The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research

It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = −0.4983, p < 0.05) and PSQI scores (r = −0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery.

[1]  A. Gearhardt,et al.  Prevalence of food addiction among patients undergoing metabolic/bariatric surgery: A systematic review and meta‐analysis , 2022, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[2]  K. Blum,et al.  Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes as Antecedents to Reward Deficiency Syndrome (RDS) Hypodopaminergia’s Effect on Addictive and Non-Addictive Behaviors in a Nuclear Family , 2022, Journal of personalized medicine.

[3]  K. Blum,et al.  Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case–Control Subjects , 2022, Journal of personalized medicine.

[4]  K. Blum,et al.  Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation , 2022, Journal of personalized medicine.

[5]  K. Blum,et al.  FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors , 2022, Journal of personalized medicine.

[6]  K. Blum,et al.  Frequency of the Dopamine Receptor D3 (rs6280) vs. Opioid Receptor µ1 (rs1799971) Polymorphic Risk Alleles in Patients with Opioid Use Disorder: A Preponderance of Dopaminergic Mechanisms? , 2022, Biomedicines.

[7]  L. Davis,et al.  Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders , 2022, medRxiv.

[8]  K. Blum,et al.  Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors , 2022, International journal of environmental research and public health.

[9]  J. Concato,et al.  Bi-Ancestral Depression GWAS in the Million Veteran Program and Meta-Analysis in >1.2 Million Subjects Highlights New Therapeutic Directions , 2021, Nature Neuroscience.

[10]  K. Blum,et al.  High Genetic Addiction Risk Score (GARS) in Chronically Prescribed Severe Chronic Opioid Probands Attending Multi-pain Clinics: an Open Clinical Pilot Trial , 2021, Molecular Neurobiology.

[11]  K. Blum,et al.  Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development. , 2021, Current psychopharmacology.

[12]  H. Sintonen,et al.  Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial. , 2020, JAMA surgery.

[13]  B. G. Rushing,et al.  Variation of the human mu-opioid receptor (OPRM1) gene predicts vulnerability to frustration , 2020, Scientific Reports.

[14]  F. Gierski,et al.  Contributions of Emotional Overload, Emotion Dysregulation, and Impulsivity to Eating Patterns in Obese Patients with Binge Eating Disorder and Seeking Bariatric Surgery , 2020, Nutrients.

[15]  J. Kennedy,et al.  A Behavioral Genetic Model of the Mechanisms Underlying the Link Between Obesity and Symptoms of ADHD , 2020, Journal of attention disorders.

[16]  L. Busetto,et al.  Predicting Responses to Bariatric and Metabolic Surgery , 2020, Current Obesity Reports.

[17]  K. Blum,et al.  Co-occurrences of substance use and other potentially addictive behaviors: Epidemiological results from the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study , 2020, Journal of behavioral addictions.

[18]  R. Tambelli,et al.  The μ‐opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers , 2020, Brain and behavior.

[19]  K. Blum,et al.  Pre-clinical models of reward deficiency syndrome: A behavioral octopus , 2020, Neuroscience & Biobehavioral Reviews.

[20]  K. Blum,et al.  In Search of Reward Deficiency Syndrome (RDS)-free Controls: The "Holy Grail" in Genetic Addiction Risk Testing. , 2020, Current psychopharmacology.

[21]  William B. Downs,et al.  Hypodopaminergia and "Precision Behavioral Management" (PBM): It is a Generational Family Affair. , 2019, Current pharmaceutical biotechnology.

[22]  K. Blum,et al.  Americas’ opioid/psychostimulant epidemic would benefit from general population early identification of genetic addiction risk especially in children of alcoholics (COAs) , 2019, Journal of Systems and Integrative Neuroscience.

[23]  J. Crowther,et al.  Eating expectancies before bariatric surgery: assessment and associations with weight loss trajectories. , 2019, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[24]  M. Marcus,et al.  Examining emotion-, personality-, and reward-related dispositional tendencies in relation to eating pathology and weight change over seven years in the Longitudinal Assessment of Bariatric Surgery (LABS) study. , 2020, Journal of psychiatric research.

