Midbrain Serotonin Transporter Availability Research Articles

A study of tryptophan, kynurenine and serotonin transporter in first-episode drug-naïve major depressive disorder

Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naïve MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naïve MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD.

Interleukin-1 family and serotonin transporter in first-episode, drug-naive major depressive disorder: A pilot study

Abnormalities of neuroinflammatory process and serotonergic system have been reported in major depressive disorder (MDD). However, most previous studies were performed in recurrent MDD and only a few studies explored the interaction of the two systems. This study examined both systems concurrently and their clinical relevance in first-episode drug-naive MDD. Thirty-four MDD patients and 34 age and gender matched healthy controls (HC) were recruited. Plasma concentrations of the cytokines of interleukin-1 (IL-1) family, including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2) were measured using enzyme-linked immune-sorbent assays. The serotonin transporter (SERT) availability in midbrain, thalamus, caudate, and putamen was examined by single-photon emission computed tomography with 123I-ADAM. There were significantly lower concentrations of pro-inflammatory IL-1β and its inhibitor, IL-1R2 in MDD than HC. The SERT availability was at the same level between groups. A negative association between IL-1Ra concentration and the SERT availability in midbrain was observed in MDD but not in HC. Both IL-1β concentration and the SERT availability in caudate negatively correlated with depression severity and the effect of IL-1β was not moderated or mediated by the SERT. In conclusion, this study demonstrated the involvement of IL-1 family in the early stage of MDD, especially for IL-1β. SERT was not the main central target of altered IL-1β and these two systems might contribute to MDD by different mechanisms. The pathophysiology might be varied between early and recurrent MDD and tuning treatment strategies at different clinical stages might be needed.

Memory performance associates with serotonin transporter in midbrain and pons in healthy subjects.

We aimed to evaluate the association between the availability of serotonin transporter (SERT) measured by ioflupane-DaTSCAN (123I-FP-CIT) and imaged by single photon emission tomography (SPET) and memory function in healthy subjects. Specific binding of 123I-FP-CIT indicating SERT was achieved using a region of interest analysis. Spherical volumes of interest for midbrain and pons were defined. The cerebellum was chosen as a reference region. Specific binding ratios (SBR) in midbrain and pons representing SERT availability were measured as follows: SBR=(target-cerebellum)/cerebellum. A hundred and eighty-one healthy subjects (117 male, 64 female) were included in this study. Specific binding ratios of both midbrain (P=0.025) and pons (P=0.006) of males was higher than that of females. None of the SBR showed a correlation with age both in males: (midbrain; P=0.736, pons; P=0.875) and in females (midbrain; P=0.294, pons; P=0.170). In all our cases, SERT availability of midbrain correlated positively with total recall score (rho=0.159, P=0.033), and delayed recall score (rho=0.149, P=0.046). In females, the correlation between SERT availability in midbrain and delayed recall score was significant (rho=0.320, P=0.010), however, not in males (rho=0.112, P=0.229). In conclusion, we demonstrated that SERT availability was associated with memory function in healthy females from the PPMI database. Further studies are needed to clarify underlying mechanisms of this phenomenon.

The Effect of Obesity on the Availabilities of Dopamine and Serotonin Transporters

The authors investigated relations between obesity, age, and sex and the availabilities of striatal dopamine transporter (DAT) and extrastriatal serotonin transporter (SERT) by 123I-FP-CIT single-photon emission computed tomography. The study population consisted of 192 healthy controls with screening 123I-FP-CIT scans. Specific bindings of 123I-FP-CIT to DAT and SERT were calculated using regions of interest. Specific binding ratios (SBRs) of DAT and SERT except pons (r = 0.2217, p = 0.0026), were not correlated with body mass index (BMI). SBRs of midbrains correlated negatively with the BMIs of obese subjects (r = −0.3126, p = 0.0496), and positively with the those of non-obese subjects (r = 0.2327, p = 0.0053). SBRs of caudate nucleus (r = −0.3175, p < 0.0001), striatum (r = −0.226, p = 0.0022), and thalamus (r = −0.1978, p = 0.0074) reduced with age, and SERT availability was higher in males. However, DAT availability was similar in males and females. In conclusion, obesity has an effect on midbrain SERT availability. In addition, BMI was correlated with pontine SERT availability but not with striatal DAT availability. SERT availability was higher in males, but DAT availability showed no gender predilection.

