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

Abstract

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.

Psychiatric morbidities of female obesity before and after dieting: an Egyptian sample

“…Furthermore, a study found that atypical depression is associated with chronic psycho-immuno-neuro-endocrinal dysfunction due to inflammatory, leptin-ghrelin, neuroendocrinal, and gut microbiome systems influenced by chronic image-associated psychological stress and sensitivity to rejection especially in young female patients that can lead to behavioral dysregulation in the form of hyperphagia, lethargy, and hypersomnia [39].…”

Psychiatric Aspects of Obesity: A Narrative Review of Pathophysiology and Psychopathology

“…These structural alterations can partly explain why obesity predisposes to psychiatric disorders development (e.g., mood disorders) and provide a theoretical frame for the association between weight status and neuropsychic functions, such as cognitive/executive functions and emotion regulation. For a more thorough examination of the mechanisms mentioned above, see the recent reviews by Stapelberg et al [9,10] and Shefer et al [8]. development and maintenance of this condition, thus lending intriguing insights to obesity medicine and representing possible targets for treatment and prevention [5,6].…”

“…It has long been known that MDD is a risk factor for obesity. Obesity, in turn, is a risk factor for MDD, and there is a bidirectional pathophysiological bond between these conditions, so that we can speak of "obesity-associated depression" and "depression-associated obesity" [10]. In particular, a metanalysis of longitudinal studies concluded that patients with obesity had a 55% increased risk of developing MDD in their lifetime, while patients suffering from MDD have a 58% risk of developing obesity [50].…”

“…Since both conditions are highly and increasingly prevalent, investigating these reciprocal connections is of particular interest in many domains of healthcare. On one hand, "obesity-associated depression" is likely determined by two types of pathogenic determinants: a biologic determinant, consisting of perturbations in the psycho-immune-neuro-endocrine network (PINE network), such as chronic subinflammatory states, imbalance in the leptin-ghrelin system and leptin-ghrelin hypo-sensitivity, insulin resistance, gut dyspermeability, dysbiosis, endocrine and autonomic dysfunctions; and a psychological determinant, related to body image dissatisfaction, low self-esteem and consequent distress [10].…”

The Gut-Brain-Axis on the Manifestation of Depressive Symptoms in Epilepsy: An Evidence-Driven Hypothesis

“…Emerging shreds of evidence have suggested a potential role of the gut microbiota in the pathophysiology of depression (Jiang et al, 2015;Zheng et al, 2016). However, there is limited literature which reviews the link between depression to gut microbiota by different groups of researchers (Slyepchenko et al, 2017;Patist et al, 2018;Schachter et al, 2018) (Figure 1).…”