B.W. Penninx

Amsterdam University Medical Center | VUmc · Department of Psychiatry

Anxiety sensitivity is associated with the onset of panic attacks, anxiety, and other common mental disorders. Anxiety sensitivity is usually seen as a relative stable trait. However, previous studies were inconclusive regarding the longitudinal stability of anxiety sensitivity and differed in study designs and outcomes. The current study examines...

Background Major depressive disorder (MDD), represent a major source of risk for suicidality. However, knowledge about risk factors for future suicide attempts (SAs) within MDD is limited. The present longitudinal study examined a wide range of putative non-clinical risk factors (demographic, social, lifestyle, personality) and clinical risk factor...

Self-esteem has not only been observed to be generally low in depression and anxiety, but also unstable. Few studies have looked at unstable self-esteem in clinical samples. The present study compared self-reported self-esteem instability across current depression (n = 60), anxiety (n = 111), and comorbid depression/anxiety (n = 71), remitted depre...

Objective: We investigated if the degree of treatment resistance of depression, as measured by the Maudsley Staging Method (MSM), is predictive of a worse depression outcome by using a large naturalistic cohort of depressed patients. Methods: 643 subjects from the general population, primary care, and secondary care who suffered from current dep...

Background Blood levels of polyunsaturated fatty acids (PUFAs) have been associated to current depression. However, it is unclear whether this association extends to remitted depression and to anxiety disorders. This study examined the relationship of PUFAs with the presence and clinical characteristics of depressive and anxiety disorders. Methods...

Objective Major depressive disorder (MDD) is common in patients with multiple sclerosis (MS) but may remain unrecognized because of overlapping symptoms and different presentation due to its specific MS-related neurobiological aetiology. We aimed to investigate the clinical profile of MDD in MS. Methods In a sample of MDD patients with MS (n = 83)...

Background: Evidence lacks on whether obesity along with major depression (MD)/anxiety leads to higher health care use (HCU) and health care-related costs (HCC) compared with either condition alone. The objective of the study was to examine the longitudinal associations of obesity, MD/anxiety, and their combination with HCU and HCC. Methods: Lon...

Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609...

Background: The oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend thes...

The monocyte–lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-famil...

Aims Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between...

Objective: The current study examined whether (a) Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms were associated with dysregulation of stress-related mechanisms, and (b) whether ADHD symptoms interact with affective disorders in their association with dysregulated stress-related mechanisms. Methods: Data were obtained from 2307 subject...

Oxidative stress is a biological process, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, in favour of the ROS. This imbalance leads to oxidative damage to lipids, proteins and DNA and ultimately cell death. Studies in rodents have shown that the brain, particularly the amygdala and hippocampus, is sensitive to oxidat...

Background: Physical inactivity has been identified as a risk factor for depression and, less often, as a long-term consequence of depression. Underexplored is whether similar bi-directional longitudinal relationships are observed for anxiety disorders, particularly in relation to three distinct indicators of activity levels - sports participation...

Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated da...

Background Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2′-deoxyguanosine (8-OHdG) reflecting oxidative lipid and...

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed...

Background: Melancholic and atypical depression are widely thought to moderate or predict outcome of pharmacological and psychological treatments of adult depression, but that has not yet been established. This study uses the data from four earlier trials comparing cognitive behavior therapy (CBT) versus antidepressant medications (ADMs; and pill...

Background Medically unexplained physical symptoms (MUPS) are highly prevalent and are associated with frequent health care use (HCU). MUPS frequently co-occur with psychiatric disorders. With this study we examined the longitudinal association between MUPS and HCU over 2 years and the influence of depressive and anxiety disorders and personality t...

Background Medically unexplained physical symptoms (MUPS) are highly prevalent and may affect work functioning. In this study we aimed to assess the longitudinal association between MUPS and work functioning over 2 years and the influence of job characteristics and depressive and anxiety disorders on this association. Methods We assessed the longi...

Background: Obesity and depression are two prevalent conditions that are costly to individuals and society. The bidirectional association of obesity with depression, in which unhealthy dietary patterns may play an important role, has been well established. Few experimental studies have been conducted to investigate whether supplementing specific n...

