Decreased cerebral opioid receptors availability related to hormonal and psychometric profile in restrictive-type anorexia nervosa

•First study on brain opioid activity using PET imaging in anorexia nervosa.•Low opioid receptor availability in reward/aversive circuits’ key structures and in hypothalamo pituitary areas.•Possible dual role of opioid system abnormalities in anorexia nervosa acting as an adaptive and a perpetuating mechanism. The opioid system role in anorexia nervosa (AN) pathophysiology is still unclear since conflicting results were reported on peripheral and cerebrospinal fluid opioids levels. The study main aim was to evaluate cerebral AN opiate receptor availability by using [11C] diprenorphine, a ligand with non-selective binding. In vivo [11C]diprenorphine cerebral non-displaceable binding potential (BPND) evaluated by PET imaging was compared between three groups : 17 undernourished restrictive-type AN patients (LeanAN), 15 AN patients having regained normal weight (RecAN) and 15 controls. A lower BPND may account for an increased opioid tone and vice versa. Serum hormones and endogenous opioids levels, eating-related and unspecific psychological traits were also evaluated. Compared to controls, LeanAN and RecAN patients had decreased [11C]diprenorphine BPND in middle frontal gyrus, temporo-parietal cortices, anterior cingulate cortex and in left accumbens nucleus. Hypothalamo-pituitary (H-P), left amygdala and insula BPND was found decreased only in LeanAN and that of putamen only in RecAN. LeanAN presented higher dynorphin A and enkephalin serum levels than in controls or RecAN. Inverse correlations were found in total group between : 24 h mean serum cortisol levels and anterior cingulate gyrus or insula BPND; eating concern score and left amygdala BPND. Positive correlation were found between leptin and hypothamus BPND; LH and pituitary BPND. Low opiate receptor availability may be interpreted as an increased opioid tone in areas associated with both reward/aversive system in both AN groups. The relationship between the opioid receptors activity and hypercorticism or specific psychometric scores in some of these regions suggests adaptive mechanisms facing anxiety but also may play a role in the disease perpetuation.