PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD.

Histone deacetylases (HDACs), typically known for regulating gene expression, also play a major role in protein regulation outside of histone modification. Emerging evidence suggests the HDACs may be novel pharmacologic targets in complex disorders such as posttraumatic stress disorder (PTSD). Histone deacetylase 6 (HDAC6) regulates microtubule function and plays a role in stress-related cortisol signaling in serotonergic regions of the brain by maintaining the nuclear translocation of glucocorticoid receptors.

Assessment of test-retest reproducibility by [F]Bavarostat for PET imaging of HDAC6.

Background: Histone deacetylase 6 (HDAC6) is an enzyme pivotal for gene regulation, influencing cellular pathways through protein deacetylation. HDAC6 is a potential therapeutic target in diseases such as cancer and neurodegenerative disorders. Koole et al.

Greater Neuroimmune System Deficit in Women Than Men With Alcohol Use Disorder.

Background: Women who drink are more vulnerable than men to many of the consequences of alcohol use, including alcohol-related cancers, cardiovascular disease, liver cirrhosis, and immune system dysfunction. Acute alcohol triggers neuroimmune cells including microglia-the brain's resident immune cells. Excessive activation can contribute to neuronal dysfunction and alcohol-induced neurodegeneration.

Cerebrospinal Fluid Biomarkers and Cognition in Alzheimer Disease and Frontotemporal Dementia in a Memory Clinic Setting.

Objective: Currently available literature on the relationships between cerebrospinal fluid (CSF) biomarkers and cognitive performance in frontotemporal dementia (FTD) is very limited and inconclusive. In this study, we investigated the association of cognitive symptoms, as measured with Montreal Cognitive Assessment (MoCA), with CSF levels of total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and amyloid β 1-42 (Aβ1-42) in a group of patients with probable FTD and Alzheimer disease (AD).

Methods: We conducted a retrospective cohort study with participants selected from the electronic records of patients seen at Yale New Haven Hospital's Memory Clinic, CT.

Self-Inflicted Head Injury in Behavioral Variant Frontotemporal Dementia with Compulsive Behaviors: A Case Report.

Here we present the case of a 56-year-old right-handed White male who developed osteomyelitis and empyema after repetitive compulsive excoriation rituals. His recent history included profound personality changes, apathy, loss of empathy, limited insight, behavioral agitation, and episodic memory loss. In addition to these progressive behavioral deficits, he had significant difficulties with executive functioning, leading to the loss of his job and inability to independently perform instrumental activities of daily living.

Network-based Molecular Constraints on Synaptic Density Alterations in Schizophrenia.

Converging neuroimaging, genetic, and post-mortem evidence show a fundamental role of synaptic deficits in schizophrenia pathogenesis. However, the underlying molecular and cellular mechanisms that drive the onset and progression of synaptic pathology remain to be established. Here, we used synaptic density positron emission tomography (PET) imaging using the [C]UCB-J radiotracer to reveal a prominent widespread pattern ( < 0.

Generating synthetic brain PET images of synaptic density based on MR T1 images using deep learning.

Purpose: Synaptic vesicle glycoprotein 2 A (SV2A) in human brains is an important biomarker of synaptic loss associated with several neurological disorders. However, SV2A tracers, such as [C]UCB-J, are less available in practice due to constrains such as cost, radiation exposure and onsite cyclotron. We therefore aim to generate synthetic [C]UCB-J PET images based on MRI in this study.

Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [F]FE-PE2I PET: independent validation with new insights.

[F]FE-PE2I PET is a promising alternative to single positron emission computed tomography-based dopamine transporter (DAT) imaging in Parkinson's disease. While the excellent discriminative power of [F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson's disease, Hoehn-Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson's disease with 2-year follow-up) cohorts.

Socioenvironmental Factors are Associated With Dopamine Transporter Availability in Healthy Individuals but not in Parkinson's Disease.

Objective: Social factors can influence the brain's dopaminergic function. This study investigated the relationship between socioenvironmental factors and dopamine transporter (DaT) availability in healthy individuals (n = 74) and those with Parkinson's disease (PD) (n = 240).

Methods: All single photon emission computed tomography (SPECT) DaT data and clinical data used in this study were obtained from the Parkinson's Progression Markers Initiative (PPMI) dataset.

Noninvasive quantification of [F]SynVesT-1 binding using simplified reference tissue model 2.

Purpose: [F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions.

Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.

A review of the kappa opioid receptor system in opioid use.

The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids.

Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG-PET and structural MRI study.

Background And Purpose: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative condition with a prevalence comparable to Alzheimer's disease for patients under 65 years of age. Limited studies have examined the association between cognition and neuroimaging in FTD using different imaging modalities.

Methods: We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both gray matter (GM) volume and glucose metabolism using magnetic resonance imaging and fluorodeoxyglucose (FDG)-PET in 21 patients diagnosed with FTD.

Does seasonal variation affect the neuroimmune system? A retrospective [C]PBR28 PET study in healthy individuals.

Introduction: The neuroimmune system performs a wide range of functions in the brain and the central nervous system. The microglial translocator protein (TSPO) has an established role as a cell marker in identification of the neuroimmune system. Previously, human studies have shown TSPO differences in neuropsychiatric disorders.

The Relationship of Cerebrospinal Fluid Biomarkers and Cognitive Performance in Frontotemporal Dementia.

Objective: Currently available literature on the relationships between cerebrospinal fluid (CSF) biomarkers and cognitive performance in frontotemporal dementia (FTD) is very limited and inconclusive. In this study, we investigated the association of cognition, as measured with Montreal Cognitive Assessment (MoCA), with CSF levels of total tau (t-tau), phosphorylated tau at threonine 181 (p-tau), and amyloid β 1-42 (Aβ1-42) in a group of patients with FTD and Alzheimer's disease (AD).

Methods: We conducted a retrospective cohort study with participants selected from the electronic records of patients seen at Yale New Haven Hospital's Memory Clinic, CT, USA.

Synaptic loss and its association with symptom severity in Parkinson's disease.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain.

Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise.

Relationship between Neuroimaging and Cognition in Frontotemporal Dementia: A [18 F]FDG PET and Structural MRI Study.

Background: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous condition with a prevalence comparable to Alzheimer's Disease for patients under sixty-five years of age. Gray matter (GM) atrophy and glucose hypometabolism are important biomarkers for the diagnosis and evaluation of disease progression in FTD. However, limited studies have systematically examined the association between cognition and neuroimaging in FTD using different imaging modalities in the same patient group.

Imaging a putative marker of brain cortisol regulation in alcohol use disorder.

Background: Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans.