ADDICTIVE BEHAVIOURS: Obesity Joins the Fold

 

Published: Drugs in Society.  September 2004

When addictive behaviours are mentioned, most people think of alcoholism, drug abuse, smoking and gambling.  Obesity can now be added to this list as commonalities are seen in behaviour and at the cellular level.  This conclusion is supported by advances in molecular biology and the expanding knowledge of the human genome which are providing insights into possible mechanisms behind addictive behaviours.  Ultimately by learning what may increase the propensity of certain individuals to be more susceptible to today’s lifestyle, different treatment programs can be developed and important new preventative measures can be taken.

The problem of addiction is not a simple one that can be wholly explained by genetics, as environmental factors are also part of the underlying cause.  Future research will evaluate if environmental effects propagate the genetic event or if a genetic propensity towards an addiction is initiated by an environmental event.  Research to date has indicated that both scenarios are possible in certain conditions.

Focusing on environmental factors, Cohen and colleagues9 found that in children from grades 5 and 7, those with a positive parental relationship had lower use of alcohol and tobacco.  In those cases, parents spent more time and communicated more frequently with their children.  In 2000, Simantov studied the environmental factors that enhanced addictive behaviours of smoking and alcohol in children.  In this study, 5513 students in grades 7 through 12 were evaluated.  Boys had significantly increased risk of smoking and alcohol use if they had experienced physical or sexual abuse, or a stressful life event.  In girls, the environmental factors that significantly enhanced the risk of smoking and alcohol use included physical or sexual abuse, stressful life event, family violence and depressive symptoms (Table 1).  Similar to the Cohen study, Simantov found that positive parental support had a significant (P<0.05) protective effect against both smoking and alcohol use for both boys and girls.  Extracurricular activities had a protective effect against smoking but not against drinking in both boys and girls (P<0.05)16.  This last finding naturally yields the question “how does celebratory drinking by a winning team seen on television influence our youth?”  Finally, increased activity of youth tended to curb obesity.

Simantov suggested that routine screening of children for abuse, violence, depression and stressful life events may allow for implementation of preventative programs16.  Likewise early screening is suggested for obesity prevention.  The American Academy of Pediatrics has recently released a policy statement on the “Prevention of Pediatric Overweight and Obesity”.  In this, they emphasise the need to monitor eating and activity patterns.  They also emphasise early detection of excessive weight gain related to children’s height2.

Table 1

Adjusted Relative Risk for Smoking and Alcohol Use
in Adolescent Boys and Girls (Simantov)16

                                                         Adjusted relative
risk if smoking
Adjusted relative
risk of alcohol use
BOYS 4.1* 2.4 – 7.0 2.2* 1.3 – 3.7
Abuse 2.4# 1.1 – 5.4 4.8# 2.4 – 9.4
Stressful Life Events        
         
GIRLS        
Abuse 1.8# 1.1 – 2.8 1.8# 1.3 – 2.6
Stressful Life Events 3.1* 1.8 – 5.6 1.9# 1.0 – 3.7
Depressive Symptoms 1.6* 1.0 – 2.4 2.0* 1.4 – 2.7
Family Violence 2.2# 1.6 – 3.2 1.4# 1.1 – 2.0
* (P<0.01)   # (P<0.05)        


At the conclusion of a four year study, Strauss found obese children had significantly lower self esteem versus non-obese children.  Obese children had increased loneliness, nervousness and sadness.  In addition, children with low self esteem were significantly more likely to smoke and/or consume alcohol17.

Similar findings are found in adult studies.  Chalmers found that overweight individuals had low ambition and low self confidence, and were submissive.  Unlike overweight people, problem drinkers were highly driven, expressed inner anxiety, and were unconventional.  Similar to findings in children, both adult groups had higher lifestyle stress scores as compared to non problem controls.  In addition, both groups had personality similarities characterized by impulsiveness, inferiority feelings, dependency, and reduced ability to persevere and consistently plan.  Problem drinkers had a significant increase in smoking (P<0.01) and dietary problems (P<0.05) as compared to controls; however people with weight problems did not have a significant smoking or drinking problem versus control8.  Bulik’s work revealed that women who were both bulimic and alcoholic were more likely to have smoked.  These women also had higher incidence of substance dependence, suicide attempts, anxiety, personality and conduct disorders, and higher scores on novelty seeking, impulsivity and immature defences versus women suffering from bulimia alone6.

