cinanserin and Depressive-Disorder--Major

Several studies have reported low brain serotonin transporter (SERT) binding in individuals with major depression. We hypothesized that the SERT standardized uptake ratio (SUR) values using [(123) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy (CBT) compared to CBT nonresponders. [(123) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed, healthy volunteers. The primary outcome measure was change over time in SUR values in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain (P = .011), right medial temporal lobe (P = .008), and left medial temporal lobe (P = .000) regions. Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe (P = .029) and right medial temporal lobe (P = .007) regions. Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region (P = .040) (vs. healthy volunteers), but to a lesser degree. The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement.

Topics: Brain; Cinanserin; Cognitive Behavioral Therapy; Depressive Disorder, Major; Female; Humans; Male; Metabolic Clearance Rate; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Serotonin Plasma Membrane Transport Proteins; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [(123)I]-ADAM SPECT. The midbrain SERT availability (SERT V(3)'') was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 +/- 0.27 vs. 0.71 +/- 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.

Topics: Adult; Brain Mapping; Cinanserin; Citalopram; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Radiopharmaceuticals; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain.. In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment.. A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT.. The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

Topics: Adult; Antidepressive Agents; Case-Control Studies; Cinanserin; Depressive Disorder, Major; Female; Functional Neuroimaging; Humans; Iodine Radioisotopes; Male; Mesencephalon; Middle Aged; Radiopharmaceuticals; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Young Adult

Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD.. Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [¹²³I] 2-((2-((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(⁹⁹m)Tc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment.. SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups.. The results with regard to the midbrain SERT level suggest the heritability of MDD.

Topics: Adult; Cinanserin; Depressive Disorder, Major; Dopamine Plasma Membrane Transport Proteins; Family; Female; Healthy Volunteers; Humans; Iodine Radioisotopes; Male; Mesencephalon; Middle Aged; Neostriatum; Organotechnetium Compounds; Radiopharmaceuticals; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

The association between hypothalamo-pituitary-adrenal (HPA) axis function and the serotonergic system could be involved in the mechanism of depression. However, neuroimaging evidence is scarce. The aim of the present study was to probe the association between dexamethasone suppression test response and serotonin transporter (SERT) availability in drug-free patients with major depressive disorder (MDD). Seventeen MDD patients (five males and twelve females) were recruited. SPECT with [(123)I] ADAM was used to measure the midbrain SERT availability, and HPA axis function was measured by the dexamethasone suppression test (DST). The association was significant when considering all participants (ρ=0.69, p=0.002). This association may have clinical implications for the treatment of MDD.

Topics: Adult; Cinanserin; Depressive Disorder, Major; Dexamethasone; Female; Humans; Hydrocortisone; Male; Mesencephalon; Pituitary-Adrenal Function Tests; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon

We examined midbrain, medial temporal lobe, and basal ganglia serotonin transporter (SERT) distribution volume ratio (DVR) values in subjects with major depressive disorder versus healthy volunteers using a selective SERT radioligand and single photon emission computed tomography (SPECT). We hypothesized that the DVR value for SERT binding would be lower in depressed versus non-depressed subjects. [(123)I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 20 drug-free depressed subjects and 10 drug-free healthy volunteers. The primary outcome measure was the DVR value for [(123)I]-ADAM uptake in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated significantly lower DVR values in the midbrain, right and left medial temporal lobe, and right and left basal ganglia. There was significant probability that lower DVR values could distinguish between depressed and non-depressed subjects in the midbrain, medial temporal lobe, and the right and left basal ganglia. These findings confirm prior observations of lower SERT binding in depression, and suggest that low SERT binding may represent a putative biomarker of depression. Future studies are needed to confirm these observations.

Topics: Adult; Brain; Brain Mapping; Cinanserin; Depressive Disorder, Major; Female; Functional Laterality; Humans; Iodine Radioisotopes; Male; Middle Aged; Predictive Value of Tests; Protein Binding; ROC Curve; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon

Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depression who are in a depressed state in comparison with healthy controls. The aim of this study was to examine the distribution volume ratios (DVRs) of SERT and DAT in drug-free and euthymic patients with a history of major depression. Subjects comprised 13 patients with a history of major depression and 26 sex- and age-matched healthy controls. The euthymic state of depression was defined as a score of 7 or less on the Hamilton Depression Rating Scale. The DVRs of SERT and DAT were approximated using SPECT, with [(123)I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There were no significant differences in the DVRs of SERT or DAT between healthy subjects and euthymic patients with a history of major depression; hence, the SERT and DAT DVRs may not therefore be trait markers for patients with major depression, which helps us to understand more about the pathophysiology of depression.

Topics: Adult; Brain; Brain Mapping; Case-Control Studies; Cinanserin; Depressive Disorder, Major; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Psychiatric Status Rating Scales; Radiopharmaceuticals; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

The serotonergic system may play an important role in the pathophysiology of major depressive disorder (MDD). Few imaging studies have examined serotonin transporter (SERT) binding in patients with MDD. We hypothesized that SERT binding activity may be altered in patients with MDD. This study compared SERT binding in patients with MDD with that in healthy controls.. We studied SERT activity in 7 patients (22-50 y old) with moderate to severe MDD and 6 healthy controls (24-56 y old) using (123)I-labeled 2-((2-((dimethylamino)methyl) phenyl)thio)-5-iodophenylamine (ADAM) and SPECT brain imaging. Subjects underwent SPECT 4 h after intravenous administration of 185 MBq (5 mCi) of (123)I-ADAM. Images were reconstructed in the axial plane, and region-of-interest demarcations were placed on the midbrain, medial temporal region, and basal ganglia region.. (123)I-ADAM binding to SERT in the midbrain was significantly lower (P = 0.01) in MDD patients (1.81 +/- 0.07) than in controls (1.95 +/- 0.13). Age-adjusted (123)I-ADAM binding in the midbrain correlated significantly with scores on the Hamilton Depression Rating Scale (r = 0.82; P = 0.02). A significant negative correlation was observed between (123)I-ADAM SERT binding in the midbrain and age in the healthy control group (r = 0.98; P = 0.0002). SERT binding in the basal ganglia or medial temporal regions of interest did not significantly differ between groups.. The findings from this preliminary study suggest the possibility of decreased SERT binding in the midbrain region of patients with MDD, with the degree of decrease correlating with the severity of depressive symptoms. There also appears to be an age-related decline in midbrain (123)I-ADAM SERT binding in healthy subjects.

Topics: Adult; Age Factors; Cinanserin; Depressive Disorder, Major; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mesencephalon; Middle Aged; Nerve Tissue Proteins; Protein Binding; Radiopharmaceuticals; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon