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Article ; Online: A Role for the Serotonin Transporter in the Largely Unknown Molecular Pathophysiology of Premenstrual Dysphoric Disorder.

Meyer, Jeffrey H

2023 Volume 93, Issue 12, Page(s) 1054–1055

MeSH term(s)	Female ; Humans ; Premenstrual Dysphoric Disorder ; Serotonin Plasma Membrane Transport Proteins/genetics
Chemical Substances	Serotonin Plasma Membrane Transport Proteins ; SLC6A4 protein, human
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.04.013
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Article: Development and Clinical Application of Positron Emission Tomography Imaging Agents for Monoamine Oxidase B.

Meyer, Jeffrey H / Braga, Joeffre

Frontiers in neuroscience

2022 Volume 15, Page(s) 773404

Abstract: Monoamine oxidase B (MAO-B) is a high-density protein in the brain mainly found on outer mitochondrial membranes, primarily in astroglia, but additionally in serotonergic neurons and in the substantia nigra in the midbrain. It is an enzyme that ... ...

Abstract	Monoamine oxidase B (MAO-B) is a high-density protein in the brain mainly found on outer mitochondrial membranes, primarily in astroglia, but additionally in serotonergic neurons and in the substantia nigra in the midbrain. It is an enzyme that participates in the oxidative metabolism of important monoamines including dopamine, norepinephrine, benzylamine, and phenylethylamine. Elevated MAO-B density may be associated with astrogliosis and inhibiting MAO-B may reduce astrogliosis. MAO-B density is elevated in postmortem sampling of pathology for many neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and alcohol use disorder. Initial development of positron emission tomography (PET) imaging agents focused on analogs of [
Language	English
Publishing date	2022-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.773404
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Article: Monoamine Oxidase B (MAO-B): A Target for Rational Drug Development in Schizophrenia Using PET Imaging as an Example.

Nisha Aji, Kankana / Meyer, Jeffrey H / Rusjan, Pablo M / Mizrahi, Romina

Advances in neurobiology

2023 Volume 30, Page(s) 335–362

Abstract: Monoamine oxidase B (MAO-B) is an important high-density enzyme involved in the generation of oxidative stress and central in the catabolism of dopamine, particularly in brain subcortical regions with putative implications in the pathophysiology of ... ...

Abstract	Monoamine oxidase B (MAO-B) is an important high-density enzyme involved in the generation of oxidative stress and central in the catabolism of dopamine, particularly in brain subcortical regions with putative implications in the pathophysiology of schizophrenia. In this chapter, we review postmortem studies, preclinical models, and peripheral and genetic studies implicating MAO-B in psychosis. A literature search in PubMed was conducted and 64 studies were found to be eligible for systematic review. We found that MAO-B could be identified as a potential target in schizophrenia. Evidence comes mostly from studies of peripheral markers, showing reduced platelet MAO-B activity in schizophrenia, together with preclinical results from MAO-B knock-out mice resulting in a hyperdopaminergic state and behavioral disinhibition. However, whether brain MAO-B is altered in vivo in patients with schizophrenia remains unknown. We therefore review methodological studies involving MAO-B positron emission tomography (PET) radioligands used to quantify MAO-B in vivo in the human brain. Given the limitations of currently available treatments for schizophrenia, elucidating whether MAO-B could be used as a target for risk stratification or clinical staging in schizophrenia could allow for a rational search for newer antipsychotics and the development of new treatments.
MeSH term(s)	Animals ; Humans ; Mice ; Brain/diagnostic imaging ; Brain/metabolism ; Monoamine Oxidase/drug effects ; Monoamine Oxidase/metabolism ; Positron-Emission Tomography/methods ; Schizophrenia/diagnostic imaging ; Schizophrenia/drug therapy ; Antipsychotic Agents/chemistry ; Antipsychotic Agents/pharmacology
Chemical Substances	Monoamine Oxidase (EC 1.4.3.4) ; Antipsychotic Agents
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Review ; Journal Article
ISSN	2190-5215
ISSN	2190-5215
DOI	10.1007/978-3-031-21054-9_14
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Article: Neuroprogression and Immune Activation in Major Depressive Disorder.

Meyer, Jeffrey H

Modern trends in pharmacopsychiatry

2017 Volume 31, Page(s) 27–36

Abstract: Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely ... ...

