Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [123I] nor-beta-CIT in DD patients (n=8) and compared it to that in MD patients (n=11) and healthy controls (n=19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [123I] nor-beta-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t=3.55, p=0.009; MD: t=5.86, p<0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [123I] nor-beta-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [123I] nor-beta-CIT binding correlated inversely with the duration of both dysthymia (rho=-0.76, p=0.03) and MD (rho=-0.83, p=0.01) in the DD group. No such finding was observed in the MD group (rho=0.26, p=0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [123I] nor-beta-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [123I] nor-beta-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [123I] nor-beta-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.