The correlation between mid-brain serotonin transporter availability and intelligence quotient in healthy volunteers

PurposeThis study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). MethodsOne hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [123I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects’ IQ using the WAIS-R. ResultsWe found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. ConclusionThis result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.

Serotonin Transporter Availability in Early Stage Parkinson’s Disease and Multiple System Atrophy

Background. Differentiating Parkinson's disease (PD) from multiple system atrophy (MSA) can be challenging especially early in the course of the disease. Previous studies have shown that midbrain serotonin transporter (SERT) availability in patients with established MSA was significantly lower compared to PD. It is unknown if this is also true for early-stage patients. Methods. 77 early-stage, untreated PD patients were recruited between 1995 and 1998, underwent [123I]β-CIT SPECT imaging, and were followed for at least five years. 16 patients were lost to followup, and in 4 the diagnosis was changed to another atypical parkinsonian syndrome, but not in MSA. In 50 patients, the PD diagnosis was unchanged at followup. In seven patients, the diagnosis was changed to MSA at followup. We retrospectively assessed baseline midbrain SERT availability as well as midbrain SERT-to-striatal dopamine transporter (DAT) ratios. Results. No difference in baseline [123I]β-CIT SERT availability was found. The midbrain SERT-to-striatal DAT ratio for whole striatum was significantly lower in patients with PD compared to MSA (P = 0.049). However, when adjusting for the disease duration at imaging this difference is not significant (P = 0.070). Conclusion. Midbrain SERT availability is not different between early-stage PD and MSA. Therefore, SERT imaging is not useful to differentiate between early PD and MSA.

Probing the association between dexamethasone-induced cortisol suppression and serotonin transporter availability among drug-free patients with major depressive disorder—A small-sample SPECT study with [123I]ADAM

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.

Availability of dopamine and serotonin transporters in opioid-dependent users—a two-isotope SPECT study

The aims of this study were to examine the differences between 32 opioid-dependent users treated with a very low dose of methadone or undergoing methadone-free abstinence and 32 controls. SPECT analysis using [(99m)Tc] TRODAT-1 to assess striatal dopamine transporter (DAT) availability and [(123)I] ADAM to assess midbrain serotonin transporter (SERT) availability were performed. Lower striatal DAT and midbrain SERT availabilities were noted in low-dose methadone users. History of metamphatamine use was associated with the lower striatal DAT. The striatal DAT of methadone-free abstainers was also lower than controls. The midbrain SERT availability tended to be higher in the methadone-free abstainers than the low-dose methadone users. The severity of depressive symptoms was negatively correlated with midbrain SERT availability in the opioid users. The availability of striatal DAT tended to be, and the availability of midbrain SERT was, lower in the opioid users. History of metamphatamine use may confound the difference in straital DAT between controls and opioid users, as midbrain SERT and depressive symptoms are also associated with opioid use and abstinence.

