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PSYCHIATRIC ASPECTS OF THE RELATIONSHIP BETWEEN EATING AND MOOD Timothy D. Brewerton, M.D., Margaret M. Heffernan, M.A. and Norman E. Rosenthal. M.0.

Key Words: anorexia nervosa, bulimia, obesity, car-

bohydrate craving, affective disorders, antidepressants Ancient associations between emotional state and food consumption continue to be of interest at the present time. The connections between the two have increasingly been recognized to be of relevance to the field of psychiatry. This is in part a result of the need i3 understand and treat effectively the growing population of patients presenting to clinicians with eating disorders, affective disorders or both, and in part a result of an eruption of knowledge over the last several years in the neurophysiology and psychobiology of brain function and dysfunction. Even though there is still much to be explored, it has become apparent from clinical and experimental research that there is indeed a relationship between eating and mood in many and, perhaps, all people. In this paper, these associations are explored by reviewing data derived from patients in whom eating and/or mood functions are disturbed, i.e., those with an eating disorder, an affective disorder or both.

Eating Disorders: Relationships to Affective Disturbances The two major eating disorders defined as “mental disorders” by the Diagnostic and Statistical Manual of Mental Disorders (DSM-Ill)’ are anorexia nervosa (AN) and bulimia (BUL). The present discussion will focus on anorexia nervosa and bulimia, but will allude to a few

Dr. Brewerton is Medical Staff Fellow, Laboratory of Clinical Science, Ms. Heffernan is a Research Assistant, Clinical Psychobiology Branch and Dr. Rosenthal is Chief, Unit of Outpatient Studies, Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892. 70

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relevant points regarding obesity. Even though psychiatric factors have been recognized as being important in obesity, this eating disorder has been traditionally and perhaps appropriately classified as a medical or metabolic disorder. As a result, a paucity of scientifically based information exists on the relationship between eating and mood in obese individuals. Anorexia Nervosa. Anorexia nervosa (AN) occurs predominantly in young females and is characterized by 1) an intense fear of being or becoming obese even as weight loss progresses; 2) a disturbance of body image, i.e., feeling “too fat;” 3) significant weight loss (> 25 percent of original or projected body weight); 4) a refusal to maintain minimal age- and heightappropriate weight; and 5) absence of any known physical etiology that would account for the weight loss.’ In addition, amenorrhea is often noted to appear before the overt weight loss and is invariably present at low weight. Many workers in the field subdivide AN into two types, “restricters” and “bulimics.”2-6The “restricter” anorexic (AN-RES) uses fasting or restriction of food intake as her primary means of inducing and maintaining weight loss, whereas the “bulimic” anorexic (AN-BUL)also has intermittent periods of bingeing and often resorts to vomiting as well as to laxative, diuretic and/or drug abuse. Associations between AN and mood changes are by no means new clinical observations.’ Morton, who in 1689 described the first documented anorectic patient (“like a skeleton only clad with skin”),econceptualized the disorder to be a result of sadness and anxious cares.g Gull, who gave the condition its present name,l0 considered it to be a morbid mental state.g Soursll noted that AN was considered to be a form of depression by psychiatrists of the early Freudian era. Freud himself made reference to the melancholia of sexually undeveloped girls with AN.12.13 In 1953 Kay sug-

