Aim: Psychomotor retardation, a slowing of mental and motor activity, is considered a cardinal feature of Major Depressive Disorder (MDD). Several lines of evidence link an underlying central dopaminergic abnormality to the expression of this psychopathological dimension. To date, few and equivocal results are available on pre-synaptic dopaminergic dysfunction in depression. The aim of this study was to assess dopamine transporter (DAT) availability in depressed pts with psychomotor retardation using 123I-FP-CIT SPET. Materials and Methods: 8 drug-free pts (2 f, 6 m, mean age: 53 ± 12 years) with MDD were enrolled in the study. All pts had marked psychomotor retardation (score>18 on the Depressive Retardation Rating Scale, DRRS). Severity of depression, levels of anxiety and anhedonia were assessed by Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Snaith Hamilton Pleasure Scale (SHPS), respectively. SPET was carried out 3 hs after 111 MBq 123I-FP-CIT intravenous injection. A semiquantitative analysis was performed on summed transaxial slices: striatum-to-occipital cortex, caudate-to- occipital cortex and putamen-to-occipital cortex uptake ratios were calculated for left and right sides. Control group consisted of 16 healthy volunteers (7 f, 9 m, mean age: 42 ± 12 years). Results: All pts had a moderate-to-severe depression (HDRS mean score: 25.5 ± 3.9); DRRS mean score was 29.3 ± 9.3. A significant decrease in DAT availability was found in bilateral striatum of depressed pts in comparison with controls (right striatum:-30%; left striatum:-31%; p<0.05, respectively). Mean 123I- FP-CIT uptake ratios were significantly lower for caudate and putamen on both sides (right caudate:-28%; right putamen:-31%; left caudate:-29%; left putamen:-33%; p<0.05). Inverse correlations between DRRS scores and DAT availability were observed in bilateral striatum (p< 0.05), with the highest Spearman’s correlation coefficients in the right caudate (Rs:-0.80, p=0.03) and right putamen (Rs:-0.81, p=0.02). No significant correlations between DAT availability and other psychometric scores (HDRSs, SHPSs and HARSs) were found. Conclusion: These preliminary results suggest that striatal DAT availability differs between depressed pts with psychomotor retardation and healthy subjects and provide evidence of a link between dopaminergic dysfunction and slowing of mental and motor activity in MDD. Our findings are in agreement with several lines of investigation suggesting a key role of dopamine deficiency in the pathophysiology of psychomotor retardation. Further studies are needed to clarify the role of DAT in MDD and to determine whether antidepressants that directly enhance dopaminergic transmission would be useful in treating pts with psychomotor retardation as principal symptom.