Objectives: Quantitative mapping of T1 relaxation in the rotating frame (T1ρ) is a magnetic resonance imaging technique sensitive to pH and other cellular and microstructural factors, and is a potentially valuable tool for identifying brain alterations in bipolar disorder. Recently, this technique identified differences in the cerebellum and cerebral white matter of euthymic patients vs healthy controls that were consistent with reduced pH in these regions, suggesting an underlying metabolic abnormality. The current study built upon this prior work to investigate brain T1ρ differences across euthymic, depressed, and manic mood states of bipolar disorder. Methods: Forty participants with bipolar I disorder and 29 healthy control participants matched for age and gender were enrolled. Participants with bipolar disorder were imaged in one or more mood states, yielding 27, 12, and 13 imaging sessions in euthymic, depressed, and manic mood states, respectively. Three-dimensional, whole-brain anatomical images and T1ρ maps were acquired for all participants, enabling voxel-wise evaluation of T1ρ differences between bipolar mood state and healthy control groups. Results: All three mood state groups had increased T1ρ relaxation times in the cerebellum compared to the healthy control group. Additionally, the depressed and manic groups had reduced T1ρ relaxation times in and around the basal ganglia compared to the control and euthymic groups. Conclusions: The study implicated the cerebellum and basal ganglia in the pathophysiology of bipolar disorder and its mood states, the roles of which are relatively unexplored. These findings motivate further investigation of the underlying cause of the abnormalities, and the potential role of altered metabolic activity in these regions.
Bibliographical noteFunding Information:
National Institute on Drug Abuse, Grant/ Award Number: R01DA037216; University of Iowa Foundation; National Institute of Mental Health, Grant/Award Number: K23MH083695, R01MH085724 and R01MH111578; National Heart, Lung, and Blood Institute, Grant/Award Number: P01HL014388 and R01HL113863; Brain and Behavior Research Foundation , Grant/ Award Number: NARSAD Independent Investigator Award and NARSAD Young Investigator Award; National Institutes of Health, Grant/Award Number: U54TR001013; University of Iowa Institute for Clinical and Translational Science, Grant/Award Number: U54TR001013; Carver Foundation
We thank Autumn Craig, Robin Follmer, Marla Kleingartner, Janie Myers, Ashley Schumacher, and Lois Warren for their assistance with participant recruitment and data collection. This work was supported in part by a gift from Roger Koch through the UI Foundation, NARSAD Young and Independent Investigator Awards from the Brain & Behavior Research Foundation (C.P.J. and V.A.M, respectively), NIMH (R01MH111578), and the University of Iowa Institute for Clinical and Translational Science (U54TR001013). Additionally, J.A.W. was supported by the Carver Foundation, Department of Veterans Affairs (Merit Award), NIMH (R01MH085724), NIDA (R01DA037216), NHLBI (R01HL113863), and a NARSAD Independent Investigator Award; and J.G.F. was supported by the NIMH (K23MH083695) and NHLBI (P01HL014388).
- basal ganglia
- bipolar disorder