gested that AN might actually be a form or used starvation to attain altered states.37 variant of affective i1lne~s.l~ Since then several Reports of affective illness in the families of investigators have documented concurrent anorectic patients further strengthen the case clinical manifestations of depressive symptomfor a relationship between disturbances of atology in up to 85 percent of AN patients “feeding and feeling” and suggest a psychoduring the active phase of their i l l n e ~ s . l ~ - ~neurophysiologic ~ a s s ~ c i a t i o n . ’ ~ , ~Con,~~,~-~ Depressive symptomatology has been retrolled family studies indicate a much higher ported to occur more often in AN-BUL patients incidence of major depression in the parthan in AN-RES patients by some,3~5~29-33 but e n t ~ (particularly ~ ~ . ~ ~ the mothers32), the not all authors6 In a recent study, Piran et grandparent^,^^ all first-degree reported that 38 percent of AN patients fulfilled and all second-degree relatives of AN paDSM-Ill criteria for a major depression (see t i e n t ~A. ~ higher ~ ~ frequency of mania40-42 as below) at the time of inpatient admission or well as substance abuse4n4 in the families of referral for admission. Herzog28 reported that ANs have also been noted. AN-BUL patients 56 percent of 82 anorectic outpatients had a compared to AN-RES patients appear to have concomitant major depression, while Cantwell a greater degree of affective disturbance in et al.32 noted the high proportion (41 percent) their fa mi lie^,^^^ although this has been an of major depression averaging 4.9 years after inconsistent finding.42 These data taken tohospitalization for AN in recovered anorectics gether could mean that AN is a form of affecat the time of followup. Hudson et aI.= studied tive disorder.40s44Another interpretation, possipatients with a lifetime history of either ANbly more meaningful in terms of developing RES or AN-BUL and found that 50 percent of effective pharmacologic treatment strategies, AN-RES and 80 percent of AN-BUL patients is that these disorders, at least in a subgroup of had a history of major depression, often before patients, share a common pathophysiology. and after the acute AN phase. Just what that common pathophysiology is, Hyperactivity and manic-like elevation of if it exists, remains an enigma. Starvation promood have also been described in AN paduces extensive metabolic and neuroendot i e n t ~ Bruch26 . ~ ~ noted ~ ~ ~that ~ ~patients can crine changes that confound interpretation. often purposely induce euphoria by eating Furthermore, the problem of finding appropriafter a prolonged fast.% ately weight-matched controls adds to the The links between nutritional deprivation challenge. Further discussion of the biochemiand altered mood characteristic of AN have cal and endocrine changes reported in AN can been examined in light of the psychological be found e l s e ~ h e r e .One ~ ~ .relevant ~~ laborachanges produced by starvation, as demontory finding, however, is worthy of note. strated in World War II conscientious objectors Weight-recovered AN-BUL patients compared during Keys’ famed Minnesota E ~ p e r i m e n t . ~ ~ to weight-recovered AN-RES patients have He noted that the outstanding psychological lower accumulated levels of the serotonin mefeatures seen in both famine and experimentabolite, 5-hydroxyindoleacetic acid (5-HIAA), tally induced early starvation are depression in their cerebrospinal fluid (CSF).46The ANand irritability, followed by apathy during the BUL patients may, therefore, represent a dislater stages. Bruch% discussed the similarities tinct subgroup with a functional deficit in the and differences between the starvation states neurotransmitter serotonin resulting in a disturof AN and of famine. It is notable, however, bance of satiety.47Low levels of CSF 5-HIAA that not all starved individuals or all AN pahave also been reported in subgroups of detients at low weight become depressed. Both pressed patient^.^^^^ Keys and Bruch acknowledged the importance In terms of treatment, the serotonin antagoof pre-morbid personality factors in shaping nist cyproheptadine has been the only pharthe starvation response. Self-starvation has macologic agent in double-blind studies to be been known to produce a sense of inner calm somewhat effective in increasing weight gain and well-being not only in anorectic patients, and improving mood in patients with AN,50,51 but in several well-known individuals who have but almost exclusively in those with AN-RES.* NUTRITION REVIEWS/SUPPLEMENT/MAY 1986

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This is presumably due to its ability to decrease satiety. Tricyclic antidepressant medications are sometimes useful, particularly in depressed AN patients; however, double-blind studies have not demonstrated significantly different responses as compared to placebo thereby suggesting some fundamental differences between AN and depression. The case against AN being an affective disorder has recently been argued by Altshuler and Weher.% The overlapping features of the two illnesses (e.g., weight loss, decrease in sexual drive, fatigue, slowed thinking and alterations in activity) are nonspecific symptoms documented to occur in a number of conditions (including starvation) and do not necessarily imply that the underlying pathological processes are the same. Bulimia. The DSM-Ill1 has defined bulimia as a condition characterized by: 1. recurrent episodes of binge eating (or, the rapid consumption of food in a discrete period of time, usually less than 2 hours); 2. at least three of the following: a. consumption of high-caloric, easily ingested food during a binge; b. inconspicuous eating during a binge; c. termination of such eating episodes by abdominal pain, sleep, social interruption or self-induced vomiting; d. repeated attempts to lose weight by severely restrictive diets, self-induced vomiting or use of cathartics or diuretics; e. frequent weight fluctuations greater than 10 Ibs due to alternating binges and fasts; 3. awareness that the eating pattern is abnormal and fear of not being able to stop eating voluntarily; 4. depressed mood and self-deprecating thoughts after eating binges; 5. the bulimic episodes are not due to AN or any known physical disorder. In relation to this last criterion, not all authors agree that BUL can be distinctly differentiated

‘K.A. Halrni eta/., unpublished data.

