneous effects of various independent and dependent variables, and their research may be biased by shared method variance. The database for this Dutch study was large (N = 1,065) and rich enough to allow multivariate analysis and multi-source information. In addition, the effect of familial vulnerability for internalizing and externalizing disorders was studied. Gender, aggressiveness, isolation, and dislikability were most strongly related to bullying and victimization. Among the many findings that deviated from or enhanced the univariate knowledge base were that not only victims and bully/victims but bullies as well were disliked and that parenting was unrelated to bullying and victimization once other factors were controlled.

Aggression↗

PubMed2004

Potential psychosocial mechanisms linking depression to immune function in elderly subjects.

Although depression and immune changes in elderly subjects constitute a considerable health risk, mechanisms underlying the association between depression and immune function are unclear. The question of whether personality and social support can explain the variation in immune function during depression was addressed in 21 elderly depressive and 23 control subjects. The following variables were studied: neuroticism, extraversion, received social support, depression-related immune parameters [i.e. numbers of lymphocytes, lymphocyte subsets CD3+, CD8+, natural killer-like T cells (NKT), CD4/CD8 ratio, and interleukin-6 (Il-6)]. We found that neuroticism reduced the association between depression and Il-6 (from 62 to 22.4%) and between depression and CD3+ (from 27.6 to 21.6%), and was also directly related to Il-6 (i.e. adjusted for age and depression). Social support reduced the association between depression and NKT cells from 25 to 18%, while it was also directly related to NKT cells. Extraversion, adjusted for age and depression, was negatively related to CD4/CD8 ratio. Subjects with high extraversion and high social support had more NKT cells. We concluded that changes in immune function during depression can partly be explained by neuroticism and received social support, whereas immune function is also directly related to these psychosocial variables. Neuroticism may exert its contribution to the risk for depression partly via Il-6 production.

Aged↗

PubMed2004

Vulnerability before, during, and after a major depressive episode: a 3-wave population-based study.

BACKGROUND: Vulnerability as defined by high levels of neuroticism, low self-esteem, and poor coping skills characterizes individuals with a history of major depressive episodes (MDEs). OBJECTIVE: To separate postmorbid vulnerability into (1) trait effects (ie, the continuation of premorbid vulnerability); (2) state effects of subthreshold (residual) symptoms on personality or its perception; and/or (3) scar effects (ie, negative personality change that develops during an MDE and persists beyond MDE remission). METHODS: Data come from the Netherlands Mental Health Survey and Incidence Study, a prospective Dutch psychiatric population-based survey. We obtained psychiatric (Composite International Diagnostic Interview) and personality data on neuroticism, depressive coping style, self-esteem, and mastery from 4796 respondents at 3 time points (T1, T2, and T3), 12 and 24 months apart. Between- and within-subjects differences were tested with repeated-measures analysis of variance and adjusted for sex, age, and time. RESULTS: After T1, 409 respondents developed an MDE, of whom 334 were MDE-free at T3. In comparison with individuals without any lifetime MDE, the 262 subjects with a first MDE had higher premorbid T1 vulnerability scores on each personality measure (0.38-0.83 effect size units). During the MDE, vulnerability scores further increased (0.33-0.52 effect size units) but returned to premorbid levels after MDE remission. We found no scar effects among subgroups with severe or long-lasting MDEs. Subthreshold residual symptoms at T3 biased comparisons between T1 and T3 if the premorbid period of T1 to MDE onset was longer than the postmorbid period of MDE remission to T3, misleadingly suggesting scar effects. We obtained similar results in the 147 subjects with recurrent MDEs. CONCLUSIONS: There was no evidence of a negative change from premorbid to postmorbid assessment for any of the personality traits. Postmorbid vulnerability reflected the continuation of premorbid vulnerability. Pre-post MDE comparisons are sensitive to prodromal and residual symptoms. Our findings suggest 2 independent simultaneous processes: (1) the ongoing expression of vulnerability as a personality deviance; and (2) synchrony of change between severity of depressive symptoms and personality deviance.

Adaptation, Psychological↗

PubMed2004

Psychosocial disability before, during, and after a major depressive episode: a 3-wave population-based study of state, scar, and trait effects.

