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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Behav. Neurosci.</journal-id>
<journal-title>Frontiers in Behavioral Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Behav. Neurosci.</abbrev-journal-title>
<issn pub-type="epub">1662-5153</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnbeh.2023.1243572</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Behavioral Neuroscience</subject>
<subj-group>
<subject>Hypothesis and Theory</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Similarities and differences regarding acute anorexia nervosa and semi-starvation: does behavioral thermoregulation play a central role?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><name><surname>Smith</surname> <given-names>Lucille Lakier</given-names></name><xref rid="c001" ref-type="corresp"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/560470/overview"/>
</contrib>
</contrib-group>
<aff><institution>Human Performance Laboratory, Department of Kinesiology, School of Health Sciences, East Carolina University</institution>, <addr-line>Greenville, NC</addr-line>, <country>United States</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001">
<p>Edited by: Fabrizio Sanna, University of Cagliari, Italy</p>
</fn>
<fn fn-type="edited-by" id="fn0002">
<p>Reviewed by: Barbara Scolnick, Boston University, United States; Emilio Gutierrez, Universidad de Santiago de Compostela, Spain</p>
</fn>
<corresp id="c001">&#x002A;Correspondence: Lucille Lakier Smith, <email>lclakier@gmail.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>10</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>17</volume>
<elocation-id>1243572</elocation-id>
<history>
<date date-type="received">
<day>20</day>
<month>06</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>09</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2023 Smith.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Smith</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Objective</title>
<p>To clarify the association between acute anorexia nervosa (AN) and semi-starvation (SS) by focusing on similarities and differences in physiology, mood, and behavior.</p>
</sec>
<sec id="sec2">
<title>Method</title>
<p>A comparison of published literature between these two groups.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>Both groups show similar hormonal and metabolic changes in response to caloric restriction and extreme weight loss (~25%). Associated changes result in a reduced body temperature (T<sub>core-low</sub>). Maintenance of body temperature within a specific range is crucial to survival. However, both groups cannot activate autonomic strategies to maintain their T<sub>core-low</sub>, such as increasing metabolic rate, constricting skin blood vessels, or shivering. Furthermore, T<sub>core-low</sub> increases the individuals&#x2019; &#x201C;coldness sensations&#x201D; throughout the body, hence the frequent reports from ANs and SSs of &#x201C;feeling cold.&#x201D; To eliminate these uncomfortable &#x201C;coldness sensations&#x201D; and, importantly, to maintain T<sub>core-low</sub>, ANs, and SSs <italic>&#x201C;select&#x201D; different thermoregulatory behavioral strategies</italic>. It is proposed that the <italic>primary differences</italic> between AN and SS, based on genetics, now manifest due to the &#x201C;selection&#x201D; of different thermo-regulatory behaviors. AN patients (ANs) &#x201C;select&#x201D; hyperactive behavior (HyAc), which increases internal metabolic heat and thus assists with maintaining T<sub>core-low</sub>; in harmony with hyperactive behavior is a lively mood. Also related to this elevated arousal pattern, ANs experience disrupted sleep. In contrast, SS individuals &#x201C;select&#x201D; a passive thermo-behavioral strategy, &#x201C;shallow torpor,&#x201D; which includes reduced activity, resulting in energy conservation. In addition, this inactivity aids in the retention of generated metabolic heat. Corresponding to this lethargic behavior, SS individuals display a listless mood and increased sleep.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>Initial <italic>similarities</italic> between the two are attributable to physiological changes related to extreme weight loss. <italic>Differences</italic> are most likely attributable to genetically programmed &#x201C;selection&#x201D; of alternate thermoregulatory strategies, primarily to maintain T<sub>core-low</sub>. However, if acute AN is prolonged and evolves into a chronic condition, AN will more closely align with starvation and more precisely reflect SS symptomology.</p>
</sec>
</abstract>
<kwd-group>
<kwd>hyperactivity (HyAc)</kwd>
<kwd>shallow torpor</kwd>
<kwd>low body temperature (Tcore-low)</kwd>
<kwd>cold sensations</kwd>
<kwd>foraging</kwd>
<kwd>evolution</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="185"/>
<page-count count="14"/>
<word-count count="13649"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Pathological Conditions</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5"><label>1.</label>
<title>Introduction</title>
<p>Anorexia Nervosa (AN) is a condition wherein an individual, usually 1&#x2013;4% of females (<xref ref-type="bibr" rid="ref180">Watson et al., 2019</xref>), self-imposes severe food restrictions and loses up to 25% of body weight. Over the decades, AN has been regarded principally as a <italic>psychogenic condition</italic>, but one with severe physiological consequences (<xref ref-type="bibr" rid="ref136">Pirke, 1987</xref>; <xref ref-type="bibr" rid="ref43">Dalle Grave et al., 2008</xref>; <xref ref-type="bibr" rid="ref171">Treasure et al., 2015</xref>; <xref ref-type="bibr" rid="ref20">Calugi et al., 2018</xref>; <xref ref-type="bibr" rid="ref180">Watson et al., 2019</xref>). A related condition is semi-starvation (SS); this, too, manifests due to a striking reduction in food consumption and dramatic weight loss (<xref ref-type="bibr" rid="ref101">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref60">Fichter et al., 1986</xref>). However, SS is typically in response to uncontrolled circumstances, such as famine, and is usually not willfully self-imposed. Furthermore, unlike AN, SS is regarded predominantly as a <italic>physiological condition with associated psychological and behavioral changes</italic> (<xref ref-type="bibr" rid="ref101">Keys et al., 1950</xref>).</p>
<p>Many researchers have questioned whether AN represents a unique condition or whether AN reflects the sequelae associated with semi-starvation (<xref ref-type="bibr" rid="ref118">Mecklenburg et al., 1974</xref>; <xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref20">Calugi et al., 2018</xref>; <xref ref-type="bibr" rid="ref135">Phillipou et al., 2018</xref>; <xref ref-type="bibr" rid="ref63">Frank et al., 2019</xref>; <xref ref-type="bibr" rid="ref31">Casper et al., 2020a</xref>). <xref ref-type="bibr" rid="ref27">Casper and Davis (1977)</xref> suggested that &#x201C;the effects of starvation are more intimately involved in the symptoms of anorexia nervosa than has heretofore been described.&#x201D; According to Garner (<xref ref-type="bibr" rid="ref68">Garner, 1997</xref>), &#x201C;One of the most important advancements in the understanding of eating disorders is the recognition that severe and prolonged dietary restriction can lead to serious physical and psychological complications. Many of the symptoms once thought to be primary features of anorexia nervosa are actually symptoms of starvation.&#x201D;</p>
<p>To better understand and thus improve the treatment of AN, <xref ref-type="bibr" rid="ref135">Phillipou et al., (2018)</xref> have suggested that it is crucial to determine which signs and symptoms are explicitly related to AN and which represent the condition of semi-starvation. The present paper will attempt to unravel these conditions by assessing the similarities and differences between AN and SS (<xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>) and determining whether <italic>acute</italic> AN represents a unique condition with distinctive psychological and physiological parameters, whether it reflects semi-starvation and its sequelae, or is a combination of these two conditions (<xref ref-type="bibr" rid="ref173">Tyszkiewicz-Nwafor et al., 2020</xref>).</p>
<p>The investigation of AN focuses primarily on published literature on <italic>acute-restrictive AN</italic> (<xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref21">Carrera et al., 2012</xref>), implying that the individual is close to the time of onset of significant weight loss (<xref ref-type="bibr" rid="ref25">Casper, 2018</xref>). However, it is difficult to verify when exactly the AN condition manifested since, typically, many months or even years pass between the earliest changes in eating, the dramatic weight loss, and the formal diagnosis (<xref ref-type="bibr" rid="ref98">Kay, 1953</xref>; <xref ref-type="bibr" rid="ref154">Scolnick and Mostofsky, 2014</xref>; <xref ref-type="bibr" rid="ref65">Frostad and Bentz, 2022</xref>).</p>
<p>Regarding SSs, the emphasis will be on the classic Minnesota Study of Semi-Starvation (MinnSS) conducted in 1943, during World War II (WWII). Keys and colleagues (<xref ref-type="bibr" rid="ref101">Keys et al., 1950</xref>) selected 36 average-weight, healthy, intelligent, psychologically well-adjusted, young white males who could get along reasonably well under trying conditions. The study consisted of:<list list-type="bullet">
<list-item>
<p>a 3-month control period during which subjects maintained average body weight,</p>
</list-item>
<list-item>
<p>a 6-month semi-starvation period (~50% of previous caloric intake), and</p>
</list-item>
<list-item>
<p>a 3-month weight recovery period.</p>
</list-item>
</list></p>
<p>This paper will focus on the 6-month semi-starvation period, during which subjects lost ~25% of body weight, similar to losses seen in AN. A team of medical doctors monitored these subjects to understand behavioral, physiological, psychological, and social changes. In addition to the dramatic reduction in food intake, subjects were <italic>required</italic> to participate in the same scheduled activities <italic>for the entire year</italic>; the purpose was to simulate wartime conditions.</p>
<p>Many notable differences exist between the MinnSS study and AN (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>). However, this remains the most comprehensive &#x201C;control group&#x201D; available. It provides impressive information and could not be conducted nowadays for ethical reasons.</p>
</sec>
<sec id="sec6"><label>2.</label>
<title>The initiation of the starvation response in ANs and SSs: leptin</title>
<p>Leptin is a hormone synthesized and released from fat tissue with its main action occurring in the CNS/hypothalamus (<xref ref-type="bibr" rid="ref95">Jequier, 2002</xref>; <xref ref-type="bibr" rid="ref127">Muller et al., 2009</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>). Blood levels are usually proportional to the amount of body fat. In this manner, it acts as a messenger molecule to inform the brain of the status of <italic>fat energy reserves</italic> in the body (<xref ref-type="bibr" rid="ref95">Jequier, 2002</xref>; <xref ref-type="bibr" rid="ref127">Muller et al., 2009</xref>).</p>
<p>At the onset of caloric restriction and weight loss, blood leptin levels <italic>decrease</italic> rapidly and dramatically (<xref ref-type="bibr" rid="ref157">Seoane-Collazo et al., 2020</xref>); these decreased levels play a major role in adapting the organism to starvation (<xref ref-type="bibr" rid="ref1">Ahima et al., 1996</xref>; <xref ref-type="bibr" rid="ref86">Hebebrand et al., 2023</xref>). Reduced leptin levels signal the hypothalamus of imminent &#x201C;danger&#x201D; related to reduced food availability (<xref ref-type="bibr" rid="ref1">Ahima et al., 1996</xref>; <xref ref-type="bibr" rid="ref127">Muller et al., 2009</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>). The hypothalamus-pituitary-target organ axes, in addition to other changes (<xref ref-type="bibr" rid="ref89">Hebebrand et al., 2019</xref>), now increase or decrease the synthesis and secretion of many energy-intensive hormones (<xref ref-type="bibr" rid="ref124">Misra and Klibanski, 2014</xref>; <xref ref-type="bibr" rid="ref151">Schorr and Miller, 2017</xref>):<list list-type="bullet">
<list-item>
<p>It decreases the synthesis of reproductive hormones, thus suppressing reproductive-related activities (<xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref124">Misra and Klibanski, 2014</xref>).</p>
</list-item>
<list-item>
<p>It decreases the release of thyroid-stimulating hormone and the activity of the sympathetic nervous system, which, among other functions, reduces metabolic rate (<xref ref-type="bibr" rid="ref60">Fichter et al., 1986</xref>; <xref ref-type="bibr" rid="ref124">Misra and Klibanski, 2014</xref>; <xref ref-type="bibr" rid="ref151">Schorr and Miller, 2017</xref>).</p>
</list-item>
<list-item>
<p>It reduces the synthesis of insulin-like growth factor, which then inhibits growth and development (<xref ref-type="bibr" rid="ref60">Fichter et al., 1986</xref>; <xref ref-type="bibr" rid="ref151">Schorr and Miller, 2017</xref>) in the face of food scarcity and thus assists with extending survival (<xref ref-type="bibr" rid="ref51">Devlin, 2011</xref>).</p>
</list-item>
</list></p>
<p>These reduced energy needs for growth and reproduction diminish the organisms&#x2019; need to draw on the primary energy source, <italic>stored fat reserves.</italic></p>
<p>Regarding ANs, leptin levels are consistently lower, by as much as ~75% compared to HC (<xref ref-type="bibr" rid="ref54">ECKERT et al., 1998</xref>; <xref ref-type="bibr" rid="ref83">HAAS et al., 2005</xref>; <xref ref-type="bibr" rid="ref52">Dostalova et al., 2007</xref>; <xref ref-type="bibr" rid="ref97">Karageorgiou et al., 2020</xref>). Also, depending on the degree and severity of the caloric deficit, leptin levels may be undetectable (<xref ref-type="bibr" rid="ref85">Hebebrand et al., 1997</xref>).</p>
<p><xref ref-type="bibr" rid="ref88">Hebebrand et al. (2022)</xref> suggest that off-label treatment with recombinant human leptin (metreleptin) may alleviate many of the emotional, cognitive, and associated behavioral symptoms reflective of AN. They also propose that this treatment could possibly break the vicious cycle that sustains this condition (<xref ref-type="bibr" rid="ref86">Hebebrand et al., 2023</xref>). <xref ref-type="bibr" rid="ref123">Milos et al. (2020)</xref> treated three <italic>severely</italic> anorexic patients; this short-term treatment proved partially successful.</p>
<p>However, the use of this treatment remains controversial. <xref ref-type="bibr" rid="ref26">Casper (2022)</xref> acknowledges that short-term high doses of metreleptin mitigated feelings of depression, inner tension, intrusive thoughts of food, and the urge to be physically active. Yet when treatment was terminated, this had little influence on the patients&#x2019; personal commitment to remain at a low weight. <xref ref-type="bibr" rid="ref62">Fraga et al. (2020)</xref>, using rats, argued that ambient temperature was more effective in reducing the amount of running and weight loss than metreleptin. Placebo-controlled clinical trials are needed to confirm or refute the usefulness of metreleptin in treating AN (<xref ref-type="bibr" rid="ref89">Hebebrand et al., 2019</xref>).</p>
<p>Regarding SS: there is a <italic>similar significant decrease in blood leptin levels</italic> in obese subjects, and normal-weight males and females <italic>due to famine, fasting, or willful caloric restriction.</italic> This decrease varies from 44 to 83% (<xref ref-type="bibr" rid="ref14">Boden et al., 1996</xref>; <xref ref-type="bibr" rid="ref36">Considine et al., 1996</xref>; <xref ref-type="bibr" rid="ref33">Chan et al., 2003</xref>; <xref ref-type="bibr" rid="ref126">Muller M.J. et al., 2015</xref>).</p>
<p>In summary, weight loss in <italic>ANs and SSs rapidly decreases blood leptin levels</italic>, altering the hormonal profile and preparing the body to withstand starvation. Specifically, there is a decrease in hormones that typically promote increased energy utilization, such as growth and reproduction. It has also been proposed that administering a leptin analog may induce psychological and behavioral changes to assist in recovery; however, this awaits clarification.</p>
</sec>
<sec id="sec7"><label>3.</label>
<title>The maintenance of body temperature in HCs, ANs, and SSs</title>
<sec id="sec8"><label>3.1.</label>
<title>Healthy controls</title>
<p>Most Healthy controls (HCs) maintain a body core temperature (T<sub>core</sub>) of 37&#x00B0;C regardless of race, gender, and geographic location. Sustaining this level within a narrow range is critical to survival as it optimizes bodily functions and prevents cellular damage (<xref ref-type="bibr" rid="ref142">Rising et al., 1992</xref>). Sustaining T<sub>core</sub> involves the use of internal metabolic heat, which is a by-product of all energy-producing processes (<xref ref-type="bibr" rid="ref111">Landsberg, 2012</xref>). This heat is then retained in the body by constricting surface/skin blood vessels and insulating body fat. If sufficient metabolic heat is not produced and retained, &#x201C;emergency&#x201D; strategies may become activated. These include shivering, activation of specialized heat-producing brown adipose tissue, and piloerection (goosebumps). However, these emergency strategies are energy demanding. Thus, HCs will initially preferably engage in a more straightforward strategy, <italic>thermoregulatory behavior</italic>. Such behaviors include wearing a sweater or turning up a thermostat, to name a few. <italic>In endotherms, thermo-behavior is the most effective and frequently utilized means of maintaining T<sub>core</sub></italic> (<xref ref-type="bibr" rid="ref143">Romanovsky, 2007</xref>; <xref ref-type="bibr" rid="ref61">Flouris, 2011</xref>)<italic>. Thermo&#x2013;behavior is our first line of thermal defense to prevent changes in core temperature</italic> (<xref ref-type="bibr" rid="ref149">Schlader, 2014</xref>).</p>
</sec>
<sec id="sec9"><label>3.2.</label>
<title>An and T<sub>core-low</sub></title>
<p>Unlike HCs, numerous studies have demonstrated that ANs have a significantly lower T<sub>core</sub>. These low values range from 35.4&#x00B0;C (<xref ref-type="bibr" rid="ref118">Mecklenburg et al., 1974</xref>; <xref ref-type="bibr" rid="ref142">Rising et al., 1992</xref>) to 36.6&#x00B0;C (<xref ref-type="bibr" rid="ref45">Davies et al., 1979</xref>); this will be referred to as T<sub>core-low</sub> instead of hypothermia since hypothermia implies a T<sub>core</sub> below 35&#x00B0;C. It is also suggested that this T<sub>core-low</sub> represents a <italic>new set point</italic> for the ANs; it does not threaten survival but is crucial for them to maintain this level to prevent further reductions, which may become life-threatening (<xref ref-type="bibr" rid="ref160">Smith, 2021</xref>).</p>
<p>The primary cause of a reduced T<sub>core-low</sub> is a <italic>significantly lower metabolic rate, which is a key provider of body heat and thus helps maintain internal body temperature.</italic> The basal metabolic rate for ANs is reduced by approximately 21% (<xref ref-type="bibr" rid="ref138">Polito et al., 2000</xref>; <xref ref-type="bibr" rid="ref133">Onur et al., 2005</xref>) to 32% (<xref ref-type="bibr" rid="ref16">Bossu et al., 2007</xref>) compared to HCs; thus, they cannot produce sufficient heat to maintain the normal 37&#x00B0;C.</p>
