Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases.

The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer's disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.

[The effect of pectin of tansy, Tanacetum vulgare L., on anxiety and overeating food rich in fats and sugars in mice in modelling binge eating].

Binge eating is repeated episodes of eating large amounts of sweet and fatty food in short periods. Dietary fibers, including pectin, significantly reduce the subjective ratings of hunger, and the amount of food eaten. However, studies showing the effect of dietary fibers on satiety use juices or yoghurts with added dietary fiber, or a kissel-like food. Thus, there is a lack of data on the effect of dietary fibres on binge eating of palatable food. The aim of the study was to assess the effect of tansy pectin on anxiety and the binge eating of palatable food in mice. Material and methods. 64 mice weighing 33.3±0.6 g were divided into two groups. Binge eating was induced in forty mice of the first group by consumption of sunflower halva (SH) in addition to regular chow for 24 h once a week. The total energy intake and separately the consumption of regular chow (RC) and SH were monitored. Tansy pectin in the form of an aqueous solution was administered to the mice using a gastric feeding tube (50 mg/kg body weight) before the last presentation of SH. Blood was obtained by cardiac puncture at the end of the last 24 h SH access period. The concentration of insulin and ghrelin in plasma samples were determined by the enzyme immunoassay. In animals of the second group, 24 hours after the administration of pectin, the level of anxiety and depression of mice was assayed with an open field test, a light-dark box test, an elevated plus-maze test, and a forced swim test. Throughout the study, water was used as a negative control, and imipramine at a dose of 20 mg/kg was used as a positive control. Results. Mice treated with tansy pectin ate 2.6 fold less SH within 3 h and 1.4 fold less within 24 h after oral administration of tansy pectin compared to control (water administration). Consumption of RC did not differ within 3 or 24 h. The total energy intake was 1.9 fold lower within 3 h in mice treated with tansy pectin. Within 24 h after pectin oral administration the total energy intake did not differ from control. Insulin plasma level was 2.5 fold lower and ghrelin plasma concentration was 25% higher in the mice that received pectin compared to control, at the end of the 24 h SH access period. The administration of tansy pectin was found to decrease anxietyrelated behaviour in mice. Its administration significantly increased the time spent in the central sector of the open field apparatus by 87%, the time spent in the light area of the light-dark box by 31%, and the time spent on the open arms of the elevated plus maze by 22% compared with the control. Conclusion. Overall, tansy pectin reduced the binge eating of SH representing highly palatable, sweet, and fatty food. Reduced intake SH lead to a decrease in insulin concentration. Blood level of ghrelin was increased in mice treated with tansy pectin at the end of the sweet and fatty food presentation period. Tansy pectin reduced the level of anxiety in mice.

Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation.

The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.

Hypothalamic expression of inflammatory mediators in an animal model of binge eating.

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain regions where they can directly or indirectly regulate food intake. In the present study, we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-α and IFN-É£) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL-18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior-tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase, IL-18 expression increased, while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder.

Binge abstinence is associated with reduced energy intake after treatment in patients with binge eating disorder and obesity.

OBJECTIVE: Binge eating disorder (BED) is strongly associated with obesity and related medical and psychiatric morbidities. Cognitive behavioral therapy (CBT) has consistently been shown to reduce binge eating frequency and improve psychological functioning, as well as to produce abstinence rates of roughly 50%. This study examined the relationship between binge abstinence and dietary and psychological outcomes after CBT for BED. METHODS: Fifty adult patients with BED received 6-month treatments using a combination of CBT and dietary counseling. Trained interviewers conducted two 24-hour dietary recall interviews on randomly selected days at baseline and at 6 months. RESULTS: Participants had significant reductions in energy, macronutrient, and sugar intake and an increase in fruit intake. They reported significant reductions in BMI and binge eating frequency (from mean = 14.24 to mean = 1.90 binge eating episodes during the previous 28 days), as well as improvements in psychological functioning. Those who became binge abstinent reported eating roughly 400 fewer calories per day and experienced greater improvements in psychological functioning than those who did not. CONCLUSIONS: Findings from this study suggest that individuals who achieve complete cessation from binge eating have significantly improved dietary and psychological outcomes that could potentially improve weight status, compared with those who continue to binge eat post-treatment.

