Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms

Key Points Question Is perceived social isolation associated with brain reactivity to food cues, obesity, and psychological symptoms? Findings In this cross-sectional study of 93 healthy, premenopausal female participants, social isolation was associated with altered brain processing of food cues in the default mode, executive control, and visual attention networks. These neural changes (especially to sweet foods) showed an association among social isolation, eating behaviors, and psychological symptoms. Meaning These findings indicate that increased loneliness may be linked to brain patterns that highlight difficulties in motivation, control, and processing of internal states in response to foods and increased alterations in eating behaviors, obesity, and psychological symptoms, suggesting future targets for obesity treatments.

eFigure 1. Graphical Abstract.Figure Legend: Perceived social isolation was associated with altered neural reactivity to food cues (especially to sweet foods) within the default mode, executive control, and visual-attention networks.These neural changes were responsible for processing internal appetite-related states, compromised executive control, and attentional bias and motivation towards external food cues.Neural responses towards specific foods leads to increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health.These findings underscore the need for holistic mind-body directed interventions that consider the intricate interplay of these factors in effectively mitigating the adverse consequences of social isolation.

eMethods
Participant recruitment and exclusion criteria: Women who were either peri-menopausal or post-menopausal, as determined by their self-reported last menstrual cycle, were not included in the study.The enrolled women underwent scanning during the follicular phase of their menstrual cycle.Individuals with major medical or neurological conditions, current or past psychiatric illnesses, comorbidities like vascular disease or diabetes, a history of weight loss or abdominal surgeries, substance use disorders, tobacco dependence (smoking half a pack or more daily), or those with metal implants were excluded.Additionally, individuals who used medications that could interfere with the central nervous system, regularly took analgesic medications, were pregnant or breastfeeding, or engaged in extreme strenuous exercise (more than 8 hours of continuous exercise per week) were also excluded.Participants who exceeded 400 pounds in weight were not included due to the weight limitations of the MRI scanner.
All procedures complied with institutional guidelines and were approved by the Institutional Review Board at UCLA's Office of Protection for Research Subjects (IRB# 20-002326).All participants provided written informed consent.
Socioeconomic status (SES) was measured using The MacArthur Scale of Subjective Social Status which is a widely used measure of subjective social status 1 .
Bioelectrical impedance analysis (BIA) fat mass percentage refers to the percentage of body mass that is composed of fat, as determined through BIA.BIA is a method used to estimate body composition by measuring the impedance (resistance) of electrical flow through the body.
Bioelectrical impedance analysis (BIA) lean body mass percentage refers to the percentage of body mass that consists of lean body tissue, as determined using BIA.In body composition analysis, lean body mass includes everything in the body except for fat mass.This can encompass muscles, bones, organs, and other non-fat tissues.
Diet Questionnaires: All participants completed the UCLA Diet Checklist, which is a questionnaire developed by our institution, intended to represent the diet that best reflects what the participant consumes on a regular basis.The specific diets incorporated into this checklist are summarized in supplemental Table S1.Participants were also allowed to choose "other" if they felt they consumed a diet that was distinct from the ones listed on the Diet Checklist.Our institution's Diet Checklist has been internally validated against the standardized Diet History Questionnaire (DHQ) III.For data analysis, we had two diet categories: the Standard American diet as one category, and all other diets not categorized as Standard American (e.g., Mediterranean, vegan, vegetarian, and gluten-free) were combined as 'Non-Standard American Diet.' Healthy Eating Index (HEI)-2015 2 was used to access the diet quality.It's a tool designed to evaluate how well a specific set of foods aligns with the Dietary Guidelines for Americans. 3The components of the HEI-2015 are largely identical to those of the HEI-2010, with the exception that saturated fat and added sugars have replaced empty calories.As a result, the HEI-2015 includes a total of 13 components.HEI-2015 scores can range from 0 to 100, with higher scores indicating better dietary quality. 4: The G-FCQ-T-r is a shorter version of the FCQ-T.This tool is used to assess for a patient's food cravings as stable traits, measuring the features of craving that is consistent over time.It has 15 items: 5 items on the lack of control overeating, 5 items on the thoughts or preoccupation with food, 2 items on intentions and plans to consume food, 2 items on emotions before or during food craving, and 1 item on cues that may trigger food craving.Scores on the FCQ-T are shown to positively associate with eating pathology, BMI, low dieting success, and increase in craving when exposed to food stimuli. 5: The RED scale is a 7-item self-report index that looks at three factors: Lack of control over eating, lack of satiation, and preoccupation with food.The scale attempts to understand why some individuals are more vulnerable to persistent weight gain than others by delving into the idea that they have a higher drive to eat due to the heightened reward they get by eating.

