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Updated: Mar 29, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Isolating the Norepinephrine Pathway Comparing Lithium in Bipolar Patients to SSRIs in Depressive Patients
Andy R Eugene1, Jolanta Masiak2, Marek Masiak2
1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Gonda 19, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Introduction:
The purpose of this investigatory neuroimaging analysis was done to better understand the pharmacodynamics of Lithium by isolating the norepinephrine pathway in the brain. To accomplish this, we compared patients with Bipolar Disorder treated with Lithium to patients diagnosed with Major Depression or Depressive Disorder who are treated with Selective Serotonin Reuptake Inhibitors (SSRIs).
Methodology:
We used Standardized Low Resolution Brain Electrotomography to calculate the whole brain, voxel-by-voxel, unpaired t-tests Statistical non-Parametric Maps. For our first electrophysiological neuroimaging investigation, we compared 46 patients (average age = 34 ± 16.5) diagnosed with Bipolar Affective Disorder to three patient groups all diagnosed with Major Depression or Depressive Episode. The first is with 48 patients diagnosed with Major Depression or Depressive Episode (average age = 49 ± 12.9), the second to 16 male depressive patients (average age = 45 ± 15.1), and the final comparison to 32 depressive females (average age = 50 ± 11.7).
Results:
The results of sLORETA three-dimensional statistical non-parametric maps illustrated that Lithium influenced an increase in neurotransmission in the right Superior Temporal Gyrus (t=1.403, p=0.00780), Fusiform Gyrus (t=1.26), and Parahippocampal Gyrus (t=1.29). Moreover, an increased in neuronal function was found was also identified at the Cingulate Gyrus (t=1.06, p=0.01200).
Conclusion:
We are proposing a translational clinical biological marker for patients diagnosed with Bipolar Disorder to guide physicians during the course of Lithium therapy and have identified neuroanatomical structures influenced by norepinephrine.
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