From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression

Stapelberg, Nicolas J. C.; Pratt, Robin; Neumann, David L.; Shum, David; Brandis, Susan; Muthukkumarasamy, Vallipuram; Stantić, Bela; Blumenstein, Michael; Headrick, John P.

doi:10.1016/j.neubiorev.2018.03.005

Cited by 43 publications

(50 citation statements)

References 216 publications

(205 reference statements)

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“…In this model, it is the physiological consequences of obesity that share in the pathogenesis of MDD: evolving low-grade inflammation, dysbiosis, ANS imbalance, leptin and ghrelin changes, together with image-related psychological stress. Considered within a systems biology framework, MDD is thought to arise via dysregulation of the PINE network by chronic stress, ultimately crossing a critical threshold or tipping point to an MDD disease state (PINE pathome) (Stapelberg et al, 2018;Stapelberg et al, 2015). This is supported by correlation of biomarkers of PINE network dysfunction and development of MDD (Verduijn et al, 2015).…”

Section: General Mechanisms Linking Obesity and Depressionmentioning

confidence: 99%

“…The relationship between depression and obesity is predominantly driven by these physiological processes (Stapelberg et al, 2015), although distinct psychological/behavioural changes may underpin a reverse association in MDD-AF (Parker et al, 2002). Nonetheless, emotional regulation is highly dependent on autonomic processes and is linked to physiological and metabolic regulatory processes described in the polyvagal (Porges, 1995(Porges, , 1997(Porges, , 1998(Porges, , 2001(Porges, , 2003 and neurovisceral integration theories (Thayer & Lane, 2000), and the PINE network model (Stapelberg et al, 2018;Stapelberg et al, 2015). Exploration of mechanistic relationships between depression and other medical conditions is facilitated by their conceptualisation within a systems biology framework (Stapelberg, Neumann, Shum, McConnell, & Hamilton-Craig, 2011;Stapelberg et al, 2018;Stapelberg et al, 2015).…”

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

“…The theory of allostasis (Sterling & Eyer, 1988) and the PINE network model (Stapelberg et al, 2015) both conceptualise depression as arising from chronic disruption of highly interlinked physiological pathways. The PINE model applies a systems biology approach to these processes, viewing them as a complex network (Stapelberg et al, 2018). When this network or PINE physiome is progressively disrupted by chronic stress, homeostasis is perturbed beyond a critical threshold, giving rise to disease (Stapelberg et al, 2018).…”

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

“…The PINE model applies a systems biology approach to these processes, viewing them as a complex network (Stapelberg et al, 2018). When this network or PINE physiome is progressively disrupted by chronic stress, homeostasis is perturbed beyond a critical threshold, giving rise to disease (Stapelberg et al, 2018). Disruption of the PINE network may promote several related diseases, with outcomes influenced by genetic predisposition, socioeconomics, and lifestyle -diathesis factors (Stapelberg et al, 2015).…”

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

“…In addition, IL-6 levels are significantly related to visceral adiposity in obese people (Park et al, 2005) and to subcutaneous adiposity (together with CRP and TNF receptor 2) (Pou et al, 2007). Characteristic inflammation in obesity may increase gut permeability, leading to neurovegetative features of depression (Stapelberg et al, 2018). Positive feedback may emerge, with inflammation increasing permeability to induce further inflammation, while cytokines such as IL-6 stimulate the HPA axis to promote obesity, insulin-resistance, and hypertension (Yudkin, Kumari, Humphries, & Mohamed-Ali, 2000).…”

Section: Immuno-inflammatory Pathways Linking Obesity and Mddmentioning

confidence: 99%

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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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Section: General Mechanisms Linking Obesity and Depressionmentioning

confidence: 99%

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

Section: Relevance Of a Systems Biology Approachmentioning

confidence: 99%

Section: Immuno-inflammatory Pathways Linking Obesity and Mddmentioning

confidence: 99%

See 3 more Smart Citations

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

Patist

Stapelberg

Toit

et al. 2018

Cogn Affect Behav Neurosci

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Analyzing the genes and pathways related to major depressive disorder via a systems biology approach

et al. 2019

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Introduction:Major depressive disorder (MDD) is a mental disorder caused by the combination of genetic, environmental, and psychological factors. Over the years, a number of genes potentially associated with MDD have been identified. However, in many cases, the role of these genes and their relationship in the etiology and development of MDD remains unclear. Under such situation, a systems biology approach focusing on the function correlation and interaction of the candidate genes in the context of MDD will provide useful information on exploring the molecular mechanisms underlying the disease. Methods:We collected genes potentially related to MDD by screening the human genetic studies deposited in PubMed (https ://www.ncbi.nlm.nih.gov/pubmed). The main biological themes within the genes were explored by function and pathway enrichment analysis.Then, the interaction of genes was analyzed in the context of protein-protein interaction network and a MDD-specific network was built by Steiner minimal tree algorithm. Results:We collected 255 candidate genes reported to be associated with MDD from available publications. Functional analysis revealed that biological processes and biochemical pathways related to neuronal development, endocrine, cell growth and/or survivals, and immunology were enriched in these genes. The pathways could be largely grouped into three modules involved in biological procedures related to nervous system, the immune system, and the endocrine system, respectively. From the MDD-specific network, 35 novel genes potentially associated with the disease were identified. Conclusion:By means of network-and pathway-based methods, we explored the molecular mechanism underlying the pathogenesis of MDD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular features of MDD. K E Y W O R D Smajor depressive disorder, network analysis, pathway cross talk 2 of 16 | FAN et Al.

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Sex‐specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice

Helman

Headrick

Vider

et al. 2022

J of Neuroscience Research

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Psychosocial stress promotes and links mood and cardiovascular disorders in a sex‐specific manner. However, findings in animal models are equivocal, in some cases opposing human dimorphisms. We examined central nervous system (CNS), behavioral, endocrine, cardiac, and hepatic outcomes in male or female C57Bl/6 mice subjected to chronic social stress (56 days of social isolation, with intermittent social confrontation encounters twice daily throughout the final 20 days). Females exhibited distinct physiological and behavioral changes, including relative weight loss, and increases in coronary resistance, hepatic inflammation, and thigmotaxic behavior in the open field. Males evidence reductions in coronary resistance and cardiac ischemic tolerance, with increased circulating and hippocampal monoamine levels and emerging anhedonia. Shared CNS gene responses include reduced hippocampal Maoa and increased Htr1b expression, while unique responses include repression of hypothalamic Ntrk1 and upregulation of cortical Nrf2 and Htr1b in females; and repression of hippocampal Drd1 and hypothalamic Gabra1 and Oprm in males. Declining cardiac stress resistance in males was associated with repression of cardiac leptin levels and metabolic, mitochondrial biogenesis, and anti‐inflammatory gene expression. These integrated data reveal distinct biological responses to social stress in males and females, and collectively evidence greater biological disruption or allostatic load in females (consistent with propensities to stress‐related mood and cardiovascular disorders in humans). Distinct stress biology, and molecular to organ responses, emphasize the importance of sex‐specific mechanisms and potential approaches to stress‐dependent disease.

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From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression

Abstract: Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.

Cited by 43 publications

References 216 publications

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

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

Analyzing the genes and pathways related to major depressive disorder via a systems biology approach

Sex‐specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice

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