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from AN. The AN-BUL has been described above and accounts for approximately 50 percent of the total AN population. Russell has coined the term “bulimia nervosa” to describe BUL patients with a history of AN.54 As one can see from the above criteria, depressed mood is an essential feature of bulimia. BUL patients have been noted by several authors to have a high frequency of depressed As many as 70 percent of BUL patients have been noted to have lifetime histories of major depression.20@ HerzogM reported that six of eight bulimic adolescents met DSM-Ill criteria for concurrent major depression. Several authors have chronicled the mood states of bulimics associated with their actual binge e p i ~ ~ d e ~ . A~wide ~ , vari~ ~ . ~ ~ ety of unpleasant feelings emerge before, during and after the binge/purge cycle. It is quite apparent that these patients experience not only depressed, worthless, guilty and suicidal feelings at various time points, but also a significant degree of anxiety, tension, irritability and anger, especially before a binge.59~61~62~68 During the actual binge, patients tend to report a dampening of unpleasant feelings, although these feelings are quick to return after the binge is over and probably promote the cycle of continued bingeing and purging. A minority of bulimics report antianxiety effects exclusively from vomiting.59 The similarities of the bulimic’s “food addiction” (i.e., cravings, impulsiveness, loss of control, secretiveness, stealing the desired substance and insatiability) to the substance abuser’s addictive behaviors have been n ~ t e d . ~ ~ . ~ ~ As in AN, family studies of normal-weight bulimic patients support a strong connection between bingeing and mood d i ~ o r d e r , ~ , ~ ~ although one recent well-designed study failed to validate an increase in the frequency of affective disorder in bulimics’ first-degree relat i v e ~ These . ~ ~ data suggest genetic overlap between bulimia and mood disturbances and raise again the likelihood that eating behavior and mood regulation share common neurobiological substrates that when disturbed produce both types of symptoms. Research in the field of eating disorders, particularly bulimia, is relatively recent compared to studies of the affective disorders.

Hence, a limited amount of laboratory data is ing diets low in TRP,87 perhaps as a result of available on bulimia. Nonetheless, behavioral lowering brain serotonin. and clinical studies in animals and humans Impulsivity, another clinical feature common suggest that altered function of the neurotransto both bulimia and some groups of depresmitter serotonin may be of major significance in sion, may also be modulated by serotonin mediating the prominent clinical symptoms in neurotransmission. Aggression toward self bulimia. and others can be conceptualized as types of The appetitive, affective and impulsive feadisinhibited behavior which involve changes in tures of bulimia have all been associated with mood. Aggressive activity in rats can be possible alterations in serotonin transmission. induced by administration of p-chloropheB l ~ n d e I l ~has ~ J shown ~ that manipulations of nylalanine (pCPA), an inhibitor of serotonin the serotonin system result in marked changes synthesis, and reversed by oral TRP adminin appetite, eating behavior and body weight istration.88 Lower levels of CSF 5-HIAA in via its inhibitory role in feeding. Generally, humans have been associated with suicide attreatments and procedures that lead to an intempts, especially by violent m e a n ~ . ~ ~ - ~ l creased availability of serotonin in the synaptic The relevance of these TRP and serotonin cleft or which directly activate serotonin recepdata for bulimia remain unclear. TRP is metors have been reported to reduce food contabolized to other potentially psychoactive sumption, particularly carbohydrate (CHO) compounds which have an effect in the brain.92 consumption. Conversely, interventions that Moreover, a recently published, elegant expereither directly or indirectly decrease serotonin iment in cats failed to demonstrate a change in receptor activation are reported to increase the electrophysiological activity of serotonergic food consumption and weight gain. Studies in neurons with manipulations of the TRP/LNAA animals have shown that L-tryptophan (TRP), ratio, despite an observed increase in brain the amino acid precursor of serotonin, comserotonin and 5-HIAA levekg3Although some petes with the large neutral amino acids bulimics claim that they binge predominantly (LNAAs) tyrosine, phenylalanine, valine, leuon carbohydrates, the three studies that have cine and isoleucine for uptake into the brain evaluated the composition of foods chosen for and subsequent synthesis to ~ e r o t o n i n . ~ ~ -binges ~ ~ have all shown that sizable quantities of This TRP/LNAA ratio is increased by carbohyprotein and fat are also present in the selected drate ingestion via insulin-induced decreases food.59-=.94 in LNAAs, thereby promoting serotonin synthePreliminary results from a study of ten norsis in the brain.73p74It may be relevant to the mal-weight bulimics and six age- and weightmood changes associated with bingeing and matched normal controls indicate a blunted purging that meals which are high in carbohyprolactin response to the intravenous infusion d r a t e ~as , ~well ~ as orally administered TRP,76of TRP in the bulimic group.g5 This reduced 79 have been reported to cause decreased prolactin response suggests a possible serovigor and sedation. An increased sense of tonergic dysfunction in normal weight bulimia, post-prandial calmness was noted by young although the exact locus of the alleged defect males given a high-carbohydrate howis not known. Heninger et aI.% have docuever, antianxiety and calming effects of TRP mented a blunted prolactin response to the have not been observed in depressed pasame dose of TRP in major depression. These tients.~8~ similar neuroendocrine response patterns sugRelatively lower levels of this TRP/LNAA gest that major depressive illness and bulimia ratio have been reported in patients with major may share common underlying alterations in manic depression" and alcoserotonin function.95 holism.85 Furthermore, this ratio has been Imipramine, phenelzine and other antidefound to be predictive of an antidepressant pressant medications have been found to be response to TRPE2as well as to imipramine.s clinically effective in both depression and a Depressed mood has been recently reported significant percentage of patients with bulito be induced in normal subjects blindly receivmia.97.98Among their multiple neurochemical NUTRITION REVIEWS/SUPPLEMENT/MAY 1986

