Social Isolation is Associated With Altered Neural Reactivity to the Sight of Food

  • A study of women published in JAMA Network Open found that women with higher perceived social isolation tend to have altered neural activity in response to pictures of food
  • This altered activity was detected in brain regions responsible for appetite and food-related motivation and included the default mode, executive control, and visual attention networks
  •  More socially isolated women also tended to be more overweight and obese, to have lower diet quality, more maladaptive eating behaviors, and poorer mental health

Sometimes, eating something will make us feel better when we are sad or experience strong negative emotions. Some foods are so tasty that eating them feels like a rewarding experience. People associate some foods with positive memories, so eating them will improve their emotional state by invoking them. But what happens when negative emotions are persistent? For example, when we generally feel lonely?

Social isolation
Perceived social isolation, also known as loneliness, is one’s subjective appraisal of his/her available social relationships and community support (Zhang et al., 2024). Loneliness is entirely subjective and does not necessarily rely on how many social connections one objectively has. A person can feel lonely while being surrounded by people.

 

Loneliness is entirely subjective and does not necessarily rely on how many social connections one objectively has.

 

Loneliness is not a pleasant feeling. Feeling lonely adversely impacts our well-being. However, studies indicate that loneliness might have a broader adverse impact on our health. Lonely individuals seem to be at an increased risk of cardiovascular diseases, cognitive decline, and unhealthy eating behaviors (Zhang et al., 2024), but also dying of cancer (Hawkley & Cacioppo, 2003; Park et al., 2020). Some authors suggest that health risks created by loneliness are on par with those created by chronic high blood pressure, obesity, or smoking (Singer, 2018).

However, it should be noted that these observations are just associations. While loneliness may lead to these adverse health effects, health problems can make socialization difficult or impossible, creating an association with loneliness.

Social isolation and eating behaviors
Loneliness may increase the risk of obesity. It may also worsen eating behaviors and eating disorders (Zhang et al., 2024). Previous studies established that negative emotions make individuals more likely to overeat (Zeeck et al., 2011). When intense emotions overwhelm an individual’s capacity to self-regulate their own emotional well-being, binge eating behaviors may emerge as a coping mechanism.

 

Loneliness may increase the risk of obesity. It may also worsen eating behaviors and eating disorders. 

 

There is both scientific and anecdotal evidence of the phenomenon of being “hangry,” i.e., becoming angry while hungry (Hedrih, 2023; Swami et al., 2022). A similar link may exist between loneliness and hunger as well.

The current study
Study author Xiaobei Zhang and his colleagues note that there is emerging evidence that the brains of individuals experiencing chronic loneliness undergo functional changes that may contribute to obesity, altered eating behaviors, and associated psychological symptoms. They wanted to explore the links between loneliness and the brain’s responses to the sight of food better.

These authors hypothesized that several brain networks will show increased activation in lonely individuals when viewing foods. The size of this increase would likely be higher in obese individuals who already have altered eating behaviors and worsened mental health. These authors also hypothesized that reactions would be particularly strong to sweet foods, given their highly rewarding nature.

The study participants were 93 women of reproductive age from Los Angeles, California. Their average age was 25, and they ranged between 18 and 50. The study authors recruited them through advertisements.

The study authors took participants’ weight and height measurements (to calculate body mass index) and estimated their body composition. Participants provided data on their diet style and quality (the UCLA Diet Checklist and the Healthy Eating Index), age, marital status, and socioeconomic status. They completed an assessment of perceived social isolation (the Perceived Isolation Scale). Based on this assessment, the study authors divided participants into two groups – the high-isolation group and the low-isolation group.

Aside from this, participants completed assessments of food craving (the General Food Craving Questionnaire), eating behaviors (the Reward-based Eating Drive, the Three-Factor Eating Questionnaire), food addiction (the Yale Food Addiction Scale), resilience (the Connor-Davidson Resilience scale), anxiety and depression symptoms (the Hospital Anxiety and Depression Scale), and affect (the Positive Affect – Negative Affect Schedule). Participants also underwent functional magnetic resonance imaging while viewing a slideshow with pictures of different types of food – unhealthy savory, unhealthy sweet, healthy savory, healthy sweet, and non-food images (i.e., pixelated images created from food pictures to serve as controls) (see Figure 1).

 

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Figure 1. Study Procedure (Zhang et al., 2024)

 

Lonely individuals had higher fat mass percentage, ate lower quality diets, and had worse mental health
Results showed that the high loneliness group of participants tended to have higher fat mass percentage and ate diets of lower quality. They showed more maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction scores) and more anxiety and depression symptoms. They also tended to have lower psychological resilience.

