Smoking status links habenular volume to glycated hemoglobin: Findings from the Human Connectome Project-Young Adult

Manish K. Jha, Joo won Kim, Paul J. Kenny, Cherise Chin Fatt, Abu Minhajuddin, Ramiro Salas, Benjamin A. Ely, Matthew Klein, Chadi G. Abdallah, Junqian Xu, Madhukar H. Trivedi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: The habenula-pancreas axis regulates the stimulatory effects of nicotine on blood glucose levels and may participate in the emergence of type 2 diabetes in human tobacco smokers. This secondary analysis of young adults from the Human Connectome Project (HCP-YA) evaluated whether smoking status links the relationship between habenular volume and glycated hemoglobin (HbA1c), a marker of long-term glycemic control. Methods: Habenula segmentation was performed using a fully-automated myelin content-based approach in HCP-YA participants and the results were inspected visually (n = 693; aged 22–37 years). A linear regression analysis was used with habenular volume as the dependent variable, the smoking-by-HbA1c interaction as the independent variable of interest, and age, gender, race, ethnicity, education, income, employment status, body mass index, and total gray matter volume as covariates. Results: Habenula volume and HbA1c were similar in smokers and nonsmokers. There was a significant interaction effect (F(1, 673)= 5.03, p = 0.025) indicating that habenular volume was related to HbA1c in a manner that depended on smoking status. Among participants who were smokers (n = 120), higher HbA1c was associated with apparently larger habenular volume (β = 6.74, standard error=2.36, p = 0.005). No such association between habenular volume and HbA1c was noted among participants who were nonsmokers (n = 573). Discussion: Blood glucose levels over an extended time period, reflected by HbA1c, were correlated with habenular volume in smokers, consistent with a relationship between the habenula and blood glucose homeostasis in smokers. Future studies are needed to evaluate how habenular function relates to glycemic control in smokers and nonsmokers.

Original languageEnglish
Article number105321
StatePublished - Sep 2021


  • Diabetes
  • Habenula
  • HbA1c
  • Imaging
  • Smoking


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