<p>Furthermore, <xref ref-type="bibr" rid="ref131">Oishi et al. (2013)</xref> using mice, have demonstrated that fasting and the induction of ketosis, in the presence of hypothermia, may further impact body temperature. Since ANs are in metabolic ketosis (<xref ref-type="bibr" rid="ref117">McCue, 2010</xref>) in the presence of T<sub>core-low</sub>, it is possible that this further exacerbates a reduction in body temperature.</p>
<p>In addition to the reduced ability to produce body heat, ANs cannot effectively <italic>retain</italic> this heat due to their inability to constrict surface blood vessels and due to having less insulating fat (<xref ref-type="bibr" rid="ref34">Chudecka and Lubkowska, 2016</xref>). Furthermore, they cannot activate secondary backup thermoregulatory responses such as shivering, piloerection, or activation of brown fat (<xref ref-type="bibr" rid="ref178">Vigersky et al., 1977</xref>; <xref ref-type="bibr" rid="ref129">Nishita et al., 1986</xref>; <xref ref-type="bibr" rid="ref17">Bredella et al., 2012</xref>).</p>
<p>However, like most humans, <italic>they can initiate the crucial tactic of thermoregulatory behavior</italic>&#x2009;; many different thermo-behavioral strategies are available. It has been proposed that the <italic>primary thermo-behavioral strategy employed by ANs</italic> is the generation of internal metabolic heat through <italic>muscle movement</italic> (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>). This behavior is most likely a result of genetic programming; AN is now considered a psycho-metabolic condition, with as much as 76% of this condition being genetically determined (<xref ref-type="bibr" rid="ref18">Bulik et al., 2019</xref>).</p>
<p>In support of the hypothesis that ANs generate heat through movement, is extensive evidence demonstrating that most ANs engage in excessive amounts of physical activity (<xref ref-type="bibr" rid="ref9">Beumont et al., 1994</xref>; <xref ref-type="bibr" rid="ref48">Davis et al., 1994</xref>, <xref ref-type="bibr" rid="ref46">1997</xref>; <xref ref-type="bibr" rid="ref2">Alberti et al., 2013</xref>; <xref ref-type="bibr" rid="ref56">El Ghoch et al., 2013</xref>; <xref ref-type="bibr" rid="ref76">Gummer et al., 2015</xref>; <xref ref-type="bibr" rid="ref25">Casper, 2018</xref>). The generated metabolic heat (<xref ref-type="bibr" rid="ref175">Vargas et al., 2019</xref>) assists with maintaining or increasing T<sub>core-low</sub>; it also aids the perfusion of warm blood to the extremities, especially the hands (<xref ref-type="bibr" rid="ref179">Vigersky et al., 1976</xref>), a primary area for the detection of cold sensations (<xref ref-type="bibr" rid="ref160">Smith, 2021</xref>).</p>
<p>Although many have claimed that the main reason for excessive movement in AN is to enhance weight loss (<xref ref-type="bibr" rid="ref104">Kiezebrink et al., 2009</xref>), several rodent studies have suggested otherwise. They have demonstrated that in a rat model referred to as activity-based anorexia, excessive running, when paired with food restriction and weight loss, represents a drive to generate body heat to assist with maintaining T<sub>core-low</sub> (<xref ref-type="bibr" rid="ref91">Hillebrand et al., 2005</xref>; <xref ref-type="bibr" rid="ref77">Gutierrez et al., 2006</xref>, <xref ref-type="bibr" rid="ref80">2008</xref>). It is proposed that the ANs&#x2019; excessive activity represents a similar function (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>). This thermo-behavioral strategy will be referred to as <italic>hyperactivity</italic> (HyAc); a more detailed discussion will follow (Section 5.1).</p>
</sec>
<sec id="sec10"><label>3.3.</label>
<title>SSs and T<sub>core-low</sub></title>
<p>Like ANs, SSs have a reduced T<sub>core</sub> and metabolic rate (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref169">Taylor and Keys, 1950</xref>; <xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>); furthermore, they too are in a state of metabolic ketosis (<xref ref-type="bibr" rid="ref117">McCue, 2010</xref>); if hypothermic, this too could lower body temperature (<xref ref-type="bibr" rid="ref131">Oishi et al., 2013</xref>). It is assumed that they cannot generate the backup thermal responses of shivering, piloerection, and activation of brown adipose tissue, although this has not been investigated. But, like ANs and other humans, they can <italic>&#x201C;select&#x201D; specific thermoregulatory behaviors</italic>. It is proposed that their central strategy is the converse of ANs. SSs &#x201C;select&#x201D; a more passive strategy that focuses on <italic>retaining</italic> whatever internal heat has been generated and <italic>passively gaining</italic> external environmental heat. This is verified by <xref ref-type="bibr" rid="ref102">Keys et al. (1950)</xref> focusing on the behavior of their semi-starved subjects and using anecdotal observations from famine and prisoner-of-war camps. This behavioral pattern will be called shallow torpor (See Section 6.1).</p>
<p>In summary, it is hypothesized that the <italic>primary difference</italic> between ANs and SSs is their &#x201C;selection&#x201D; of <italic>different</italic> thermo-behavioral strategies (<xref ref-type="bibr" rid="ref3">Barakat et al., 2023</xref>) most likely genetically determined. So, while ANs engage in HyAc to generate internal metabolic heat, SSs &#x201C;select&#x201D; a more inactive strategy that focuses on <italic>retaining</italic> whatever internal heat has been generated and <italic>passively gaining</italic> external environmental heat.</p>
</sec>
</sec>
<sec id="sec11"><label>4.</label>
<title>&#x201C;Feeling cold&#x201D; <italic>initiates</italic> engagement in thermoregulatory behavior</title>
<sec id="sec12"><label>4.1.</label>
<title>ANs and SSs &#x201C;feel cold&#x201D;</title>
<p>&#x201C;Feeling cold&#x201D; has been a prominent complaint for ANs (<xref ref-type="bibr" rid="ref167">Swenne and Engstrom, 2005</xref>; <xref ref-type="bibr" rid="ref20">Calugi et al., 2018</xref>) and SSs (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>). <italic>Surprisingly, this does not appear to be consciously related to changes in the body T<sub>core-low</sub></italic> (<xref ref-type="bibr" rid="ref94">Jacquot et al., 2014</xref>; <xref ref-type="bibr" rid="ref176">Vargas et al., 2018</xref>). Instead, feelings of body coldness are derived from sensations in the peripheral skin (<xref ref-type="bibr" rid="ref144">Romanovsky, 2014</xref>). These &#x201C;unpleasant&#x201D; perceptions are then transmitted to the brain/hypothalamus, motivating engagement in thermo-behavior to lessen this discomfort (<xref ref-type="bibr" rid="ref61">Flouris, 2011</xref>; <xref ref-type="bibr" rid="ref94">Jacquot et al., 2014</xref>; <xref ref-type="bibr" rid="ref176">Vargas et al., 2018</xref>).</p>
</sec>
<sec id="sec13"><label>4.2.</label>
<title>ANs and cold sensations</title>
<p>Many researchers have reported that cold intolerance is a common complaint among ANs and is usually unrelated to ambient temperature (<xref ref-type="bibr" rid="ref110">Lampert and Lau, 1976</xref>; <xref ref-type="bibr" rid="ref114">Luck and Wakeling, 1980</xref>; <xref ref-type="bibr" rid="ref152">Schwabe et al., 1981</xref>; <xref ref-type="bibr" rid="ref159">Silverman, 1983</xref>; <xref ref-type="bibr" rid="ref39">Crisp, 1984a</xref>; <xref ref-type="bibr" rid="ref11">Bhanji and Mattingly, 1991</xref>; <xref ref-type="bibr" rid="ref108">Kurklinsky et al., 2011</xref>; <xref ref-type="bibr" rid="ref21">Carrera et al., 2012</xref>; <xref ref-type="bibr" rid="ref44">Das and Maiti, 2013</xref>). In addition to these overall feelings of coldness, ANs complain especially of having cold hands (<xref ref-type="bibr" rid="ref129">Nishita et al., 1986</xref>). &#x201C;Fingers, toes, hands, and feet were usually blue and cold&#x201D; (<xref ref-type="bibr" rid="ref110">Lampert and Lau, 1976</xref>).</p>
<p>Recently it has been demonstrated that the hand skin temperature of ANs is the <italic>only</italic> skin surface area significantly lower (~2&#x00B0;C) than that of HCs. Surprisingly, all other surface areas of the body are the same or warmer than that of HCs, implying that metabolic <italic>heat cannot be effectively retained</italic> (<xref ref-type="bibr" rid="ref34">Chudecka and Lubkowska, 2016</xref>). Thus, the hands are most likely the primary source for generating overall body thermal sensations (<xref ref-type="bibr" rid="ref176">Vargas et al., 2018</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>), with the skin temperature of the wrist being the best predictor of thermal sensations and of <italic>motivation</italic> to initiate thermoregulatory behavior (<xref ref-type="bibr" rid="ref94">Jacquot et al., 2014</xref>).</p>
</sec>
<sec id="sec14"><label>4.3.</label>
<title>SSs and cold sensations</title>
<p>Like ANs, SSs suffer from extreme sensations of coldness. <xref ref-type="bibr" rid="ref103">Keys et al. (1950)</xref> reported that cold temperatures were poorly tolerated during the starvation phase of the MinSS, despite the room&#x2019;s adequate heating. &#x201C;Many subjects slept under heavy blankets and wore extra clothing during the day in hot summer weather.&#x201D; In addition, subjects always requested that their food, coffee, and tea be served unusually hot. To feel warm, &#x201C;all the men had learned to have long, hot showers &#x201C;(<xref ref-type="bibr" rid="ref64">Franklin et al., 1948</xref>), and when possible, would bask in the sun (<xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>), and gather about the steam radiators (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>).</p>
<p>In another food-restricted study, the Carnegie study (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>), the researchers commented on the subjects&#x2019; extreme sensitivity to cold. They noted that these men&#x2019;s hand temperature, like ANs, was approximately 2&#x00B0;C lower than that of HCs.</p>
