Investigating markers of neuroprogression in Anorexia Nervosa

Aim of the investigation:
To examinehippocampal function and neurogenesis in eating disordersby:
-Self-report measures of specific eating disorder psychopathology and comorbid features (depression, anxiety, OCD).
-Hippocampal cognitive functiontests, which are mainly memory and learning tests.
-Measuring blood markers influencing neurogenesis


Preparation of the main study: In order to prepare for the main study, Johanna Keeler will perform a systematic scoping review on hippocampal volume, function and connectivity in anorexia nervosa. This will help to map out the available evidence for reduced hippocampal integrity in AN as well as helping to identify key measures that are used. Other preparatory work will include qualitative interviews with a subset of individuals with SE-AN (n=10) or AN (n=10) to explore their self-reported cognitive abilities relevant to the hippocampus (e.g. memory, learning, spatial recognition)and potentially relevant related AN symptoms (strict dietary rules, avoidance of certain foods, rigidity, routines).

Outcomes: It follows from the novel conceptualisation discussed above that hippocampal function (memory, learning, imagery and cognitive flexibility) will be impaired in SE-AN. In a preparatory project, we found abnormalities in fear learning in AN with a failure to develop inhibitory (extinction) learning (Lambert et al. 2020). The proposed proof-of-concept study will allow us to investigate other domains of hippocampal learning. The obtained neuropsychological parameters could be future markers of disease severity and progression, and they will help to understand the connection of with molecular messengers that influence hippocampal neurogenesis such as cytokines, hormones and growth factors. These molecules could become future biomarkers of AN and its therapy success. In recent studies we have shown that interleukin (IL-6)levels are elevated in people with acute AN (Dalton, Bartholdy et al. 2018) and come back to normal during successful therapy (Dalton et al. 2020). However, it is unclear whether these changes are related to hippocampal changes and neuropsychological improvements. As there are medications available which modify the effect of or even block cytokines, and as these medications have been demonstrated to have antidepressant effects in specific patient groups (e.g. Tyring et al. 2006), our project might identify additional and novel drug targets for future pharmacological treatment of AN.