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Pediatrics

Stressing diets? Amygdala networks, cumulative cortisol, and weight loss in adolescents with excess weight

Abstract

Objective

The amygdala is importantly involved in stress and obesity, but its role on weight change and diet-related stress remains unexplored among adolescents with excess weight. We aimed to examine the functional connectivity of the Central and Basolateral amygdala nuclei (CeA and BLA) among adolescents, and to explore the longitudinal association between brain connectivity measures and diet-related cortisol and weight loss in adolescents with excess weight.

Methods

We compared resting-state functional connectivity between adolescents with excess (EW, N = 34; Age = 16.44 ± 1.66) and normal weight (NW, N = 36; Age = 16.50 ± 1.40) using a seed-based (CeA and BLA) whole-brain approach. Then, in a subset of 30 adolescents with EW, followed-up after 3-months of dietary/lifestyle intervention, we explored for interactions between connectivity in the CeA/BLA networks and weight loss. Regression analyses were performed to explore the relationship between accumulated cortisol and weight loss, and to test the potential effect of the amygdala networks on such association.

Results

In EW compared with NW, the CeA regions showed higher functional connectivity with anterior portions, and lower connectivity with posterior portions of the cingulate cortex, while the left BLA regions showed lower connectivity with the dorsal caudate and angular gyrus. In addition, higher connectivity between the left CeA-midbrain network was negatively associated with weight loss. Hair cortisol significantly predicted weight change (p = 0.012). However, this association was no longer significant (p = 0.164) when considering the CeA-midbrain network in the model as an additional predictor.

Conclusions

Adolescents with EW showed functional connectivity alterations within the BLA/CeA networks. The CeA-midbrain network might constitute an important brain pathway regulating weight change.

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Fig. 1: Between-group differences in the functional connectivity of the different seeds of the amygdala (right/left CeA and left BLA).
Fig. 2: Plot showing the significant negative correlation between the functional connectivity of the CeA-midbrain network (MNI coordinates x, y, z: 14, −14, −12) and the weight loss after a 3 months' intervention in adolescents with excess weight.

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References

  1. NCD-Risc: Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390:2627–42.

    Google Scholar 

  2. Dockray S, Susman EJ, Dorn LD. Depression, cortisol reactivity and obesity in childhood and adolescence. J Adolesc Health. 2009;45:344–50.

    PubMed  PubMed Central  Google Scholar 

  3. Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav. 2007;91:449–58.

    CAS  PubMed  Google Scholar 

  4. Martín-Pérez C, Contreras-Rodríguez O, Vilar-López R, Verdejo-García A. Hypothalamic networks in adolescents with excess weight: stress-related connectivity and associations with emotional eating. J Am Acad Child Adolesc Psychiatry. 2019; 58:211–220.e5.

  5. Sun X, Kroemer NB, Veldhuizen MG, Babbs AE, Araujo IE, Gitelman DR, et al. Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility. J Neurosci. 2015;35:7964–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Tomiyama AJ, Mann T, Vinas D, Hunger JM, DeJager J, Taylor SE. Low calorie dieting increases cortisol. Psychosom Med. 2011;72:357–64.

    Google Scholar 

  7. Lowe MR, Butryn ML. Hedonic hunger: a new dimension of appetite? Physiol Behav. 2007;91:432–9.

    CAS  PubMed  Google Scholar 

  8. Pankevich DE, Teegarden SL, Hedin AD, Jensen CL, Bale TL. Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating. Journal of Neuroscience. 2010;30:16399–407.

    CAS  PubMed  Google Scholar 

  9. Paolini BM, Laurienti PJ, Simpson SL, Burdette JH, Lyday RG, Rejeski WJ. Global integration of the hot-state brain network of appetite predicts short term weight loss in older adult. Front Aging Neurosci. 2015;7. https://doi.org/10.3389/fnagi.2015.00070.

  10. Hermann P, Gál V, Kóbor I, Kirwan B, Kovács P, Kitka T, et al. Efficacy of weight loss intervention can be predicted based on early alterations of fMRI food cue reactivity in the striatum. NeuroImage: Clin. 2019;101803. https://doi.org/10.1016/j.nicl.2019.101803.

  11. Siep N, Roefs A, Roebroeck A, Havermans R, Bonte ML, Jansen A. Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex. Behav Brain Res. 2008;198:149–58.

    PubMed  Google Scholar 

  12. Zhang Q, Li H, Guo F.Amygdala, an important regulator for food intake. Front Biol.2011;6:82–5.

    CAS  Google Scholar 

  13. Veer IM, Oei NYL, Spinhoven P, van Buchen MA, Elzinga BM, Rombouts SARB. Endogenous cortisol is associated with functional connectivity between the amygdala and medial prefrontal cortex. Psychoneuroendocrinology. 2012;37:1039–47.

    CAS  PubMed  Google Scholar 

  14. Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cognit Sci. 2010;15:85–93.

    Google Scholar 

  15. Van Marle HJF, Hermans EJ, Qin S, Fernández G. Enhanced resting-state connectivity of amygdala in the immediate aftermath of acute psychological stress. NeuroImage. 2010;53:348–54.