Genetics is also attributed to addictive personalities.  Science has been searching many complex regulatory pathways for answers.  For instance, over 430 genes and chromosomal regions have been associated with obesity11.

Certain peptide hormones regulate food intake.  These hormones may also have a role in neurobiological pathways that regulate both obesity and alcoholism.  Cholecystokinin and corticotropin releasing factor (CRF) decreases both food and alcohol consumption18.  CRF is also involved with the behavioural response to stress, which is a risk factor for addictive behaviour.  In rats, a CRF 1 receptor antagonist decreased self administration of cocaine13.  This effect may be species specific as this finding was not evident in rhesus monkies5.  The hormone Leptin decreases food intake, conversely it increases alcohol thirst18.  Leptin also inhibits the synthesis of Neuropeptide Y (NPY).

NPY is a neuropeptide that regulates food and alcohol intake and emotional response.  Mice lacking the ability to make NPY have heightened withdrawal anxiety7.  NPY has 5 receptor types found within different regions of the brain and the body.  The Y1 receptor found in various brain regions is involved in the response to alcohol and food intake18.  Mice lacking NPY receptor Y1 were found to have increased ethanol consumption7.  The Y5 receptor is known to have a role in the regulation of food intake.  The role of NPY with food and alcohol intake is not simple.  NPY receptors are located within different regions of the brain with varying effects on food intake regulation18.  The scope of this paper does not allow this issue to be further elucidated.

Melanocortins (MC) are pituitary peptide hormones that have a role in the neurobiological response to drug abuse.  For example, central MC signaling is altered under stimulant drug and opiate use, while release of MC from the hypothalamus regulates food intake and body weight.  This has been confirmed by the use of MC agonist which decreases food intake and body weight.  As receptors are integral to a hormone’s effect, the lack of the receptor should have a null or opposing effect on the hormone.  The MC4R (receptor), if found lacking, results in obesity and hyperphagic (period of over consumption) in mice.  Genetic research has also revealed that MC hormonal system is also related to the control of alcohol consumption.  Mice purposively bred to consume high levels of ethanol have disorders of the central MC system18.  MTII, a drug that mimics MC effects at the MC3R and MC4R (receptors), was infused into mice that habitually consume large amounts of alcohol.  MTII use resulted in a decrease in both alcohol and food consumption7.

The hormonal cascade for both MC and NPY utilizes the enzyme Protein Kinase A.  Mice lacking subunit II beta of Protein Kinase A have significantly higher ethanol consumption than normal mice.  This increased consumption was specific to alcohol as no change in consumption of a sweet or bitter solution was evident.  These mice also had higher levels of baseline anxiety and were less sensitive to the sedative effects of alcohol7.

The relationship between addictions and the two neuropeptides Dopamine and endogenous Opioid peptides have been extensively studied.  These neuropeptides are neurotransmitters that are involved in the reward pathway.  Dopamine release gives a sensation of thrill, while opioid gives a feeling of euphoria or relaxation.  Natural rewards such as food, sex and other enjoyable activities stimulate these neurotransmitters.  In addition, unnatural rewards like drug abuse, excessive gambling, alcohol abuse, compulsive sex, risk seeking adventures and sports also influence the reward pathway.  Blum’s reward deficiency hypothesis proposes that certain individuals’ genetic makeup is possibly defective in the reward pathway function.  This may lead these individuals to seek abusive or emotionally elevating behaviours so as to stimulate their reward pathway3, 4.

In 10 out of 11 controlled studies using opioid antagonists, results showed a decrease in short term food intake20.  Most of these studies indicated that the decrease in food intake was not due to drug induced nausea.  In addition, Opioid receptor agonists effect the treatment of alcohol abuse and binge eating20, supporting the genetic similarities of different addictive behaviours.  Studies also indicate that acute alcohol consumption increases the gene expression of the opioids endorphin and enkephalin, whilst chronic alcohol exposure decreases opioid gene expression.  Finally, in rats selectively bred for a high rate of alcohol consumption, an increase in the opioid beta endorphin gene expression is seen.  These facts all support the premise that opioid mediates excessive alcohol intake12.

In obese individuals, research indicates that the D2 receptor of dopamine is significantly (P<0.0075) lower in the striatum region of the brain as compared to controls.  The individual’s BMI was found to correlate negatively with D2 receptors (r=0.84)19.  In addition, a significant association with the D2 receptor A1 allele and severe alcoholism has been found.  However other studies dispute these findings.  Multiple regression analysis has indicated that the A1 allele was significantly (P=0.0003) associated with multiple substance abuse14.