 

The high loneliness group of participants tended to have a higher fat mass percentage and eat lower-quality diets. 

 

Lonely individuals tended to have altered brain reactivity to food pictures
Participants in the high social isolation group also tended to have altered brain reactivity to the pictures of food in regions of the brain belonging to the default mode, executive control, and visual attention networks compared to the low social isolation group (see Figure 2).

 

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Figure 2. Study results (Zhang et al., 2024)

 

The default mode network is a brain network active during rest and involved in self-referential thoughts, mind-wandering, and daydreaming. The executive control network is responsible for high-level cognitive functions such as decision-making, problem-solving, and maintaining attention to tasks. The visual attention network directs attention to visual stimuli, enabling the processing and prioritization of visual information in the environment.

Neural responses to sweet foods were associated with altered eating behaviors and psychological symptoms. Statistical analysis showed that these altered brain responses may mediate the relationship between loneliness and maladaptive eating behaviors, increased body fat composition, and diminished positive emotions.

 

The study confirmed the link between social isolation and obesity. 

 

Conclusions
The study confirmed the link between social isolation and obesity. It identified altered brain responses to the sight of food in women who reported higher feelings of loneliness. These findings underscore the need for overweight and obesity treatments to take into account the whole psychological and social situation of an individual rather than focusing on eating behaviors alone.

The paper “Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms” was authored by Xiaobei Zhang, Soumya Ravichandran, Gilbert C. Gee, Tien S. Dong, Hiram Beltrán-Sánchez, May C. Wang, Lisa A. Kilpatrick, Jennifer S. Labus, Allison Vaughan, and Arpana Gupta.

 

References

Hawkley, L. C., & Cacioppo, J. T. (2003). Loneliness and pathways to disease. Brain, Behavior, and Immunity, 17(1, Supplement), 98–105. https://doi.org/10.1016/S0889-1591(02)00073-9

Hedrih, V. (2023). Food and Mood: Is the Concept of ‘Hangry’ Real? CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/food-and-mood-is-the-concept-of-hangry-real/

Park, C., Majeed, A., Gill, H., Tamura, J., Ho, R. C., Mansur, R. B., Nasri, F., Lee, Y., Rosenblat, J. D., Wong, E., & McIntyre, R. S. (2020). The Effect of Loneliness on Distinct Health Outcomes: A Comprehensive Review and Meta-Analysis. Psychiatry Research, 294, 113514. https://doi.org/10.1016/j.psychres.2020.113514

Singer, C. (2018). Health Effects of Social Isolation and Loneliness. Journal of Aging and Care, 28(1), 4–8.

Swami, V., Hochstöger, S., Kargl, E., & Stieger, S. (2022). Hangry in the field: An experience sampling study on the impact of hunger on anger, irritability, and affect. PLOS ONE, 17(7), e0269629. https://doi.org/10.1371/JOURNAL.PONE.0269629

Zeeck, A., Stelzer, N., Linster, H. W., Joos, A., & Hartmann, A. (2011). Emotion and eating in binge eating disorder and obesity. European Eating Disorders Review, 19(5), 426–437. https://doi.org/10.1002/erv.1066

Zhang, X., Ravichandran, S., Gee, G. C., Dong, T. S., Beltrán-Sánchez, H., Wang, M. C., Kilpatrick, L. A., Labus, J. S., Vaughan, A., & Gupta, A. (2024). Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms. JAMA Network Open, 7(4), e244855. https://doi.org/10.1001/jamanetworkopen.2024.4855

A High-Fat Diet Increases Anxiety-Related Behaviors in Rats by Altering Gut Microbiota-Brain Communication

  • A study on rats published in Biological Research found that a high-fat diet alters gut microbiota composition and makes them obese
  • This alteration changes specific aspects of communication between gut microbiota and the brain, increasing the expression of genes related to the neurotransmitter serotonin in a part of the brain that is involved in anxiety-related behaviors
  • These changes make rats show more anxiety-related behaviors

Most people understand that eating lots of high-calorie food will make us gain weight. That is rather straightforward. However, human bodies have an intricate food intake regulation mechanism that tells us when to eat and when we have had enough. That mechanism is crucial for our survival. Without it, we could starve to death without ever feeling a desire to eat. Or we could eat so much that we die from overeating without ever noticing that we have eaten too much. Luckily, this never happens as our food intake mechanism works and works well. So, if we have this mechanism that regulates our food intake, how does obesity develop?