    PubMed  Google Scholar 

  16. Taren AA, Gianaros PJ, Greco CM, Lindsay EK, Fairgrieve A, Brown K, et al. Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial. Soc Cognitive Affect Neurosci. 2015;10:1758–68.

    Google Scholar 

  17. Horstmann A. The brain’s got a taste for good food. In: Avena NM editor. Hedonic eating: how the pleasure of food affects our brains and behavior. Oxford University Press: New York, USA; 2015. p. 39–56.

  18. Kullmann S, Heni M, Veit R, Ketterer C, Schick F, Häring H-U, et al. The obese brain: association of body mass index and insulin sensitivity with resting state network functional connectivity. Hum Brain Mapp. 2011;33:1052–61.

    PubMed  PubMed Central  Google Scholar 

  19. Lips MA, Wijngaarden MA, Van der Grond J, Van Buchem MA, De Groot GH, Rombouts SA, et al. Resting-state functional connectivity of brain regions involved in cognitive control, motivation, and reward is enhanced in obese females. Am J Clin Nutr. 2014;100:524–31.

    CAS  PubMed  Google Scholar 

  20. Kahathuduwa CN, Davis T, O’Boyle M, Boyd LA, Chin S-H, Paniukov D, et al. Effects of 3-week total meal replacement vs. typical food-based diet on human brain functional magnetic resonance imaging food-cue reactivity and functional connectivity in people with obesity. Appetite. 2018;120:431–41.

    PubMed  Google Scholar 

  21. Fowler CH, Miernicki ME, Rudolph KD, Telzer EH. Disrupted amygdala-prefrontal connectivity during emotion regulation links stress-reactive rumination and adolescent depressive symptoms. Dev Cogn Neurosci. 2017;27:99–106.

    PubMed  PubMed Central  Google Scholar 

  22. Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA, et al. Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat Neurosci. 2012;15:1736–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bzdok D, Laird AR, Zilles K, Fox PT, Eickhoff SB. An investigation of the structural, connectional, and functional subspecialization in the human amygdala. Hum Brain Mapp. 2013;34:3247–66.

    PubMed  Google Scholar 

  24. Campbell-Smith EJ, Holmes NM, Lingawi NW, Panayi MC, Westbrook RF. Oxytocin signaling in basolateral and central amygdala nuclei differentially regulates the acquisition, expression, and extinction of context-conditioned fear in rats. Learn Mem. 2015;22:247–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zseli G, Vida B, Szilvásy-Szabó A, Tóth M, Lechan RM, Fekete C. Neuronal connections of the central amygdalar nucleus with refeeding-activated brain areas in rats. Brain Struct Funct. 2018;223:391–414.

    PubMed  Google Scholar 

  26. Roozendaal B, Koolhaas JM, Bohus B. The role of the central amygdala in stress and adaption. Acta Physiol Scand, Suppl. 1997;640:51–54.

    CAS  Google Scholar 

  27. Kim J, Zhang X, Muralidhar S, LeBlanc SA, Tonegawa S. Basolateral to central amygdala neural circuits for appetitive behaviors. Neuron. 2017;93:1464–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al. Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA. 2003;100:11696–701.

    CAS  PubMed  Google Scholar 

  29. Petrovich GD, Holland PC, Gallagher M. Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating. J Neurosci.2005;25:8295–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Petrovich GA, Ross CA, Mody P, Holland PC, Gallagher M. Central, but not basolateral, amygdala is critical for control of feeding by aversive learned cues. J Neurosci. 2009;29:15205–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Mietus-Snyder ML, Lustig RH. Childhood obesity: adrift in the “limbic triangle”. Annu Rev Med. 2008;59:147–62.

    CAS  PubMed  Google Scholar 

  32. Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab. 2010;21:159–65.

    CAS  PubMed  Google Scholar 

  33. Tryon MS, Carter CS, DeCant R, Laugero KD. Chronic stress exposure may affect the brain´s response to high calorie food cues and predispose to obesogenic eating habits. Physiol Behav. 2013;120:233–42.

    CAS  PubMed  Google Scholar 

  34. Sixty-fourth world health assembly. Resolution WHA 64.28: Youth and health risks. Geneva, World Health Organization; 2011.

  35. Ogden CL, Flegal KM. Changes in terminology for childhood overweight and obesity. National Health Stat Report. 2010;25:1–5.

    Google Scholar 

  36. Russell E, Koren G, Rieder M, Van Uum S. Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions. Psychoneuroendocrinology. 2012;37:589–601.

    CAS  PubMed  Google Scholar 

  37. Vanaelst B, Huybrechts I, Bammann K, Michels N, Vriendt T, et al. Intercorrelations between serum, salivary, and hair cortisol and child‐reported estimates of stress in elementary school girls. Psychophysiology. 2012;49:1072–81.

