Neural correlates and sex hormonal associations of impaired feedback-learning in adolescent patients with anorexia nervosa - a longitudinal fMRI study.

Introduction: Anorexia nervosa (AN) is a somato-psychiatric disease that mostly begins in adolescence, involving endocrine changes including amenorrhea. It is difficult to treat as most patients have difficulties embracing change and thus, the disease often takes a chronic course. Underlying pathomechanisms including moderate neuropsychological deficits of learning and memory remain insufficiently understood. As learning and memory have been shown to be estradiol-dependent in healthy controls (HC), we conducted this assessment to investigate the impact of reduced estradiol in patients on verbal learning, memory and the underlying brain-alterations. Methods: We studied feedback-learning in 20 adolescent patients with AN at admission and following short-term weight restoration, compared to 26 age- and sex-matched HC using fMRI. Learning performance and brain alterations were compared between groups and longitudinally within the patients and their interdependence with sex hormone levels as well as clinical parameters was explored. Results: Reduced brain activity at admission could be shown in left occipital as well as calcarine, lingual and fusiform gyrus, Ncl. caudatus and thalamus compared to HC. Following weight-restoration, activity increased along with patients' learning rate. Exploratory analyses showed brain activations to be relatively higher with shorter illness duration, its improvement was significantly greater in less starved patients. Estradiol levels were associated with learning in HC but not in patients. Discussion: Feedback-learning appears deteriorated in the acute state of AN. Neural hypoactivity might make re-learning and psychotherapy more difficult thus requiring adequate renourishment first. No direct link to sex hormone-reduction in patients could be shown in this study.