Ziel/Aim Bariatric surgery is the most effective method to treat morbid obesity. The extent of weight loss achieved is subject to many factors. We investigated whether 5-HTT availability in the dorsal raphe nucleus (DRN) measured pre-surgically is associated with reduction of body mass index (BMI) in patients undergoing Roux-en-Y gastric bypass (RYGB) surgery.

Ziel/Aim The S1R acts as a neuromodulator and may play a pivotal role for cognitive and behavioral processes in neuropsychiatric disorders. Cognitive dysfunction is common in UP. Using S1R-specific (-)-F-18-Fluspidine PET, the aim of this study was to investigate the S1R availability and its relationship to depressive and cognitive symptoms in untreated patients with acute EO-UP.

Ziel/Aim Cholinergic modulation of food intake is assumed as nicotinic acetylcholine receptors (nAChR).1 Specifically, α4β2* nAChR are widely expressed in brain feeding circuits. To assess the effects of visual food stimuli on α4β2* nAChR availability in vivo, we applied simultaneous PET-MRI with α4β2* nAChR-specific (-)-[18F]Flubatine in normal-weight volunteers (NW) under basic (basC) and stimulus conditions (stimC).

Background Pulmonary hypertension (PH) is a hemodynamic condition characterized by progressive remodeling of the pulmonary vasculature resulting in right heart failure and death. Serotonin transporter (SERT) is assumed to be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time SERT in vivo availability in the lungs of patients with COPD and PH.

Ziel/Aim Im Rahmen einer klinischen Studie zur Bestimmung der Verfügbarkeit von Sigma1-Rezeptoren mit Hilfe des selektiven Rezeptorliganden [F-18]Fluspidine unter Medikation mit dem Dopaminstabilisator Pridopidine sollte für das kinetische Modelling die Inputfunktion des Tracers bestimmt werden

Ziel/Aim Pridopidine is an investigational drug that was designed as dopamine stabilizer to treat motor symptoms in HD. As shown precinically, Pridopidine has much higher affinity to S1Rs as compared to D2/D3 Rs. S1R activation mediates neuroprotection and mental enhancement. To clarify the mechanism of action of Pridopidine and observed clinical outcomes in prior clinical trials, we quantified, using S1R-specific (-)-F-18-Fluspidine and D2/D3 R-specific F-18-Fallypidrefe PET, the S1R occupancy (S1RO) and D2/D3R occupancy (D2/D3RO) by Pridopidine at previously used clinical doses in HV and HD.

Ziel/Aim Emotional dysregulation is thought to be a major contributor to overconsumption of food. However, the neurobiological underpinnings of an association between ER and neurotransmission, i.e. the central NA system, have not been investigated yet. The aim of our study was therefore to investigate central NAT availability applying NAT-specific [11C]MRB and PET in relation to ER in individuals with obesity (OB) and in normal-weight, healthy volunteers (NW).

Ziel/Aim In der Regel wird ein konventioneller Ansatz zur Versuchsplanung gewählt, d. h. nur ein Parameter wird systematisch geändert. Bei Problemen, bei denen mehrere Faktoren betroffen sind, verläuft dann die Versuchsoptimierung entsprechend langsam. Abhilfe schafft hier DoE für die Untersuchung eines mehrdimensionalen Parameterraums bei dem gleichzeitig mehrere Reaktionsparameter geändert werden und optimierte Prozessparameter mit einer relativ geringen Anzahl von Versuchen bestimmt werden können.

Ziel/Aim Ein Polymorphismus des BDNF-Gens (Val66Met), der die BDNF-Aktivität beeinträchtigt, wurde bereits mit Übergewicht und Adipositas in Verbindung gebracht. Ob BDNF Val66Met die serotonerge Neurotransmission oder das Essverhalten beeinflusst, ist unklar.

The central noradrenaline (NA) system, which modulates cognitive processes such as attention and working memory, has been implicated in the pathopyhisology of attention-deficit/hyperactivity disorder (ADHD). In particular, the NA transporters (NAT) seems to play a key role in ADHD as a treatment target for prescribed drugs such as methylphenidate and atomoxetine. However, changes of NAT availability have not been described so far in adults with ADHD.