    PubMed  Google Scholar 

  38. Serra-Majem LL, Aranceta J, Ribas L, Sangil M, Pérez C. El cribado de riesgo nutricional en Pediatría. Validación del test rápido KRECE PLUS y resultados en la población española. In: Serra LL, Aranceta J editors. Crecimiento y desarrollo: Dimensión alimentaria y nutricional. Masson: Barcelona, España; 2013, p. 45–55.

  39. Whitefield-Gabrielli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2012;2:125–41.

    Google Scholar 

  40. Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage. 2012;59:2142–54.

    PubMed  Google Scholar 

  41. Brett M, Valabregue R, Poline J. Region of interest analysis using an SPM toolbox. Neuroimage. 2003;16 (Supplement 1).

  42. Baur V, Hänggi J, Langer N, Jäncke L. Resting-state functional and structural connectivity within an insula-amygdala route specifically index state and trait anxiety. Biol Psychiatry. 2013;1:85–92.

    Google Scholar 

  43. Song XW, Dong ZY, Long XY, Li SF, Zuo XN, Zhu CZ, et al. REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One. 2011;6:e25031.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Gentili C, Ricciardi E, Gobbini MI, Santarelli MF, Haxby JV, Pietrini P, et al. Beyond amygdala: default mode network activity differs between patients with social phobia and healthy controls. Brain Res Bull. 2009;79:409–13.

    PubMed  Google Scholar 

  45. Veer IM, Oei NYL, Spinhoven P, van Buchem MA, Elzinga BM, Rombouts SARB. Beyond acute social stress: Increased functional connectivity between amygdala and cortical midline structures. NeuroImage. 2011;57:1534–41.

    PubMed  Google Scholar 

  46. Doucet GE, Rasgon N, McEwen BS, Micali N, Frangou S. Elevated body mass index is associated with increased integration and reduced cohesion of sensory-driven and internally guided resting-state functional brain networks. Cerebr Cortex. 2017;28:988–97.

    Google Scholar 

  47. Hare TA, Tottenham N, Galvan A, Voss HU, Glover GH, Casey BJ. Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task. Biol Psychiatry. 2008;63:927–34.

    PubMed  PubMed Central  Google Scholar 

  48. Kim J, Loucks RA, Palmer AL, Brown AC, Solomon KM, Marchante AN, et al. The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety. Behav Brain Res. 2011;223:403–10.

    PubMed  PubMed Central  Google Scholar 

  49. Kujawa A, Wu M, Klumpp H, Pine DS, Swain JE, Fitzgerald KD, et al. Altered development of amygdala-anterior cingulate cortex connectivity in anxious youth and young adults. Biol Psychiatry Cogn Neurosci Neuroimag. 2016;1:345–52.

    Google Scholar 

  50. Kubiak T, Vogele C, Siering M, Schiel R, Weber H. Daily hassles and emotional eating in obese adolescents under restricted dietary conditions-the role of ruminative thinking. Appetite. 2008;51:206–9.

    PubMed  Google Scholar 

  51. Gearhardt AN, Yokum S, Orr PT. (2011). Neural correlates of food addiction. Arch Gen Psychiatry. 2011;68:808.

    PubMed  PubMed Central  Google Scholar 

  52. Musgrove DR, Eberly LE, Klimes-Dougan B, Basgoze Z, Thomas KM, Mueller BA, et al. Impaired bottom-up effective connectivity between amygdala and subgenual anterior cingulate cortex in unmedicated adolescents with major depression: results from a dynamic causal modeling analysis. Brain Connect. 2015;5:608–19.

    PubMed  PubMed Central  Google Scholar 

  53. Nummenmaa L, Hirvonen J, Hannukainen JC, Immonen H, Lindroos MM, Salminen P, et al. Dorsal and its limbic connectivity mediate abnormal anticipatory reward processing in obesity. PLoS One. 2012;7:e31089.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Stice E, Spoor S, Bohon C, Veldhuizen MG, Small DM. Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study. J Abnorm Psychol. 2008;117:924–35.

    PubMed  PubMed Central  Google Scholar 

  55. Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010;30:13105–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Jackson SE, Kirschbaum C, Steptoe A. Hair cortisol and adiposity in a population-based sample of 2527 men and women aged 54 to 87 years. Obesity. 2017;25:539–44.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study has been funded by the Project NEUROECOBE (HUM-6635), granted by the Andalusian Council of Innovation, Science and Industry, Spain. OCR is funded by Postdoctoral “PERIS” Contract (SLT006/17/00236) from the Health Department of the Catalan Government, Spain. JVR is supported by a grant from the Spanish Ministry of Science, Innovation and Universities (FJCI-2017-33396). AVG was funded by grants MRF1141214 from the Australian Medical Research Future Fund and GNT1140197 from the National Health and Medical Research Council.

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Correspondence to Oren Contreras-Rodríguez.

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Martín-Pérez, C., Contreras-Rodríguez, O., Verdejo-Román, J. et al. Stressing diets? Amygdala networks, cumulative cortisol, and weight loss in adolescents with excess weight. Int J Obes 44, 2001–2010 (2020). https://doi.org/10.1038/s41366-020-0633-4

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