[25]  M. Casagrande,et al.  Emotion and overeating behavior: effects of alexithymia and emotional regulation on overweight and obesity , 2019, Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity.

[26]  N. Ozaki,et al.  A battery of self-screening instruments and self-reported body frame could not detect eating disorders among college students , 2019, BMC Research Notes.

[27]  Jon F. Davis,et al.  Changes in Alcohol Use after Metabolic and Bariatric Surgery: Predictors and Mechanisms , 2019, Current Psychiatry Reports.

[28]  A. Geliebter,et al.  A Longitudinal Preliminary Study of Addiction-Like Responses to Food and Alcohol Consumption Among Individuals Undergoing Weight Loss Surgery , 2019, Obesity Surgery.

[29]  T. Wadden,et al.  Psychopathology, disordered eating, and impulsivity as predictors of outcomes of bariatric surgery. , 2019, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[30]  K. Blum,et al.  Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors , 2018, Front. Psychiatry.

[31]  P. Christiansen,et al.  Psychological issues and alcohol misuse following bariatric surgery , 2018, Nature Reviews Endocrinology.

[32]  A. Gearhardt,et al.  Associations of Food Addiction in a Sample Recruited to Be Nationally Representative of the United States , 2018, European eating disorders review : the journal of the Eating Disorders Association.

[33]  K. Blum,et al.  Molecular role of dopamine in anhedonia linked to reward deficiency syndrome (RDS) and anti- reward systems. , 2018, Frontiers in bioscience.

[34]  M. Ananth,et al.  Suboptimal maternal diets alter mu opioid receptor and dopamine type 1 receptor binding but exert no effect on dopamine transporters in the offspring brain , 2018, International Journal of Developmental Neuroscience.

[35]  K. Blum,et al.  The Food and Drug Addiction Epidemic: Targeting Dopamine Homeostasis. , 2017, Current pharmaceutical design.

[36]  I. König,et al.  What is precision medicine? , 2017, European Respiratory Journal.

[37]  S. Sancak,et al.  Are dopaminergic genotypes risk factors for eating behavior and obesity in adults? , 2017, Neuroscience Letters.

[38]  Gregory M. Fosco,et al.  The Difficulties in Emotion Regulation Scale Short Form (DERS-SF): Validation and Replication in Adolescent and Adult Samples , 2015, Journal of Psychopathology and Behavioral Assessment.

[39]  B. Wolfe,et al.  Treatment of Obesity: Weight Loss and Bariatric Surgery. , 2016, Circulation research.

[40]  U. Hegerl,et al.  Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences, arousal regulation and sleep , 2016, Chronobiology international.

[41]  C. Plewnia,et al.  A Putative Association of COMT Val(108/158)Met with Impulsivity in Binge Eating Disorder. , 2016, European eating disorders review : the journal of the Eating Disorders Association.

[42]  K. Brownell,et al.  Development of the Yale Food Addiction Scale Version 2.0. , 2016, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[43]  E. D. Klonsky,et al.  Are Iranian obese women candidate for bariatric surgery different cognitively, emotionally and behaviorally from their normal weight counterparts? , 2015, Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity.

[44]  H. Landolt,et al.  Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. , 2015, Sleep medicine reviews.

[45]  K. Blum,et al.  Coupling Neurogenetics (GARS™) and a Nutrigenomic Based Dopaminergic Agonist to Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for Carbohydrate Addiction Algorithms , 2015, Journal of reward deficiency syndrome.

[46]  S. Brethauer,et al.  Standardized outcomes reporting in metabolic and bariatric surgery. , 2015, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[47]  K. Blum,et al.  Molecular Genetic Testing in Reward Deficiency Syndrome (RDS): Facts and Fiction , 2015, Journal of reward deficiency syndrome.

[48]  J. Zubieta,et al.  Effects of the Mu Opioid Receptor Polymorphism (OPRM1 A118G) on Pain Regulation, Placebo Effects and Associated Personality Trait Measures , 2015, Neuropsychopharmacology.

[49]  R. Wise,et al.  Obesity and symptoms of depression contribute independently to the poor asthma control of obesity. , 2014, Respiratory medicine.

