123I] ADAM brainstem binding correlates with the loudness dependence of auditory evoked potentials

The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 +/- 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson's correlations: rho = -0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = -0.60, p < 0.05) but were pronounced in the female group (rho = -0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.     

Use of a single [<Superscript>123</Superscript>I]-FP-CIT SPECT to predict the severity of clinical symptoms of Parkinson disease

The aim of this study was to assess the ability of a single SPECT performed in the early stage of Parkinson’s disease (PD) to predict disease severity in 19 patients with early PD. [¹²³I]-FP-CIT striatal uptake was expressed as a ratio of specific:nonspecific uptake for defined brain areas. Clinical severity was determined by the UPDRS at baseline and 12–15 months following the SPECT procedure. [¹²³I]-FP-CIT uptake in the contralateral putamen and striatum was correlated with UPDRS score at baseline, with a more significant correlation after 1-year interval. [¹²³I]-FP-CIT uptake in all areas was correlated with bradykinesia and rigidity subscores only at follow up visit. Significant correlations were found between [¹²³I]-FP-CIT uptake in the contralateral striatum, putamen and caudate and the difference between motor scores of 1-year interval (ΔUPDRS). These results suggest that disease severity might be anticipated by a single SPECT at an early stage of the disease.     

Midbrain serotonin transporters in de novo and L‐DOPA‐treated patients with early Parkinson’s disease – a [123I]‐ADAM SPECT study

Background: Dopaminergic availability is known to linearly decline in Parkinson’s disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [¹²³I]‐ADAM and single‐photon emission tomography (SPECT) in drug‐naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurence of the characteristic motor symptoms. Methods: Nine de novo patients with PD and 9 age‐matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [¹²³I]‐FP‐CIT SPECT. Results: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. Conclusions: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.     

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Summary. 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 [¹²³I]-ADAM SPECT. The midbrain SERT availability (SERT V₃″) 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.     

I-123] ADAM and SPECT in patients with borderline personality disorder and healthy control subjects

OBJECTIVE: Serotonergic dysfunction is considered to be involved in the pathophysiology of borderline personality disorder (BPD). The aim of this study was to investigate serotonin transporter availability in patients with BPD as a marker of the central serotonergic system. METHODS: Eight unmedicated patients with BPD and 9 healthy control subjects received single photon emission computed tomography (SPECT) 4 hours after injection of 185 MBq [I-123] ADAM (2-([2-([dimethylamino]methyl)phenyl]thio)). As a measure of brain serotonin transporter (SERT) availability, ratios of specific-to-nonspecific [I-123] ADAM binding for the brainstem and hypothalamus were calculated with an occipital reference. Levels of impulsiveness and depressive symptoms were assessed with the Barratt Impulsiveness Scale and the Beck Depression Inventory. RESULTS: Mean specific-to-nonspecific ratios showed a 43% higher brainstem and a 12% higher hypothalamus ADAM binding in patients, compared with control subjects. We found significant correlations of ADAM binding with both age and impulsiveness but not depression. Associations of BIS scores with ADAM binding remained significant after controlling for age and depression (r = 0.69, p < 0.01). CONCLUSION: The study provides evidence of a serotonergic dysfunction in patients with BPD and suggests a serotonergic component in the pathophysiology of the disorder. SERT binding reflected the level of impulsiveness as a common feature in BPD.     

Association between serotonin transporter availability and hostility scores in healthy volunteers—A single photon emission computed tomography study with [123I] ADAM

The present study examined the relationship between serotonin transporter (SERT) availability and hostility scores in healthy volunteers. SERT availability was measured by using SPECT with [¹²³I] ADAM in 10 healthy participants. Hostility was measured with the Cook–Medley Hostility Scale. Hostile attribution, but not the other subscales of hostility, was negatively correlated with SERT availability. Central serotoninergic activities may play a role in hostility.     

Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers

Objective

Serotonin modulates human behavior and emotion. Recent evidence implies that a higher level of serotonergic activity could be associated with a higher level of perceived social support. This study aimed to examine the correlation between serotonin transporter (SERT) availability and perceived social support scores in healthy volunteers.

Methods

111 healthy participants, 50 males and 61 females, were enrolled from the community and completed the Measurement of Support Function questionnaire. Single photon emission computed tomography (SPECT) with [¹²³I] ADAM was performed to examine SERT availability.

Results

Perceived social support was positively correlated with SERT availability (Spearman's ρ = 0.29, p < 0.01; χ² = 7.57, p < 0.01), particularly in males (Spearman's ρ = 0.37, p < 0 .01; χ² = 11.77, p < 0.01). Censored regressions indicated that these associations are not influenced by a ceiling effect and remained significant after controlling the effect of age.

Conclusions

This result confirmed the correlation between perceived social support and central serotonergic activity. However, this correlation was present only in males.     

Visual assessment of dopaminergic degeneration pattern in <Superscript>123</Superscript>I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease

The aim of this study was to investigate whether visual assessment of ¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (¹²³I-FP-CIT) single photon emission computed tomography (SPECT) in addition to quantitative analyses can help to differentiate idiopathic Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). From a consecutive series of patients examined with ¹²³I-FP-CIT SPECT (n = 190) over a three-year period we identified 165 patients with a clinical diagnosis of PD (n = 120) or APS (n = 45). ¹²³I-FP-CIT SPECT results were analysed visually and quantitatively and compared for PD and APS and for the subgroup of patients with early PD and APS (disease duration <5 years). According to predefined visual patterns of dopaminergic degeneration the results were graded as normal (grade 5) or abnormal (grade 1–4), distinguishing a posterior-anterior degeneration pattern (“egg shape”) from a global and severe degeneration pattern (“burst striatum”). Visual assessment of ¹²³I-FP-CIT SPECT showed significant different dopaminergic degeneration patterns for PD and APS patients. A grade 1 (“burst striatum”) degeneration pattern was predominantly associated with APS patients. In contrast to that, a grade 2 (egg shape) degeneration pattern was the characteristic finding in PD patients. In a subgroup of patients with early disease, visual assessment with identification of the burst striatum degeneration pattern provided 90% positive predictive value and 99% specificity for the diagnosis of APS. Quantitative analysis of striatal binding ratios failed to depict these different degeneration patterns in PD and APS patients. Visual assessment of the pattern of dopaminergic loss in ¹²³I-FP-CIT SPECT shows different patterns of dopaminergic degeneration for PD and APS patients. Therefore, it could provide valuable information to distinguish APS from PD patients, especially in early stages of disease. Within the first 5 years of disease, the occurrence of a burst striatum degeneration pattern has a high positive predictive value of APS.     

Lower availability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder – a preliminary two-ligand SPECT study

PurposeSerotonin 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.MethodsEight 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 [^99mTc] 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.ResultsSERT 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.ConclusionsThe results with regard to the midbrain SERT level suggest the heritability of MDD.     

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease

Objective: One of the most frequent psychiatric symptoms in patients with Wilson's disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. Methods: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus–hypothalamus and the midbrain–pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2β-carbomethoxy-3β-(4 [¹²³I]iodophenyl)tropane ( [¹²³I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. Results: A significant negative correlation was found between HAMD and SERT density in the thalamus–hypothalamus region (r = −0.49, p = 0.02), but not in the midbrain–pons (r = −0.31, p = 0.15). Conclusions: We conclude that depression in patients with Wilson's disease is correlated with alterations of serotonergic neurotransmission in the thalamus–hypothalamus region. Received: 24 July 2002, Received in revised form: 20 November 2002, Accepted: 28 November 2002 Correspondence to Wieland Hermanns, MD     

Preserved serotonin transporter binding in de novo Parkinson’s disease: negative correlation with the dopamine transporter

Recent imaging and neuropathological studies indicate reduced serotonin transporter (SERT) in advanced Parkinson’s disease (PD). However, data on SERT in early PD patients are sparse. Following the hypothesis that the serotonergic system is damaged early in PD, the aim of our study was to investigate SERT availability by means of PET imaging. Since the loss of dopaminergic neurons is the pathologic hallmark of PD and SERT might be associated with psychiatric co-morbidity, we further sought to correlate SERT availability with the availability of dopamine transporter (DAT) and depressive or motor symptoms in early PD. We prospectively recruited nine early PD patients (4 female, 5 male; 42–76 years) and nine age matched healthy volunteers (5 female, 4 male; 42–72 years). Diagnosis of PD was confirmed by the UK brain bank criteria and DAT imaging. SERT availability was measured by means of [¹¹C]DASB PET. For neuropsychiatric assessment done on the day of PET we applied UPDRS parts I, II and III, Beck’s Depression Inventory, Hamilton Rating Scale for Depression, Mini-Mental State Examination and Demtect. SERT was not reduced in any of 14 investigated regions of interest in the nine PD patients compared to healthy controls (p > 0.13). SERT was negatively associated with DAT in the striatum (r = −0.69; p = 0.04) but not within the midbrain. There was no correlation of SERT availability with depressive symptoms. No alteration of SERT binding in our patients suggests that the serotonergic system is remarkably preserved in early PD. Correlation with DAT might point to a compensatory regulation of the serotonergic system in early stages of PD.     

