Ultimate explanations concern the adaptive rationale for organism design

My understanding is that proximate explanations concern adaptive mechanism and that ultimate explanations concern adaptive rationale. Viewed in this light, the two kinds of explanation are quite distinct, but they interact in a complementary way to give a full understanding of biological adaptations. In contrast, Laland et al. (2013)—following a literal reading of Mayr (Science 134:1501–1506, 1961)—have characterized ultimate explanations as concerning any and all mechanisms that have operated over the course of an organism’s evolutionary history. This has unfortunate consequences, such as allowing random drift to form the basis for ultimate explanations, and allowing proximate and ultimate explanations to bleed into each other until their distinction is meaningless. Here, I suggest Laland et al’s explanatory framework of “reciprocal causation” is not conducive to successful biological science, and that they have misunderstood key elements of the theory of Darwinian adaptation.     

Atypical responses to morphine in mice: a possible relationship to anorexia nervosa?

According to our previously proposed auto-addiction hypothesis of chronic anorexia nervosa, patients become addicted to an initial period of dieting through endogenous opioid mediated mechanisms. Morphine causes hyperactivity and anorexia in the mouse, symptoms of anorexia nervosa but responses opposite to those of most species including rats and normal human subjects. This suggests that the atypical opioid systems in the mouse may resemble those of the chronic anorexia nervosa patient in contrast to those of most species including the normal human. Characterization of this atypical opioid system may be useful in understanding the pathophysiology of anorexia nervosa.     

The persistence of gender stereotypes in the face of changing sex roles: Evidence contrary to the sociocultural model

Prevailing explanations for gender differences rest upon the sociocultural model, which treats personality as a consequence of socialization for social roles. Though sex roles and attitudes toward them have changed dramatically in the United States over the past three decades, a review of 18 longitudinal studies of gender stereotypes and self-ratings shows stability in perceptions of sex-typed personality traits. Our study of 3600 students surveyed in six waves from 1974 to 1991 also shows stability and even a slight increase in sex typing. This accumulating evidence is inconsistent with the sociocultural explanation. It is more consistent with the currently emerging sociobiological research that holds gender differences reflect innate differences between the sexes resulting from their different reproductive strategies. We conclude that valid social psychological explanations for gendered personality traits cannot rest upon sociocultural models alone but must include interaction of this unchanging genetic underlay with changeable social structures and processes.     

The Endocrinopathies of Anorexia Nervosa

ObjectiveTo describe the hormonal adaptations and alterations in anorexia nervosa.MethodsWe performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.ResultsAnorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.ConclusionsThe effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously. (Endocr Pract. 2008;14:1055-1063)     

Human pancreatic polypeptide responsiveness to insulin-induced hypoglycemia in anorexia nervosa

Patients with anorexia nervosa occasionally suffer from hypoglycemic comas. We investigated the role of human pancreatic polypeptide (HPP) in insulin-induced hypoglycemia (0.1 U/kg of regular insulin). Ten female patients with anorexia nervosa (20.7 +/- 2.0 years, mean +/- SEM; 34.9 +/- 1.7 kg, mean +/- SEM) and 8 age-matched female controls (20.9 +/- 0.6 years, 51.5 +/- 0.8 kg) were tested. In the patients with anorexia nervosa, testing was performed before and after the restoration of body weight (45.0 +/- 0.8 kg). There was no significant difference in glucose nadir between patients with anorexia nervosa and the control subjects. However, glucose recovery from nadir was delayed in patients with anorexia nervosa. In anorexia nervosa patients, the plasma pancreatic glucagon responses to insulin-induced hypoglycemia did not differ from those of the controls. Results also showed, however, that HPP responses to insulin-induced hypoglycemia were significantly higher in patients with anorexia nervosa than in controls (p less than 0.01). The increased HPP responses were still present after the restoration of body weight in anorexia nervosa patients. A complete body weight recovery or a longer period of time may be required to normalize the HPP response to insulin-induced hypoglycemia in patients with anorexia nervosa, after the restoration of body weight.     

Prolonged suppression of gonadotropin secretion after weight recovery in an anorectic patient with Turner's syndrome: reduced gonadal function in anorexia nervosa is independent in part on nutrition

Two hypotheses have been postulated as to the pathogenesis of hypogonadotropinemia in anorexia nervosa; one is starvation and weight loss and the other is a psychological factor to influence gonadotropin secretion. Our patient suffered from very rare concurrence of Turner's syndrome and anorexia nervosa and a study of this experiment in nature provided important evidences concerning decreased secretion of gonadotropins in the eating disorder. The patient was diagnosed as Turner's syndrome when she was 6 years old. Her gonadotropin levels were elevated to the castrated ranges (LH 61.8 IU/l; FSH 175.8 IU/l) after 8 years of age. She was noticed to be anorectic at the age of 13 years. Serum levels of the pituitary gonadotropins were lowered (LH 2.9 IU/l; FSH 3.0 IU/l) and their responses to luteinizing hormone-releasing hormone were decreased beneath the normal prepubertal limits. After one year of the anorectic period, she recovered the weight though her gonadotropin levels remained in the very low ranges (LH 2.7 IU/l; FSH 2.5 IU/l). The results suggest that hypogonadism in anorexia nervosa is not solely caused by nutritional deficiency but rather by other factors such as psychological abnormalities.     

Integrated circuits and molecular components for stress and feeding: implications for eating disorders

Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress‐induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders.     

Cancer Incidence among Patients with Anorexia Nervosa from Sweden,Denmark and Finland

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.     

Serum leptin levels in patients with anorexia nervosa before and after partial refeeding, relationships to serum lipids and biochemical nutritional parameters.

Leptin is a protein hormone produced by adipocytes that provide information about the body fat content. It was previously reported that serum leptin levels were decreased in patients with anorexia nervosa in comparison with healthy control subjects. The aim of our study was to compare serum leptin levels in patients with anorexia nervosa (n=11, initial mean BMI=15.4 kg/m2) before and after partial recovery with control age-matched subjects (n=11, mean BMI= 20.3 kg/m2) and to study the relationships of leptin levels, serum lipids and biochemical nutritional parameters. We found that serum leptin concentrations in patients with anorexia nervosa were significantly reduced in comparison with control subjects (3.61 vs 9.37 ng.ml(-1), p<0.01). Serum cholesterol, triglycerides, total protein and albumin in patients with anorexia nervosa either before or after partial recovery did not differ from the control group. After partial recovery, a significant increase in serum leptin was observed (4.83 vs 3.61 ng.ml(-1), p<0.05), but the values still remained significantly lower than in the control group (p<0.01) Leptin levels correlated positively with the body mass index in the control group and anorexia nervosa group before recovery. The correlation with BMI in the anorexia nervosa group after refeeding was not significant. No significant correlation was found between leptin concentrations and serum lipids, total protein, albumin and prealbumin, respectively. Serum leptin thus represents a sensitive parameter that reflects the nutritional status in patients with anorexia nervosa suitable for long-term follow up during refeeding therapy.     

Causal structure and hierarchies of models

Economics prefers complete explanations: general over partial equilibrium, microfoundational over aggregate. Similarly, probabilistic accounts of causation frequently prefer greater detail to less as in typical resolutions of Simpson’s paradox. Strategies of causal refinement equally aim to distinguish direct from indirect causes. Yet, there are countervailing practices in economics. Representative-agent models aim to capture economic motivation but not to reduce the level of aggregation. Small structural vector-autoregression and dynamic stochastic general-equilibrium models are practically preferred to larger ones. The distinction between exogenous and endogenous variables suggests partitioning the world into distinct subsystems. The tension in these practices is addressed within a structural account of causation inspired by the work of Herbert Simon’s, which defines cause with reference to complete systems adapted to deal with incomplete systems and piecemeal evidence. The focus is on understanding the constraints that a structural account of causation places on the freedom to model complex or lower-order systems as simpler or higher-order systems and on to what degree piecemeal evidence can be incorporated into a structural account.     

Anorexia nervosa,amenorrhea, and adaptation

Female mammals under stress or in poor physical condition often delay puberty or otherwise suppress reproduction. This capacity is adaptive because it enables females to avoid reproduction when environmental conditions are not conducive to the survival of offspring. Because amenorrhea is one of the key diagnostic criteria for this condition, anorexia nervosa is discussed in an evolutionary context. It is suggested that anorexia nervosa may delay puberty in girls who are disposed to early maturity. Since there is some evidence that early and late maturers have different life histories in modern societies, the reproductive delay associated with anorexia nervosa exhibits features compatible with an evolved reproductive strategy. Insofar as anorexia nervosa is a modern phenomenon, it is unlikely that the syndrome per se is the result of selection. Rather, anorexia nervosa appears to be a reflection of the female ability to alter maturation rates and reproductive function in response to environmental conditions.     

Preadipocyte factor-1 concentrations in patients with anorexia nervosa: the influence of partial realimentation

Preadipocyte factor-1 (Pref-1) is a member of epidermal growth-factor like family of proteins that regulates adipocyte and osteoblast differentiation. Experimental studies suggest that circulating Pref-1 levels may be also involved in the regulation of lipid and glucose metabolism and energy homeostasis. We hypothesized that alterations in Pref-1 levels may contribute to the ethiopathogenesis of anorexia nervosa or its underlying metabolic abnormalities. We measured Pref-1 concentrations and other hormonal, biochemical and anthropometric parameters in eighteen patients with anorexia nervosa and sixteen healthy women and studied the influence of partial realimentation of anorexia nervosa patients on these parameters. The mean duration of realimentation period was 46±2 days. At baseline, anorexia nervosa patients had significantly decreased body mass index, body weight, body fat content, fasting glucose, serum insulin, TSH, free T4, leptin and total protein. Partial realimentation improved these parameters. Baseline serum Pref-1 levels did not significantly differ between anorexia nervosa and control group (0.26±0.02 vs. 0.32±0.05 ng/ml, p=0.295) but partial realimentation significantly increased circulating Pref-1 levels (0.35±0.04 vs. 0.26±0.02 ng/ml, p<0.05). Post-realimentation Pref-1 levels significantly positively correlated with the change of body mass index after realimentation (r=0.49, p<0.05). We conclude that alterations in Pref-1 are not involved in the ethiopathogenesis of anorexia nervosa but its changes after partial realimentation could be involved in the regulation of adipose tissue expansion after realimentation.     

Problematic Exercise in Anorexia Nervosa: Testing Potential Risk Factors against Different Definitions

“Hyperactivity” has a wide prevalence range of 31% to 80% in the anorexia nervosa literature that could be partly due to the plethora of definitions provided by researchers in this field. The purpose of this study was two-fold: 1) To assess the variance across prevalence rates of problematic exercise encountered in patients with anorexia nervosa, in relation to seven different definitions found in the literature. 2) To examine how core eating disorder symptoms and the dimensions of emotional profile are associated with these different definitions and the impact of these definitions on the assessment of patients’ quality of life. Exercise was evaluated in terms of duration, intensity, type and compulsion using a semi-structured questionnaire administered to 180 women suffering from severe anorexia nervosa. Seven different definitions of problematic exercise were identified in the literature: three entailing a single dimension of problematic exercise (duration, compulsion or intensity) and four combining these different dimensions. Emotional profile scores, obsessive-compulsive symptoms, eating disorder symptomatology, worries and concerns about body shape, self-esteem and quality of life were assessed using several established questionnaires. The prevalence of problematic exercise varied considerably from, 5% to 54%, depending on the number of criteria used for its definition. The type and level of eating disorder symptomatology was found to be associated with several definitions of problematic exercise. Surprisingly, a better self-reported quality of life was found among problematic exercisers compared to non-problematic exercisers in three of the definitions. The different definitions of problematic exercise explain the broad prevalence ranges and the conflicting associations generally reported in the literature between problematic exercise and eating disorder-related psychological parameters. There is an urgent need for a valid consensus on the definition of problematic exercise in anorexia nervosa. This will support the development of further research on the etiology and treatment of problematic exercise.     

Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects

Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor ( CNR1 ) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa.     

Hypothalamic pituitary adrenal function in patients with anorexia nervosa.

Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.     

Anorexia nervosa viewed as an extreme weight condition: genetic implications

In anorexia nervosa, psychopathological features and reduced body weight are inseparable, suggesting a prominent role of behavioral factors in achievement and maintenance of extreme underweight. Due to the considerably higher prevalence of this eating disorder in females, anorexia nervosa contributes to the left end of the distribution of the body mass index, especially in the female sex. By reviewing the relevant literature we examined whether genetic research in anorexia nervosa can profit from considering this disorder as an extreme weight condition. For this purpose we compared genetic studies pertaining to both anorexia nervosa and the heritability of the body mass index. Whereas previous genetic studies in anorexia nervosa have mostly concentrated on the assessment of the familial psychopathology, further studies are warranted that additionally attempt to analyze the complex phenotype body weight in relatives of affected probands. Further insight into pathogenetic mechanisms underlying anorexia nervosa might be gained by contrasting the epidemiological, psychopathological and prognostic factors with those in severe obesity. Thus, epidemiological studies suggest that females are more likely to develop both extreme underweight and extreme obesity. A possible explanation for this phenomenon is that the, on average, higher percentage of total body weight composed of fat mass might predispose females towards the development of both extreme weight conditions.     

Resting tachycardia, a warning sign in anorexia nervosa: case report

Background

Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.

Case presentation

A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.

Conclusions

Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.     

Identifying Predictors of Activity Based Anorexia Susceptibility in Diverse Genetic Rodent Populations

Animal studies are very useful in detection of early disease indicators and in unravelling the pathophysiological processes underlying core psychiatric disorder phenotypes. Early indicators are critical for preventive and efficient treatment of progressive psychiatric disorders like anorexia nervosa. Comparable to physical hyperactivity observed in anorexia nervosa patients, in the activity-based anorexia rodent model, mice and rats express paradoxical high voluntary wheel running activity levels when food restricted. Eleven inbred mouse strains and outbred Wistar WU rats were exposed to the activity-based anorexia model in search of identifying susceptibility predictors. Body weight, food intake and wheel running activity levels of each individual mouse and rat were measured. Mouse strains and rats with high wheel running activity levels during food restriction exhibited accelerated body weight loss. Linear mixed models for repeated measures analysis showed that baseline wheel running activity levels preceding the scheduled food restriction phase strongly predicted activity-based anorexia susceptibility (mice: Beta  =  −0.0158 (±0.003 SE), P<0.0001; rats: Beta  =  −0.0242 (±0.004 SE), P<0.0001) compared to other baseline parameters. These results suggest that physical activity levels play an important role in activity-based anorexia susceptibility in different rodent species with genetically diverse background. These findings support previous retrospective studies on physical activity levels in anorexia nervosa patients and indicate that pre-morbid physical activity levels could reflect an early indicator for disease severity.     

Long-Term Physiological Alterations and Recovery in a Mouse Model of Separation Associated with Time-Restricted Feeding: A Tool to Study Anorexia Nervosa Related Consequences

Background

Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.

Aim

To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.

Methods

C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.

Results

Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.

Conclusion

This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.