Altered SPECT 123I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa

Abstract

Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using 123I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). “Depression–Dejection” and “Confusion” POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children with AN. This may be a state-related change, which could be used to monitor and guide the treatment of eating disorders.

Exploring the utility of RDoC in differentiating effectiveness amongst antidepressants: A systematic review using proposed psychometrics as the unit of analysis for the Negative Valence Systems domain

“…Indeed, it is still not possible to differentiate between GAD from MDD based on a review of a multimodal neuroimaging evidence to date although the same study found a correlation between limbic/paralimbic activity and the combined sample including healthy controls based on levels of general distress [ 60 ]. Of course, similarity between the DSM diagnoses of MDD and GAD and the RDoC constructs of response to Loss and PT do not constitute equivalence, but evidence using POMS:Tension and Depression also suggest a convergence in correlation between PT and Loss on the one hand, and impaired activity of the anterior cingulate cortex [ 61 , 62 ] and amygdala [ 63 ], as well as reduced GABA-A receptor binding in the posterior cingulate cortex and left superior frontal regions [ 64 ] on the other. Increasing evidence that physiological paradigms such as startle response are a reliable differentiator of fear or distress [ 65 ] suggests that a more biologically-grounded conceptualisation of NVS constructs is simply AT vs non-AT.…”

SPECT and PET in Eating Disorders

“…Subjects with weight gain demonstrated increases of tracer binding in the posterior cingulate cortex and occipital gyrus. These findings were interpreted as evidence for decreased GABA(A)-benzodiazepine binding in AN, related to anxiety, which normalizes after successful treatment (Nagamitsu et al 2016).…”

Structural and functional changes in the central nervous system in the course of anorexia nervosa

“…Nagamitsu et al noted the correlation between 123 Iiomazenil binding by cortical GABA receptors and clinical symptoms of anorexia in children [16]. Higher EAT-26 scores were significantly associated with lower GABA iomazenil-binding activity especially in the anterior cingulate cortex.…”

“…Nagamitsu i wsp. zwrócili uwagę na współzależność pomiędzy wiązaniem I 123 -iomazenilu przez korowe receptory GABA, a objawami klinicznymi anoreksji u dzieci [16]. Wyższe wyniki w teście EAT-26 oraz zaburzenia nastroju były mocno powiązane z mniejszym wiązaniem hamującym GABA w niektórych regionach mózgu, szczególnie przedniej części zakrętu obręczy.…”