Reward-based Eating Drive (RED)
Three-Factor Eating Questionnaire (TFEQ) 6 : The TFEQ is a 51-item questionnaire which measures three factors of human eating behavior: cognitive restraint of eating (21 items), disinhibition (16 items), and hunger (14 items).Each question is scored either with a 0 or a 1, and the three factors are scored separately, resulting with a final score with three numbers (for example, the maximum possible score is 21-16-14).
Yale Food Addiction Scale (YFAS) 7 : The YFAS is a survey designed to assess whether a patient exhibits signs of addiction towards food, especially those high in food and sugar.It is a 25-item survey, which is based upon the seven substance dependence criteria that are detailed in the DSM-IV, and patients answer questions based on which ones are applicable to them over the past 12 months.Some questions can be answered with a yes/no, while others ask for a frequency (between 'never' to 'four or more times a week or daily'.Food addiction symptoms in our study were measured by the continuous symptom count, reflecting the number of symptoms presented by the respondent. 8is a 25-item self-rated survey, designed to assess a patient's ability to thrive despite facing adversity.It was created to show that resilience can be quantified, is influenced by health, and can improve after treatment.In this survey, each item is rated 0-4.The higher the overall score, the greater the resilience of the patient.Spielberger State Trait Anxiety Inventory (STAI) 9

is a 40-item
The Hospital Anxiety and Depression Scale (HAD) 10 is a 14-item questionnaire.The questions are scored on a scale of 0 to 3, corresponding to how much the individual identifies with the question for the past week.It is a well-validated brief inventory for assessment of symptoms of anxiety and depression that has been widely used in studies of medical populations.
Positive Affect Negative Affect Schedule (PANAS) 11 is a psychometric scale developed to measure the largely independent constructs of positive and negative affect, both as states and traits.Positive and negative affect have been shown to relate to other personality states and traits, such as anxiety.Through a factor analysis a list of 10 descriptors for PA scale (attentive, interested, alert, excited, enthusiastic, inspired, proud, determined, strong and active); and 10 descriptors for NA scale (distressed, upset-distressed; hostile, irritable-angry; scared, afraidfearful; ashamed, guilty; nervous, and jittery) are measured.

Brain Magnetic Resonance Imaging
Whole-brain structural and functional data was acquired using a 3.0T Siemens Prisma MRI scanner (Siemens, Erlangen, Germany).Additional detailed information on the standardized acquisition protocols and quality control measures are provided in previously published studies.
Food cue task: Pictures include the following types: unhealthy (high calorie) savory, unhealthy (high calorie) sweet, healthy (low calorie) savory, healthy (low calorie) sweet, and non-food, comprising pixelated images created from food pictures (as a control comparison).All food images were uploaded to E-prime software; 20 half were copied and pixelated to control for color, brightness and contrast.Images were arranged into blocks of 6, comprising either unaltered or pixelated images only, with a total of 18 blocks.Each image was shown for 3 seconds.A black screen with a white crosshair was displayed for 12 seconds before the first block of images, inbetween each block of images, and after the final block of images.Two slideshows (order 1 and order 2) were created using the same 18 blocks of images arranged in different orders.Participants watched both sets of images in the scanner.
Brain data preprocessing procedure: The fMRI Expert Analysis Tool (FEAT; version 6.0) included in the FMRIB Software Library (FSL) was used for preprocessing. 21Preprocessing included motion correction, brain extraction, 100-s high-pass filtering and spatial smoothing with a 5-mm full-width at half-maximum (FWHM) Gaussian kernel.In addition to six motion parameters, nuisance regressors for time points corresponding to motion outliers were included using the FSL motion outliers program (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLMotionOutliers), which defined outlier time points using the upper threshold of the 75th percentile plus 1.5 times the interquartile range.Functional data were aligned to each participant's structural image, and then registered into Montreal Neurological Institute (MNI) standard space using affine transformation through FSL's Linear Image Registration Tool (FLIRT).

eTable 1 :
Diet Checklist CategoriesFocus is on plant-based foods.Includes fruits, vegetables, dried beans and peas, grains, seeds, and nuts.VegetarianDiet excludes all meat but will allow animal-derived ingredients, i.e. honey and gelatin Lacto-Vegetarian Diet includes plant foods plus dairy products, no eggs Ovo-Vegetarian Diet includes plant foods plus eggs, no dairy Lacto-Ovo-Vegetarian Diet includes both dairy products and eggs Pescatarian Diet includes fruits, vegetables, dried beans and peas, grains, seeds, and nuts.Excludes all meat except fish.Raw Vegan/ Raw Food Consumption of unprocessed vegan foods that have not been heated above 115 degrees Fahrenheit (46 degrees Celsius) Gluten-Free Diet includes most foods but avoids the protein, gluten, which is found in wheat, barley, and rye.Diet limits foods high in sugar and carbohydrates (fructose, lactose, fructans, galactans, and polyols).