The development of obesity


Many argue that the world has been undergoing an obesity epidemic in the past several decades. The share of overweight and obese people has been increasing worldwide (Wong et al., 2022). This coincided with the wider availability of highly processed, energy-dense industrial foods, many of which contain additives and combinations of high-calorie ingredients not found in nature (Gearhardt et al., 2023; Hedrih, 2023; Monteiro et al., 2019; Wilding, 2001).

 

The share of overweight and obese people has been increasing worldwide, coinciding with the wider availability of highly processed, energy-dense industrial foods

 

While obesity in humans is thought to be caused by an interplay of many different factors (Wilding, 2001), studies on rodents consistently indicate that feeding them high-fat diets will dysregulate their food intake mechanisms, making them obese (Ikemoto et al., 1996, Lippert et al., 2020). Unlike normal chow for laboratory rodents, which is rich in carbohydrates but contains little fat, this obesity-inducing high-fat diet for laboratory rodents is rich both in fats and carbohydrates. This is similar to highly processed, industrial energy-dense foods considered a key generator of obesity in humans by many (Wilding, 2001).

Obesity and anxiety


Various changes in brain activity accompany the development of obesity. Studies have reported low-grade inflammation of the hypothalamus in obese individuals, the part of the brain that plays a key role in food intake regulation (Thaler et al., 2013), and specific alterations of activity in various other parts of the brain (Bhatt et al., 2023).

 

Various changes in brain activity accompany the development of obesity

 

Studies have also linked obesity with anxiety disorders. Researchers believe that inflammation of specific areas of the brain, thought to play a role in the development of obesity, might also lead to increased anxiety (De Noronha et al., 2024) (see Figure 1).

 

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Figure 1. Impact of Obesity on brain activity and anxiety disorders

 

The current study


Study author Sylvana I. S. Rendeiro de Noronha and her colleagues note that previous studies indicate that feeding rats a high-fat diet leads to obesity and anxiety-like behaviors. However, the mechanism that produces this effect remains unknown, and these researchers wanted to explore it.

They hypothesized that eating a high-fat diet would alter the diversity and composition of the gut microbiome. This will, in turn, change the communication between the brain and gut microbiota (through the microbiota-gut-brain axis), leading to increased expression of serotonergic genes (genes involved in the synthesis, transport, reception, and breakdown of the neurotransmitter serotonin) in the caudal part of the dorsomedial dorsal raphe nucleus subregion of the brain (De Noronha et al., 2024). This subregion of the brain is associated with stress- and anxiety-related behavior. Therefore, these changes could lead to an increase in anxiety-like behaviors, explaining their association with the consumption of a high-fat diet (see Figure 2).

 

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Figure 2. Hypothesis (Rendeiro de Noronha et al., 2024)

 

The study was conducted on 5-6-week-old male Wistar rats (a strain often used in research). The rats weighed around 100 grams each, and researchers housed them in groups of 4 in acrylic cages. They had free access to food and water.

Rats were divided into two groups. One group of 12 rats ate normal rat food (11% fat), while researchers fed the other group a high-fat diet (45% fat) for nine weeks. When the experimental diet started, rats were in a period of life corresponding to middle adolescence (5 weeks). They reached what can be considered adulthood by the time treatment ended and testing began.

The study authors used a series of behavioral tests to evaluate the presence of anxiety-like behaviors in these rats. They also collected rats’ feces to evaluate the composition of their gut microbiota. In the end, the rats were killed, and the study authors analyzed their brain tissue.

 

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Figure 3. Study Procedure (Rendeiro de Noronha et al., 2024)

 

High-fat diet-induced obesity, some anxiety-related behaviors, and altered rats’ gut microbiota composition


Rats fed the high-fat diet developed obesity. They also showed increased anxiety-related behaviors on one behavioral test (elevated plus-maze). Still, in two other tests (light/dark box test and open field test), there were no differences between the two groups of rats.

Feces analysis showed that high-fat diet rats had different gut microbiota composition compared to rats that ate normal food. High-fat diet rats tended to have more bacteria belonging to the Firmicutes phylum in their guts. They also had higher abundances of bacteria belonging to Allobaculum, Blautia, and Dorea genera. On the other hand, rats that ate a normal diet tended to have more bacteria belonging to the genera Lactobacillus and Prevotella.

A high-fat diet increases the expression of serotonergic genes


A high-fat diet increases the expression of specific genes involved in the brain’s serotonin system. Notably, the expression of tph2, htr1a, and slc6a4 mRNA was increased in subregions of the dorsal raphe nucleus region of the brain, just as the study authors hypothesized.