Short term vs. long term test–retest reproducibility of I-ADAM for the binding of serotonin transporters in the human brain

Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test–retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52–0.94 across different brain regions over 1 month, whereas the ICC was - 0.24 – 0.63 over a 1 -year period. The 1 -month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1 -year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal–Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test–retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.     

Increased serotonin transporter availability in the brainstem of migraineurs

Abstract For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central serotonergic system is located in the raphe nuclei and the adjacent reticular formation in the brainstem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand ¹²³I-ADAM [2-((2-((dimethylamino) methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine serotonergic system being involved in the pathophysiology of migraine. Nineteen migraine patients and 10 healthy, age- and sex-matched controls were enrolled. The neuroimaging study was performed interictally during the pain-free interval. Single Photon Emission Computed Tomography (SPECT)-images were coregistered with MRI-scans. Region of interest (ROI)-analysis revealed a highly significant increase of ¹²³I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, ¹²³IADAM uptake in the thalamus did not differ significantly between migraineurs and controls. Our study demonstrates for the first time a significant increase of brainstem SERT-availability in migraineurs, suggesting a dysregulation of the brainstem serotonergic system. It remains to be elucidated whether the altered SERT-availability is causally related to migraine pathophysiology or whether it reflects secondary pathophysiological mechanisms.     

Association between serotonin transporter availability and hostility scores in healthy volunteers - a single photon emission computed tomography study with [(123)I] ADAM

The present study examined the relationship between serotonin transporter (SERT) availability and hostility scores in healthy volunteers. SERT availability was measured by using SPECT with [(123)I] ADAM in 10 healthy participants. Hostility was measured with the Cook-Medley Hostility Scale. Hostile attribution, but not the other subscales of hostility, was negatively correlated with SERT availability. Central serotoninergic activities may play a role in hostility.     

ADAM is an effective tool for in vivo study of serotonergic function: validation in rat models

ADAM, 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine, is a recently described SPECT tracer for exploration of the serotonin transporter. We evaluated its potential to detect abnormalities in serotonergic function in the rat using 1) a model of serotonergic neuron lesion induced with 5,7-dihydroxytryptamine (5,7-DHT), and 2) experimental induction of acute decrease in endogenous brain serotonin levels. Cerebral biodistribution studies of [125I]ADAM were performed in normal conditions, in 5,7-DHT-lesioned rats, and after acute serotonin depletion obtained with p-chlorophenylalanine (pCPA). Around 50% reduction in accumulation of ADAM was observed in the hypothalamus and hippocampus 3 weeks after lesion of serotonergic neurons, whereas a more modest decrease of 15-30% occurred in the thalamus, frontal cortex, and striatum. This demonstrated the ability of the tracer to detect serotonergic neuron loss in vivo. After inducing acute 5-HT depletion with pCPA, we observed an increase in in vivo [125I]ADAM binding in all brain areas studied. The higher in vivo binding of [125I]ADAM in pCPA-treated rats than in controls was mainly due to an increase in specific binding to the SERT, as demonstrated by greatly reduced binding in the presence of a saturating dose of paroxetine. This may indicate in vivo competition between ADAM and 5-HT for binding to the SERT. The present findings thus demonstrate that ADAM is a specific SERT radioligand which can be used for in vivo study of central serotonin systems, and supports its use as a tracer for SPECT studies in human disorders involving dysfunction of serotonergic neurotransmission.     

Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression

Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [¹¹C]DASB. SERT binding potentials (BP_ND) were quantified voxel‐wise with the multilinear reference tissue model 2. In addition, SERT BP_ND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole‐brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t = 5.85, P < 0.05 corrected and t = 5.07, P < 0.1 corrected) when comparing MDD patients (R² = 0.11 and 0.24) to healthy subjects (R² = 0.72 and 0.66, P < 0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations. Hum Brain Mapp 35:3857–3866, 2014. © 2014 Wiley Periodicals, Inc.     

Ghrelin Antagonized 1-Methyl-4-Phenylpyridinium (MPP<Superscript>+</Superscript>)-Induced Apoptosis in MES23.5 Cells

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) acting to stimulate growth hormone release. In the previous study, we have observed the neuroprotective effects of ghrelin on dopaminergic neurons in vivo in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -treated Parkinson’s disease mice. In order to illustrate the underlying mechanisms, in the present study, we conducted our experiment in vitro in 1-methyl-4-phenylpyridinium (MPP⁺)-treated MES23.5 cells that could express GHS-R1a. Ten- to 1,000-μmol/L MPP⁺ treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-μmol/L MPP⁺ treatment was chosen to do the further experiments. MES23.5 cells treated with 200 μmol/L MPP⁺ showed decreased mitochondrial transmembrane potential, an elevated level of reactive oxidative species production and activation of caspase-3. Additionally, these cells also showed apoptotic morphological changes. Pretreatment with different doses of ghrelin (10⁻¹²–10⁻⁷ mol/L) could abolish the MPP⁺-induced apoptotic changes in a dose-dependent manner. These results suggested that ghrelin could antagonize MPP⁺-induced apoptosis in MES23.5 cells. The protective effects of ghrelin involved the restoration of mitochondria function. Juanjuan Dong and Ning Song contributed equally to this work.     