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effects, these compounds are known to potentiate central serotonin function.wslOO Obesity. Psychiatric research on the relationship between obesity and mood has been sparse and largely anecdotaI.lo1 However, there are a number of reports that are pertinent to this review. It has been established that severely obese individuals have a high incidence of untoward emotional reactions when attempting to lose weight by dieting, but not by gastric bypass surgery.102-1M These emotional reactions were predominantly preoccupation with food, irritability, anxiety and depression, all of which are seen in AN, BUL and starvation states. The favorable adjustment to loss of weight secondary to gastric bypass surgery attests to the importance of body image in the regulation of mood and ~ e l f - e s t e e m . ~ ~ ~ - l ~ ~ Halmi et al. examined 80 morbidly obese patients after gastric bypass surgery for lifetime prevalence rates of DSM-lll-defined psychiatric diagnoses.lo5 The authors found that depressive disorders occurred in 28.7 percent of their sample. Unfortunately, the authors did not examine a control group for comparison, yet concluded that their findings in obese patients were not significantly different from the rate of depression reported in one study of a US. urban community. Conversely, Hopkinson and Bland interviewed 73 morbidly obese female candidates for intestinal bypass surgery referred for psychiatric evaluation and found that 28 percent had had a history of major depression for which they had been treated.lm In addition, they found that 78 percent of the total sample (including 57 percent of the patients with treated depression) reported periodic depressed moods often associated with CHO craving. Other authors have also reported a high degree of clinical depression in grossly obese individual^,^^^*^^ although these findings are not conclusive. Wurtman et al. have described a group of obese patients (at least > 18 percent normal body weight) who report cravings for CHO-rich foods, which they ingest in large quantities as snacks.109-110 This group of patients differs from bulimic patients in that their eating habits 82


are more moderate. They generally do not binge to the same degree, do not purge, and are less secretive about their habits. After screening their population of obese CHO cravers and noncravers for overt psychopathology, they found that 44 of 63 CHO cravers (70percent) met criteria for a lifetime history of major depression, while 15 of 19 (79 percent) non-CHO cravers met the same criteria.* Both of these figures are much higher than one would expect to find in the general population, and are similar to the figures for major depression reported in BUL or AN populations. Although preliminary, these data suggest that obese patients with cravings (? CHOs > nonCHOs) may have a vulnerability similar to that of bulimics. CHO-craving obese individuals may have a deficiency in their satiety mechanism. In laboratory animals, blockade of serotonin function in the ventromedial hypothalamus results in marked increases in food ingestion and weight gain.47s71Both TRP and fenfluramine, a serotonin agonist that is a clinically efficacious antiobesity agent,lll have been reported by Wurtman et at. to decrease CHO intake selectively in obese subjects.112 In summary, there appears to be a robust relationship between affective disturbances and all the eating disorders.