[50]  K. Blum,et al.  Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS) , 2014, Molecular Neurobiology.

[51]  A. Kübler,et al.  A short version of the Food Cravings Questionnaire—Trait: the FCQ-T-reduced , 2014, Front. Psychol..

[52]  C. Sutton,et al.  Correlations between night eating, sleep quality, and excessive daytime sleepiness in a severely obese UK population. , 2013, Sleep medicine.

[53]  G. Zhai,et al.  Food Addiction: Its Prevalence and Significant Association with Obesity in the General Population , 2013, PloS one.

[54]  William B. Downs,et al.  Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note. , 2013, Journal of addiction research & therapy.

[55]  A. Bardone-Cone,et al.  Eating Expectancies in Relation to Eating Disorder Recovery , 2013, Cognitive Therapy and Research.

[56]  Maite Garolera,et al.  Dopamine Genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and Executive Function: Their Interaction with Obesity , 2012, PloS one.

[57]  B. Israel,et al.  Associations between socioeconomic status and allostatic load: effects of neighborhood poverty and tests of mediating pathways. , 2012, American journal of public health.

[58]  K. Smarr,et al.  Measures of depression and depressive symptoms: Beck Depression Inventory‐II (BDI‐II), Center for Epidemiologic Studies Depression Scale (CES‐D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9) , 2011, Arthritis care & research.

[59]  B. Ham,et al.  DRD2/ANKK1 TaqI A polymorphism affects corticostriatal activity in response to negative affective facial stimuli , 2011, Behavioural Brain Research.

[60]  G. Stefano,et al.  Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders , 2011, Medical science monitor : international medical journal of experimental and clinical research.

[61]  S. Fukuhara,et al.  Association between number of comorbid conditions, depression, and sleep quality using the Pittsburgh Sleep Quality Index: results from a population-based survey. , 2010, Sleep medicine.

[62]  C. Mellado,et al.  Psychological Characteristics of Morbidly Obese Candidates for Bariatric Surgery , 2010, Obesity surgery.

[63]  K. Reynolds,et al.  Global burden of obesity in 2005 and projections to 2030 , 2008, International Journal of Obesity.

[64]  A. Pinchera,et al.  Axis I and II disorders and quality of life in bariatric surgery candidates. , 2008, The Journal of clinical psychiatry.

[65]  K. Lesch,et al.  22q11.2 deletion syndrome as a natural model for COMT haploinsufficiency-related dopaminergic dysfunction in ADHD. , 2007, The international journal of neuropsychopharmacology.

[66]  Lin He,et al.  Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). , 2006, Human molecular genetics.

[67]  J. Endicott,et al.  Quality-of-life impairment in depressive and anxiety disorders. , 2005, The American journal of psychiatry.

[68]  P. Gaszner,et al.  Noninvasive genotyping of dopamine receptor D4 (DRD4) using nanograms of DNA from substance-dependent patients. , 2002, Current medicinal chemistry.

[69]  D. Comings,et al.  Molecular heterosis as the explanation for the controversy about the effect of the DRD2 gene on dopamine D2 receptor density , 1999, Molecular Psychiatry.

[70]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[71]  D. Garner,et al.  The Eating Attitudes Test: psychometric features and clinical correlates , 1982, Psychological Medicine.

[72]  K. Blum,et al.  The Benefits of Genetic Addiction Risk Score (GARS™) Testing in Substance Use Disorder (SUD). , 2018, International journal of genomics and data mining.

[73]  M. van den Berge,et al.  The asthma–obesity relationship: underlying mechanisms and treatment implications , 2018, Current opinion in pulmonary medicine.

[74]  H. Pang,et al.  The GABRB3 Polymorphism and its Association with Schizophrenia , 2017, Journal of Molecular Neuroscience.

[75]  R. McCabe,et al.  The Weight Influenced Self-Esteem Questionnaire (WISE-Q): factor structure and psychometric properties. , 2013, Body image.

[76]  Shannon N Zenk,et al.  Psychosocial stress and social support as mediators of relationships between income, length of residence and depressive symptoms among African American women on Detroit's eastside. , 2006, Social science & medicine.