Browse through our Medical Journals...
Anorexia Nervosa: A Suggestion for an Altruistic Paradigm from an Evolutionary Perspective
William Sheehan, Rice Memorial Hospital, 301 Becker Avenue, S.W., Willmar, Minnesota, 56201, USA.
Steven Thurber, Woodland Centers, 1125 S.E. Sixth Street, Willmar, Minnesota, 56201, USA.
Data are reviewed from human and infra-human studies on dynamic, sometimes paradoxical interactions involving dietary intake, serum cholesterol and serotonin levels, and behaviors such as risk-taking, aggression, foraging, and food-related complacency. In theory, anorexia nervosa is posited as a genetic variant yielding an altruistic phenotype and an adaptive advantage under exiguous food conditions.
Keywords: Cholesterol-serotonin relationships, anorexia nervosa, altruistic phenotype
The relationship between naturally occurring low cholesterol concentrations (<160 to 180 mg/dl) and excessive mortality due to deaths from suicide is one of the most robustly determined results in psychiatry (Muldoon et. al., 1990; Lindberg et. al., 1992). At the same time, a number of studies have shown that low CSF 5-H1AA concentration was associated with frequent and more violent suicide attempts. Collectively, these studies have revealed that both low cholesterol and low CSF 5-H1AA carry increased risks of violence and suicide.
Some studies have suggested that serum cholesterol may be a marker for central serotonergic activity (Roy et. al., 1989; Virkkunen et. al., 1989). It has also been argued that dietary fats or cholesterol may directly influence brain lipids and the fluidity of the cell membrane, with secondary effects on neurotransmitters or their membrane-bound receptors; serotonin may be especially sensitive to these effects, because its binding can be increased or decreased in vitro by the addition or removal of cholesterol from brain synaptic membranes (Heron, et. al., 1980). In addition to its effects on mood and behavior (especially aggression), it is believed that the central serotonin system plays a major role in the control of food intake and body weight gain (Wurtman & Wurtman, 1998; Halford et. al., 1998; Simansky et. al., 1993).
Diet, Cholesterol-Serotonin and Food-Related Behaviors
Whatever the precise physiological underpinnings of the putative cholesterol-serotonin relationship, the connection itself appears to be well established. Moreover, a plausible evolutionary explanation for this relationship has been offered (Kaplan et. al. 1997). Based on primate studies, Kaplan et. al. found that when monkeys (of the same weight and receiving the same caloric intake) were fed a low-cholesterol diet, they were significantly more aggressive and had lower levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-H1AA), in their CSF than did monkeys on a high cholesterol level. They argue that, rather than being an accidental relationship, natural selection may have shaped the behavioral and physiological responses induced by a reduction in total cholesterol to provide an adaptive advantage. “Specifically,” they write, “during periods of caloric abundance individuals would be physiologically prompted, perhaps via high central serotonergic activity, to exhibit behavioral complacency…. In contrast, scarcity, particularly in calories derived from animal sources, would reduce plasma cholesterol and, perhaps via low central serotonergic activity, trigger impulsive, risk-taking behavior such as hunting or competitive foraging.”
In this regard, it is well-known that modern-day hunters in traditional cultures almost universally exhibit a preference for fatty species, and further target them at the times of the year when they contain the most fat. This is documented by a number of studies of modern hunter/nomads especially of those inhabiting sub-Arctic conditions, where, during late winter and early spring, when stored food supplies dwindle or are used up entirely, lean meat may become the principal source of energy. But a diet containing even an abundance of lean meat but little fat leads to a condition that has been described as “rabbit starvation,” in which the individual grows weak and thin and eventually will die if unable to procure fat. A well-known proverb has it that man cannot live by bread alone. If a Copper Eskimo cited by Speth and Spegelman can be believed, it is also true that “People cannot live on lean meat alone, but if they have enough fat they can survive indefinitely”(Speth & Spegelman, 1983).
Since the body’s energy needs must be fulfilled first before protein needs are met, under conditions of marginal or inadequate caloric intake, the amino acids of ingested protein are degraded, and the nonnitrogenous residues are converted to glucose or fat or are oxidized directly to meet the body’s energy needs. This utilization of amino acids for energy makes protein unavailable to the body for its normal uses, and thus body protein is not replenished. Under conditions of severe caloric shortage, skeletal muscle protein will also be broken down to provide glucose for organs – including brain – that do not use fat for energy. Under such conditions, the protein-sparing effect of carbohydrate is much greater than that of fat.
