The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing ␣-melanocyte-stimulating hormone (␣-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and͞or BN patients studied had in their plasma Abs that bind to melanotropes and͞or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to ␣-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with ␣-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with ␣-MSH or adrenocorticotropic hormone. Additionally, 3 AN͞BN sera bound to luteinizing hormonereleasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN͞BN staining. These data provide evidence that a significant subpopulation of AN͞BN patients have autoantibodies that bind to ␣-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry͞LHRH system and͞or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and͞or could be involved in the pathophysiology or clinical presentation of AN͞BN, and to what extent increased stress is an important factor for production of these autoantibodies.A norexia nervosa (AN) and bulimia nervosa (BN) are two officially recognized eating disorders that affect Ϸ3% of women during their lifetime (1). Both illnesses usually make their debut at young age and are characterized by hyperactivity and exaggerated concern about body shape and weight, and they often occur in the same patients (2). AN is manifested by an aversion to food, often resulting in life-threatening weight loss and amenorrhea, whereas BN includes large uncontrolled eating episodes followed by compensatory vomiting without significant change in body weight. Even if the cause(s) of AN and BN is still unclear, a body of data exists suggesting a primary neurobiological origin (3), and neuropeptides also have been implicated in these disorders (4). These assumptions are paralleled by growing evidence for a role of hypothalamic peptidergic neurons in conditions associated with energy deprivation or energy excess, providing a concept for central mechanisms controlling food intake and body weight (5-7). In a search of possible mechanisms implicating hypothalamic peptidergic neurons in the etiology and pathogenesis of AN͞BN, we hypothesized that hypothalamic systems responsible for the regulation of food intake could be targeted by autoantibodies...

Our findings support a role for family stress in development of both overweight and underweight among young children. This is likely to be attributed to behavioural mechanisms but a more direct metabolic influence of stress could also be involved.

Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.