2026 ECNP Congress

PS02-2098

Reduced putamen dopamine transporter availability independently predicts major depressive disorder diagnosis

Antonio Maria D'Onofrio — D.A. Pizzuto, A. Simonetti, M. Pettorruso, G. Martinotti, G. Sani, D. Di Giuda, G. Camardese · Università Cattolica del Sacro Cuore, Department of Neuroscience- Section of Psychiatry, Rome, Italy

2026 ECNP Congress

Background

Converging neurobiological evidence implicates dopaminergic dysfunction in the pathophysiology of major depressive disorder (MDD), with dopamine transporter (DAT) availability representing a promising neuroimaging biomarker. However, prior studies have been limited by small sample sizes and methodological heterogeneity, leaving the independent contribution of striatal DAT availability to MDD diagnosis insufficiently characterized.

Aims

We aimed to assess striatal DAT availability differences between patients with MDD and healthy controls (HC) in what represents, to the best of our knowledge, the largest sample investigated to date, and to evaluate the independent predictive value of regional DAT measures for MDD diagnosis beyond demographic variables.

Methods

Participants were retrospectively selected from a large database of 123I-FP-CIT single-photon emission computed tomography scans collected at the Nuclear Medicine Unit of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome. The final analytic sample comprised 180 participants: 111 patients with MDD and 69 HC. MDD diagnosis was established according to DSM-5 criteria, and only patients with a Hamilton Depression Rating Scale (HDRS) total score ≥18 were included. Subjects with conditions potentially affecting dopaminergic functioning, including Parkinson’s disease, bipolar disorder, psychotic disorders, and treatment with dopaminergic agents, were excluded. Striatal DAT availability was quantified using BasGanV2 software. Given strong inter-hemispheric correlations, bilateral mean indices were derived for caudate and putamen to address multicollinearity. Multivariable logistic regression was performed with diagnostic group as the dependent variable and age, gender, bilateral mean caudate, and bilateral mean putamen DAT availability as predictors. Model discrimination was evaluated via receiver operating characteristic curve analysis with DeLong’s method, internal validation via bootstrap resampling (1,000 iterations), and calibration via Brier score. All analyses were conducted in R version 4.5.1.

Results

Groups were comparable for age and gender distribution (all p > 0.05). Depressive symptom severity was markedly higher in MDD patients than in HC, with a large effect size (p < 0.0001, Cohen’s d = 1.21). Patients with MDD showed reduced DAT availability across all striatal regions, with the most pronounced difference observed in the right putamen (p = 0.0001, Cohen’s d = 0.722). In the multivariable logistic regression model, lower bilateral mean putamen DAT availability was the only independent predictor of MDD diagnosis (OR = 0.19, 95% CI = 0.06–0.52, p = 0.002), whereas caudate DAT availability, age, and gender were not significant. The addition of striatal DAT measures significantly improved model fit beyond demographics alone (ΔR² = 0.108, p = 0.0006), with the full model achieving an area under the curve of 0.69, supported by acceptable internal validation and calibration.

Conclusions. In the largest sample examined to date, reduced putamen DAT availability emerged as an independent neuroimaging predictor of MDD diagnosis, accounting for meaningful variance beyond demographic factors. These findings strengthen the evidence for a selective putaminal dopaminergic deficit in MDD and support the potential utility of DAT imaging as a diagnostic adjunct in clinically complex presentations.

References

  1. Mizuno Y, Ashok AH, Bhat BB, Jauhar S, Howes OD. Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies. J Psychopharmacol. 2023 Nov;37(11):1058-1069. doi: 10.1177/02698811231200881.
  2. Pettorruso M, d’Andrea G, Martinotti G, Cocciolillo F, Miuli A, Di Muzio I, Collevecchio R, Verrastro V, De-Giorgio F, Janiri L, di Giannantonio M, Di Giuda D, Camardese G. Hopelessness, Dissociative Symptoms, and Suicide Risk in Major Depressive Disorder: Clinical and Biological Correlates. Brain Sci. 2020 Aug 5;10(8):519. doi: 10.3390/brainsci10080519.
  3. Camardese G, De Risio L, Di Nicola M, Pucci L, Cocciolillo F, Bria P, Giordano A, Janiri L, Di Giuda D. Changes of dopamine transporter availability in depressed patients with and without anhedonia: a 123I-N-ω-fluoropropyl-carbomethoxy-3β- (4-Iodophenyl)tropane SPECT study. Neuropsychobiology. 2014;70(4):235-43. doi: 10.1159/000368117.