<p>So, both ANs and SSs experience profound sensations of coldness, especially in the extremities, which act as &#x201C;bait&#x201D; to induce thermo-behavior and thus reduce this discomfort. Simultaneously, and most importantly, this thermo-behavior assists with maintaining T<sub>core-low</sub>. It will now be proposed that the <italic>&#x201C;selection&#x201D; of thermo-behavior differentiates ANs from SSs.</italic> However, before discussing these <italic>differences,</italic> it should be noted that both groups display <italic>additional behaviors that are similar</italic>, especially those related to hunger and eating (<xref rid="tab1" ref-type="table">Table 1</xref>).</p>
<table-wrap position="float" id="tab1"><label>Table 1</label>
<caption>
<p>Additional similarities related to hunger, eating behavior, self-mutilation, and libido.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">
<bold>Similarities</bold>
</th>
<th align="left" valign="top">
<bold>Anorexic patients</bold>
</th>
<th align="left" valign="top">
<bold>Semi-starved individuals</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">
<bold>Hunger sensations (Related to Leptin and Ghrelin Levels)</bold>
</td>
<td align="left" valign="top"><bold>Experience unrelenting hunger sensations</bold> (<xref ref-type="bibr" rid="ref66">Garfinkel, 1974</xref>; <xref ref-type="bibr" rid="ref164">Speakman and Mitchell, 2011</xref> <xref ref-type="bibr" rid="ref151">Schorr and Miller, 2017</xref>)</td>
<td align="left" valign="top"><bold>Experience unrelenting hunger sensations</bold> (<xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>; <xref ref-type="bibr" rid="ref132">Olson et al., 2020</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Leptin: the &#x201C;satiety&#x201D; hormone</bold>
</td>
<td><bold>A dramatic decrease in blood leptin with weight loss</bold> (<xref ref-type="bibr" rid="ref54">Eckert et al., 1998</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>)</td>
<td><bold>A dramatic decrease in blood leptin with weight loss</bold> (<xref ref-type="bibr" rid="ref127">Muller T.D. et al., 2009</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Ghrelin: the &#x201C;hunger&#x201D; hormone</bold>
</td>
<td align="left" valign="top"><bold>Significantly elevated</bold> (<xref ref-type="bibr" rid="ref161">Sodersten et al., 2016a</xref>)</td>
<td align="left" valign="top"><bold>Significantly elevated</bold> (<xref ref-type="bibr" rid="ref126">Muller T.D. et al., 2015</xref>; <xref ref-type="bibr" rid="ref130">Nuttall et al., 2016</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Eating Behavior</bold>
</td>
<td align="left" valign="top"><bold>Slow eating, cutting food into small pieces, toying with food, etc.</bold> (<xref ref-type="bibr" rid="ref10">Beumont et al., 1997</xref>; <xref ref-type="bibr" rid="ref68">Garner, 1997</xref>)</td>
<td align="left" valign="top"><bold>Slow eating, cutting food into small pieces, toying with food, etc.</bold> (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref68">Garner, 1997</xref>; <xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Obsessional interest in food</bold>
</td>
<td align="left" valign="top"><bold>Immersed in food-related behaviors: thinking, reading, talking</bold> (<xref ref-type="bibr" rid="ref179">Vigersky et al., 1976</xref>; <xref ref-type="bibr" rid="ref69">Garner et al., 1982</xref>; <xref ref-type="bibr" rid="ref10">Beumont et al., 1997</xref>)</td>
<td align="left" valign="top"><bold>Immersed in food-related behaviors: thinking, reading, talking</bold> (<xref ref-type="bibr" rid="ref10">Beumont et al., 1997</xref>; <xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Make strange concoctions, possibly a form of pica</bold>
</td>
<td align="left" valign="top"><bold>Possibly related to nutritional deficiencies</bold> (<xref ref-type="bibr" rid="ref29">Casper et al., 1980</xref>; <xref ref-type="bibr" rid="ref10">Beumont et al., 1997</xref>; <xref ref-type="bibr" rid="ref117">McCue, 2010</xref>; <xref ref-type="bibr" rid="ref122">Miao et al., 2015</xref>)</td>
<td align="left" valign="top"><bold>Possibly related to nutritional deficiencies</bold> (<xref ref-type="bibr" rid="ref64">Franklin et al., 1948</xref>; <xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>; <xref ref-type="bibr" rid="ref117">McCue, 2010</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Hoarding/stealing food</bold>
</td>
<td align="left" valign="top"><bold>Possibly a survival strategy</bold> (<xref ref-type="bibr" rid="ref41">Crisp et al., 1980</xref>; <xref ref-type="bibr" rid="ref182">Yao et al., 2017</xref>)</td>
<td align="left" valign="top"><bold>Possibly a survival strategy</bold> (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Body image</bold>
</td>
<td align="left" valign="top"><bold>Distorted body image</bold> (<xref ref-type="bibr" rid="ref35">Ciwoniuk et al., 2022</xref>)</td>
<td align="left" valign="top"><bold>Distorted body image</bold> (<xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Self-injurious/mutilation behavior</bold>
</td>
<td align="left" valign="top"><bold>Some engage in self-mutilation</bold> (<xref ref-type="bibr" rid="ref40">Crisp, 1984b</xref> <xref ref-type="bibr" rid="ref183">Yaryura-Tobias et al., 1995</xref>)</td>
<td align="left" valign="top"><bold>Some engage in self-mutilation</bold> (<xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">
<bold>Libido</bold>
</td>
<td align="left" valign="top"><bold>A dramatic decrease in sexual-related interests/activities</bold> (<xref ref-type="bibr" rid="ref37">Crisp, 1967</xref>; <xref ref-type="bibr" rid="ref141">Price et al., 2020</xref>)</td>
<td align="left" valign="top"><bold>A dramatic decrease in sexual-related interests/activities</bold> (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="sec15"><label>5.</label>
<title>ANs and &#x201C;selection&#x201D; of thermo-behavior which coordinates with mood and sleep</title>
<sec id="sec16"><label>5.1.</label>
<title>ANs and hyperactivity</title>
<p>It is well established that as many as 78% (<xref ref-type="bibr" rid="ref48">Davis et al., 1994</xref>) of ANs engage in <italic>excessive</italic> amounts of physical activity during the acute phase of the disorder (<xref ref-type="bibr" rid="ref9">Beumont et al., 1994</xref>; <xref ref-type="bibr" rid="ref48">Davis et al., 1994</xref>, <xref ref-type="bibr" rid="ref46">1997</xref>; <xref ref-type="bibr" rid="ref2">Alberti et al., 2013</xref>; <xref ref-type="bibr" rid="ref56">El Ghoch et al., 2013</xref>; <xref ref-type="bibr" rid="ref76">Gummer et al., 2015</xref>; <xref ref-type="bibr" rid="ref25">Casper, 2018</xref>). This surprising display of stamina continues even after significant weight loss (<xref ref-type="bibr" rid="ref179">Vigersky et al., 1976</xref>; <xref ref-type="bibr" rid="ref31">Casper et al., 2020</xref>). Many researchers have claimed that the primary reason for this HyAc is due to the relentless pursuit of weight loss (<xref ref-type="bibr" rid="ref104">Kiezebrink et al., 2009</xref>); however, this has been disputed (<xref ref-type="bibr" rid="ref78">Gutierrez and Birmingham, 2020</xref>).</p>
<p>To illustrate this excessive engagement in physical activity, <xref ref-type="bibr" rid="ref48">Davis et al. (1994)</xref> administered questionnaires to 45 ANs and reported the following: 78% described their physical activity during the <italic>acute phase</italic> of their disorder as &#x201C;excessive;&#x201D; 93% of the patients described their exercise as &#x201C;out of control&#x201D; and &#x201C;compulsive;&#x201D; 75% reported that during the period of maximum weight loss, physical activity increased as their weight and food intake decreased. There were frequent comments from the ANs, such as &#x201C;All I was doing was exercising&#x201D; and &#x201C;The lower my weight got, the more energy I had.&#x201D; Furthermore, this increased urge to move continued despite increased levels of physical fatigue (<xref ref-type="bibr" rid="ref31">Casper et al., 2020</xref>).</p>
<p>Many terms have been used to describe this excessive activity (<xref ref-type="bibr" rid="ref47">Davis et al., 1999</xref>; <xref ref-type="bibr" rid="ref121">Meyer et al., 2008</xref>, <xref ref-type="bibr" rid="ref120">2011</xref>). However, the terminology used here, hyperactivity (HyAc), will reflect the <italic>total daily activity</italic> of ANs (<xref ref-type="bibr" rid="ref160">Smith, 2021</xref>) and includes three overlapping categories:<list list-type="bullet">
<list-item>
<p>Excessive Exercise (ExEx), involves &#x201C;formal&#x201D; exercise such as walking/jogging, weight training, volleyball, yoga, etc.</p>
</list-item>
<list-item>
<p>Non-Exercise Activity Thermogenesis (NEAT) includes <italic>all</italic> movements during awake periods (<xref ref-type="bibr" rid="ref112">Levine, 2007</xref>), such as performing daily chores, attending school/work, etc.</p>
</list-item>
<list-item>
<p>Spontaneous Physical Activity (SPA) involves fidgety, restless behavior (<xref ref-type="bibr" rid="ref5">Belak et al., 2017</xref>).</p>
</list-item>
</list></p>
<p>ANs find many ways of producing daily movement <italic>in excess</italic>. The execution of all these movements produces body heat to varying degrees. The generated metabolic heat now assists with T<sub>core-low</sub> (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>).</p>
<p>In addition to HyAc to maintain T<sub>core-low</sub>, ANs <italic>use other means to maintain/increase body temperature</italic>. This may include wearing extra clothing, sitting close to heaters, and drinking warm fluids (<xref ref-type="bibr" rid="ref166">Strumia, 2013</xref>).</p>
<p>Furthermore, HyAc may produce added benefits (<xref ref-type="bibr" rid="ref67">Garland et al., 2011</xref>; <xref ref-type="bibr" rid="ref71">Giel et al., 2013</xref>). These include reduced appetite, decreased anxiety, prevention or reduction of depressive-like behavior, and increased feelings of well-being (<xref ref-type="bibr" rid="ref148">Scheurink et al., 2010</xref>; <xref ref-type="bibr" rid="ref90">Hicks et al., 2019</xref>).</p>