Heated hatha yoga to target cortisol reactivity to stress and affective eating in women at risk for obesity-related illnesses: A randomized controlled trial.

OBJECTIVE: Cortisol reactivity to stress is associated with affective eating, an important behavioral risk factor for obesity and related metabolic diseases. Yoga practice is related to decreases in stress and cortisol levels, thus emerging as a potential targeted complementary intervention for affective eating. This randomized controlled trial examined the efficacy of a heated, hatha yoga intervention for reducing cortisol reactivity to stress and affective eating. METHOD: Females (N = 52; ages 25-46 years; 75% White) at risk for obesity and related illnesses were randomly assigned to 8 weeks of Bikram Yoga practice or to waitlist control. Cortisol reactivity to a laboratory stress induction were measured at Weeks 0 (pretreatment) and 9 (posttreatment). Self-reported binge eating frequency and coping motives for eating were assessed at Weeks 0, 3, 6, and 9. RESULTS: Among participants with elevated cortisol reactivity at pretreatment ("high reactors"), those randomized to the yoga condition evidenced greater pre- to posttreatment reductions in cortisol reactivity (p = .042, d = .85), but there were not significant condition differences for the "low reactors" (p = .178, d = .53). Yoga participants reported greater decreases in binge eating frequency (p = .040, d = .62) and eating to cope with negative affect (p = .038, d = .54). CONCLUSIONS: This study provides preliminary support for the efficacy of heated hatha yoga for treating physiological stress reactivity and affective eating among women at risk for obesity-related illnesses. (PsycINFO Database Record

Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli.

It was recently reported that activation of a subset of lateral hypothalamus (LH) GABAergic neurons induced both appetitive (food-seeking) and consummatory (eating) behaviors in vGat-ires-cre mice, while inhibition or deletion of GABAergic neurons blunted these behaviors. As food and caloric-dense liquid solutions were used, the data reported suggest that these LH GABAergic neurons may modulate behaviors that function to maintain homeostatic caloric balance. Here we report that chemogenetic activation of this GABAergic population in vGat-ires-cre mice increased consummatory behavior directed at any available stimulus, including those entailing calories (food, sucrose, and ethanol), those that do not (saccharin and water), and those lacking biological relevance (wood). Chemogenetic inhibition of these neurons attenuated consummatory behaviors. These data indicate that LH GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli.

Large, binge-type meals of high fat diet change feeding behaviour and entrain food anticipatory activity in mice.

Male C57BL/6 mice fed ad libitum on control diet but allowed access to a palatable high fat diet (HFD) for 2 h a day during the mid-dark phase rapidly adapt their feeding behaviour and can consume nearly 80% of their daily caloric intake during this 2 h-scheduled feed. We assessed food intake microstructure and meal pattern, and locomotor activity and rearing as markers of food anticipatory activity (FAA). Schedule fed mice reduced their caloric intake from control diet during the first hours of the dark phase but not during the 3-h period immediately preceding the scheduled feed. Large meal/binge-like eating behaviour during the 2-h scheduled feed was characterised by increases in both meal number and meal size. Rearing was increased during the 2-h period running up to scheduled feeding while locomotor activity started to increase 1 h before, indicating that schedule-fed mice display FAA. Meal number and physical activity changes were sustained when HFD was withheld during the anticipated scheduled feeding period, and mice immediately binged when HFD was represented after a week of this "withdrawal" period. These findings provide important context to our previous studies suggesting that energy balance systems in the hypothalamus are not responsible for driving these large, binge-type meals. Evidence of FAA in HFD dark phase schedule-fed mice implicates anticipatory processes in binge eating that do not involve immediately preceding hypophagia or regulatory homeostatic signalling.

Intermittent access to sweet high-fat liquid induces increased palatability and motivation to consume in a rat model of binge consumption.

