Related Experiment Video
Updated: Jun 18, 2026

Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression
Published on: April 10, 2026
Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: the impact of
Jonathan Savitz1, Allison C Nugent, Wendy Bogers
1Section on Neuroimaging in Mood and Anxiety Disorders, NIH/NIMH/MAP, Bethesda, MD 20892, USA. savitzj@mail.nih.gov
Abstract:
MRI-based reports of both abnormally increased and decreased amygdala volume in bipolar disorder (BD) have surfaced in the literature. Two major methodological weaknesses characterizing extant studies are treatment with medication and inaccurate segmentation of the amygdala due to limitations in spatial and tissue contrast resolution. Here, we acquired high-resolution images (voxel size=0.55 x 0.55 x 0.60 mm) using a GE 3T MRI scanner, and a pulse sequence optimized for tissue contrast resolution. The amygdala was manually segmented by one rater blind to diagnosis, using coronal images. Eighteen unmedicated (mean medication-free period 11+/-10 months) BD subjects were age and gender matched with 18 healthy controls, and 17 medicated (lithium or divalproex) subjects were matched to 17 different controls. The unmedicated BD patients displayed smaller left and right amygdala volumes than their matched control group (p<0.01). Conversely, the BD subjects undergoing medication treatment showed a trend towards greater amygdala volumes than their matched HC sample (p=0.051). Right and left amygdala volumes were larger (p<0.05) or trended larger, respectively, in the medicated BD sample compared with the unmedicated BD sample. The two control groups did not differ from each other in either left or right amygdala volume. BD patients treated with lithium have displayed increased gray matter volume of the cortex and hippocampus relative to untreated BD subjects in previous studies. Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications.
Insights
Unmedicated bipolar disorder (BD) patients show smaller amygdala volumes. Medication treatment for BD may lead to increased amygdala volume, suggesting neuroplastic changes moderated by mood stabilizers.
Area of Science:
- Neuroimaging
- Psychiatry
- Neuroscience
Background:
- Conflicting MRI findings exist regarding amygdala volume in bipolar disorder (BD).
- Previous studies are limited by medication effects and suboptimal amygdala segmentation.
- High-resolution imaging and manual segmentation are crucial for accurate volumetric analysis.
Purpose of the Study:
- To investigate amygdala volume differences in unmedicated and medicated BD patients compared to healthy controls.
- To examine the influence of mood-stabilizing medication on amygdala volume in BD.
- To explore potential medication-induced neuroplastic changes in the BD amygdala.
Main Methods:
- Acquired high-resolution 3T MRI scans (0.55x0.55x0.60 mm voxel size) with optimized pulse sequences.
- Manually segmented amygdala volumes by a single rater blind to diagnosis.
- Matched 18 unmedicated BD patients and 17 medicated BD patients with respective healthy control groups.
Main Results:
- Unmedicated BD patients exhibited significantly smaller left and right amygdala volumes than controls (p<0.01).
- Medicated BD patients showed a trend towards larger amygdala volumes compared to controls (p=0.051).
- Medicated BD patients had larger (p<0.05) or trending larger left amygdala volumes than unmedicated BD patients.
Conclusions:
- Bipolar disorder is associated with reduced amygdala volume in unmedicated individuals.
- Mood-stabilizing medications may increase amygdala volume in BD patients.
- Neuroplastic changes in the BD amygdala may be modulated by medication treatment.
Related Concept Videos
Bipolar Disorder
Mania and Antimanic Drugs: Overview
Depressive Disorders: MDD and Dysthymia

