Healthcare resource utilization and costs of using Cariprazine as the first versus subsequent adjunctive therapy for major depressive disorder.

Aim: Inadequate response to antidepressant therapy (ADT) is common in major depressive disorder (MDD); atypical antipsychotic (AA) adjunctive therapy may be effective for these patients. This study aimed to compare healthcare resource utilization (HRU) and costs between patients initiating the AA cariprazine as their first adjunctive therapy vs those initiating cariprazine subsequently.

Methods: The Merative MarketScan® Commercial Database (January 1, 2015, to June 30, 2021) was used to identify US adults with MDD and ≥1 pharmacy claim for cariprazine adjunctive to ADT in 2018 or after.

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.

Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [C]UCB-J PET.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [C]UCB-J PET. Participants included 31 older adults with AD and 16 with normal cognition.

Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls.

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.

The Humanistic and Economic Burden Associated with Major Depressive Disorder: A Retrospective Cross-Sectional Analysis.

Introduction: Major depressive disorder (MDD) is a debilitating and costly condition. This analysis characterized the health-related quality of life (HRQoL), health care resource utilization (HCRU), and costs between patients with versus without MDD, and across MDD severity levels.

Methods: The 2019 National Health and Wellness Survey was used to identify adults with MDD, who were stratified by disease severity (minimal/mild, moderate, moderately severe, severe), and those without MDD.

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.

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.

The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [C]UCB-J.

Purpose: Aging is a major societal concern due to age-related functional losses. Synapses are crucial components of neural circuits, and synaptic density could be a sensitive biomarker to evaluate brain function. [C]UCB-J is a positron emission tomography (PET) ligand targeting synaptic vesicle glycoprotein 2A (SV2A), which can be used to evaluate brain synaptic density in vivo.

Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET.

Objective: Multimodal imaging techniques have furthered our understanding of how different aspects of Alzheimer's disease (AD) pathology relate to one another. Diffusion tensor imaging (DTI) measures such as mean diffusivity (MD) may be a surrogate measure of the changes in gray matter structure associated with AD. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used to quantify synaptic loss, which is the major pathological correlate of cognitive impairment in AD.

Evaluating infusion methods and simplified quantification of synaptic density with [C]UCB-J and [F]SynVesT-1 PET.

For some positron emission tomography studies, radiotracer is administered as bolus plus continuous infusion (B/I) to achieve a state of equilibrium. This approach can reduce scanning time and simplify data analysis; however, the method must be validated and optimized for each tracer. This study aimed to validate a B/I method for quantification of synaptic density using radiotracers which target the synaptic vesicle glycoprotein 2 A: [C]UCB-J and [F]SynVesT-1.

Imaging the brain's immune response to alcohol with [C]PBR28 TSPO Positron Emission Tomography.

In humans, the negative effects of alcohol are linked to immune dysfunction in both the periphery and the brain. Yet acute effects of alcohol on the neuroimmune system and its relationships with peripheral immune function are not fully understood. To address this gap, immune response to an alcohol challenge was measured with positron emission tomography (PET) using the radiotracer [C]PBR28, which targets the 18-kDa translocator protein, a marker sensitive to immune challenges.

Principal component analysis of synaptic density measured with [C]UCB-J PET in early Alzheimer's disease.

Background: Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD). We used principal component analysis (PCA) to identify regional patterns of covariance in synaptic density using [C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance.

Methods: [C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85.

Perceptions of prescription opioids among marginalized patients with hematologic malignancies in the context of the opioid epidemic: a qualitative study.

Purpose: Opioids are essential for treating pain in hematologic malignancies (HM), yet are heavily stigmatized in the era of the opioid epidemic. Stigma and negative attitudes towards opioids may contribute to poorly managed cancer pain. We aimed to understand patient attitudes towards opioids for HM pain management, particularly among historically marginalized populations.

Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates.

Purpose: Currently, there are multiple active clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of glioblastoma. The noninvasive quantification of baseline PARP expression using positron emission tomography (PET) may provide prognostic information and lead to more precise treatment. Due to the lack of brain-penetrant PARP imaging agents, the reliable and accurate in vivo quantification of PARP in the brain remains elusive.

Investigating CNS distribution of PF-05212377, a P-glycoprotein substrate, by translation of 5-HT receptor occupancy from non-human primates to humans.

PF-05212377 (SAM760) is a potent and selective 5-HT antagonist, previously under development for the treatment of Alzheimer's disease. In vitro, PF-05212377 was determined to be a P-gp/non-BCRP human transporter substrate. Species differences were observed in the in vivo brain penetration of PF-05212377 with a ratio of the unbound concentration in brain/unbound concentration in plasma (C /C ) of 0.

Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder.

Background: Understanding the neurobiology underlying bipolar disorder (BD) versus major depressive disorder (MDD) is crucial for accurate diagnosis and for driving the discovery of novel treatments. A promising target is the metabotropic glutamate receptor 5 (mGluR5), a modulator of glutamate transmission associated with synaptic plasticity. We measured mGluR5 availability in individuals with MDD and BD for the first time using positron emission tomography.