Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight

Highlights

• Overweight people show reduced concentrations of hippocampal N-acetylaspartate (NAA).

• Reduced NAA reflects reduced neuronal viability.

• There is an inverse relationship between BMI and hippocampal NAA.

• Worry scores are independently associated with lower NAA.

• Generalized anxiety disorder did not show low hippocampal NAA.

Abstract

Objective

We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis – a form of neuroplasticity – and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS).

Methods

We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging (¹H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables.

Results

Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA.

Conclusion

Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.