Preventing obesity among Brazilian adolescent girls: Six-month outcomes of the Healthy Habits, Healthy Girls-Brazil school-based randomized controlled trial.

BACKGROUND: School-based trials to prevent and reduce prevalence of pediatric obesity in low-income countries are necessary. In Brazil, addressing adolescent obesity is a public health priority. OBJECTIVE: To evaluate the impact of a group randomized controlled trial involving a 6-month multicomponent school-based obesity prevention program targeting adolescent girls. METHODS: The Healthy Habits, Healthy Girls-Brazil program recruited participants (n=253; 16.05±0.05 years) from ten eligible public technical schools in São Paulo, Brazil. The program was adapted from an Australian intervention study, which is based on the Social Cognitive Theory. The primary outcome measure was body mass index (BMI), and secondary outcomes included BMI z score, waist circumference, and various sedentary and dietary health-related behaviours. RESULTS: Although changes in BMI were not statistically significant, differences favored the intervention group (adjusted mean difference, -0.26kg/m(2),se SE=0.018, p=0.076). Statistically significant intervention effects were found for waist circumference (-2.28cm; p=, p=0.01), computer screen time on the weekends (0.63h/day, p; p=0.02), total sedentary activities on the weekends (-0.92h/day, p<0.01), and vegetable intake (1.16servings/day, p=0.01). CONCLUSION: These findings provide some evidence for the benefit of a school-based intervention to prevent unhealthy weight gain in adolescent girls living in low-income communities.

12 month changes in dietary intake of adolescent girls attending schools in low-income communities following the NEAT Girls cluster randomized controlled trial.

Poor dietary habits and obesity are more prevalent in lower socio-economic status (SES) communities. The NEAT Girls cluster randomized controlled trial was a school-based obesity prevention program targeting adolescent girls in low SES schools in NSW, Australia. The aim was to evaluate the 12-month impact of key nutrition program messages on dietary intake and food behaviors. Diet was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Individual foods were categorized into nutrient-dense or energy-dense, nutrient-poor food groups and the percentage contribution to total energy intake calculated. Participants were aged 13.2±0.5years (n=330). There were no statistically significant group-by-time effects for dietary intake or food related behaviors, with 12-month trends suggesting more intervention group girls had improved water intakes (59% consuming⩽three glasses per day to 54% at 12 months vs. 50% to 61% in controls, p=0.052), with a greater proportion consuming < one sweetened beverage per day (24-41% vs. 34-37% in controls, p=0.057). Further research including more intensive nutrition intervention strategies are required to evaluate whether dietary intake in adolescent girls attending schools in low SES communities can be optimized.

Iodine-123 labeled reboxetine analogues for imaging of noradrenaline transporter in brain using single photon emission computed tomography.

Preliminary investigation of the radioiodinated (S,S)-reboxetine analogue, (123) I-INER, in baboons showed this tracer to have promise for imaging the noradrenaline transporter (NAT) using single photon emission computed tomography (SPECT). More recently, the radioiodinated (R,S)-stereoisomer of (123) I-INER, (123) I-NKJ64, has been synthesized and preliminary evaluation in rats has been reported. This article reports the brain distribution and pharmacokinetic properties of (123) I-NKJ64 in baboons and compares results with (123) I-INER data in the same species. SPECT studies were conducted in two ovariectomized adult female baboons using two different protocols: (1) bolus of (123) I-INER or (123) I-NKJ64; and (2) bolus plus constant infusion of (123) I-NKJ64 with reboxetine (2.0 mg/kg) administration at equilibrium. Following bolus injection, both radiotracers rapidly and avidly entered the baboon brain. The regional brain accumulation of (123) I-NKJ64 did not match the known distribution of NAT in baboon brain, contrasting with previous results obtained in rats. Conversely, the regional distribution of (123) I-INER was consistent with known distribution of NAT in baboon brain. No displacement of (123) I-NKJ64 was observed following administration of reboxetine. This contrasts with previous data obtained for (123) I-INER, where 60% of specific binding was displaced by a lower dose of reboxetine. These data suggest that (123) I-NKJ64 may lack affinity and selectivity for NAT in baboon brain and (123) I-INER is the most promising iodinated reboxetine analogue developed to date for in vivo imaging of NAT in brain using SPECT. This study highlights the importance of species differences during radiotracer development and the stereochemical configuration of analogues of reboxetine in vivo.

Development and evaluation of social cognitive measures related to adolescent dietary behaviors.