<p>Although it has been stressed that HyAc is primarily a strategy to maintain T<sub>core-low</sub> (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>) many view HyAc in ANs as an <italic>ancient behavioral pattern aimed at encouraging foraging or migration during times of food shortages</italic> (<xref ref-type="bibr" rid="ref30">Casper et al., 1991</xref>; <xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>; <xref ref-type="bibr" rid="ref154">Scolnick and Mostofsky, 2014</xref>). However, engaging in HyAc for foraging and maintaining T<sub>core-low</sub> are <italic>not</italic> mutually exclusive. If the ancient AN felt compelled to move, this would have maintained T<sub>core-low</sub> and enhanced her chances of finding food.</p>
<p>Using a well-established rodent model, the activity-based anorexia model (ABA), it has been demonstrated that providing heat to the &#x201C;anorexic&#x201D; ABA-rodent reduces activity and weight loss (<xref ref-type="bibr" rid="ref146">Routtenberg and Kuznesof, 1967</xref>; <xref ref-type="bibr" rid="ref57">Epling and Pierce, 1996</xref>; <xref ref-type="bibr" rid="ref91">Hillebrand et al., 2005</xref>; <xref ref-type="bibr" rid="ref77">Gutierrez et al., 2006</xref>; <xref ref-type="bibr" rid="ref177">Vazquez et al., 2006</xref>; <xref ref-type="bibr" rid="ref145">Roura et al., 2020</xref>).</p>
<p>Applying translational reasoning, it has been hypothesized that providing heat to ANs, <italic>may reduce the compulsion to move</italic> and thus assist with weight gain (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>; <xref ref-type="bibr" rid="ref160">Smith, 2021</xref>). However, the effectiveness of heat application in human ANs, remains equivocal.</p>
<p><xref ref-type="bibr" rid="ref75">Gull (1997)</xref> was the first to report that warming the spine, wearing warm clothing, and being kept in a warm bed for a time would promote recovery in ANs. In 2001 Gutierrez and Vasquez (<xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez, 2001</xref>) successfully treated three <italic>hyperactive</italic> ANs on an outpatient basis using three different heat treatments. All three patients showed an immediate reduction in overactivity. When assessed 30&#x2009;months later, BMI for all three had improved dramatically, and activity patterns remained reduced. However, these were case reports with no control group. Additionally, compliance could not be assessed because the study was conducted on an outpatient basis.</p>
<p>In a Randomized Control Trial (RCT), <xref ref-type="bibr" rid="ref7">Bergh et al. (2002)</xref> assigned 13 ANs to a Treatment group. The treatment consisted of using a computerized device (a Mandometer) during lunchtime to monitor food intake, rate of eating, and satiety. In addition, they supplied external heat by having subjects rest in a warm room (up to 40&#x00B0;C) for 1&#x2009;h after lunch and confined subjects to a wheelchair or allowed them to walk slowly in the clinic. The Control group (n&#x2009;=&#x2009;16) received no treatment. The outcome was significantly different between the treated and control groups. Fourteen patients in the treatment group went into remission after a median of 14.4&#x2009;months, and 75% remained in remission at 12&#x2009;months. They concluded that their treatment had a beneficial effect but also suggested that it was unclear what contribution each modality made (Mandometer, heat, reduced movement?). In a subsequent study, <xref ref-type="bibr" rid="ref184">Zandian et al. (2017)</xref> reported that applying heat (room at 32&#x00B0;C) for 30&#x2009;min after lunch significantly reduced anxiety.</p>
<p><xref ref-type="bibr" rid="ref12">Birmingham et al. (2004)</xref> tested the hypothesis that heat would increase the rate of weight gain. They randomized 21 subjects to a Heat or Control Group and applied heat for ~4&#x2009;h daily for 21&#x2009;days using a heated vest. Subjects reported enjoying the heating experience but did not show an improvement in eating behavior. Surprisingly, exercise behavior was not monitored, so whether heat impacted physical activity is unknown. In addition, the average BMI of these subjects was 17.5, suggesting a borderline condition. Also, these subjects would be considered chronic ANs since AN had lasted for approximately 13.6&#x2009;years. These and other design factors may have confounded their results.</p>
<p><xref ref-type="bibr" rid="ref32">Cerrato et al. (2012)</xref> hypothesized that <italic>ambient/seasonal t</italic>emperature would impact the amount of <italic>hyperactivity</italic> in acute AN; they monitored daily movement using an accelerometer for 3 consecutive days. They assigned 15 ANs to a Warm Group between Spring and Summer (April &#x2013; October), during which the mean ambient temperature was 16&#x00B0;C. Activity levels of the Cold group were monitored between Autumn and Winter (October&#x2013;April) with a mean ambient temperature of 4.5&#x00B0;C. The results demonstrated that the Cold Group was significantly more physically active than the Warm Group (<italic>p</italic>&#x2009;=&#x2009;0.003). They concluded that keeping patients warm may be a beneficial treatment option for reducing hyperactivity, which is typically refractory to treatment.</p>
<p>The following research design is proposed to address the question of whether applying heat 24/7 for an extended period (possibly 3&#x2009;weeks&#x2013;3&#x2009;months) would assist with rehabilitation by <italic>increasing the ANs T</italic><sub><italic>core-low</italic></sub>, <italic>reducing</italic> aspects of <italic>HyAc</italic>, and resulting in a <italic>spontaneous increase in food intake</italic>.</p>
<p>On admittance to a clinic, ANs would be randomly assigned to an experimental (EXP) or control (C) group. EXP ANs would engage in bed rest for most of the day/night, using an electric blanket and keeping the blanket&#x2019;s temperature as high as is comfortable; ambient room temperature should also be elevated. In addition, they should be allowed to sit (with the heated blanket) and move around the clinic to a limited extent (partly to assess spontaneous movement and reduce musculoskeletal deterioration that occurs with bed rest). After baseline measurements are assessed on day 1, the following dependent variables should be <italic>continuously</italic> monitored in the EXP:<list list-type="bullet">
<list-item>
<p>T<sub>core</sub> using ingested capsules (<xref ref-type="bibr" rid="ref15">Bongers et al., 2018</xref>).</p>
</list-item>
<list-item>
<p>Wrist skin temperature using a surface thermistor (<xref ref-type="bibr" rid="ref94">Jacquot et al., 2014</xref>).</p>
</list-item>
<list-item>
<p>A multi-sensor monitor (Sensewear Mini Armband) to monitor sleep patterns (<xref ref-type="bibr" rid="ref116">Martinez-Sanchez et al., 2020</xref>; <xref ref-type="bibr" rid="ref86">Hebebrand et al., 2023</xref>).</p>
</list-item>
<list-item>
<p>A pedometer to monitor the amount of spontaneous walking.</p>
</list-item>
<list-item>
<p>A heart rate monitor to ensure that ANs do not surreptitiously engage in moderate/high-intensity exercise.</p>
</list-item>
<list-item>
<p>A modified shoe-based accelerometer to monitor foot and hand fidgeting (<xref ref-type="bibr" rid="ref5">Belak et al., 2017</xref>).</p>
</list-item>
<list-item>
<p>Three meals a day and snacks should be provided, and amounts eaten be recorded for spontaneous ingestion.</p>
</list-item>
<list-item>
<p>An indwelling catheter to monitor daily changes in circulating hormones such as leptin and ghrelin, as well as reproductive and metabolic hormones.</p>
</list-item>
<list-item>
<p>Assessment of body weight.</p>
</list-item>
<list-item>
<p>Use of appropriate psychological questionnaires.</p>
</list-item>
</list></p>
<p>The C would be exposed to a treatment regime <italic>typical for that particular clinic</italic>. In addition, daily, T<sub>core-low</sub>, wrist skin temperature, total amount of movement, and food intake should be recorded.</p>
<p>The statistical analyses could involve a one-way ANOVA of the EXP group as well as a correlational analysis and multiple regression using all dependent variables. A 2-way ANOVA could be used to compare the results of the EXP and C groups.</p>
<p>In summary, it is proposed that the primary purpose of HyAc is to maintain T<sub>core-low</sub>. In addition, other positive benefits, such as reduced appetite and increased anxiolysis, also accrue; this assists in reinforcing HyAc. However, when viewed in terms of ancient times, HyAc also represents foraging/migration behavior, increasing the ANs&#x2019; chance of locating food (<xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>). Regarding the effectiveness of heat as a treatment for ANs, definitive research is needed to determine whether heat application 24/7 in human ANs, initially reported by <xref ref-type="bibr" rid="ref81">Gutierrez and Vazquez (2001)</xref> would produce a similar outcome as is seen in the ABA model (<xref ref-type="bibr" rid="ref82">Gutierrez et al., 2002</xref>; <xref ref-type="bibr" rid="ref12">Birmingham et al., 2004</xref>; <xref ref-type="bibr" rid="ref91">Hillebrand et al., 2005</xref>).</p>
</sec>
<sec id="sec17"><label>5.2.</label>
<title>Mood/attitude and psychological comorbidities during the acute phase of AN</title>
<p>The <italic>buoyant mood and feelings of well-being</italic> of the ANs correspond to her hypermobility, although, such behavior appears disproportionate to such severe weight loss (<xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref23">Casper, 2006</xref>, <xref ref-type="bibr" rid="ref24">2016</xref>, <xref ref-type="bibr" rid="ref25">2018</xref>). ANs seem to lack awareness of fatigue and weakness in the acute phase and insist on <italic>not</italic> being tired (<xref ref-type="bibr" rid="ref37">Crisp, 1967</xref>; <xref ref-type="bibr" rid="ref23">Casper, 2006</xref>; <xref ref-type="bibr" rid="ref86">Hebebrand et al., 2023</xref>). Most maintain they never felt better (<xref ref-type="bibr" rid="ref22">Casper, 1998</xref>). Until weight loss is profound, they deny feeling ill or fatigued (<xref ref-type="bibr" rid="ref179">Vigersky et al., 1976</xref>) and are contented with their physical state (<xref ref-type="bibr" rid="ref28">Casper and Heller, 1991</xref>). They also lack concern regarding the seriousness of the health risks of extreme weight loss (<xref ref-type="bibr" rid="ref28">Casper and Heller, 1991</xref>; <xref ref-type="bibr" rid="ref75">Gull, 1997</xref>). They continue to function by attending school and work, and many become enthusiastically involved in numerous activities (<xref ref-type="bibr" rid="ref25">Casper, 2018</xref>).</p>
<p>Many researchers/clinicians have ascribed psychological comorbidities, such as depression, as a precipitating factor in AN (<xref ref-type="bibr" rid="ref13">Blinder et al., 2006</xref>). However, Crisp (<xref ref-type="bibr" rid="ref40">Crisp, 1984b</xref>) suggests that the degree of depression in AN is about the same as that found in other populations and is well below that in depressive illness. This is supported by <xref ref-type="bibr" rid="ref50">Delvenne et al. (1992)</xref> who concluded that there is no association between AN and depression.</p>
<p>Others have concluded that there is no neurosis specific to anorexia nervosa (<xref ref-type="bibr" rid="ref99">Kay and Leigh, 1954</xref>) and <italic>no consistent precipitating</italic> psychological pathology before the onset of AN (<xref ref-type="bibr" rid="ref8">Bergh et al., 2013</xref>). Furthermore, most ANs initially seek medical attention because of drastic weight loss and not for psychological support.</p>
<p>If any psychological symptoms manifest, these are <italic>preceded</italic> by weight loss (<xref ref-type="bibr" rid="ref153">Scolnick, 2018</xref>). <xref ref-type="bibr" rid="ref162">Sodersten et al. (2016b</xref>, <xref ref-type="bibr" rid="ref163">2019)</xref> suggest that any <italic>manifestation of psychological factors is related to the experience of semi-starvation</italic> since this also occurs in healthy individuals exposed to extreme food restrictions. &#x201C;It is possible that there are some ANs who have co-morbid depression, anxiety, obsessions, compulsions, or delusions. However, none of the 100&#x2009;s of ANs we have treated to recovery have had such co-morbid disorders &#x2013; their mental symptoms resolve as their eating behavior normalizes&#x201D; (<xref ref-type="bibr" rid="ref8">Bergh et al., 2013</xref>). After full clinical recovery, most reach complete psychological recovery (<xref ref-type="bibr" rid="ref178">Vigersky et al., 1977</xref>; <xref ref-type="bibr" rid="ref7">Bergh et al., 2002</xref>; <xref ref-type="bibr" rid="ref19">Bulik et al., 2007</xref>; <xref ref-type="bibr" rid="ref162">Sodersten et al., 2016b</xref>).</p>
<p>In summary, if present, many co-morbid symptoms are predominantly a result of the starvation response; &#x201C;there is no need to postulate that mental factors predispose individuals to the illness&#x201D; (<xref ref-type="bibr" rid="ref93">Ioakimidis et al., 2011</xref>). However, it is acknowledged that the question of co-morbidities associated with AN remains controversial (<xref ref-type="bibr" rid="ref124">Misra and Klibanski, 2014</xref>; <xref ref-type="bibr" rid="ref3">Barakat et al., 2023</xref>).</p>
</sec>
<sec id="sec18"><label>5.3.</label>
<title>ANs and disrupted sleep</title>
<p>In keeping with their energetic behavior and animated mood, ANs are restless sleepers (<xref ref-type="bibr" rid="ref86">Hebebrand et al., 2023</xref>). Sleep disturbances are part of their high arousal pattern (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>; <xref ref-type="bibr" rid="ref105">Kleppe et al., 2023</xref>). They have trouble falling asleep (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>); they wake more frequently during the night (<xref ref-type="bibr" rid="ref37">Crisp, 1967</xref>; <xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>); these awake periods are more prolonged than those of HC (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>; <xref ref-type="bibr" rid="ref109">Lacey et al., 1976</xref>). They also have a lesser total amount of sleep (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>; <xref ref-type="bibr" rid="ref109">Lacey et al., 1976</xref>; <xref ref-type="bibr" rid="ref50">Delvenne et al., 1992</xref>; <xref ref-type="bibr" rid="ref115">Malcolm et al., 2022</xref>) and have significantly less REM sleep (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>). Another striking feature is that they wake early (<xref ref-type="bibr" rid="ref42">Crisp et al., 1971</xref>). This insomnia is associated with low body weight; weight gain significantly improves many aspects of sleep (<xref ref-type="bibr" rid="ref109">Lacey et al., 1976</xref>). Unlike severely depressed patients, ANs <italic>rarely complain</italic> of sleep problems (<xref ref-type="bibr" rid="ref38">Crisp, 1980</xref>).</p>
<p>In a narrative review, <xref ref-type="bibr" rid="ref86">Hebebrand et al. (2023)</xref> supported the findings that the majority of individuals with eating disorders suffer from sleep disturbances. This was more pronounced with binging/purging type ANs than restrictive AN. In addition, the <italic>severity</italic> of the eating disorder and activity levels were associated with sleeping disorders. They further reported that administration of human recombinant leptin, metreleptin, to five ANs, substantially improved sleep quality within one to 2&#x2009;days; however, more research is needed to verify its usefulness.</p>
<p>Interestingly, sleep is closely aligned with thermoregulation in <italic>healthy</italic> adults (<xref ref-type="bibr" rid="ref95">Jequier, 2002</xref>; <xref ref-type="bibr" rid="ref134">Parmeggiani, 2003</xref>; <xref ref-type="bibr" rid="ref168">Szymusiak, 2018</xref>). <xref ref-type="bibr" rid="ref107">Krauchi (2007)</xref> has demonstrated that HCs (mainly women) who have trouble falling asleep, frequently have cold hands; he refers to this as &#x201C;vasospastic syndrome.&#x201D; This may account for the ANs delay in falling asleep, as she, too, has cold hands (<xref ref-type="bibr" rid="ref34">Chudecka and Lubkowska, 2016</xref>).</p>
<p>It is also suggested that frequent wakings, longer times remaining awake, and early morning arousal may also be related to thermoregulation and sensations of coldness (<xref ref-type="bibr" rid="ref107">Krauchi, 2007</xref>; <xref ref-type="bibr" rid="ref147">Sauchelli et al., 2016</xref>), as well as unrelenting hunger (<xref ref-type="bibr" rid="ref72">Goldstein et al., 2018</xref>). Cold sensations would encourage movement to increase metabolic heat and thus bolster the all-important T<sub>core-low</sub>, while hunger sensations would further motivate the need to forage for food.</p>
<p>In summary, ANs are HyAc, with the primary survival focus being maintaining T<sub>core-low</sub>. Their mood is upbeat and reflects their energetic behavior; this is associated with a disrupted sleep pattern compared to HCs.</p>
</sec>
</sec>
<sec id="sec19"><label>6.</label>
<title>SSs and &#x201C;selection&#x201D; of thermoregulatory behavior, coordinates with mood, and sleep</title>
<sec id="sec20"><label>6.1.</label>
<title>SSs and shallow torpor</title>
<p>SSs from the MinnSS, like ANs, have a T<sub>core-low</sub> and experience extreme sensations of coldness. Like ANs, they need to reduce the discomfort of coldness and, in so doing, defend body temperature in the face of food deprivation. So, what behavioral thermoregulatory strategies do they adopt to satisfy these needs?</p>
<p>It is proposed that the primary behavioral thermoregulatory strategy &#x201C;selected&#x201D; by SSs is diametrically opposite to HyAc (<xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref26">Casper, 2022</xref>). SSs become tired, listless, and apathetic; these behaviors aim at conserving energy (<xref ref-type="bibr" rid="ref169">Taylor and KEYS, 1950</xref>; <xref ref-type="bibr" rid="ref27">Casper and Davis, 1977</xref>; <xref ref-type="bibr" rid="ref73">Gorsky and Calloway, 1983</xref>; <xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>).</p>
<p>MinnSSs decreased the cost of daily activity from 1,567 to 451 Kcals per day, a 58% decrease (<xref ref-type="bibr" rid="ref64">Franklin et al., 1948</xref>). During the first week of food reduction, SSs appeared fine; thereafter, overt movements became noticeably slower. &#x201C;They climbed steps warily, one step at a time&#x201D; (<xref ref-type="bibr" rid="ref169">Taylor and Keys, 1950</xref>). One subject got stuck in the revolving doors of a downtown store and &#x201C;never had the strength to push it open&#x201D; (<xref ref-type="bibr" rid="ref169">Taylor and Keys, 1950</xref>). In the later part of the 6-month fast, housekeeping chores and laboratory duties were neglected (<xref ref-type="bibr" rid="ref64">Franklin et al., 1948</xref>). Participation in education programs for relief workers finally collapsed (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>).</p>
<p>However, because of the requirements of the experimental condition, an overall level of activity <italic>had to be maintained</italic>. Subjects were obliged to walk to and from the mess hall, hike about 20&#x2009;miles per week, and perform various other duties to simulate conditions of natural famine (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>).</p>
<p>Although MinnSSs reported that physical exertion tired them and was avoided, occasionally, some exercised deliberately to lose weight to obtain extra bread rations or to prevent a reduction in food allocations because they had not lost enough weight (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>). Some researchers have suggested that this additional activity implied that they remained &#x201C;fairly active&#x201D; (<xref ref-type="bibr" rid="ref57">Epling and Pierce, 1996</xref>). On the contrary, all observations indicated that voluntary physical activity was markedly curtailed (<xref ref-type="bibr" rid="ref102">Keys et al., 1950</xref>).</p>
