Dopaminergic dysfunction in the left putamen of patients with major depressive disorder

J Affect Disord. 2024 Jul 15:357:107-115. doi: 10.1016/j.jad.2024.04.044. Epub 2024 Apr 16.

Abstract

Introduction: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation.

Objectives: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder.

Methods: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale.

Results: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048).

Conclusion: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.

Keywords: Antidepressants; Basal ganglia; Dopamine; Mood disorders.

MeSH terms

  • Adult
  • Aged
  • Anhedonia / physiology
  • Depressive Disorder, Major* / diagnostic imaging
  • Depressive Disorder, Major* / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins* / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Putamen* / diagnostic imaging
  • Putamen* / metabolism
  • Retrospective Studies
  • Tomography, Emission-Computed, Single-Photon*
  • Tropanes

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Tropanes
  • Dopamine
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane