Spatiotemporal Dynamics of Stress-Induced Network Reconfigurations Reflect Negative Affectivity

Kühnel, Anne; Czisch, Michael; Sämann, Philipp G.; Binder, Elisabeth B.; Kroemer, Nils B.; Brückl, Tanja; Spoormaker, Victor I.; Erhardt, Angelika; Grandi, Norma C.; Ziebula, Julius; Elbau, Immanuel G.; Namendorf, Tamara; Lucae, Susanne

doi:10.1016/j.biopsych.2022.01.008

Cited by 10 publications

(34 citation statements)

References 128 publications

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“…FC between the insula and the NAcc has been linked to processing of unexpected taste, and global brain connectivity of the insular ingestive cortex and the striatum during milkshake intake is reduced in obesity . More broadly, discrepancies between interoceptive signals forwarded by the insula and exteroceptive signals have been hypothesized to drive depression . Taken together, our findings corroborate the idea that core symptoms of depression can be mapped onto alterations in the reward circuit in line with established functional characteristics of these regions—even though depression cannot be categorically classified from their FC profiles or more extensive sets of potential neuroimaging biomarkers …”

Section: Discussionsupporting

confidence: 78%

“…55 More broadly, discrepancies between interoceptive signals forwarded by the insula 72 and exteroceptive signals have been hypothesized to drive depression. 73,74 Taken together, our findings corrobo- Median weights after 10 iterations A, Schematic summary of the elastic net model. We obtained individual seed-based functional connectivity profiles and used an elastic net to select the best features for cross-validated associations across the whole sample of patients.…”

Section: Discussionmentioning

confidence: 99%

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Functional Connectivity of the Nucleus Accumbens and Changes in Appetite in Patients With Depression

Kroemer

Teckentrup

et al. 2022

JAMA Psychiatry

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ImportanceMajor depressive disorder (MDD) is characterized by a substantial burden on health, including changes in appetite and body weight. Heterogeneity of depressive symptoms has hampered the identification of biomarkers that robustly generalize to most patients, thus calling for symptom-based mapping.ObjectiveTo define the functional architecture of the reward circuit subserving increases vs decreases in appetite and body weight in patients with MDD by specifying their contributions and influence on disease biomarkers using resting-state functional connectivity (FC).Design, Setting, and ParticipantsIn this case-control study, functional magnetic resonance imaging (fMRI) data were taken from the Marburg-Münster FOR 2107 Affective Disorder Cohort Study (MACS), collected between September 2014 and November 2016. Cross-sectional data of patients with MDD (n = 407) and healthy control participants (n = 400) were analyzed from March 2018 to June 2022.Main Outcomes and MeasuresChanges in appetite during the depressive episode and their association with FC were examined using fMRI. By taking the nucleus accumbens (NAcc) as seed of the reward circuit, associations with opposing changes in appetite were mapped, and a sparse symptom-specific elastic-net model was built with 10-fold cross-validation.ResultsAmong 407 patients with MDD, 249 (61.2%) were women, and the mean (SD) age was 36.79 (13.4) years. Reduced NAcc-based FC to the ventromedial prefrontal cortex (vmPFC) and the hippocampus was associated with reduced appetite (vmPFC: bootstrap r = 0.13; 95% CI, 0.02-0.23; hippocampus: bootstrap r = 0.15; 95% CI, 0.05-0.26). In contrast, reduced NAcc-based FC to the insular ingestive cortex was associated with increased appetite (bootstrap r = −0.14; 95% CI, −0.24 to −0.04). Critically, the cross-validated elastic-net model reflected changes in appetite based on NAcc FC and explained variance increased with increasing symptom severity (all patients: bootstrap r = 0.24; 95% CI, 0.16-0.31; patients with Beck Depression Inventory score of 28 or greater: bootstrap r = 0.42; 95% CI, 0.25-0.58). In contrast, NAcc FC did not classify diagnosis (MDD vs healthy control).Conclusions and RelevanceIn this study, NAcc-based FC reflected important individual differences in appetite and body weight in patients with depression that can be leveraged for personalized prediction. However, classification of diagnosis using NAcc-based FC did not exceed chance levels. Such symptom-specific associations emphasize the need to map biomarkers onto more confined facets of psychopathology to improve the classification and treatment of MDD.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Functional Connectivity of the Nucleus Accumbens and Changes in Appetite in Patients With Depression

Kroemer

Teckentrup

et al. 2022

JAMA Psychiatry

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“…Moreover, for 148 participants (N=89 women), levels of peripheral immune marker and cortisol concentrations were available. As previously reported, we excluded participants with missing or low-quality data for each analysis separately (N=148-192, (Kühnel et al, 2022)).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, baseline levels of cytokines such as macrophage migration inhibitory factor (MIF) and IL-6 were associated with subsequent stress-induced cortisol responses (Edwards et al, 2010; Kunz-Ebrecht et al, 2003) highlighting the interdependence of the immune and endocrine system in orchestrating stress responses (Rohleder, 2019). Furthermore, inflammation induced by vaccination (Harrison et al, 2009) and in depression (Aruldass et al, 2021) as well as obesity (Park et al, 2020; Syan et al, 2021) have been linked to changes in functional connectivity in brain networks related to interoception and default mode processing that are also implicated in stress-reactivity and anxiety symptoms (Kühnel et al, 2022). Likewise, both obesity and mental stress-related disorders such as depression share genetic factors that are also associated with higher risk for inflammation (Kappelmann et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…To this end, we used stress-induced changes in brain response (i.e., activation changes). Moreover, we derived dynamic functional connectivity and activation trajectories within a putative stress network (Kühnel et al, 2022) and used a cross-validated elastic net to predict interindividual differences in BMI from these imaging features. We then evaluated whether BMI-associated increases in baseline cortisol or inflammation markers contributed to altered neural stress reactivity in obesity.…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced brain responses are associated with BMI in women

Kühnel¹,

Hagenberg²,

Knauer-Arloth³

et al. 2023

Preprint

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BackgroundStress is associated with elevated risk for overweight and obesity, especially in women. Since body mass index (BMI) is correlated with increased inflammation and reduced baseline cortisol, obesity may lead to altered stress responses. However, it is not well understood whether stress-induced changes in brain function scale with BMI and if peripheral inflammation contributes to this.MethodsWe investigated the subjective, autonomous, endocrine, and neural stress response in a transdiagnostic sample (N=192, 120 women, MBMI=23.7±4.0 kg/m2; N=148, 89 women, with cytokines). First, we used regression models to examine effects of BMI on stress reactivity. Second, we predicted BMI based on stress-induced changes in activation and connectivity using cross-validated elastic-nets. Third, to link stress responses with inflammation, we quantified the association of BMI-related cytokines with model predictions.ResultsBMI was associated with higher negative affect after stress and an increased response to stress in the substantia nigra and the bilateral posterior insula (pFWE<.05). Moreover, stress-induced changes in activation of the hippocampus, dACC, and posterior insula predicted BMI in women (pperm<.001), but not in men. BMI was associated with higher baseline cortisol while cytokines were not associated with predicted BMI scores.ConclusionsStress-induced changes in the hippocampus and posterior insula predicted BMI in women, indicating that acute brain responses to stress might be more strongly related to a higher BMI in women compared to men. Altered stress-induced changes were associated with baseline cortisol but independent of cytokines, suggesting that the endocrine system and not inflammation contributes to stress-related changes in BMI.

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Understanding Posttraumatic Stress Disorder With Clues From the Dynamic Brain

Goldfarb

2023

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Spatiotemporal Dynamics of Stress-Induced Network Reconfigurations Reflect Negative Affectivity

Cited by 10 publications

References 128 publications

Functional Connectivity of the Nucleus Accumbens and Changes in Appetite in Patients With Depression

Functional Connectivity of the Nucleus Accumbens and Changes in Appetite in Patients With Depression

Stress-induced brain responses are associated with BMI in women

Understanding Posttraumatic Stress Disorder With Clues From the Dynamic Brain

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