Study authors believe that this increased gene expression was what produced the increase in anxiety-like behaviors. (see Figure 4).

 

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Figure 4. Research findings (Rendeiro de Noronha et al., 2024)

 

Conclusions


The study demonstrated how a high-fat diet altered the gut microbiome in rats and led to obesity. This altered gut microbiome altered signaling to the brain through the microbiome-gut-brain axis, increasing the expression of specific genes involved in the serotonergic system in the part of the brain involved in anxiety-like behaviors. This increase, in turn, increased anxiety-like behaviors. 

This study was done on rats. Humans are a different species, but they share many physiological similarities. Because of this, it is likely that these mechanisms work in a similar way in humans as well and that the effects of a high-fat diet would not be too dissimilar.

The paper “High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats” was authored by Sylvana I. S. Rendeiro de Noronha, Lauro Angelo Gonçalves de Moraes, James E. Hassell Jr., Christopher E. Stamper, Mathew R. Arnold, Jared D. Heinze, Christine L. Foxx, Margaret M. Lieb, Kristin E. Cler, Bree L. Karns, Sophia Jaekel, Kelsey M. Loupy, Fernanda C. S. Silva, Deoclécio Alves Chianca-Jr. , Christopher A. Lowry, and Rodrigo Cunha de Menezes.

 

 

References

Bhatt, R. R., Todorov, S., Sood, R., Ravichandran, S., Kilpatrick, L. A., Peng, N., Liu, C., Vora, P. P., Jahanshad, N., Gupta, A., & Bhatt, R. R. (2023). Integrated multi-modal brain signatures predict sex-specific obesity status. Brain Communications, 5(2), 1–14. https://doi.org/10.1093/BRAINCOMMS/FCAD098

De Noronha, S. I. S. R., De Moraes, L. A. G., Hassell, J. E., Stamper, C. E., Arnold, M. R., Heinze, J. D., Foxx, C. L., Lieb, M. M., Cler, K. E., Karns, B. L., Jaekel, S., Loupy, K. M., Silva, F. C. S., Chianca-, D. A., Lowry, C. A., & De Menezes, R. C. (2024). High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats. Biological Research, 57(1), 23. https://doi.org/10.1186/s40659-024-00505-1

Gearhardt, A. N., Bueno, N. B., DiFeliceantonio, A. G., Roberto, C. A., Jiménez-Murcia, S., & Fernandez-Aranda, F. (2023). Social, clinical, and policy implications of ultra-processed food addiction. BMJ, e075354. https://doi.org/10.1136/bmj-2023-075354

Hedrih, V. (2023). Scientists Propose that Ultra-Processed Foods be Classified as Addictive Substances. CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/scientists-propose-that-ultra-processed-foods-be-classified-as-addictive-substances/

Ikemoto, S., Takahashi, M., Tsunoda, N., Maruyama, K., Itakura, H., & Ezaki, O. (1996). High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils. Metabolism, 45(12), 1539–1546. https://doi.org/10.1016/S0026-0495(96)90185-7

Lippert, R. N., Hess, S., Klemm, P., Burgeno, L. M., Jahans-Price T, Walton, M. E., Kloppenburg, P., & Brüning, J. C. (2020). Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice. Journal of Clinical Investigation, 130(7), 3761–3776.

Monteiro, C. A., Cannon, G., Levy, R. B., Moubarac, J. C., Louzada, M. L. C., Rauber, F., Khandpur, N., Cediel, G., Neri, D., Martinez-Steele, E., Baraldi, L. G., & Jaime, P. C. (2019). Ultra-processed foods: What they are and how to identify them. Public Health Nutrition, 22(5), 936–941. https://doi.org/10.1017/S1368980018003762

Thaler, J. P., Guyenet, S. J., Dorfman, M. D., Wisse, B. E., & Schwartz, M. W. (2013). Hypothalamic Inflammation: Marker or Mechanism of Obesity Pathogenesis? Diabetes, 62(8), 2629–2634. https://doi.org/10.2337/DB12-1605

Wilding, J. P. H. (2001). Causes of obesity. Practical Diabetes International, 18(8), 288–292. https://doi.org/10.1002/PDI.277

Wong, M. C., Mccarthy, C., Fearnbach, N., Yang, S., Shepherd, J., & Heymsfield, S. B. (2022). Emergence of the obesity epidemic: 6-decade visualization with humanoid avatars. The American Journal of Clinical Nutrition, 115(4), 1189–1193. https://doi.org/10.1093/AJCN/NQAC005

 

 

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