Background This longitudinal study aims to investigate differences in long-term disability between social anxiety disorder (SAD), panic disorder with agoraphobia (PDA), panic disorder without agoraphobia (PD), generalized anxiety disorder (GAD) and multiple anxiety disorders (multiple AD), focusing on the effects of different course trajectories (r...

The genetic architecture of human reproductive behavior—age at first birth (AFB) and number of children ever born (NEB)—has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood...

Significance Alcohol is a widely consumed drug in western societies that can lead to addiction. A small shift in consumption can have dramatic consequences on public health. We performed the largest genome-wide association metaanalysis and replication study to date (>105,000 individuals) and identified a genetic basis for alcohol consumption during...

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) receiv...

Objective: Early recognition of individuals at risk for depressive and anxiety disorders is key in influencing onset and course of these disorders. Parental history is a potent risk factor for the development of these disorders in offspring. However, knowledge about the magnitude of this risk is limited as large-scale longitudinal studies with a f...

Background Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening ins...

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether chil...

Background: Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder...

Perspective: Biological stress systems and adverse life events are not associated with the improvement of chronic multi-site musculoskeletal pain over 6 years follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve.

Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in lifestyle factors relate to 2-year changes in cardiac...

Background: The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age. Method: Data came from 1404 participants wit...

This study aimed to identify course trajectories of anxiety disorder using a data-driven method and to determine the incremental predictive value of clinical and psychological variables over and above diagnostic categories. 703 patients with DSM-IV panic disorder with or without agoraphobia, agoraphobia, social phobia, or generalized anxiety disord...

Importance: Considerable partner resemblances have been found for a wide range of psychiatric disorders, meaning that partners of affected individuals have an increased risk of being affected compared with partners of unaffected individuals. If this resemblance is reflected in genetic similarity between partners, genetic risk is anticipated to acc...

In the version of this article initially published online, the affiliations for Bertram Muller-Myhsok and Patricia Pozo-Rosich were incorrect or incomplete. These errors have been corrected for the print, PDF and HTML versions of this article.

Background There is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for example, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM crite...

Background: Depression and anxiety have been related to poorer self-reported physical functioning over time; however, objective measures of physical function are less frequently examined. This study assessed the 6-year trajectory of hand-grip strength and lung function in persons with depressive and/or anxiety disorders. Methods: At four waves (...

Background Immunometabolic dysregulation (low-grade inflammation and metabolic dysregulation) has been associated with the onset and more severe course of multiple psychiatric disorders, partly due to neuroanatomical changes and impaired neuroplasticity. We examined the effect of multiple markers of immunometabolic dysregulation on hippocampal and...

Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multi...

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were n...

Study objective: The temporal relationships between sleep, depressive symptoms and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multi-site musculoskeletal pain over 6 years, and whether this association is mediated by depressive symptoms. Methods: 1860 subjects of the Netherl...

Evidence has shown that the DSM-5 anxious distress specifier captures a clinically valid construct that predicts a worse clinical course. Although of importance for treatment planning and monitoring, however, the specifier's ability to predict treatment outcome is unknown. This is the first study to examine the ability of the DSM-5 anxious distress...

Background: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome wide association studies (GWAS) to identify risk-associated variants are needed. Objective: To develop a method that aggregates the evidence for association with disease risk acro...

The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has shown to subsequently increase the risk of cardiovascular morbidity and mortality. These somatic consequences can be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, phys...

Objective and background: Insomnia is a neglected topic in psychiatric epidemiological studies. Despite the fact that insomnia is a common phenomenon and usually co-occurs with mental disorders, it remains to be addressed to what extent insomnia is associated with remitted and current common mental disorders and with impaired functioning in the po...

Table S1. Associations of both psychopathology indicators and antidepressants with metabolic syndrome components across baseline, 2‐ and 6‐year assessments

Objective: ADHD may predispose to obesity, a metabolic syndrome component. Affective disorders are also associated with MetSyn and ADHD. This study examined whether ADHD confers any added risk of MetSyn and obesity-related associations in a large sample with varying stages of affective disorders. Method: Participants included 2,303 adults from t...

Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with se...

Background: Childhood maltreatment (CM) has been associated with altered brain morphology, which may partly be due to a direct impact on neural growth, e.g. through the brain-derived neurotrophic factor (BDNF) pathway. Findings on CM, BDNF and brain volume are inconsistent and have never accounted for the entire BDNF pathway. We examined the effec...

Background: Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. Aims: To assess mortality risk in people with anxiety disord...

Objective: A range of biological, social and psychological factors, including depression and anxiety disorders, is thought to be associated with higher body mass index (BMI). Depression and anxiety disorders are associated with specific psychological vulnerabilities, like personality traits and cognitive reactivity, that may also be associated wit...

Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be p...

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Objective: This study examined the relationship between leukocyte telomere length (LTL), a marker of cell aging, and psychiatric disorders in adults compared with controls using meta-analytic methods. Methods: Data were abstracted from studies examining the relationship between LTL and adult psychiatric disorders. In addition to an overall estim...

Consortia members and extended acknowledgments. (DOCX)

Background Sparse Gaussian graphical models are popular for inferring biological networks, such as gene regulatory networks. In this paper, we investigate the consistency of these models across different data platforms, such as microarray and next generation sequencing, on the basis of a rich dataset containing samples that are profiled under both...

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus...

Background: Depressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the rel...

It has been postulated that many peripheral and (neuro)biological systems are involved in psychiatric disorders such as depression. Some studies found associations of depression and antidepressant treatment with insulin-like growth factor 1 (IGF-I) – a pleiotropic hormone affecting neuronal growth, survival and plasticity – but evidence is mixed. W...

Background: Limited successes of gene finding for major depressive disorder (MDD) may be partly due to phenotypic heterogeneity. We tested whether the genetic load for MDD, bipolar disorder, and schizophrenia (SCZ) is increased in phenotypically more homogenous MDD patients identified by specific clinical characteristics. Methods: Patients (n =...

Objective: We evaluated whether the association between Adult Attention-Deficit/Hyperactivity Disorder (ADHD) and Seasonal Affective Disorder (SAD) was mediated by the circadian rhythm. Method: Data of 2239 persons from the Netherlands Study of Depression and Anxiety (NESDA) were used. Two groups were compared: with clinically significant ADHD s...

Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baselin...

Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the...

Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must...

Female (A) and male (B) demographic, health, and lifestyle characteristics for MDD, CMA, and remitted MDD patients and controls. Values are shown as mean ± the standard deviation. Differences between controls and conditions were assessed using Welch's t-test (continuous data) or Fisher's exact test (categorical data). Variables in bold were signifi...

Further description of logistic regression model. (PDF)

Description of variables. It should be noted that medication use was evaluated by self-reporting and inspection of drug containers used in the past month. Abbreviations: ATC (Anatomical Therapeutic Chemical). (PDF)

List of serum molecules measured with multiplex immunoassay. Analytes analyzed in this study (i.e., with <30% missing assay values) are marked in a ✓. Analytes measured in plasma in the work of Domenici et al. (2010) are marked with a ✓ in the last column. (PDF)

ROC curves from the 50 repeated ten-fold cross-validations illustrating classification of MDD patients from controls for males (A) and females (B). Bold, dotted lines are average ROC curves from Fig 5 in the main text. (TIF)

Analytes with significant interactions between log2-transformed serum concentration and sex in MDD compared to controls (A) and a comparison with results using multiple imputation (B). In (A), a simple missing value imputation method was used (see main text). In (B), interaction p-values from multiple imputation are also presented for assays with m...

Analytes with overlapping significant interactions between sex and log2-transformed serum concentration in MDD and (A) CMA and (B) remitted MDD compared to controls. Odds ratios (OR) represent the ratio of odds of the condition associated with a two-fold increase in the untransformed serum concentration of that analyte from the logistic model. Rati...