Investigating amygdala nuclei volumes in military personnel with post-traumatic stress disorder, major depressive disorder, and adjustment disorder: A retrospective cross-sectional study using clinical routine data

Abstract: Background: Post-traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and Adjustment Disorder (AdjD) are highly prevalent among military personnel, often presenting diagnostic challenges due to overlapping symptoms and reliance on self-reporting. The amygdala, particularly the basolateral complex involved in fear-related memory formation and extinction recall, plays a crucial role in emotional processing. Abnormalities in these amygdala nuclei are implicated in PTSD and may distinguish it from other disorders like MDD and AdjD, where these mechanisms are less central. Investigating structural differences in specific amygdala nuclei could enhance diagnostic precision and inform targeted interventions. Goal: This study aimed to explore volumetric differences in amygdala nuclei among patients with PTSD, MDD, comorbid PTSD and MDD (PTSD+MDD), and AdjD using routine clinical MRI data. We hypothesized that patients with PTSD would exhibit distinct amygdala nuclei volumes compared to those with MDD or AdjD. Additionally, we examined the influence of symptom duration, prior medication, and psychotherapeutic experience on amygdala volumes. Methods: We conducted a retrospective cross-sectional study with 185 military personnel (162 men, 23 women) diagnosed with PTSD (n = 50), MDD (n = 70), PTSD+MDD (n = 38), and AdjD (n = 27). High-resolution T1-weighted MRI scans were obtained using a 3T Siemens Skyra scanner. Amygdala subfields were automatically segmented and volumetrized using FreeSurfer software. Analysis of covariance (ANCOVA) models compared amygdala nuclei volumes across diagnostic groups, controlling for estimated total intracranial volume (eTIV), age, and gender. Exploratory analyses included symptom duration, medication use, and prior psychotherapy as additional covariates. Sensitivity analyses further examined the impact of depressive episode type (first vs. recurrent), severity (mild, moderate, severe), and AdjD symptom duration. Results: The main analyses revealed no significant differences in the volumes of the basolateral and medial amygdala nuclei among the PTSD, MDD, PTSD+MDD, and AdjD groups. Exploratory analyses did not identify significant associations between amygdala volumes and symptom duration, medication use, or prior psychotherapy. Sensitivity analyses also showed no significant volumetric differences related to depressive episode type, severity, or AdjD symptom duration. Conclusion: Our findings suggest that, within this military population, amygdala nuclei volumes measured using routine clinical MRI data do not significantly differ among patients with PTSD, MDD, PTSD+MDD, and AdjD. This indicates that structural amygdala volumetry alone may not suffice to distinguish between these stress-related disorders in clinical settings. The study highlights the complexity of diagnosing overlapping mental health conditions and underscores the need for comprehensive approaches that integrate neuroimaging with clinical assessments. Future research should include healthy control groups, consider additional brain regions and functional connectivity, and employ longitudinal designs to better understand the temporal dynamics of amygdala changes and their relation to symptomatology.

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