Considering the urgent need of more suitable PET radioligands for imaging of nicotinic acetylcholine receptors (nAChR) of the α4β2 subtype we recently developed the second generation radiotracers (-)-F18-Flubatine and (+)-F18-Flubatine and investigated them for the first time in humans. Both showed favorable imaging characteristics. Aim of this study was to compare (-)-F18-Flubatine and (+)-F18-Flubatine in healthy controls focusing on their kinetic characteristics and assess potential fields of application.

Whether there is an influence of the APOE ε4 allele on α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) availability in Alzheimer's dementia (AD) is under debate. To analyze the effect of APOE ε4 on α4β2-nAChR availability in mild AD in vivo, we investigated patients with mild AD (CDR = 1), positive for APOE ε4 (AD-APOE ε4+) and negative for APOE ε4 (AD-APOE ε4-) using the recently developed α4β2-nAChR-specific radioligand (-)-F-18-Flubatine and PET.

PH is a hemodynamic condition of various causes characterized by progressive remodeling of the pulmonary vasculature resulting in right heart failure and death. The role of the serotonin transporter (SERT) in the pathogenesis of PH in chronic-obstructive pulmonary disease (COPD) is still discussed controversial. The study investigated lung SERT availability of patients with COPD and PH, with COPD, with idiopathic pulmonary arterial hypertension (IPAH) and healthy volunteers (HV) for the first time in vivo.

We have previously demonstrated that Sig-1R availability is increased in unmedicated acute MDD (MDD) using (-)-F-18-Fluspidine PET. In order to assess whether the Sig-1R pathophysiology in MDD is progressive, we investigated the relationship between Sig-1R and disease duration (DS), number of depressive episodes (DE) and Hamilton Score (HAMD) in this ongoing (-)-F-18-Fluspidine PET trial.

Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for morbid obesity, but the specific mechanisms underlying its weight lowering effects remain elusive. One current assumption is that changes in brain reward processing through the central monoaminergic system substantially contributes to the outcome of RYGB on body weight. We investigated whether there is a change in reward sensitivity in patients with severe obesity (BMI> 40 kg/m2) before and 6 months after RYBG surgery and whether this relates to changes in central serotonin transporter (SERT) availability and BMI.

A polymorphism in the promoter region of the human serotonin transporter (5-HTT)-coding SLC6A4 gene (5-HTTLPR) has been implicated in moderating susceptibility to stress-related psychopathology and to possess regulatory functions on human in vivo 5-HTT availability. However, data on a direct relation between 5-HTTLPR and in vivo 5-HTT availability have been inconsistent. Additional factors such as epigenetic modifications of 5-HTTLPR might contribute to this association. This is of particular interest in the context of obesity, as an association with 5-HTTLPR hypermethylation has previously been reported. Here, we tested the hypothesis that methylation rates of 14 cytosine–phosphate–guanine (CpG) 5-HTTLPR loci, in vivo central 5-HTT availability as measured with [11C]DASB positron emission tomography (PET) and body mass index (BMI) are related in a group of 30 obese (age: 36±10 years, BMI>35 kg/m2) and 14 normal-weight controls (age 36±7 years, BMI<25 kg/m2). No significant association between 5-HTTLPR methylation and BMI overall was found. However, site-specific elevations in 5-HTTLPR methylation rates were significantly associated with lower 5-HTT availability in regions of the prefrontal cortex (PFC) specifically within the obese group when analyzed in isolation. This association was independent of functional 5-HTTLPR allelic variation. In addition, negative correlative data showed that CpG10-associated 5-HTT availability determines levels of reward sensitivity in obesity. Together, our findings suggest that epigenetic mechanisms rather than 5-HTTLPR alone influence in vivo 5-HTT availability, predominantly in regions having a critical role in reward processing, and this might have an impact on the progression of the obese phenotype.