Altered habenula to locus coeruleus functional connectivity in past anorexia nervosa suggests correlation with suicidality: a pilot study

Purpose: Despite anorexia nervosa having the highest mortality rate of mental illnesses, little is known regarding the brain mechanisms involved. Given that lack of interest for food in anorexic patients is related to alterations in the reward system, we tested the hypothesis that patients with past anorexia nervosa (pAN) have altered resting state functional connectivity (RSFC) between the habenula (a major component of the reward system) and its targets. Methods: RSFC between the habenula and major targets (locus coeruleus, median and dorsal raphe nuclei, substantia nigra, and ventral tegmental area) was studied in 14 psychiatric inpatients with pAN and 14 psychiatric inpatient controls (PC, never-anorexic patients in same clinic, matched for comorbidities). Next, we tested possible correlations between RSFC and suicidal ideation, depression, and anxiety as determined by self-report questionnaires. Results: Left habenula/locus coeruleus RSFC was lower in pAN patients compared to PC. The left habenula/locus coeruleus RSFC was positively correlated with suicidal ideation (past 2 months) in pAN patients, but not in controls. Conclusions: pAN patients showed long lasting alterations in habenular connectivity. This may have clinical implications, possibly including future evaluation of the habenula as a therapeutic target and the need to carefully monitor suicidality in pAN patients. No level of evidence: Basic science.