Though dietary fats are not known to have a major effect on the production of any brain neurotransmitter, dietary carbohydrates do. A dietary carbohydrate’s ability to enhance the uptake of circulating tryptophan (the precursor amino acid of serotonin) is dependent on its glycemic index – its ability to promote insulin secretion (Wurtman & Wurtman, 1995). Insulin itself has little or no effect on plasma tryptophan levels but it does markedly lower the plasma levels of “large neutral amino acids” which compete with tryptophan for passage across the blood-brain barrier. This decrease allows more tryptophan to enter the brain and explains why dietary carbohydrates, which lack tryptophan, increase brain levels of this amino acid much more than protein-rich foods, which do contain it.
In conditions of decreased food intake, the cholesterol-serotonin hypothesis implies that as cholesterol levels decrease serotonin levels will also drop, and aggressive, foraging type behavior increases. However, these trends are reversed again in conditions of starvation. In starvation, healthy, nonobese subjects show a paradoxical increase of total serum cholesterol levels (Savendahl et. al., 1999). From an evolutionary perspective, it would appear that aggressive foraging behavior, which requires high energy consumption, is a strategy that is abandoned at the point where the maintenance of high energy strategies is no longer sustainable in favor of a more behaviorally complacent conservation strategy associated with elevated brain serotonin levels.
Anorexia Nervosa and Cholesterol-Serotonin
Anorexia nervosa is a condition in which patients maintain themselves in semi-starvation states, and tend (despite the extremely low levels of exogenous cholesterol intake in anorexia nervosa) to maintain normal or elevated total serum cholesterol levels. Among anorectic patients, those with initial high cholesterol levels have the worst nutritional status and the high cholesterol levels are not related to de novo synthesis (Feillet et. al., 2000) (This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for the apparently paradoxical evolution of cholesterol synthesis during renutrition.)
In contrast to individuals with impulsive and non-premeditated aggressive behaviors who show low levels of cerebral spinal fluid (CSF) 5-H1AA, anorectic patients have been found to have elevated levels of CSF 5-H1AA. Behaviors noted after recovery from anorexia nervosa, such as obsessions with symmetry, exactness, perfectionist, and negative affect, tend to be opposite in character to behaviors displayed by people with low 5-H1AA levels. Indeed, it has been proposed that the abnormally high levels of serotonin activity in the brains of anorectics is the aversive variant that leads them to use starvation as a mode of “self-medication.” Since starvation prevents tryptophan from getting into the brain, by eating less anorectics reduce the serotonin activity in their brains. Thus they remain “calm” even on the verge of dying of malnutrition (Kaye et. al., 2003).
Anorexia Nervosa, Altruistic Phenotype, and the Adaptive Advantage
Several lines of evidence are converging to suggest that anorexia nervosa may represent a robust phenotypic variant rather than being a condition primarily shaped by social or learning processes. In that case, evolutionary concepts may help to illuminate the basis of a condition that seems so paradoxical in the modern environment – patients starving in the midst of abundance.
Though it is an often lethal condition in the modern world, anorexia may have conferred significant adaptive advantages to small groups of humans under naturalistic conditions who would have faced intermittent periods of extreme scarcity. Recall that in humans, the large brain absorbs 20 to 25% of calories at rest. The need for vital nutrients, as significant as it is for adults, is even more extreme for infants. The newborn’s brain consumes 60% of calories at rest, and the brain continues to be a voracious consumer of energy as it doubles in size in the first year.
There seem to have been several evolutionary adaptations that allowed humans to derive the energy needed to develop their large brains. One seems to have been a shift from a heavily vegetarian diet to a more digestible energy-rich diet including meat; this led to a reduction in gut size (it is much smaller in humans than in, say, chimpanzees), thus freeing up energy for a larger brain. That change in diet may have benefited mothers most by allowing them to take in extra energy themselves, so that the fetus could pull as much energy as needed from her without killing her. During the critical years between gestation and age 4 (when the brain reaches 85% of its full adult size), the mother provides most of the energy in gestation, then in lactation, which continues for three to four years in hunter-gatherers. This huge transfer of energy from the mother to the infant marks, in fact, an investment of the whole group. Under such conditions, sociobiologists often invoke mechanisms involving altruism.
We suggest that anorexics may have a hardwired predisposition to an altruistic phenotype, in sociobiological terms, exhibited under extreme conditions of scarcity. There would be obvious advantages to the group of the anorectic’s seemingly paradoxical behavior – maintaining constantly elevated cholesterol and serotonin levels at baseline, without the fluctuations involving increased aggression and feeding behavior that characteristically occur in conditions of scarcity prior to the attainment of actual starvation states. While remaining reproductively unavailable themselves (they are thin and sickly-appearing, disinterested in sex, and ammenorheic), they nevertheless maintain a high rate of activity serviceable to the group. (It is notable that they usually enjoy doing for others such necessary things as cooking and cleaning, while diverting very few caloric resources to their own maintenance.) As with other celibate or nonreproducing individuals, their genes would be selected for indirectly by enabling the progeny of their relatives who do reproduce to have a better chance of survival and to propagate their genes.
The gene variant underlying the anorectic phenotype seems to involve the 5-HT2A receptor (Audenaert et. al., 2003; Frank et. al., 2002; Frank et. al, 2001). Audenaert et. al. used single photo emission computed tomography (SPECT) brain imaging to show a reduction of 5-HT2A receptor binding index in fifteen individuals with anorexia nervosa. The reduced binding was most commonly seen in the left frontal cortex, the left and right parietal cortex, and the left and right occipital cortex. The abnormal serotonin activity in the left frontal cortex may explain the depressive symptoms many anorectics exhibit, while that in the parietal lobes may be linked to delusions about body type. A positron emission tomography (PET) study by Frank et. al. (2002) of recovered anorectics, which found similar evidence of disturbed 5-HT neuronal function, suggested that indeed the reduction of 5-HT2A receptor binding is a preexisting trait in individuals with anorexia nervosa rather than being a result of the disorder. This does not prove but is certainly consistent with an evolutionary and sociobiological interpretation of this perplexing disorder.
Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and cholesterol levels in schizophrenic patients with and without suicide attempts. Acta Psychiatrca Scandinavica, 2003 Sep;108(3):208-14.
Feillet F, Feillet-Coudray C, Bard JM, Parra HJ, Favre E, Kabuth B, Fruchart JC, Vidailhet M. Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa. International Journal of Clinical Chemistry and Applied Molecular Biology, 2000 Apr;294(1-2):45-56.
Halford JCG, Wanninayake SCD, Blundell JE: Behavioral satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacology Biochemistry and Behavior, 1998, 61, 159-168.
Heron DS, Shinitzky M, Hershkowitz M, Samuel D: Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes. Proceedings of the National Academy of Sciences ,1980, 77:7463-7467.
Kaplan J, Klein K, Manuck S: Cholesterol meets Darwin: public health and evolutionary implications of the cholesterol-serotonin hypothesis. Evolutionary Anthropology (1997) 6:28-37.
Kaye W, Barbarich N, Putnam K, Gendall K, Fernstrom J, Fernstrom M, McConaha C, Kishore A. Anxiolytic effects of acute tryptophan depletion in anorexia nervosa. International Journal of Eating Disorders (2003) 33:257-267.
Lindberg G, Rastam L, Gullberg B, Eklund G. Low serum cholesterol concentration and short term mortality from injuries in men and women. British Medical Journal 1992;305:277-279.
Muldoon M, Manuck S, Matthews K. Lowering cholesterol concentrations and mortality: a review of primary prevention trials. British Medical Journal 1990; 301:309-314.
Roy A, DeJong J, Linnoila M: Cerebrospinal fluid monoamine metabolites and suicidal behavior in depressed patients: a five-year follow-up study. Archives of General Psychiatry,1989, 46:609-612.
Savendahl L, Underwood LE. Fasting increases serum total cholesterol, LDL cholesterol and apolipoprotein B in healthy, nonobese humans. Journal of Nutrition, 1999, Nov;129(11):2005-2008.
Simansky K, Eberle-Wang K, Geary N: Serotonergic mechanisms and ingestion: pharmacological facts and physiological promises. Appetite, 1993, 21, 220.
Speth JD and Spegelman KA: Energy Source, Protein Metabolism, and Hunter-gatherer subsistence strategies. Journal of Anthropological Archaeology, vol. 2, no. 1 (1983), pp. 1-31.
Virkkunen M, DeJong J, Bartko J, Linnoila M: Psychobiological concomitants of history of suicide attempts among violent offenders and impulsive fire setters. Archives of General Psychiatry, 1989, 46:604-606.
Wurtman RJ, Wurtman JJ: Serotonergic mechanisms and obesity. J Nutritional Biochemistry, 1998, 9, 511-515.
Wurtman RJ, Wurtman JJ. Brain Serotonin, Carbohydrate-Craving, Obesity and Depression. Obesity Research, 1995; 3(Suppl 4):477S-480S.
First Published December 2006