BACKGROUND: This study aimed to develop and evaluate the reliability and factorial validity, of social-cognitive measures related to adolescent healthy eating behaviors. METHODS: A questionnaire was developed based on constructs from Bandura's Social Cognitive Theory and included the following scales: self-efficacy, intentions (proximal goals), situation (perceived environment), social support, behavioral strategies, outcome expectations and expectancies. The questionnaire was administered with a two week test-retest among secondary school students (n = 173, age = 13.72 ± 1.24). Confirmatory factor analysis was employed to examine model-fit for each scale using multiple indices including: chi-square index, comparative-fit index (CFI), goodness-of-fit index (GFI), and the root mean square error of approximation (RMSEA). Reliability properties were also examined (ICC and Cronbach's alpha). RESULTS: The reliability and factorial validity of each scale is supported: fit indices suggest each model to be an adequate-to-exact fit to the data; internal consistency was acceptable-to-good (α = 0.65-0.79); rank order repeatability was strong (ICC = 0.81-0.89). CONCLUSIONS AND IMPLICATIONS: Results support the reliability and factorial validity of social cognitive scales relating to healthy eating behaviors among adolescents. As such, the developed scales have utility for identifying potential social cognitive correlates of adolescent dietary behavior, mediators of dietary behavior change and validity testing of theoretical models based on Social Cognitive Theory.

Rationale and study protocol for the supporting children's outcomes using rewards, exercise and skills (SCORES) group randomized controlled trial: a physical activity and fundamental movement skills intervention for primary schools in low-income communities.

BACKGROUND: Many Australian children are insufficiently active to accrue health benefits and physical activity (PA) levels are consistently lower among youth of low socio-economic position. PA levels decline dramatically during adolescence and evidence suggests that competency in a range of fundamental movement skills (FMS) may serve as a protective factor against this trend. METHODS/DESIGN: The Supporting Children's Outcomes Using Rewards Exercise and Skills (SCORES) intervention is a multi-component PA and FMS intervention for primary schools in low-income communities, which will be evaluated using a group randomized controlled trial. The socio-ecological model provided a framework for the 12-month intervention, which includes the following components: teacher professional learning, student leadership workshops (including leadership accreditation and rewards, e.g., stickers, water bottles), PA policy review, PA equipment packs, parental engagement via newsletters, FMS homework and a parent evening, and community partnerships with local sporting organizations. Outcomes will be assessed at baseline, 6- and 12-months. The primary outcomes are PA (accelerometers), FMS (Test of Gross Motor Development II) and cardiorespiratory fitness (multi-stage fitness test). Secondary outcomes include body mass index [using weight (kg)/height (m2)], perceived competence, physical self-esteem, and resilience. Individual and environmental mediators of behavior change (e.g. social support and enjoyment) will also be assessed. The System for Observing Fitness Instruction Time will be used to assess the impact of the intervention on PA within physical education lessons. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA behavior change will be explored. DISCUSSION: SCORES is an innovative primary school-based PA and FMS intervention designed to support students attending schools in low-income communities to be more skilled and active. The findings from the study may be used to guide teacher pre-service education, professional learning and school policy in primary schools. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12611001080910.

Explaining dietary intake in adolescent girls from disadvantaged secondary schools. A test of Social Cognitive Theory.

Much of the research on the determinants of dietary behavior has been guided by Bandura's Social Cognitive Theory (SCT), yet few studies have tested the utility of its proposed structural paths. The aim of this paper was to test the capacity of SCT to explain dietary behaviors in a sample of 357 adolescent girls (13.2±0.5 years) from 12 secondary schools located in low-income communities in New South Wales, Australia. Participants completed validated SCT scales assessing nutrition-related self-efficacy, intention, behavioral strategies, family support, situation, outcome expectations, and outcome expectancies. Participants completed a validated food frequency questionnaire, from which, the percentage of total kilojoules from core-foods, non-core foods and saturated fat were calculated. The theoretical models were tested using structural equation modeling in AMOS. The models explained 48-51% and 13-19% of the variance in intention and dietary behavior, respectively. The models provided an adequate fit to the data, and self-efficacy was positively associated with healthy eating and inversely associated with unhealthy eating. However, the pathway from intention to behavior was not statistically significant in any of the models. While this study has demonstrated the utility of SCT constructs to explain behavior in adolescents girls, the proposed structural pathways were not supported. Further study of the role that implementation intentions play in explaining adolescent girls' dietary behaviors is required.

Fgfr3 regulates development of the caudal telencephalon.

