Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife

Rudaz, Dominique; Vandeleur, Caroline L.; Gebreab, Sirak Zenebe; Gholam‐Rezaee, Mehdi; Strippoli, Marie‐Pierre F.; Lasserre, Aurélie M.; Glaus, Jennifer; Castelao, Enrique; Pistis, Giorgio; Känel, Roland von; Marques‐Vidal, Pedro; Waeber, Gérard; Vollenweider, Péter; Preisig, Martin

doi:10.1016/j.jad.2017.07.016

Cited by 21 publications

(14 citation statements)

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“…However, considering that we found significant associations between MDD subtypes and cardiometabolic variables in our analyses, the absence of an effect of MDD subtypes on the associations between life-event stress and cardiometabolic variables is hardly attributable to the high prevalence of MDD. Hence, the absence of an effect of MDD subtypes on these associations is rather explained by the absence of an association between life-event stress and the atypical subtype (36), whereas this subtype has repetitively been shown to be associated with cardiovascular risk factors (33)(34)(35)(36). Conversely, the unspecified MDD subtype is likely to be strongly associated with life-event stress (36), but not with cardiovascular risk (34,35,49).…”

Section: Lifetime Psychosocial Stress and Cardiometabolic Riskmentioning

confidence: 99%

“…Studies have also revealed associations between psychosocial stress and major depressive disorder (MDD) (31) and between MDD and CVDs (32). Recent research suggests that the association between MDD and cardiometabolic risk factors is entirely attributable to the atypical depression subtype (characterized by increased appetite, increased sleep, and leaden paralysis) (33)(34)(35)(36). However, the interplay between psychosocial stress and psychological factors on the risk cardiometabolic abnormality has hardly been studied.…”

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confidence: 99%

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Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community

Gebreab¹,

Vandeleur

Rudaz

et al. 2018

Psychosom Med

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Section: Lifetime Psychosocial Stress and Cardiometabolic Riskmentioning

confidence: 99%

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confidence: 99%

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community

Gebreab¹,

Vandeleur

Rudaz

et al. 2018

Psychosom Med

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“…However, investigations on neuroticism have been limited to a few inflammatory parameters: for example, C-reactive protein (CRP) or interleukin (IL)-6, for which the relationship with neuroticism could not be confirmed ( 6 ). Importantly, neuroticism is considered a risk factor for the development and onset of major depression and certain subtypes of depression ( 7 – 9 ). However, the biological mechanisms for this relationship are not yet well understood.…”

Section: Introductionmentioning

confidence: 99%

Serum Markers of Inflammation Mediate the Positive Association Between Neuroticism and Depression

et al. 2018

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Background: The personality trait neuroticism has been implicated in a poor response to stress, may relate to increased concentrations of cytokines and the development of depression. Inflammatory mechanisms may also be associated with the onset, severity and symptoms of depression. Both are related to poor antidepressant treatment outcome. Therefore, mediators of inflammation may bridge the relationship between neuroticism and depression.Methods: To disentangle these interrelationships, the associations between neuroticism (according to NEO-PIR-N), depressive symptoms (BDI-II scores) and serum levels of hsCRP, TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF were investigated in a group of 212 participants, consisting of 37 depressed and 175 non-depressed subjects. A mediation model was used to investigate whether the impact of neuroticism on depressive symptoms may be mediated by cytokines.Results: Regression analyses revealed that IFN-γ, IL-5, and IL-12-levels, but none of the anti-inflammatory cytokines, were associated with the overall neuroticism score and several of the cytokines were related to the different facets of neuroticism. TNF-α, IFN-γ, IL-5, IL-12, and IL-13 were further related to the severity of depressive symptoms, as well as the somatic-affective and the cognitive dimensions of depression. Pro-inflammatory IFN-γ, IL-5 and IL-12 were identified as mediators of the positive prediction of depression severity by the degree of neuroticism.Conclusions: The current findings demonstrate that conditions related to long-term stress, such as depression and high neuroticism, are related to an up-regulation of inflammatory agents. Neuroticism may increase stress perception and, thus, increase the production of pro-inflammatory messenger molecules which are involved in the development of depression. This evidence may contribute to future anti-inflammatory interventions, particularly in subjects with high neuroticism who are at risk for developing depression. Furthermore, depressed patients with high neuroticism and cytokine levels may require early escalations in the intensity of treatment, along with additional therapeutic elements to increase the rate of treatment success.

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“…Recent studies have attempted to identify subtypes of depressive illness based on methodologies such as latent class analysis (Lamers et al, 2010) or causative factors (Rudaz et al, 2017). Different depression subtypes have been identified, comparable to MDD-MF and MDD-AF; the latter exhibiting a stronger association with obesity (Lamers et al, 2010;Levitan et al, 2012;Hasler et al, 2004;Glaus et al, 2013).…”

Section: Directionality Of Obesity-depression Associationsimportance mentioning

confidence: 99%

The brain-adipocyte-gut network: Linking obesity and depression subtypes

Patist

Stapelberg

Toit

et al. 2018

Cogn Affect Behav Neurosci

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Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.

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Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife

Cited by 21 publications

References 83 publications

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community

Serum Markers of Inflammation Mediate the Positive Association Between Neuroticism and Depression

The brain-adipocyte-gut network: Linking obesity and depression subtypes

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