Genetics is thought to contribute approximately 50% to variance in behaviour and in certain conditions up to 70 – 95%15.  The remaining variance is associated with environmental factors which by their nature are hard to quantify.  Behavioural disorders are considered polygenic in nature, with each gene contributing only moderately to the disorder.  Continuing research is required to further clarify the role and interaction of genetics and the environment in addictive behaviours.  This report gives a brief glimpse into some of these factors and also brings to evidence the epidemic of obesity can now be included within the profile of addictive behaviours.

References

1. Allison, D.B., and Heshka, S.  1993.  Toward an empirically derived typology of obese persons: derivation in a nonclinical sample.  Int J. Eating Disorders 13(1):93-108.

2. American Academy of Pediatrics.  2003.  Prevention of Pediatric Overweight and Obesity.  Pediatrics 112(2).

3. Blum, K., Cull, J.G., Braverman, E.R. and Comings, D.E.  1996b.  Reward Deficiency Syndrome.  Am. Scientist, 84:132-145.

4. Blum, K., Sheridan, P.L., Wood, R.C., Braverman, E.R., Chon, J.H., Cull, J.G., and Comings, D.E.  1996.  The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.  J. R. Soc. Med. 89:396-400.

5. Broadbear, J.H., Winger, G. and Woods, J.H.  1999.  Cocaine reinforced responding in rhesus monkey; pharmacological attenuation of the hypothalamic-pituitary-adrenal axis response.  J. Pharmacol Exp Ther 290:1347–1355.

6. Bulik, C.M. and Joyce, O.F.  1997.  Lifetime co morbidity of alcohol dependence in women with bulimia.  Addictive Behaviours 22(4):437-446.

7. Centreline:  2003.  Alcoholism and Obesity: Overlapping Brain Pathways?  Bowles Centre for Alcohol studies.  School of Medicine, University of North Carolina at Chapel Hill.  14(1).

8. Chalmers, D.K., Bowyer, C.A. and Olenick, N.L.  1990.  Problem Drinking and Obesity:  A comparison in personality patterns and lifestyle.  Int J of Addictions 25(7):803-817.

9. Cohen, D.A., Richardson, J. and LaBree, L.  1994.  Parenting behaviours and the onset of smoking and alcohol use: a longitudinal study.  94(3):368-375.

10. Comings, D.E. and Blum, K.  2000.  Reward deficiency syndrome: genetics aspects of behavioural disorders.  Progress in Brain Research Vol.126 chapter 20, 325-341.

11. Elia, M.  2004.  Obesity: what does it represent?  Asia Pacific J Clin Nut.  13 (suppl S1 – S180).  S34.

12. Froehlich, J.C.  Opioid peptides.   www.niaaa.nih.gov/publications/arh21-2/132.pdf

13. Goeders, N.E., Peltier, R.L. and Guerm, G.F.  1998.  Ketoconazole reduces low dose cocaine self-administration in rats.  Drug Alcohol Depend 53:67-77.

14. Nobel, K.P.  2003.  D2 Dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes.  AM J. Med Genetics (Neuropsychiatric Genetics) 116B:103-125.

15. Plomin, R.  1990.  The role of inheritance in behaviour.  1990.  Science 248:183-186.

16. Simantov, E., Schoen, C. and Klein, J.D.  2000.  Health Compromising Behaviours: Why do adolescents smoke or drink?  Archives of Pediatrics and Adolescent Medicine 154(10):1025-1033.

17. Strauss, R. S.  2000.  Childhood Obesity and self esteem.  Pediatrics 105(10).

18. Thiele, T. E., Navarro, M., Spata, D. R., Free, J. R., Knapp, D. J. and Cubero, I.  2003.  Alcoholism and obesity: overlapping neuropeptide pathways?  Neuropeptides 37:321-337.

19. Wang, G.J., Volkow, N. D., Logan, J., Pappas, N. R., Wong, C. T., Zhu, W., Netusil, N. and Fowler, J. S.  Brain dopamine and obesity.  2001.  Lancet, 357(9253):354-357.

20. Yeomans, M. R. and Gray, R. W.  2002.  Opioid peptides and the control of human ingestive behaviour.  Neuroscience and Behavioural Reviews 26:713-728.

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