BACKGROUND: Psychosocial disability after remission from a unipolar major depressive episode (MDE) can be due to (1) residual symptoms (state effect), (2) the continuation of premorbid disability (trait effect), and/or (3) disability that developed during the MDE and persisted beyond recovery (scar effect). METHODS: Data came from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective Dutch psychiatric population-based survey. We obtained psychiatric data (Composite International Diagnostic Interview) and information on psychosocial functioning (work, housekeeping, spouse/partner, and leisure-time domains) from 4796 respondents in 1996 (T1), 1997 (T2), and 1999 (T3). We evaluated trait effects using between-subject comparisons, and state and scar effects using within-subject comparisons. RESULTS: In 216 and 118 respondents, a first and a recurrent MDE developed, respectively, after T1 that remitted before T3. Compared with never-MDE individuals, first-MDE subjects had higher disability scores long before their episode (effect size, 0.42-0.57 U). During the MDE, disability further increased in first- and recurrent-MDE subjects (effect size, 0.44-0.79 U), but returned to its premorbid level after MDE remission, except in subjects who experienced a severe recurrent episode. If the premorbid period (T1 to MDE onset) was longer than the postmorbid period (MDE remission to T3), disability at T3 was higher than at T1, misleadingly suggesting scar effects. The reverse occurred if the premorbid period was shorter than the postmorbid period. CONCLUSIONS: Postmorbid psychosocial disability reflects largely the continuation of premorbid psychosocial disability. Scarring does not occur routinely, but may occur in a severe recurrent episode. Within-subject premorbid-postmorbid comparisons are sensitive to state effects of prodromal and residual symptoms. These findings point at the following 2 independent processes: (1) the ongoing expression of trait vulnerability to depression in mild psychosocial dysfunctioning; and (2) synchrony of change between severity of depressive symptoms and psychosocial disability.

Adult↗

PubMed2004

Temperament profiles associated with internalizing and externalizing problems in preadolescence.

This study investigates how temperament factors are linked to internalizing and externalizing problems in a Dutch population sample of preadolescents (N = 2230). Internalizing and externalizing problems were assessed by the Child Behavior Checklist and the Youth Self-Report and temperament was evaluated by the parent-version of the Revised Early Adolescent Temperament Questionnaire. Temperament profiles were examined in children with (a) neither internalizing nor externalizing problems, (b) only internalizing problems, (c) only externalizing problems, and (d) both internalizing and externalizing problems. The results suggest clearly diverging temperament profiles for these groups of children, with High-Intensity Pleasure and Shyness (representing the broad dimension of Surgency) steering the conditional probability of internalizing and externalizing problems (direction markers), Frustration mainly being related to maladaptation in general (severity marker), and Fear and Effortful Control being associated with both the severity and the direction of internalizing and externalizing problems, respectively. Girls and boys differed in the distribution across the problem groups, but the associations between temperament and psychopathology were comparable for both genders.

Affective Symptoms↗

PubMed2003

Do depressive episodes lead to accumulation of vulnerability in the elderly?

The vulnerability-accumulation (or scarring) hypothesis postulates that the experience of depression induces a lasting increase in vulnerability, and through this raises the risk of recurrence. We examined the validity of the vulnerability-accumulation model for depressive episodes in later life. The sample comprised 26 elderly persons who had remitted from a depressive episode and 96 control respondents who were all selected from the participants of a large community survey among persons aged 57 years or more. Several psychosocial vulnerability indicators were assessed premorbidly, during the depressive episode and after remission. High levels of psychological distress, low life satisfaction, chronic somatic diseases, high neuroticism, and low scores on extraversion, mastery, and self-efficacy appeared to be predictors of depression in this sample. During the depressive episode, psychological distress was higher and life satisfaction, physical, role, and social functioning, as well as feelings of self-efficacy lower than before the episode. Physical and role functioning, cognitive function, and self-efficacy were lower after remission compared to premorbid levels, but (other) personality indices had not changed after remission compared to premorbid levels. Furthermore, we failed to find differences between first and recurrent episodes. Support for the vulnerability-accumulation model was limited at the most. Although psychosocial scarring may occur in the elderly, our findings tentatively suggest that this accumulation does not manifest itself in major vulnerability indicators such as neuroticism.

Aged↗

PubMed2003

Psychosocial and vascular risk factors of depression in later life.

BACKGROUND: Research on the aetiology of late-life depression has typically focused on either risk factors from the psychosocial stress-vulnerability domain or degenerative biological changes (for instance, vascular disease). We examined whether vascular risk factors could be interpreted within the stress-vulnerability model of depression. METHODS: The data came from a case-control design, nested in a community survey of elderly people. We compared 83 persons with a recently started episode of major or minor depression with 83 controls, with respect to the occurrence of stressful life events, long-term difficulties, neuroticism, and vascular risk factors (hypertension, heart disease, stroke). RESULTS: The (non-significant) association of vascular risk factors and onset of depressive episodes was not modified by neuroticism or the presence of long-term difficulties. Quite unexpectedly, vascular risk factors seemed to neutralize the depressogenic effect of stressful life events. The effect of vascular risk was significantly stronger in depressive episodes not preceded by a life event than in onsets following an event. CONCLUSIONS: Vascular risk factors cannot be interpreted within the stress-vulnerability model, but represent another pathway to depression. Why vascular risk factors reduce the depressogenic effect of stressful life events is not clear. Replication is critical to exclude the possibility of a chance finding.

Cardiovascular Diseases↗