Assessing dopaminergic function in Parkinson’s disease: levodopa kinetic-dynamic modeling and SPECT

Abstract. Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinsons disease (PD). [¹²³I]-FP-CIT SPECT imaging of striatal dopamine transporters has also been introduced for the evaluation of presynaptic dopaminergic homeostasis. We aimed to assess the intrapatient relation between levodopa PK-PD and SPECT measures of dopaminergic function in PD. Thirty-five PD patients, 1 to 4 on the Hoehn and Yahr (H&Y) scale, enrolled in the study. Each patient was examined by levodopa PK-PD modeling and SPECT imaging. Primary measure outcomes were the levodopa half-life in the effect compartment (t1/2_eq) for PKPD modeling and the ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT. Levodopa t1/2_eq was highly significantly correlated with H&Y scale (r = –0.815, p < 0.0001), Unified Parkinsons disease Rating Scale (UPDRS) (r = –0.691, p < 0.0001) and PD symptom duration (r = –0.647, p < 0.0001). SPECT contralateral putamen SP/NSP ratio showed the most significant correlations with clinical indicators of disease severity: H&Y, r = –0.526, p < 0.002; UPDRS, r = –0.523, p < 0.002; symptom duration, r = –0.513, p < 0.002. Significant correlations were observed between levodopa t1/2_eq and putamen SP/NSP ratios, yielding the closest correlation for the contralateral region (r = 0.522, p < 0.002). An indirect PK-PD dopaminergic functional variable and direct SPECT measures of presynaptic dopaminergic system homeostasis were in close agreement with clinical data and correlated to each other. Levodopa PK-PD modeling can be a practical clinical tool indirectly assessing the functional integrity of the nigrostriatal dopaminergic system in PD patients.     

Clinical and [<Superscript>123</Superscript>I]FP-CIT SPET imaging follow-up in patients with drug-induced parkinsonism

We recently found that patients with drug-induced parkinsonism (DIP) may have normal (group I) or abnormal (group II) putamen [¹²³I]FP-CIT DAT (dopamine transporter) binding. In this study we reassessed clinical features and DAT binding in 19 of the original 32 patients (10 of group I and 9 of group II) after a 19–39-month follow-up period and tested the effects of chronic levodopa treatment in both cohorts of patients. In group I patients, [¹²³I]FP-CIT SPET (single photon emission tomography) was still normal in all patients at follow-up; DAT binding and UPDRS (Unified Parkinson’s Disease Rating Scale) motor score values did not differ from baseline. In group II patients, [¹²³I]FP-CIT SPET was still abnormal at follow-up; putamen DAT binding was significantly reduced and UPDRS III score higher compared to baseline. Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II. No adverse psychiatric effects were observed in any of the patients. This study shows that DAT binding imaging may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals in the context of a progressive degenerative parkinsonism. Patients with DIP may benefit from levodopa therapy, particularly when dopamine nerve terminal defects are present, and this should be considered in the therapeutic management of these patients.     

Elevated brain serotonin transporter availability in patients with obsessive-compulsive disorder.

BACKGROUND: A central serotonergic dysfunction is considered to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate the serotonin transporter availability in patients with OCD as an in vivo marker of the central serotonergic system. METHODS: Nine unmedicated (7 drug-naive) patients with OCD and 10 healthy control subjects were included and received single photon emission computed tomography (SPECT) 20.75 +/- 1.51 hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). As a measure of brain serotonin transporter availability, a ratio of specific-to-nonspecific [(123)I]beta-CIT binding for the midbrain-pons (V(3)" = [midbrain/pons-occipital]/occipital) was used. RESULTS: Mean specific-to-nonspecific ratios showed a 25% higher midbrain-pons [(123)I]beta-CIT binding in the patients as compared with healthy controls (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The difference remained significant after adjustment for clinical variables and controlling for age and gender. Stratification of the patients according to onset of the disorder revealed significant differences between controls and patients with early (childhood, adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides evidence of a serotonergic dysfunction in patients with OCD and suggests a serotonergic component in the pathophysiology of the disorder.