Affective Disorders: Relationships to Eating Disturbances Just as disturbancesof mood are common in the eating disorders, so are disturbances of appetite and weight regulation cardinal features of the affective disorders. For the purpose of this discussion, two general types of affective disorders will be considered: major depression (also known as “endogenous,” “endogenomorphic” or “typical”) and atypical depressions (also known as “nonendogenous”or “nonendogenomorphic”).The atypical depressions, which are of particular relevance to the premise of this paper, are hysteroid dysphoria and seasonal affective disorder (SAD). In addition, the effects of antidepressant drugs on eating and weight gain will also be examined. Major depression. Major depression refers ‘R.J. Wurtman el a/,, 1985,personal communication.

to a DSM-Ill-defined mood disorder of severe degree that may or may not have psychotic symptoms.’ The depressed mood or dysphoria must be prominent and last at least 2 weeks. In addition, four of the following associated symptoms must also be present: 1) poor appetite or significant weight loss (when not dieting) or increased appetite or significant weight gain; 2) insomnia or hypersomnia; 3) psychomotor agitation or retardation; 4) loss of interest or pleasure in usual activities (anhedonia), or decrease in sexual drive; 5) loss of energy or fatigue; 6) feelings of worthlessness, self-reproach or excessive or inappropriate guilt; 7) complaints or evidence of diminished ability to think or concentrate; or 8) recurrent thoughts of death, suicidal ideation, wishes to be dead or suicide attempt. In its “primary” form, the illness is not due to any known physical illness. It is most often associated with loss of appetite rather than weight gain and with insomnia rather than hypersomnia. Diurnal variation of mood is frequently present with the symptoms tending to be worse in the morning hours. as well as There have been reports of spring1l3 late faIl1l4peaks in its incidence. This form of depression is often also referred to as “endogenous” or “endogenomorphic,” particularly when there are associated psychotic symptoms. Patients with this condition frequently fail to show normal suppression of cortisol secretion in response to dexamethasone,l15 and others show a blunted thyrotropin (TSH) response to the administration of thyrotrophin Bulimic patients releasing hormone (TRH).ll6 have also been reported to have a high degree of DST (dexamethasone suppression test) nonsuppression as well as blunted TSH responses,65but these abnormalities do not necessarily coincide with ?he presence of clinical depression. These data once again raise the possibility of a common pathophysiology between major depression and bulimia.= Weight loss during severe depression and weight gain on recovery were originally noted by Kraepelin117and later by Kraines.l18 In a recent study by Leckman et aI.,ll9 70 percent of patients with major depression reported eating and weight disturbances. They found that appetite disturbances were highly correlated with feelings of guilt. Although no such formal

relationship has been established in the eating disorders, depression and guilt are commonly observed there as well. Given the issues discussed above regarding TRP, serotonin and depression, investigators have used TRP and other neurotransmitter precursors normally found in the diet as potential antidepressant treatments either alone or in combination with other agents.lm-12* It is thus possible that dietary constituents might contribute to the precipitation, exacerbation, maintenance and/or alleviation of major depression. Even though the precedent exists in medicine in the form of a host of nutritional deficiency diseases, such notions have not as yet been developed along formal lines of investigation by psychiatric researchers. One recent report, however, has documented vitamin deficiencies of riboflavin and pyridoxine in patients with affective illness. These disturbances were not related to prescription drug intake during the 3 weeks prior to admission.ln It is conceivable, therefore, that the eating disturbances so common to affective illnesses may perhaps amplify the associated mood disturbances. Atypical depression. Technically, the diagnosis of “atypical depression” as defined by DSM-Ill1 is reserved for affective syndromes that cannot be classified elsewhere. However, in common clinical practice the term usually refers to a more specific entity which has also been called “nonendogenomorphic depression,” and, less often, “neurotic depres~ i o n . ” l * ~The - l ~concept of “atypical depression” has its roots in British p s y ~ h i a t r y . l ~ ~ - l ~ West and Dally128and Sargantla+lm were the first to contrast ”typical” or endogenomorphic depressives with “atypical” depressives, who exhibited prominent anxiety, emotional lability, overreactivity, fatigue, lethargy, irritability, reversed diurnal variation, a clear history of a precipitating stress and a poor response to electroconvulsive therapy.12e12s-131.132 Robinson et al.lm later added weight gain and initial insomnia to the list of features. Klein has defined “hysteroid dysphoria” as a subtype of atypical depression characterized by frequent, brief depressive episodes in response to interpersonal rejection. This syndrome occurs primarily in women with classically hysterical feaNUTRITION REVIEWS/SUPPLEMENT/MAY 1986 83

