Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression.

Background: Using [F]altanserin, a serotonin 2A receptor (5-HTR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HTR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HTR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HTR and neuroticism are both modulated by HPA axis function.

Effect of Antidepressant Treatment on 5-HT Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder.

Background: Brain serotonin 4 receptor (5-HTR) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HTR levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment.

Methods: Ninety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HTR binding prior to antidepressant treatment with escitalopram.

An In Vivo High-Resolution Human Brain Atlas of Synaptic Density.

Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A).

Multimodal brain age prediction using machine learning: combining structural MRI and 5-HT2AR PET-derived features.

To better assess the pathology of neurodegenerative disorders and the efficacy of neuroprotective interventions, it is necessary to develop biomarkers that can accurately capture age-related biological changes in the human brain. Brain serotonin 2A receptors (5-HT2AR) show a particularly profound age-related decline and are also reduced in neurodegenerative disorders, such as Alzheimer's disease. This study investigates whether the decline in 5-HT2AR binding, measured in vivo using positron emission tomography (PET), can be used as a biomarker for brain aging.

Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited.

Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.

Background: A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR).

The association between brain serotonin transporter binding and impulsivity and aggression in healthy individuals.

The serotonin system plays a critical role in the modulation of impulsive aggression. Although serotonin transporters (SERT) are key in modulating synaptic serotonin levels, few studies have investigated the role of SERT levels in human impulsive aggression. The aim of this study was to investigate whether brain SERT levels are associated with trait impulsive aggression.

Association between brain serotonin 4 receptor binding and reactivity to emotional faces in depressed and healthy individuals.

Brain serotonergic (5-HT) signaling is posited to modulate neural responses to emotional stimuli. Dysfunction in 5-HT signaling is implicated in major depressive disorder (MDD), a disorder associated with significant disturbances in emotion processing. In MDD, recent evidence points to altered 5-HT receptor (5-HTR) levels, a promising target for antidepressant treatment.

Kinetic models for estimating occupancy from single-scan PET displacement studies.

The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative design in which the drug is administered during an on-going scan (i.e.

Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction.

Importance: The cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals.

Objective: To map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state.

Design, Setting, And Participants: This case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark.

On the Long-term Archiving of Research Data.

Accessing research data at any time is what FAIR (Findable Accessible Interoperable Reusable) data sharing aims to achieve at scale. Yet, we argue that it is not sustainable to keep accumulating and maintaining all datasets for rapid access, considering the monetary and ecological cost of maintaining repositories. Here, we address the issue of cold data storage: when to dispose of data for offline storage, how can this be done while maintaining FAIR principles and who should be responsible for cold archiving and long-term preservation.

Designing drug occupancy studies with PET neuroimaging: Sample size, occupancy ranges and analytical methods.

Molecular neuroimaging is today considered essential for evaluation of novel CNS drugs; it is used to quantify blood-brain barrier permeability, verify interaction with key target and determine the drug dose resulting in 50% occupancy, IC. In spite of this, there has been limited data available to inform on how to optimize study designs. Through simulations, we here evaluate how IC estimation is affected by the (i) range of drug doses administered, (ii) number of subjects included, and (iii) level of noise in the plasma drug concentration measurements.

Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study.

Concurrent anxiety is frequent in major depressive disorder and a shared pathophysiological mechanism between anxiety and other depressive symptoms is plausible. The serotonin 4 receptor (5-HTR) has been implicated in both depression and anxiety. This is the first study to investigate the association between the cerebral 5-HTR binding and anxiety in patients with depression before and after antidepressant treatment and the association to treatment response.

An Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates.

Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-β or tau. Despite many attempts, it has not been possible to develop an appropriate radioligand for imaging aggregated α-synuclein in the brain for diagnosing, e.g.

The Impact of Hormonal Contraceptive Use on Serotonergic Neurotransmission and Antidepressant Treatment Response: Results From the NeuroPharm 1 Study.

Background: Hormonal contraceptive (HC) use has been associated with an increased risk of developing a depressive episode. This might be related to HC's effect on the serotonergic brain system as suggested by recent cross-sectional data from our group, which show that healthy oral contraceptive (OC) users relative to non-users have lower cerebral serotonin 4 receptor (5-HT4R) levels. Here, we determine if cerebral 5-HT4R binding differs between HC non-users, OC users, and hormonal intrauterine device (HIUD) users among women with an untreated depressive episode.

Dorsal striatal dopamine induces fronto-cortical hypoactivity and attenuates anxiety and compulsive behaviors in rats.

Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes.

A high-resolution in vivo atlas of the human brain's benzodiazepine binding site of GABA receptors.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABA receptors (GABARs), generated on the basis of in vivo [C]flumazenil Positron Emission Tomography (PET) data.

Parkinson patients have a presynaptic serotonergic deficit: A dynamic deep brain stimulation PET study.

Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Apart from alleviating the motor symptoms, Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how turning DBS off affects the serotonergic system.

False positive rates in positron emission tomography (PET) voxelwise analyses.

Issues with inflated false positive rates (FPRs) in brain imaging have recently received significant attention. However, to what extent FPRs present a problem for voxelwise analyses of Positron Emission Tomography (PET) data remains unknown. In this work, we evaluate the FPR using real PET data under group assignments that should yield no significant results after correcting for multiple comparisons.

Visual stimuli induce serotonin release in occipital cortex: A simultaneous positron emission tomography/magnetic resonance imaging study.

Endogenous serotonin (5-HT) release can be measured noninvasively using positron emission tomography (PET) imaging in combination with certain serotonergic radiotracers. This allows us to investigate effects of pharmacological and nonpharmacological interventions on brain 5-HT levels in living humans. Here, we study the neural responses to a visual stimulus using simultaneous PET/MRI.

Nondisplaceable Binding Is a Potential Confounding Factor in C-PBR28 Translocator Protein PET Studies.

The PET ligand C-PBR28 (-((2-(methoxy-C)-phenyl)methyl)--(6-phenoxy-3-pyridinyl)acetamide) binds to the 18-kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, V, is frequently the reported outcome measure. Since V is the sum of the ligand-specific distribution volume (V) and the nondisplaceable-binding distribution volume (V), differences in V across subjects and groups will have an impact on V Here, we used a recently developed method for simultaneous estimation of V (SIME) to disentangle contributions from V and V Data from 4 previously published C-PBR28 PET studies were included: before and after a lipopolysaccharide challenge (8 subjects), in alcohol use disorder (14 patients, 15 controls), in first-episode psychosis (16 patients, 16 controls), and in Parkinson disease (16 patients, 16 controls).

Striatal Volume Increase After Six Weeks of Selective Dopamine D Receptor Blockade in First-Episode, Antipsychotic-Naïve Schizophrenia Patients.

Patients with chronic schizophrenia often display enlarged striatal volumes, and antipsychotic drugs may contribute via the dopamine D receptor (DR) blockade. Separating the effects of disease from medication is challenging due to the lack of a proper placebo-group. To address this, we conducted a longitudinal study of antipsychotic-naïve, first-episode schizophrenia patients to test the hypothesis that selective blockade of DR would induce a dose-dependent striatal volume increase.