Marieke Wichers

Bio: Marieke Wichers is an academic researcher from University Medical Center Groningen. The author has contributed to research in topics: Population & Psychopathology. The author has an hindex of 61, co-authored 229 publications receiving 12012 citations. Previous affiliations of Marieke Wichers include University of Groningen & European Graduate School.

Cytokines and major depression.

Abstract: In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.

Critical slowing down as early warning for the onset and termination of depression.

Abstract: About 17% of humanity goes through an episode of major depression at some point in their lifetime. Despite the enormous societal costs of this incapacitating disorder, it is largely unknown how the likelihood of falling into a depressive episode can be assessed. Here, we show for a large group of healthy individuals and patients that the probability of an upcoming shift between a depressed and a normal state is related to elevated temporal autocorrelation, variance, and correlation between emotions in fluctuations of autorecorded emotions. These are indicators of the general phenomenon of critical slowing down, which is expected to occur when a system approaches a tipping point. Our results support the hypothesis that mood may have alternative stable states separated by tipping points, and suggest an approach for assessing the likelihood of transitions into and out of depression.

What Do Centrality Measures Measure in Psychological Networks

Abstract: Centrality indices are a popular tool to analyze structural aspects of psychological networks. As centrality indices were originally developed in the context of social networks, it is unclear to what extent these indices are suitable in a psychological network context. In this article we critically examine several issues with the use of the most popular centrality indices in psychological networks: degree, betweenness, and closeness centrality. We show that problems with centrality indices discussed in the social network literature also apply to the psychological networks. Assumptions underlying centrality indices, such as presence of a flow and shortest paths, may not correspond with a general theory of how psychological variables relate to one another. Furthermore, the assumptions of node distinctiveness and node exchangeability may not hold in psychological networks. We conclude that, for psychological networks, betweenness and closeness centrality seem especially unsuitable as measures of node importance. We therefore suggest three ways forward: (a) using centrality measures that are tailored to the psychological network context, (b) reconsidering existing measures of importance used in statistical models underlying psychological networks, and (c) discarding the concept of node centrality entirely. Foremost, we argue that one has to make explicit what one means when one states that a node is central, and what assumptions the centrality measure of choice entails, to make sure that there is a match between the process under study and the centrality measure that is used. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A network approach to psychopathology: New insights into clinical longitudinal data

Abstract: In the network approach to psychopathology, disorders are conceptualized as networks of mutually interacting symptoms (e.g., depressed mood) and transdiagnostic factors (e.g., rumination). This suggests that it is necessary to study how symptoms dynamically interact over time in a network architecture. In the present paper, we show how such an architecture can be constructed on the basis of time-series data obtained through Experience Sampling Methodology (ESM). The proposed methodology determines the parameters for the interaction between nodes in the network by estimating a multilevel vector autoregression (VAR) model on the data. The methodology allows combining between-subject and within-subject information in a multilevel framework. The resulting network architecture can subsequently be analyzed through network analysis techniques. In the present study, we apply the method to a set of items that assess mood-related factors. We show that the analysis generates a plausible and replicable network architecture, the structure of which is related to variables such as neuroticism; that is, for subjects who score high on neuroticism, worrying plays a more central role in the network. Implications and extensions of the methodology are discussed.

IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity

Abstract: Studies show that administration of interferon (IFN)-α causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-α-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-α treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood–brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-α treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-α-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.

Applied Longitudinal Data Analysis Modeling Change And Event Occurrence

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Network Analysis: An Integrative Approach to the Structure of Psychopathology

Abstract: In network approaches to psychopathology, disorders result from the causal interplay between symptoms (e.g., worry → insomnia → fatigue), possibly involving feedback loops (e.g., a person may engage in substance abuse to forget the problems that arose due to substance abuse). The present review examines methodologies suited to identify such symptom networks and discusses network analysis techniques that may be used to extract clinically and scientifically useful information from such networks (e.g., which symptom is most central in a person's network). The authors also show how network analysis techniques may be used to construct simulation models that mimic symptom dynamics. Network approaches naturally explain the limited success of traditional research strategies, which are typically based on the idea that symptoms are manifestations of some common underlying factor, while offering promising methodological alternatives. In addition, these techniques may offer possibilities to guide and evaluate therape...