t u r e ~ lwho ~ ~ are described as “attention j u n k i e ~ . ” l ~ They ~ , l ~ ~easily become overinvolved romantically with the opposite sex and can experience a profound pseudomystical elation. Upon rejection, they are prone to acute severe depressions characterized by leaden feeling, hypersomnia and craving for sweets.1 2 4 ~ 1 3 ~ Patients with hysteroid dysphoria and/or atypical depression are reported to have particularly good therapeutic responses to the monoamine oxidase inhibitor (MAOI) class of antidepressant drugs.124-126p131Based on these findings, Klein has further postulated that regulation of phenylethylamine (PEA), a neurotransmitter-like substance resembling amphetamine and the MAOls phenelzine and tranylcypromine, may be abnormal in hysteroid dysphorics.lM PEA is metabolized by MA0 in platelets. In patients treated with MAOls, platelet MA0 inhibition is highly correlated with antidepressant response.126v133 It has been noted that hysteroid dysphoric patients often tend to binge on chocolate, a food loaded with pEA.124.126,131 Rosenthal et a/.52,135 have identified a group of phototherapy-responsive depressed patients with annually occurring episodes of depression in the fall and winter alternating with periods of remission or hypomania in the spring and summer. SAD differs from some other types of atypical depressions, in particular those studied by Liebowitz et al.,125in that SAD patients tend to lack the hypersensitivity to attention and rejection, but rather exhibit hypersensitivityto climatic changes, especially the amount of ambient light. The seasonality and response to light in atypical depressives without a clear-cut history of regular winter depressions have not been formally investigated. Of 125 patients with SAD, 71 percent reported a history of increased appetite during depression, whereas only 17 percent reported an appetite decrease. CHO craving was reported by 67 percent of this population,136and was one of the earliest symptoms of this socalled “winter depression.” It is conceivable that the craving corresponds to a central serotonin deficiency and that light treatment, by reversing this deficiency, might decrease the 84


craving and other symptoms of SAD. Drug effects on appetite and weight. The therapeutic effects of antidepressant medications on mood and eating patterns in some patients have been presented. However, increased appetite, particularly for CHOs, and weight gain (over and above any initial weight loss) are often bothersome side effects in depressed patients taking tricyclic antidepressant medications or MAOls, sometimes necessitating drug ~ i t h d r a w a l . l ~ ~K1eit-1’~~ - l ~ * noted that the CHO-craving, but not the antidepressant effect, of antidepressants may be eliminated with dose reduction. This drug-induced weight gain has not been observed in all studies of depressed patientslm and has not been shown in normal subjects14 or described in patients with BUL.geAs mentioned previously, equivocal appetite and weight responses are seen in AN. Paradoxically, animals given tricyclic antidepressants exhibit decreased appetite and decreased rate of weight gain.l4-l6 At this time it is unclear why antidepressants should have different effects on weight and appetite in animals and humans or in different individuals. It should be noted that these drugs have multiple effects on different neurotransmitter systems, which makes it difficult to explain their behavioral effects on the basis of any particular mechanism.

Summary In reviewing the symptoms, family studies, pharmacological responses and selected laboratory data relevant to the eating and affective disorders, the many areas of overlap between these conditions become apparent. Each set of criteria for each disorder is distinct, yet there are many patients in whom the symptoms are mixed to the extent that a clear diagnosis of one or the other condition cannot be made. The conditions may occur at different times in the life of a single patient, and in such cases the sequence in which the conditions appear seems variable. The entire database taken together suggests complicated interrelationships within the neuronal networks modulating food intake’ and mood 0 ~ t p u t .Many l ~ ~ questions remain ‘S.F. Leibowitz, unpublished data

unanswered and these pose a formidable challenge to students of appetite and mood regulation. Researchers in the area of the eating disorders have benefited greatly from methodology established in earlier studies of the affective disorders and other psychiatric conditions. Over the years the need for standardized criteria, discrimination between symptoms and syndromes, balanced control populations and many other methodological issues have become apparent, and this knowledge is being used to good effect in studies of the eating disorders. Researchers in the field of affective disorders would do well to pay much more heed to disturbances of eating and inquire more carefully about, and even measure, the amount and type of food eaten. Division of depressives into overeating and undereating subgroups may lead to novel ways of examining biological data. 0

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