Binge eating disorders are characterized by discrete episodes of rapid and excessive food consumption. In rats, giving intermittent access to sweet fat food mimics this aspect of binge eating. These models typically employ solid food; however, the total amount consumed depends on motivation, palatability and satiety, which are difficult to dissociate with solid food. In contrast, lick microstructure analysis can be used to dissociate these parameters when the ingestant is a liquid. Therefore, we developed a binge model using a liquid emulsion composed of corn oil, heavy cream and sugar. We show that rats given intermittent access to this high-fat emulsion develop binge-like behavior comparable to that previously observed with solid high-fat food. One feature of this behavior was a gradual escalation in consumption across 2.5 weeks of intermittent access, which was not apparent in rats given lower-fat liquid on the same access schedule. Lick microstructure analysis suggests that this escalation was due at least in part to increases in both motivation to consume and palatability-driven consumption.

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors.

Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague-Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet or a sweet, high-fat diet supplemented with standard rodent chow. Naloxone-precipitated withdrawal was also not seen in rats fed a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substances of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize "food addiction" may be subtyped based on the nutritional composition of the food consumed.

Disorders of fuel metabolism: medical complications associated with starvation, eating disorders, dietary fads, and supplements.

Disorders of fuel metabolism as they relate to abnormal fuel intake,abnormal fuel expenditure, and dietary supplements are the focus of this article. The emergency physician should be aware of the medical complications that can occur as a result of starvation states,eating disorders, fad diets, hypermetabolic states, and ergogenic aids. Knowledge and understanding of the complications associated with these disorders will facilitate the diagnosis and management of patients who present to the emergency department with any of the disorders reviewed.

Binge eating and satiety in bulimia nervosa and binge eating disorder: effects of macronutrient intake.

OBJECTIVE: The current study tested the hypothesis that supplemental dietary protein would reduce binge eating frequency and test meal intake in women with bulimia nervosa (BN) or binge eating disorder (BED). METHOD: Eighteen women with BN or BED ingested high-carbohydrate or high-protein supplements (280 kcal) three times daily over two 2-week periods. On the morning after each period, participants were given a high-protein or high-carbohydrate supplement (420 kcal) 3 hr before an ad libitum meal. RESULTS: Binge eating episodes occurred less frequently during protein supplementation (1.12 episodes per week) than during carbohydrate supplementation (2.94 episodes per week) or baseline (3.01 episodes per week). Participants reported less hunger and greater fullness, and consumed less food at test meals, after protein than after carbohydrate (673 vs. 856 kcal). DISCUSSION: Adding protein to the diets of women with BN and BED reduced food intake and binge eating over a 2-week period. These findings may have implications for the longer-term treatment of these disorders.

Neuropeptides in eating disorders.

The past decade has witnessed a dramatic acceleration in research on the role of the neuropeptides in the regulation of eating behavior and body weight homeostasis. This expanding research focus has been driven in part by increasing public health concerns related to obesity and the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN). Preclinical advances have been facilitated by the development of new molecular and behavioral research methodologies. With a focus on clinical investigations in AN and BN, this article reviews research on selected hypothalamic and gut-related peptide systems with prominent effects on eating behavior. Studies of the orexigenic peptides neuropeptide Y and the opioid peptides have shown state-related abnormalities in patients with eating disorders. With respect to gut-related peptides, there appears to be substantial evidence for blunting in the meal-related release of the satiety promoting peptide cholecystokinin in BN. Fasting plasma levels of the orexigenic peptide ghrelin have been found to be elevated in patients with AN. As discussed in this review, additional studies will be needed to assess the role of nutritional and body weight changes in neuropeptide alterations observed in symptomatic eating disorder patients, and to identify stable trait-related abnormalities in neuropeptide regulation that persist in individuals who have recovered from an eating disorder.

Adiponectin in anorexia nervosa and bulimia nervosa.

To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight controls, six healthy constitutionally thin subjects, and nine obese subjects. Moreover, changes in levels were reevaluated after nutritional treatment and weight gain in 13 patients with AN. Serum adiponectin concentrations in AN and bulimia nervosa were significantly lower than those in normal-weight controls. These results were unexpected because the levels were high in constitutionally thin subjects and low in obese subjects, which provide a negative correlation with body mass index (BMI) and body fat mass. In contrast, serum leptin levels correlated very well with BMI and fat mass among all the patients and controls. The insulin resistance was significantly low in AN and high in obese subjects. The concentrations of adiponectin after weight recovery increased to the normal level despite a relatively small increase in BMI. These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it.

Hypothalamic digoxin, hemispheric chemical dominance, and eating behavior.

The isoprenoid pathway produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in eating disorders. The patterns were compared in those with right hemispheric and left hemispheric dominance. The serum HMG CoA reductase activity, RBC membrane Na+-K+ ATPase activity, serum digoxin, magnesium, tryptophan catabolites (serotonin, quinolinic acid, strychnine, and nicotine), and tyrosine catabolites (morphine, dopamine, and noradrenaline) were measured in anorexia nervosa, bulimia nervosa, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. Digoxin synthesis was increased with upregulated tryptophan catabolism and downregulated tyrosine catabolism in those with anorexia nervosa and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism and upregulated tyrosine catabolism in those with bulimia nervosa and left hemispheric chemical dominance. The membrane Na+-K+ ATPase activity and serum magnesium were decreased in anorexia nervosa and right hemispheric chemical dominance while they were increased in bulimia nervosa and left hemispheric chemical dominance. Hypothalamic digoxin and hemispheric chemical dominance play a central role in the regulation of eating behavior. Anorexia nervosa represents the right hemispheric chemically dominant/hyperdigoxinemic state and bulimia nervosa the left hemispheric chemically dominant/hypodigoxinemic state.

Eating disorders: a review of the literature with emphasis on medical complications and clinical nutrition.

Eating disorders, including anorexia nervosa, bulimia nervosa, binge-eating disorder, and atypical eating disorder (eating disorder not otherwise specified or NOS), are estimated to occur in 5-10 million young and adult women and one million males in the United States. The etiology of eating disorders is complex and appears to include predisposing genetic factors and serotonin dysregulation, as well as psychological factors that include a history of trauma and childhood sexual abuse. Both anorexia nervosa and bulimia nervosa are medical conditions complicated by multiple neuroendocrine dysfunctions, nutritional deficiencies, and psychiatric diagnoses. Medical complications, specific nutritional deficiencies, and research involving the therapeutic use of inositol and zinc are reviewed.

Serotonergic dysfunction across the eating disorders: relationship to eating behaviour, purging behaviour, nutritional status and general psychopathology.

BACKGROUND: Several recent studies have pointed to a dysfunction of serotonin transmission in patients with eating disorders. Notwithstanding, it is not known whether serotonergic abnormalities are related primarily to eating and/or purging behaviour, nutritional status or general psychopathological dimensions. Therefore, by using a validated neuroendocrine strategy, we investigated central serotonergic function in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder who differ on the above parameters. METHODS: Plasma prolactin response to D-fenfluramine (30 mg p.o.) or placebo was measured in 58 drug-free female volunteers, comprising 15 underweight anorexic women, 18 bulimic women, 10 women with binge-eating disorder and 15 female healthy controls. Behavioural assessment included ratings of eating disorder symptoms, depression, aggression and food-related obsessions and compulsions. RESULTS: A significantly decreased prolactin response to D-fenfluramine was found in underweight anorexic women and in bulimics with high frequency bingeing ( > 2 binge episodes/day), but not in patients with binge-eating disorder or in bulimics with low frequency bingeing (< I binge episode/day). In the whole bulimic group, a negative correlation emerged between frequency of bingeing and prolactin response. No significant correlation was found between physical or psychopathological measures and the hormonal response in any group. CONCLUSIONS: These results confirm our previous findings of an impaired serotonergic transmission in underweight anorexics and in bulimics with high frequency bingeing, but not in patients with less severe bulimia nervosa. Moreover, they show, for the first time, that the hypothalamic serotonergic system is not altered in women with binge-eating disorder.

[Fourier analysis of pupil oscillations for measuring central activation in psychosomatic patients]. / Fourieranalyse der Pupillenoszillationen zur Messung der zentralen Aktiviertheit bei psychosomatischen Patienten.

