Greater activation of glia, a key component of neuroinflammation, is an important process to target in neuropsychiatric illnesses. However, the magnitude of gliosis varies across cases so low-cost predictors are needed to stratify subjects for clinical trials. Here, several such blood serum measures were assessed in relation to TSPO V, an index of translocator protein density, measured with positron emission tomography.
View Article and Find Full Text PDFImportance: Monoamine oxidase B (MAO-B) is an important, high-density enzyme in the brain that generates oxidative stress by hydrogen peroxide production, alters mitochondrial function, and metabolizes nonserotonergic monoamines. Recent advances in positron emission tomography radioligand development for MAO-B in humans enable highly quantitative measurement of MAO-B distribution volume (MAO-B VT), an index of MAO-B density. To date, this is the first investigation of MAO-B in the brain of major depressive disorder that evaluates regions beyond the raphe and amygdala.
View Article and Find Full Text PDFBackground: People with major depressive disorder frequently exhibit increasing persistence of major depressive episodes. However, evidence for neuroprogression (ie, increasing brain pathology with longer duration of illness) is scarce. Microglial activation, which is an important component of neuroinflammation, is implicated in neuroprogression.
View Article and Find Full Text PDFImportance: For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO).
View Article and Find Full Text PDFBackground: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer's, and Parkinson's Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of moclobemide and the occupancy of phenelzine at typical clinical dosing.
View Article and Find Full Text PDFImportance: The neuroinflammatory hypothesis of major depressive disorder is supported by several main findings. First, in humans and animals, activation of the immune system causes sickness behaviors that present during a major depressive episode (MDE), such as low mood, anhedonia, anorexia, and weight loss. Second, peripheral markers of inflammation are frequently reported in major depressive disorder.
View Article and Find Full Text PDFThis article describes the kinetic modeling of [(11)C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[(11)C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90- minute PET scans after an intravenous injection of [(11)C]SL25.
View Article and Find Full Text PDFRationale: BMS-820836, a novel triple monoamine reuptake inhibitor, is an experimental monotherapy for sufferers of major depressive disorder who have had an inadequate response to an existing antidepressant treatment.
Objectives: This study was conducted to evaluate the safety and tolerability, pharmacokinetics (PK), and serotonin transporter (SERT) and dopamine transporter (DAT) occupancy for single doses of BMS-820836 in healthy subjects.
Methods: Healthy subjects were assigned to seven BMS-820836 dose panels (0.
Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain).
View Article and Find Full Text PDFMonoamine oxidase-A (MAO-A), a key brain enzyme which metabolizes monoamines, is implicated in the pathophysiology of stress-related illnesses, including major depressive disorder, addiction, and violent behavior. Chronic stressors and glucocorticoid-administration typically associate with elevated MAO-A levels/activity. However, the relationship of shorter stress or glucocorticoid exposures and MAO-A levels/activity is not well established.
View Article and Find Full Text PDFContext: Greater prefrontal cortex and anterior cingulate cortex monoamine oxidase A (MAO-A) binding is associated with depressed mood. Substances in cigarette smoke, such as harman, inhibit MAO-A, and cigarette withdrawal is associated with depressed mood. Dysphoria during cigarette withdrawal predicts relapse.
View Article and Find Full Text PDFContext: Highly significant elevations in regional brain monoamine oxidase A (MAO-A) binding were recently reported during major depressive episodes (MDEs) of major depressive disorder (MDD). The relationship between MAO-A levels and selective serotonin reuptake inhibitor (SSRI) treatment, recovery, and recurrence in MDD is unknown.
Objectives: To determine whether brain MAO-A binding changes after SSRI treatment, whether brain MAO-A binding normalizes in subjects with MDD in recovery, and whether there is a relationship between prefrontal and anterior cingulate cortex MAO-A binding in recovery and subsequent recurrence of MDE.