Cerebral Glucose Utilisation in Hepatitis C Virus Infection-Associated Encephalopathy

Patients with hepatitis C virus (HCV) infection frequently show neuropsychiatric symptoms. This study aims to help clarify the neurochemical mechanisms behind these symptoms and to add further proof to the hypothesis that HCV may affect brain function. Therefore, 15 patients who reported increasing chronic fatigue, mood alterations, and/or cognitive decline since their HCV infection underwent neurologic and neuropsychological examination, magnetic resonance imaging, (18)F-fluoro-deoxy-glucose positron emission tomography of the brain, and single photon emission tomography of striatal dopamine and midbrain serotonin transporter (SERT) availability. None of the patients had liver cirrhosis. Patients' data were compared with data of age-matched controls. In addition, regression analysis was performed between cognitive deficits, and mood and fatigue scores as dependent variables, and cerebral glucose metabolism, dopamine, or SERT availability as predictors. Patients showed significant cognitive deficits, significantly decreased striatal dopamine and midbrain SERT availability, and significantly reduced glucose metabolism in the limbic association cortex, and in the frontal, parietal, and superior temporal cortices, all of which correlated with dopamine transporter availability and psychometric results. Thus, the study provides further evidence of central nervous system affection in HCV-afflicted patients with neuropsychiatric symptoms. Data indicate alteration of dopaminergic neurotransmission as a possible mechanism of cognitive decline.

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. We included 49 depressed outpatients (mean+/-SD 42.3 +/- 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for >or=4 weeks, and 49 healthy controls matched for age (+/-2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [(123)I]beta-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP(ND)) in the midbrain and diencephalon with cerebellar binding as a reference. In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis x gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis x gender interaction (p = 0.002) and an additional smoking x gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis x gender and gender x smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

Season and gender modify in-vivo serotonin transporter binding in depressed patients and healthy controls

Background: The pathogenesis of major depressive disorder (MDD) is not unraveled. Involvement of the serotonin system is undoubted. More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We measured SERT and studied modifying effects of age, gender and other clinical variables in MDD patients versus healthy controls. Methods: Forty-nine depressed outpatients (42.3±8.3 [SD] years) with a Hamilton Depression Rating Scale above 18, who were drug-naive or drug-free for =4 weeks, and 49 age(±2 years) and sex-matched healthy controls were studied in a case-control design. Subjects were scanned with single photon emission computed tomography (SPECT) using [I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BDND) in midbrain (MID) and (hypo-) thalamus (THAL) with cerebellar binding as a reference. Results: In simple comparisons between patients and controls, we found no significant differences in SERT availability in MID or THAL. However, a significant interaction of gender on SERT in patients versus controls was found in MID (ANCOVA; p=0.048) and THAL (ANCOVA; p=0.012). Depressed males had lower, and depressed females higher SERT availability versus controls. In MID we found significant confounding by the season when patients were scanned (ANCOVA; p=0.017), with higher SERT availability in winter. Furthermore, patients with a current episode of N2 years seemed to have significant higher MID SERT availability than patients ill ≤2 years and healthy controls. Conclusion: This study points to a complex interaction of sex, season and the duration of the current episode of MDD on the serotonergic system in the pathogenesis of MDD, which should be considered in future studies.

Changes in midbrain serotonin transporter availability in atypically depressed subjects after one year of psychotherapy

Background Psychotherapy is an effective treatment method for depression, but no differences in the psychotherapy response have been found between the subtypes of depression. The effect of psychotherapy on neurotransmitter transporter functions has never been recorded in depressed subjects. Methods Depressive outpatients ( N = 19) received psychodynamic psychotherapy for 12 months. All subjects fulfilled the DSM-IV criteria for depression, and 8 were classified as having atypical depression. The severity of depression was assessed with the 29-item Hamilton Depression Rating Scale (HAM-D-29). Midbrain serotonin transporter (SERT) and striatum dopamine transporter (DAT) densities were recorded using single photon emission computed tomography (SPECT) brain imaging with the [ 123I]nor-β-CIT radioligand before and after psychotherapy. Results Midbrain SERT density significantly increased during psychotherapy in atypicals but not in nonatypicals. There were no changes in the levels of DAT. Conclusions The psychotherapy-related SERT elevation of atypically depressed subjects may be due to some unknown adaptive mechanisms inducing an increase in either the levels of SERT or serotonergic nerve terminals and therefore enhancing serotonergic activity and improving mood.