The aim of the study was to answer the question if there are any differences in the central activation of different groups of psychosomatic patients and patients with eating disorders, which was measured by means of Fourier analysis of pupillary oscillations. A total of 132 patients (110 f, 22 m) with a mean age of 29.69 years (standard deviation: 9.9) participated in the study. In anorectic and bulimic patients high central activation was observed. Different groups of psychosomatic patients showed significant differences in their central nervous activation. In the group of subjects with the ICD-10 diagnosis F 41.3 (mixed anxiety disorders) the highest amplitudes was observed not only in the particular frequency bands but also in the total spectrum (power), which reflects high central activation. Reduced activation was found in subjects with somatoform autonomic function disorder of the upper and lower gastrointestinal tract (F 45.3). The measurement of central activation in psychosomatic disorders could have consequences for therapeutic interventions.

[Phototherapy in psychiatry: clinical update and review of indications]. / Photothérapie en psychiatrie: actualité clinique et revue des indications.

Phototherapy introduced in 1984 by Rosenthal as a treatment for SAD (Seasonal Affective Disorder) is the first therapeutic answer to season-related psychopathology. Findings in chronobiology have largely contributed to pathophysiological theories of disorders in the internal circadian system. Actual researches on the etiology of SAD covers fields as retinal deficiency (i.e. disorder of photoreceptors), phase disturbance of the internal circadian rhythms given by internal oscillators and neuroendocrinologically drived disorders, supposing that melatonin is the main mediator of human circadian systems in the CNS. Disorders of the neurotransmitters are an other explored cue. Recent longitudinal studies show a prevalence of seasonal depressive symptoms in general population up to 10%. In populations treated for depression the prevalence of SAD is up to 20%. The SAD sex-ratio (women/men) of 3/1 is found repeatedly. Above 55 years SAD get rare. Effectiveness of phototherapy is showed in nearly all controlled studies. Bright light for patients with mild SAD appears to be most effective as is also the authors clinical impression through the practice of phototherapy in Geneva since 1991. A true placebo for bright light is still to be found according to enable evaluation of potentially important impact that unspecific therapeutic factors may trigger in phototherapy. Actually possible new indications for phototherapy are being explored: bright light for non seasonal depression has been tested with features with SAD; effectiveness in bulimia has been suggested and recently sleep disorders in psychogeriatric patients have been improved. Non seasonal circadian disorders such as jet lag might be sensitive to light.

Neurobiological and psychopharmacological basis in the therapy of bulimia and anorexia.

1. Eating disorders can be found in several psychiatric pathologies: schizophrenia, delusional disorder (somatic type), bipolar disorders, major depressive disorder, borderline personality disorder, generalized anxiety disorder, body dysmorphic disorder, somatization disorder and conversion disorder. 2. Although their clinical features have been defined, relatively little is known about the role of neurobiological patterns in the pathogenesis of these disorders. Several CNS neurotransmitters and neuromodulators are involved in the regulation of eating behavior in animals and have been implicated in symptoms such as depression and anxiety often observed in patients with eating disorders. The authors will review some studies on NA, DA, 5-HT, beta-endorphins, CRH, VP, OT, CCK, NPY and PYY involved in eating disorders. Furthermore, we will highlight some of the studies on drug therapy of eating disorders taking into account the effects of these agents on neurotransmitters and neuromodulators. 3. Antidepressant drugs have long been used for anorexia nervosa and bulimia, these disorders been claimed to be affective equivalent. Antidepressant agents seem to be effective in reducing the frequency of binge-eating episodes, purging behavior and depressive symptomatology. It is notable that antidepressant agents have been proved to be effective in patients with chronic bulimic symptoms, even in cases persisting for many years and in patients who had repeatedly failed courses of alternative therapeutic approaches. In all of the positive studies, antidepressant agents appeared effective even in bulimic subjects who did not display concomitant depression. 4. Few controlled studies on use of medications for anorexia nervosa have been published. Central serotonergic receptor-blocking compounds such as cyproheptadine cause marked increase in appetite and body weight. Zinc supplementation or cisapride could be a therapeutic option in addition to psychological and other approaches in anorexia nervosa. 5. There is no therapy as yet which is fully effective in alimentary disorders. Psychotropic drugs give some relief from symptoms, but they cannot cure the disorders. An integrated approach, either pharmacological or psychological, is still recommendable.