Greater Translocator Protein Distribution Volume in Neurocircuitry of Anorexia Nervosa

AI Summary

Increased [18F]FEPPA VT across examined brain regions in AN, notably ACC, ventral striatum, dorsal caudate and thalamus, ~52% mean elevation.
ACC [18F]FEPPA VT correlated positively with eating concerns and rumination severity (EDE r=0.58; IDAS-II r=0.66).
Findings indicate neuroinflammation and gliosis in AN with no significant association to BMI, suggesting gliosis-targeted interventions warrant study.

TL;DR (AI Generated)

The primary objective is to determine whether [18F]FEPPA total distribution volume ([18F]FEPPA VT), PET index of translocator protein density and inflammatory marker of gliosis, is elevated in AN in anterior cingulate cortex (ACC), ventral striatum (VS), dorsal caudate (DC), dorsal putamen (DP), thalamus, orbitofrontal cortex and insula.

Secondary objectives are to determine the relationship of [18F]FEPPA VT in ACC to rumination severity and [18F]FEPPA VT to body mass index (BMI).

RESULTS: [18F]FEPPA VT was elevated in AN in all ROI (linear mixed model (LMM), group effect, P = 4×10-7), particularly ACC, VS, DC and thalamus (mean 52% elevation; LMM, region by group interaction, P = 4×10-4).

Basic summary

Biol Psychiatry. 2026 Nov 13:S0006-3223(26)01680-X. doi: 10.1016/j.biopsych.2026.11.003. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory stimuli are associated with onset of anorexia nervosa (AN) but whether inflammation occurs in the brain of AN is unknown. The primary objective is to determine whether [¹⁸F]FEPPA total distribution volume ([¹⁸F]FEPPA V_T), PET index of translocator protein density and inflammatory marker of gliosis, is elevated in AN in anterior cingulate cortex (ACC), ventral striatum (VS), dorsal caudate (DC), dorsal putamen (DP), thalamus, orbitofrontal cortex and insula. Secondary objectives are to determine the relationship of [¹⁸F]FEPPA V_T in ACC to rumination severity and [¹⁸F]FEPPA V_T to body mass index (BMI).

METHODS: [¹⁸F]FEPPA V_T was measured in 20 medication free AN participants and 20 healthy controls. Correlations of [¹⁸F]FEPPA V_T with rumination severity, and BMI, were determined.

RESULTS: [¹⁸F]FEPPA V_T was elevated in AN in all ROI (linear mixed model (LMM), group effect, P = 4×10^-7), particularly ACC, VS, DC and thalamus (mean 52% elevation; LMM, region by group interaction, P = 4×10^-4). ACC [¹⁸F]FEPPA V_T correlated positively with eating concerns (Eating Disorder Examination, r = 0.58, P = .007; Inventory of Depression and Anxiety Symptoms-II, r = 0.66, P = .002). There were no significant correlations between [¹⁸F]FEPPA V_T and BMI.

CONCLUSIONS: Greater [¹⁸F]FEPPA V_T is strong evidence for neuroinflammation and gliosis, particularly in ACC, VS, DC and thalamus in AN. Given such, it may be of interest to assess interventions that influence gliosis towards curative roles in future clinical trials in AN.

PMID:43025774 | DOI:10.1016/j.biopsych.2026.11.003

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