Demonstration of Disturbed Activity of External Globus Pallidus Projecting Neurons in Depressed Patients by the AgNOR Staining Method

Background: The external globus pallidus (EGP) is thought to play the most important integrating and conveying role in the striatopallidal system involved in the transfer from motivation to action. The aim to find a morphological biomarker of disturbed EGP activity in depression was approached by the karyometric analysis of large projecting neurons.

Methods: The study was performed on paraffin-embedded brains from 19 depressed patients from both the major depressive disorder (MDD) and the bipolar disorder (BD) diagnostic groups encompassing 10 suicides and from 24 controls. The karyometric parameters of EGP neurons bilaterally were evaluated by argyrophilic nucleolar organiser (AgNOR) silver staining method.

Results: A significantly decreased AgNOR area was found in the left EGP neurons in depressed patients compared to controls. The distinctness of the diagnostic groups and suicidal vs non-suicidal patients was not shown in the statistical comparisons. The AgNOR parameter which was decreased correlated positively with the mean dose of benzodiazepines in non-suicidal patients.

Limitations: A major limitation of this study is the relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the whole lifespan of patients.

Conclusion: The results suggest disturbed, most likely decreased, activity of the left EGP projecting neurons in depressed patients, a disturbed activity that should hypothetically be counteracted by the applied pharmacotherapy in non-suicidal patients.