The fibroblast growth factor receptor 3 (Fgfr3) is expressed in a rostral(low) to caudal(high) gradient in the developing cerebral cortex. Therefore, we hypothesized that Fgfr3 contributes to the correct morphology and connectivity of the caudal cortex. Overall, the forebrain structures appeared normal in Fgfr3(-/-) mice. However, cortical and hippocampal volumes were reduced by 26.7% and 16.3%, respectively. Hypoplasia was particularly evident in the caudo-ventral region of the telencephalon where proliferation was mildly decreased at embryonic day 18.5. Dysplasia of GABAergic neurons in the amygdala and piriform cortex was seen following GAD67 immunohistochemistry. Dye-tracing studies and diffusion magnetic resonance imaging and tractography detected a subtle thalamocortical tract deficit, and significant decreases in the stria terminalis and lateral arms of the anterior commissure. These results indicate the subtle role of Fgfr3 in formation of caudal regions of the telencephalon affecting some brain projections.

High-resolution diffusion tensor imaging of fixed brain in a mouse model of Pelizaeus-Merzbacher disease: comparison with quantitative measures of white matter pathology.

Diffusion tensor imaging (DTI) is a powerful technique for the noninvasive assessment of the central nervous system. To facilitate the application of this technique to in vivo studies, we characterised a mouse model of the leukodystrophy, Pelizaeus-Merzbacher disease (PMD), comparing high-resolution ex vivo DTI findings with quantitative histological analysis of selected areas of the brain. The mice used in this study (Plp1-transgenic) carry transgenic copies of the Plp1 gene and are models for PMD as a result of gene duplication. Plp1 transgenic mice display a mild ataxia and experience frequent seizures around the time at which they were imaged. Axial (λ(1) ) and radial (RD) diffusivities and fractional anisotropy (FA) data were analysed using an exploratory whole-brain voxel-based method, a voxel-based approach using tract-based spatial statistics (TBSS), and by application of conventional region of interest (ROI) analyses to selected white matter tracts. Raw t value maps and TBSS analyses indicated widespread changes throughout the brain of Plp1-transgenic mice compared with the wild-type. ROI analyses of the corpus callosum, anterior commissure and hippocampal fimbria showed that FA was reduced significantly, whereas λ(1) and RD were increased significantly, in Plp1-transgenic mice compared with the wild-type. The DTI data derived from ROI analyses were subsequently compared with histological measures taken in the same regions. These revealed an almost complete absence of myelin, preservation of axons, marked astrocytosis and increased or unchanged cell densities. These data contribute to our growing understanding of the basis of anisotropic water diffusion in the normal and diseased nervous system.

¹²³I-NKJ64: a novel single photon emission computed tomography radiotracer for imaging the noradrenaline transporter in brain.

Dysregulation of noradrenergic function has been implicated in a variety of psychiatric and neurodegenerative disorders, including depression and Alzheimer's disease. The noradrenaline transporter (NAT) is a major target for antidepressant drugs, including reboxetine, a selective noradrenaline reuptake inhibitor. Therefore, the development of a radiotracer for imaging of the NAT is desirable. In this study, NKJ64, a novel iodinated analog of reboxetine, was radiolabeled and evaluated as a potential single photon emission computerized tomography (SPECT) radiotracer for imaging the NAT in brain. Biological evaluation of the novel radiotracer, ¹²³/¹²5I-NKJ64, was carried out in rats using: in vitro ligand binding assays; in vitro and ex vivo autoradiography; in vivo biodistribution studies and ex vivo pharmacological blocking studies. ¹²5I-NKJ64 displayed saturable binding with high affinity for NAT in cortical homogenates (K(D) = 4.82 ± 0.87 nM, mean ± SEM, n = 3). In vitro and ex vivo autoradiography showed the regional distribution of ¹²³I-NKJ64 binding to be consistent with the known density of NAT in brain. Following i.v. injection there was rapid uptake of ¹²³I-NKJ64 in brain, with maximum uptake of 2.93% ± 0.14% (mean ± SEM, n = 3) of the injected dose. The specific to nonspecific ratio (locus coeruleus:caudate putamen) of ¹²³I-NKJ64 uptake measured by ex vivo autoradiography was 2.8 at 30 min post i.v. injection. The prior administration of reboxetine significantly reduced the accumulation of ¹²³I-NKJ64 in the locus coeruleus (>50% blocking). The data indicate that further evaluation of ¹²³I-NKJ64 in nonhuman primates is warranted in order to determine its utility as a SPECT radiotracer for imaging of NAT in brain.

SSRI antidepressants do not confound single photon emission computed tomography (SPECT) imaging studies using the alpha4beta2 nicotinic acetylcholine receptor [123I]5-I-A85380 ligand: in vivo and in vitro evidence.

