2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Depressive-Disorder

We investigated the striatal and extrastriatal DAT availability (SPM8) by [(123)I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p < 0.05) lower tracer binding in PD with depression was found in left cingulate cortex, persistent after correction for age, disease severity and duration, and inversely correlated with depression scores (r -0.336, p < 0.05). Our data indicate a significant association between PD depression and cingulate dopaminergic denervation supporting the dopaminergic hypothesis of PD depression.

Topics: Aged; Brain Mapping; Caudate Nucleus; Depressive Disorder; Dopamine; Gyrus Cinguli; Humans; Parkinson Disease; Putamen; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Depression frequently accompanies in Parkinson's disease (PD). Previous research suggested that dopamine (DA) and serotonin systems are closely linked with depression in PD. However, comprehensive studies about the relationship between these two neurotransmitter systems are limited. Therefore, the purpose of this study is to evaluate the effect of dopaminergic destruction on the serotonin system. The interconnection between motor and depression was also examined. Two PET scans were performed in the 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats: [(18) F]FP-CIT for DA transporters and [(18) F]Mefway for serotonin 1A (5-HT(1A)) receptors. Here, 6-OHDA is a neurotoxin for dopaminergic neurons. Behavioral tests were used to evaluate the severity of symptoms: rotational number for motor impairment and immobility time, acquired from the forced swim test for depression. Region-of-interests were drawn in the striatum and cerebellum for the DA system and hippocampus and cerebellum for the 5-HT system. The cerebellum was chosen as a reference region. Nondisplaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, the degree of DA depletion was negatively correlated with rotational behavior (R(2)  = 0.79, P = 0.003). In 6-OHDA lesioned rats, binding values for 5-HT(1A) receptors was 22% lower than the sham operated group. This decrement of 5-HT(1A) receptor binding was also correlated with the severity of depression (R(2)  = 0.81, P = 0.006). Taken together, this research demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior. The degree of dopaminergic dysfunction was positively correlated with the impairment of the serotonin system. Severity of motor symptoms was also closely related to depressive behavior.

Topics: Animals; Brain; Depressive Disorder; Disease Models, Animal; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Movement Disorders; Oxidopamine; Piperazines; Positron-Emission Tomography; Pyridines; Radiopharmaceuticals; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Serotonin; Tropanes

Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes.. Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment.. Depressed patients with and without anhedonia showed significantly lower (123)I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of (123)I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer.. We suppose that a hypofunction of the striatal dopaminergic system may be a 'state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state.

Topics: Adult; Anhedonia; Corpus Striatum; Depressive Disorder; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon; Tropanes

Serotonin transporters (SERT) are a major target for antidepressant medication, although there have been limited in vivo studies of SERT availability in patients being treated with antidepressants. It is not known whether SERT availability differs in treatment-responsive and -nonresponsive patients receiving long-term treatment. In this study, we used single photon emission computed tomography (SPECT) to compare SERT residual availability in unipolar responders and nonresponders during long-term antidepressant treatment. Dopamine transporter (DAT) availability was also assessed in the same patients to examine the relationship between the two transporter systems.. Twenty-four medicated unipolar patients were recruited, of whom 11 were responders and 13 were nonresponders. All patients underwent SPECT with [123I] beta-carbomethoxy-3-beta-(4 iodophenyl)tropane. Brain SERT was measured in the brain stem and diencephalon, and DAT was measured in the striatum. Residual availability was calculated as a ratio of specific to nonspecific uptake, with the occipital region used as the nonspecific reference region.. There was no difference between responders and nonresponders in SERT availability. Dopamine transporter availability was similar in responders and nonresponders, and there was no association between SERT and DAT availability.. Serotonin transporter availability does not discriminate responders and nonresponders during long-term treatment with antidepressants.

Topics: Adult; Aging; Antidepressive Agents; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder; Female; Humans; Image Processing, Computer-Assisted; Male; Mianserin; Middle Aged; Mirtazapine; Radiopharmaceuticals; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes; Venlafaxine Hydrochloride