<p>Similarly, decreased energy expenditure is a typical response to energy restriction in internment camps and during famines<italic>: &#x201C;</italic>The first indications of a deficiency of food are languor, exhaustion, and general debility&#x201D; (<xref ref-type="bibr" rid="ref64">Franklin et al., 1948</xref>) &#x201C;One can conclude that the natural tendency is to conserve energy during starvation by cutting down on all but a minimal level of essential activity&#x201D; (<xref ref-type="bibr" rid="ref140">Prentice et al., 1992</xref>). This decrease in energy expenditure reduces the depletion of stored fat reserves (<xref ref-type="bibr" rid="ref51">Devlin, 2011</xref>).</p>
<p>Since SSs also need to maintain T<sub>core-low</sub> but do not generate internal metabolic heat through physical activity, as do ANs, how do SSs maintain T<sub>core-low</sub>? It is proposed that the primary thermoregulatory behavior adopted by most undernourished, emaciated humans focuses on <italic>retaining metabolic heat or passively gaining metabolic heat</italic> instead of actively generating internal heat.</p>
<p>SSs wear additional layers of clothing to retain metabolic heat, use blankets, wraps, and the like, and assume specific body postures that reduce environmental exposure, such as curling up (<xref ref-type="bibr" rid="ref84">Hart et al., 1962</xref>). They also use shelters (houses, huts, igloos) to protect themselves from the elements (<xref ref-type="bibr" rid="ref181">Wyndham and Morrison, 1958</xref>). To <italic>passively gain</italic> metabolic heat, SSs absorb heat from external sources such as basking in the sun, taking long hot showers, using hot-water bottles and heaters, turning up the thermostat, making a fire, and eating <italic>hot</italic> food and drinks (<xref ref-type="bibr" rid="ref172">Tucker, 2006</xref>). The <italic>advantage</italic> of this <italic>inactive strategy</italic> is that less stored energy (fat) is used.</p>
<p>Numerous mammals and birds conserve energy by hibernating during food shortages (frequently compounded by low ambient temperatures). Hibernation involves drastically reducing T<sub>core</sub>, BMR, and movement. This behavior may last weeks to months, reducing the energy required to sustain life. &#x201C;Daily torpor&#x201D; or &#x201C;shallow torpor&#x201D; is a less intense form of energy conservation compared to hibernation (<xref ref-type="bibr" rid="ref150">Schmidt, 2014</xref>). <italic>Shallow torpor</italic> requires periods of inactivity throughout the day. It has <italic>been defined as a temporary physiological state characterized by a controlled lowering of metabolic rate, body temperature, and physical activity below what is considered normal</italic> (<xref ref-type="bibr" rid="ref119">Melvin and Andrews, 2009</xref>). It is an evolved behavioral strategy to facilitate survival in response to food shortages (<xref ref-type="bibr" rid="ref6">Berger, 1984</xref>) and is &#x201C;the most effective means for energy conservation available to endotherms&#x201D; (<xref ref-type="bibr" rid="ref70">Geiser, 2013</xref>).</p>
<p>It is now proposed that SSs and other semi-starved victims engage in shallow torpor when confronted with food shortages and weight loss, frequently compounded by low ambient temperatures. Shallow torpor serves two functions: firstly, it reduces energy needs and thus <italic>draws less</italic> on stored body fat reserves. Secondly, it enables individuals to engage in passive heat-retention/acquisition behaviors.</p>
</sec>
<sec id="sec21"><label>6.2.</label>
<title>SSs mood/psychological state</title>
<p>The mood of the MinnSSs corresponded with their reduced activity levels; they became depressed and apathetic, although individual differences were marked (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>). Emotional and personality changes started developing within 2&#x2009;months of the semi-starvation period. The humor and high spirits, which had been an outstanding quality of the group during the initial three-month Control Phase, gradually disappeared. They became irritable; some had temper outbursts and would sulk; a few had violent urges; they lacked self-discipline and self-control. They were indecisive, sensitive to noise, and unable to concentrate. They began spending more time alone, saying it became &#x201C;too tiring&#x201D; to contend with others. Some symptoms, such as moodiness and depression, became more severe as semi-starvation progressed. This occurred in subjects who were initially emotionally well-balanced and had &#x201C;made as good an adjustment to life as people usually do.&#x201D; (<xref ref-type="bibr" rid="ref103">Keys et al., 1950</xref>).</p>
<p>Furthermore, <xref ref-type="bibr" rid="ref64">Franklin et al. (1948)</xref> reported that certain subjects developed symptoms of &#x201C;<italic>semi-starvation neurosis</italic>,&#x201D; ranging in intensity from mild to severe. However, in most cases, these symptoms receded during the following rehabilitation period. Eventually, they returned to pre-starvation &#x201C;normal,&#x201D; although four of the 36 subjects were disqualified due to the development of semi-starvation-induced &#x201C;<italic>experimental neurosis</italic>&#x201D; (<xref ref-type="bibr" rid="ref96">Kalm and Semba, 2005</xref>). This is supported by (<xref ref-type="bibr" rid="ref59">Fessler, 2003</xref>).</p>
</sec>
<sec id="sec22"><label>6.3.</label>
<title>SSs and sleep</title>
<p>The sleeping behavior of SSs also corresponded to their lethargic movements and mood. Although the length of sleep during the night was not changed in the MinnSS, &#x201C;the men frequently took naps during the day&#x201D; (<xref ref-type="bibr" rid="ref101">Keys et al., 1950</xref>).</p>
<p><xref ref-type="bibr" rid="ref101">Keys et al. (1950)</xref> reported that in Prisoner of War Camps in WWII, the desire for sleep increased; the number of hours that an adult male would wish to remain in bed, partly dozing but mostly in genuine deep sleep, steadily rose from 8&#x2009;h to 16&#x2009;h or more out of the 24 h. During sleep, BMR and body temperature decrease, and there is reduced movement; these adaptations further decrease energy needs (<xref ref-type="bibr" rid="ref150">Schmidt, 2014</xref>; <xref ref-type="bibr" rid="ref125">Monnard et al., 2017</xref>).</p>
<p>The following example illustrates how a group of present-day Russian peasants has learned to deal with food shortages and cold ambient temperatures; this custom has existed since time immemorial (<xref ref-type="bibr" rid="ref92">Human Hibernation, 2000</xref>): &#x201C;At the first fall of snow, the whole family gathers around the stove, lies down, ceases to wrestle with the problems of human existence, and quietly goes to sleep. Once a day, everyone wakes up to eat a piece of hard bread, of which an amount sufficient to last 6&#x2009;months has providently been baked in the previous autumn. When the bread has been washed down with the draught of water, everyone goes to sleep again. The members of the family take &#x2026; turn [s] to watch and keep the fire alight. After 6&#x2009;months of this reposeful existence, the family wakes up, shakes itself, goes out to see if the grass is growing, and by-and-by sets to work at summer tasks.&#x201D;</p>
<p>In summary: to deal with the two issues of feeling cold/maintenance of T<sub>core/low</sub> and reduced food availability, SSs focus on being inactive; this behavioral pattern is referred to as shallow torpor. In keeping with this strategy, SSs demonstrate a depressive mood and extended hours of sleep (<xref rid="fig1" ref-type="fig">Figure 1</xref>).</p>
<fig position="float" id="fig1"><label>Figure 1</label>
<caption>
<p>Proposed sequence of events leading to AN and SS, and the subsequent &#x201C;selection&#x201D; of thermo-behaviors. AN, anorexia nervosa; SS, semi-starvation; BMR, basal metabolic rate; T<sub>core-low</sub>, reduced body temperature; HyAc, hyperactivity.<inline-graphic xlink:href="fnbeh-17-1243572-i002.tif"/>&#x2009;=&#x2009;increase. <inline-graphic xlink:href="fnbeh-17-1243572-i001.tif"/>&#x2009;=&#x2009;decrease.</p>
</caption>
<graphic xlink:href="fnbeh-17-1243572-g001.tif"/>
</fig>
</sec>
</sec>
<sec id="sec23"><label>7.</label>
<title>Vignette</title>
<p>The following hypothetical scenario is presented to contextualize the above ideas.</p>
<p>From about 2 million years ago to about 12,000&#x2009;years ago, hunter-gatherer culture was humans&#x2019; only way of life (<xref ref-type="bibr" rid="ref58">Fessler, 2002</xref>; <xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>). ANs and SSs thermo-behavioral &#x201C;strategies&#x201D; were most likely operational during these times (<xref ref-type="bibr" rid="ref58">Fessler, 2002</xref>; <xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>).</p>
<p>To illustrate responses to reduced food availability and cold temperatures, suppose, ~14,000&#x2009;years ago, a Clan of hunter-gatherers lived in a temperate region of the Northern Hemisphere with hot summers and cold winters (<xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>; <xref ref-type="bibr" rid="ref177">Vazquez et al., 2006b</xref>; <xref ref-type="bibr" rid="ref155">Scolnick and Mostofsky, 2015</xref>). This Clan possibly consisted of ~70 individuals, including 30 females.</p>
<p>To obtain food, males hunted larger game, and women and children foraged for berries, fruits, bulbs, and the like (<xref ref-type="bibr" rid="ref58">Fessler, 2002</xref>). As a result, everyone was well-fed in summer and most likely built-up excess body fat in preparation for winter shortages.</p>
<p>As winter approached and ambient temperatures declined, hunted, and foraged food became scarce. The men ventured out less frequently as game became sparser; the group became more reliant on the 30 women, the primary foragers (<xref ref-type="bibr" rid="ref58">Fessler, 2002</xref>). Since foraged food was gradually depleted in nearby areas, the women were obliged to walk <italic>greater distances</italic> but collected <italic>less food</italic>.</p>
<p>Foraging was an energy-intensive activity (<xref ref-type="bibr" rid="ref139">Pontzer et al., 2012</xref>). Thus, all 30 females began losing weight over subsequent weeks and months due to increased energy expenditure and reduced caloric consumption. Eventually, all 30 females lost approximately 25% of body weight; associated with this weight loss was a reduction in metabolic rate, T<sub>core</sub>, and related changes (<xref ref-type="bibr" rid="ref88">Hebebrand et al., 2022</xref>). All 30 females now faced two primary survival challenges: <italic>reduced availability of food and maintenance of T<sub>core-low</sub>,</italic> probably exacerbated by decreases in ambient temperatures (<xref ref-type="bibr" rid="ref117">McCue, 2010</xref>).</p>
<p>With this weight loss, it is proposed that foraging became unsustainable <italic>for 29/30</italic> women (~99%). Most became lethargic and adopted the strategy of shallow torpor. They winterized shelters, remained in caves, used animal skins to keep warm, built fires, and slept for extended periods. Most of their energy was derived from stored body fat.</p>
<p>The 30<sup>th</sup> woman (1%), with a genetic predisposition to AN, adopted a diametrically opposite strategy: she became hyperactive. This hyperactivity would help maintain her T<sub>core-low</sub> and increase her chances of locating food. The problem with this restless behavior was that it was highly energy-consuming, necessitating increased foraging and, in some cases, migrating to warmer regions where more food was available (<xref ref-type="bibr" rid="ref74">Guisinger, 2003</xref>). AN migration most likely <italic>contributes</italic> to the fact that female DNA is more diverse in many groups than male DNA (<xref ref-type="bibr" rid="ref156">Seielstad et al., 1998</xref>).</p>
<p>With the onset of warmer weather and food availability, SSs and ANs would <italic>regain lost weight.</italic> In ANs, this would reduce HyAc, normalize T<sub>core-low</sub>, and re-establish mood and sleep patterns. In SSs, shallow torpor would diminish, and they, too, would re-establish &#x201C;normal&#x201D; behaviors. When weight was regained, possibly more fat would accumulate in both groups (<xref ref-type="bibr" rid="ref53">Dulloo et al., 1996</xref>; <xref ref-type="bibr" rid="ref55">El Ghoch et al., 2014</xref>); this would better prepare these females for a possible repeat scenario. From this perspective, changes in ANs and SSs may be regarded as <italic>seasonal</italic> (<xref ref-type="bibr" rid="ref79">Gutierrez et al., 2013</xref>; <xref ref-type="bibr" rid="ref154">Scolnick and Mostofsky, 2014</xref>, <xref ref-type="bibr" rid="ref155">2015</xref>).</p>
<p>In modern-day ANs, despite the frequent abundance of food and availability of heat, ANs <italic>inappropriately express HyAc behavior</italic>. It is proposed that this behavior remains a <italic>vestigial substitute for temperature regulation and foraging.</italic> In contrast, SSs do not adopt a strategy of shallow torpor in the presence of warmth and copious food.</p>
</sec>
<sec sec-type="conclusions" id="sec24"><label>8.</label>
<title>Conclusion</title>
<p>In answer to <xref ref-type="bibr" rid="ref135">Phillipou et al.&#x2019;s (2018)</xref> question of whether psychologists are treating AN or SS, it is proposed that the <italic>initial</italic> physiological response to reduced caloric intake and weight loss in both groups are <italic>similar</italic>. The organism does not distinguish between weight loss due to willful food refusal or externally imposed circumstances such as famine. These physiological alterations aim at extending survival (<xref ref-type="bibr" rid="ref51">Devlin, 2011</xref>).</p>
<p>It is proposed that these changes represent homeorhesis (as opposed to homeostasis). Homeorhesis reflects <italic>an orchestrated change during a specific physiological state,</italic> such as during a 9-month pregnancy (<xref ref-type="bibr" rid="ref4">Bauman and Currie, 1980</xref>) or in association with injury and/or infection and the manifestation of &#x201C;sickness behavior&#x201D; (<xref ref-type="bibr" rid="ref158">Shattuck and Muehlenbein, 2015</xref>). &#x201C;<italic>The body adopts alternate strategies</italic> to <italic>promote optimal functioning during atypical circumstances.</italic>&#x201D; (<xref ref-type="bibr" rid="ref4">Bauman and Currie, 1980</xref>). When the cause for these changes is eliminated (in the case of ANs and SSs this would be increased caloric consumption and weight gain), the body reverts to its &#x201C;standard&#x201D; homeostatic state (<xref ref-type="bibr" rid="ref4">Bauman and Currie, 1980</xref>).</p>
<p>The <italic>primary differences</italic> between ANs and SSs represent different strategies that each adopts to promote the maintenance of body temperature. For ANs this includes hyperactive behavior, an energetic mood, and reduced sleep. For SSs, behavior becomes lethargic; they display a depressive mood and an extensive increase in sleep. These thermo-behavioral &#x201C;selections&#x201D; are most likely genetically based, with the genetic component in ANs ranging from 32 to 76% (<xref ref-type="bibr" rid="ref18">Bulik et al., 2019</xref>; <xref ref-type="bibr" rid="ref165">Steiger and Booij, 2020</xref>; <xref ref-type="bibr" rid="ref3">Barakat et al., 2023</xref>). Such changes could involve central re-programming of brain neurotransmitters, neuromodulators, and associated receptors (<xref ref-type="bibr" rid="ref137">Pirke et al., 1984</xref>; <xref ref-type="bibr" rid="ref58">Fessler, 2002</xref>; <xref ref-type="bibr" rid="ref113">Levine and Kotz, 2005</xref>; <xref ref-type="bibr" rid="ref170">Teske et al., 2008</xref>; <xref ref-type="bibr" rid="ref162">Sodersten et al., 2016b</xref>; <xref ref-type="bibr" rid="ref185">Zup et al., 2022</xref>; <xref ref-type="bibr" rid="ref3">Barakat et al., 2023</xref>). Although there is considerable information on central changes in ANs, there is less information on these factors in SSs, possibly since their response to semi-starvation seems to be a &#x201C;natural&#x201D; adjustment (<xref rid="fig2" ref-type="fig">Figure 2</xref>).</p>
<fig position="float" id="fig2"><label>Figure 2</label>
<caption>
<p>Schematic diagram suggesting that if acute AN becomes chronic, symptoms will more closely resemble SS. AN, anorexia nervosa; SS, semi-starvation.</p>
</caption>
<graphic xlink:href="fnbeh-17-1243572-g002.tif"/>
</fig>
<p>Although behavioral differences are proposed during <italic>acute</italic> AN, it is suggested that if this condition continues for an extended period, <italic>acute AN will progress into a chronic state</italic> (<xref ref-type="bibr" rid="ref40">Crisp, 1984b</xref>; <xref ref-type="bibr" rid="ref49">De Filippo et al., 2016</xref>). At this point, psychologists are probably treating SS and associated symptoms as well as inappropriate habit formation (<xref ref-type="bibr" rid="ref174">Uniacke et al., 2018</xref>). If this assumption is correct, this would <italic>stress the importance of early detection and intervention</italic> (<xref ref-type="bibr" rid="ref100">Kaye and Bulik, 2021</xref>; <xref ref-type="bibr" rid="ref106">Koreshe et al., 2023</xref>).</p>
<p>Finally, it is suggested that the &#x201C;adoption&#x201D; of shallow torpor by SSs may be a more successful survival strategy than ANs&#x2019; hyperactive strategy. The rationale for attesting to this is that the number of females who &#x201C;practiced&#x201D; shallow torpor during times of food shortages and wintry weather <italic>appears</italic> to be much larger (96&#x2013;99.09%) than ANs who adopted the strategy of HyAc (0.91&#x2013;4%; <xref ref-type="bibr" rid="ref180">Watson et al., 2019</xref>).</p>
</sec>
<sec sec-type="data-availability" id="sec25">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec id="sec26">
<title>Author contributions</title>
<p>The author confirms being the sole contributor of this work and has approved it for publication.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="sec27">
<title>Funding</title>
<p>This work was supported by the East Carolina University, an institutional partner, funds 50%.</p>
</sec>
<ack>
<p>Thank you to the following individuals for reviewing this manuscript. Joseph A, Houmard, Professor, Sport, Exercise, Recreation and Kinesiology, Director, Human Performance Laboratory, East Carolina University. Andrew McKune, Professor, Research Institute for Sport and Exercise, The University of Canberra. Much appreciation to Tami Marie Santeramo, Interlibrary Loan Coordinator, Laupus Health Sciences Library, East Carolina Univer.</p>
</ack>
<sec sec-type="COI-statement" id="sec28">
<title>Conflict of interest</title>
<p>The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="sec100" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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</ref-list>
<glossary>
<def-list>
<title>Abbreviations</title>
<def-item>
<term>MinnSS(s)</term>
<def>
<p>Minnesota Study of Semi-Starvation (<italic>subjects</italic>)</p>
</def>
</def-item>
<def-item>
<term>AN(s)</term>
<def>
<p>anorexia nervosa (<italic>patients</italic>)</p>
</def>
</def-item>
<def-item>
<term>SS(s)</term>
<def>
<p>semi-starved (<italic>individuals</italic>)</p>
</def>
</def-item>
<def-item>
<term>HCs</term>
<def>
<p>healthy controls</p>
</def>
</def-item>
<def-item>
<term>HyAc</term>
<def>
<p>hyperactivity</p>
</def>
</def-item>
</def-list>
</glossary>
</back>
</article>