PURPOSE: In clinical molecular imaging the interaction between antidepressant medication and SPECT ligands is a significant potential confound. This study measured nAChR availability, as determined by SPECT imaging, on and off selective serotonin reuptake inhibitors in first episode depressed patients. METHODS: Five patients in their first episode of major depressive disorder (MDD) on a single SSRI underwent [(123)I]5-I-A85380- SPECT neuroimaging prior to stopping their medication and again 6 weeks following medication cessation. Autoradiography of post mortem brain tissue with [(125)I]5-I-A85380 in the presence or absence of four commonly prescribed antidepressants was also assessed. RESULTS: SSRI antidepressants did not affect the relative binding availability of alpha4beta2 nicotinic acetylcholine receptors for the [(123)I]5-I-A85380 ligand in vivo. Radioligand binding in vitro was unaffected by a single, high pharmacological concentration of antidepressants. CONCLUSION: SPECT imaging studies using [(123)I]5-I-A85380 to measure alpha4beta2 nAChR availability in depressed patients are unlikely to be confounded to a major degree by concurrent antidepressant medication.

New iodinated quinoline-2-carboxamides for SPECT imaging of the translocator protein.

With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (K(i) 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195.

The Nutrition and Enjoyable Activity for Teen Girls (NEAT girls) randomized controlled trial for adolescent girls from disadvantaged secondary schools: rationale, study protocol, and baseline results.

BACKGROUND: Child and adolescent obesity predisposes individuals to an increased risk of morbidity and mortality from a range of lifestyle diseases. Although there is some evidence to suggest that rates of pediatric obesity have leveled off in recent years, this has not been the case among youth from low socioeconomic backgrounds. The purpose of this paper is to report the rationale, study design and baseline findings of a school-based obesity prevention program for low-active adolescent girls from disadvantaged secondary schools. METHODS/DESIGN: The Nutrition and Enjoyable Activity for Teen Girls (NEAT Girls) intervention will be evaluated using a group randomized controlled trial. NEAT Girls is a 12-month multi-component school-based intervention developed in reference to Social Cognitive Theory and includes enhanced school sport sessions, interactive seminars, nutrition workshops, lunch-time physical activity (PA) sessions, PA and nutrition handbooks, parent newsletters, pedometers for self-monitoring and text messaging for social support. The following variables were assessed at baseline and will be completed again at 12- and 24-months: adiposity, objectively measured PA, muscular fitness, time spent in sedentary behaviors, dietary intake, PA and nutrition social-cognitive mediators, physical self-perception and global self-esteem. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA and nutrition behavior change will be explored. DISCUSSION: NEAT Girls is an innovative intervention targeting low-active girls using evidence-based behavior change strategies and nutrition and PA messages and has the potential to prevent unhealthy weight gain and reduce the decline in physical activity and poor dietary habits associated with low socio-economic status. Few studies have reported the long-term effects of school-based obesity prevention programs and the current study has the potential to make an important contribution to the field. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12610000330044.

Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.

Acute hyperglycaemia and chronic hypertension worsen stroke outcome but their impact on collateral perfusion, a determinant of penumbral life span, is poorly understood. Laser-speckle contrast imaging (LSCI) was used to determine the influence of these stroke comorbidities on cortical perfusion after permanent middle cerebral artery occlusion (pMCAO) in spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar rats. Four independent studies were conducted. In animals without pMCAO, cortical perfusion remained stable over 180 min. Following pMCAO, cortical perfusion was markedly reduced at 30 min then gradually increased, via cortical collaterals, over the subsequent 3.5 h. In the contralateral non-ischaemic hemisphere, perfusion did not change over time. Acute hyperglycaemia (in normotensive Wistar) and chronic hypertension (SHRSP) attenuated the restoration of cortical perfusion after pMCAO. Inhaled nitric oxide did not influence cortical perfusion in SHRSP following pMCAO. Thus, hyperglycaemia at the time of arterial occlusion or pre-existing hypertension impaired the dynamic recruitment of cortical collaterals after pMCAO. The impairment of collateral recruitment may contribute to the detrimental effects these comorbidities have on stroke outcome.

Design and synthesis of (2R,3S)-iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter.

A stereoselective 10-step synthesis of iodophenoxy analogues of (2R,3S)-reboxetine has been developed with the aim of generating a new SPECT imaging agent for the noradrenaline transporter (NAT). In vitro testing of these compounds against various mono-amine transporters showed an ortho-iodophenoxy analogue to have excellent affinity (K(i) 8.4 nM) and good selectivity for NAT.

New iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter.

A new route for the stereoselective synthesis of iodinated reboxetine analogues has been developed for the generation of SPECT imaging agents for the noradrenaline transporter (NAT). (2S,3S)- and (2R,3R)-iodoreboxetine were prepared and biological testing against various mono-amine transporters showed these compounds to be potent and selective for NAT.

Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats.

BACKGROUND: Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit. METHODS: Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging. RESULTS: Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient-derived lesion volume 2-4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group. CONCLUSIONS: Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear.

Implementing Resistance Training in Secondary Schools: A Cluster Randomized Controlled Trial.

PURPOSE: Guidelines recommend that young people engage in muscle-strengthening activities on at least 3 d·wk. The purpose of this study was to examine the effect of a school-based intervention focused on resistance training (RT) for adolescents. METHODS: The "Resistance Training for Teens" intervention was evaluated using a cluster-randomized, controlled trial with 607 adolescents (50.1% girls; 14.1 ± 0.5 yr) from 16 secondary schools. Teachers were trained to deliver the intervention, which included the following: (i) an interactive student seminar; (ii) a structured physical activity program, focused on RT; (iii) lunchtime fitness sessions; and (iv) Web-based smartphone apps. The primary outcome was muscular fitness (MF) and secondary outcomes included body mass index, RT skill competency, flexibility, physical activity, self-efficacy, and motivation. Assessments were conducted at baseline, 6 months (postprogram; primary end point), and 12 months (follow-up). Outcomes were assessed using linear mixed models, with three potential moderators tested using interaction terms (and subgroup analyses where appropriate). RESULTS: For the primary outcome (MF), a group-time effect was observed at 6 months for the upper body (2.0 repetitions; 95% confidence interval (CI), 0.8-3.2), but not the lower body (-1.4 cm; 95% CI, -4.7-1.9). At 6 months, there were intervention effects for RT skill competency and self-efficacy, but no other secondary outcomes. Effects for upper body MF and RT skill competency were sustained at 12 months. Despite overall no effect for body mass index, there was a group-time effect at 12 months among students who were overweight/obese at baseline (-0.55 kg·m; 95% CI, -1.01 to -0.08). CONCLUSIONS: The school-based RT intervention resulted in immediate and sustained improvements in upper body MF and RT skill competency, demonstrating an effective and scalable approach to delivering RT within secondary schools.

Chronic photoperiod disruption does not increase vulnerability to focal cerebral ischemia in young normotensive rats.

Photoperiod disruption, which occurs during shift work, is associated with changes in metabolism or physiology (e.g. hypertension and hyperglycaemia) that have the potential to adversely affect stroke outcome. We sought to investigate if photoperiod disruption affects vulnerability to stroke by determining the impact of photoperiod disruption on infarct size following permanent middle cerebral artery occlusion. Adult male Wistar rats (210-290 g) were housed singly under two different light/dark cycle conditions ( n = 12 each). Controls were maintained on a standard 12:12 light/dark cycle for nine weeks. For rats exposed to photoperiod disruption, every three days for nine weeks, the lights were switched on 6 h earlier than in the previous photoperiod. T2-weighted magnetic resonance imaging was performed at 48 h after middle cerebral artery occlusion. Disruption of photoperiod in young healthy rats for nine weeks did not alter key physiological variables that can impact on ischaemic damage, e.g. blood pressure and blood glucose immediately prior to middle cerebral artery occlusion. There was no effect of photoperiod disruption on infarct size after middle cerebral artery occlusion. We conclude that any potentially adverse effect of photoperiod disruption on stroke outcome may require additional factors such as high fat/high sugar diet or pre-existing co-morbidities.

An atypical role for the myeloid receptor Mincle in central nervous system injury.

The C-type lectin Mincle is implicated in innate immune responses to sterile inflammation, but its contribution to associated pathologies is not well understood. Herein, we show that Mincle exacerbates neuronal loss following ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a model of transient middle cerebral artery occlusion but did not alter outcomes following heart or gut ischemia. High functional scores in Mincle KO animals using the focal cerebral ischemia model were accompanied by reduced lesion size, fewer infiltrating leukocytes and less neutrophil-derived cytokine production than isogenic controls. Bone marrow chimera experiments revealed that the presence of Mincle in the central nervous system, rather than recruited immune cells, was the critical regulator of a poor outcome following transient middle cerebral artery occlusion. There was no evidence for a direct role for Mincle in microglia or neural activation, but expression in a subset of macrophages resident in the perivascular niche provided new clues on Mincle's role in ischemic stroke.

Serotonin transporter residual availability during long-term antidepressant therapy does not differentiate responder and nonresponder unipolar patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Serotonin transporter availability does not discriminate responders and nonresponders during long-term treatment with antidepressants.