Abstract	Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation. These are markers of processes involved in immune activation, oxidative stress, and chronic glucocorticoid exposure. Positron emission tomography studies of the TSPO distribution volume, a marker of microglial activation, provide strong evidence for microglial activation throughout the gray matter of the brain during MDE of MDD. In postmortem studies, GFAP reductions in the orbitofrontal cortex, anterior cingulate cortex, and hippocampus indicate a deficit in reactive astroglia. Elevated MAO-A levels are present throughout the gray matter of the brain, including affect-modulating brain regions, starting in high-risk states for MDE such as the early postpartum period, perimenopause, heavy cigarette smoking, heavy alcohol intake, and prior to MDE recurrence. Evidence is accumulating for glutamate dysregulation, with some findings of reduced glutamate transporter density in the orbitofrontal cortex, and decreased mGluR5 density. Collectively, these changes suggest an imbalance in the immune system with increased microglial activation and decreased astroglial activation, continued elevations of the MAO-A level, and, likely, the development of extracellular glutamate dysregulation. Many of these imbalances involve processes implicated in increased oxidative stress, apoptosis, and neurodegeneration. Future studies are required to assess potential therapeutics targeting these processes to ameliorate progression of MDD.
MeSH term(s)	Apoptosis ; Brain/immunology ; Brain/pathology ; Depressive Disorder, Major/immunology ; Depressive Disorder, Major/pathology ; Female ; Glutamic Acid/metabolism ; Humans ; Male ; Microglia/immunology ; Oxidative Stress ; Perimenopause
Chemical Substances	Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2017-07-24
Publishing country	Switzerland
Document type	Journal Article
ISSN	1662-2685
ISSN	1662-2685
DOI	10.1159/000470804
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Article ; Online: Promising leads and pitfalls: a review of dietary supplements and hormone treatments to prevent postpartum blues and postpartum depression.

Dowlati, Yekta / Meyer, Jeffrey H

Archives of women's mental health

2020 Volume 24, Issue 3, Page(s) 381–389

Abstract: Prevention of postpartum depression (PPD) is important because it typically has a 13% prevalence rate, impactful immediate symptoms with greater risk of suicide, and higher long-term risk of psychiatric symptoms in both the mother and family. There are ... ...

Abstract	Prevention of postpartum depression (PPD) is important because it typically has a 13% prevalence rate, impactful immediate symptoms with greater risk of suicide, and higher long-term risk of psychiatric symptoms in both the mother and family. There are no universal approaches across all childbearing women that have proven to be preventative for PPD, so it is hoped that dietary and/or hormonal interventions will be developed. There are some effective preventative approaches for PPD, such as psychotherapy and medical management, for the highest risk cases, like when there is a past history of a major depressive episode. The purpose is to review studies that assess dietary and hormonal interventions for prevention of PPD and/or postpartum blues, a high-risk state for PPD. Studies that assess dietary and hormonal interventions for prevention of PPD which included a comparison group were reviewed, including omega-3 fatty acids, mineral and vitamin supplements, amino acid combinations, allopregnanolone, progesterone, and thyroxine. Presently, development of dietary supplements and hormonal products for prevention of PPD is at an early stage with most trials showing results that are either preliminary, not definitive, trend level or variable across studies. Even so, a few directions are not recommended for further investigation such as progesterone and thyroxine. On the other hand, studies of allopregnanolone for prophylaxis of PPD are needed. Also, given the number of trend level findings and the multifactorial etiology of PPD, it may be prudent to investigate combined interventions rather than monotherapies. There is still a major need to develop a dietary supplement that creates resiliency against the biological changes in early postpartum associated with risk for mood disorders and/or PPD.
MeSH term(s)	Depression, Postpartum/prevention & control ; Depressive Disorder, Major ; Dietary Supplements ; Female ; Hormones ; Humans ; Postpartum Period ; Risk Factors
Chemical Substances	Hormones
Language	English
Publishing date	2020-11-17
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	1463529-X
ISSN	1435-1102 ; 1434-1816
ISSN (online)	1435-1102
ISSN	1434-1816
DOI	10.1007/s00737-020-01091-3
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Zs.A 5115: Show issues

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Article: The Effect of Oral L-cysteine on Breast Milk and Plasma Cysteine Concentrations.

Dowlati, Yekta / Maheux, Maxim / Meyer, Jeffrey H

Neuropsychiatric disease and treatment

2020 Volume 16, Page(s) 3163–3172

Abstract: Purpose: Greater oxidative signaling is implicated in major depressive disorder; hence, there is considerable interest in developing oral supplements with anti-oxidant properties to prevent or treat mood disorders, such as postpartum depression. L- ... ...

Abstract	Purpose: Greater oxidative signaling is implicated in major depressive disorder; hence, there is considerable interest in developing oral supplements with anti-oxidant properties to prevent or treat mood disorders, such as postpartum depression. L-cysteine is a precursor for glutathione, an important antioxidant in the brain. So, developing L-cysteine as a dietary supplement may be useful, provided oral supplementation substantially raises its concentration in blood plasma yet does not affect its total concentration in breast milk. This study assessed the effect of oral L-cysteine on its concentration in breast milk and blood plasma of breastfeeding mothers. Participants and methods: Twenty-four health breastfeeding women were randomly assigned to 0, 1.5, or 3 g of oral L-cysteine. Free and total cysteine in breast milk; and free cysteine in plasma were measured. While breast milk is the gold standard, measurement of infant formulas provides indices of nutritional intake considered safe. Therefore, free cysteine was also measured in six different formulas. Results: Total cysteine in breast milk was not affected by oral L-cysteine (Repeated Measures of ANOVA (rANOVA), intervention effect: Conclusion: The negligible effect of oral cysteine administration on its total concentration in breast milk was favorable, but the minimal effect on its blood plasma concentration more strongly argues against further development of oral L-cysteine in postpartum, as well as other conditions.
Language	English
Publishing date	2020-12-21
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2186503-6
ISSN	1178-2021 ; 1176-6328
ISSN (online)	1178-2021
ISSN	1176-6328
DOI	10.2147/NDT.S255205
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Article: Neurochemical imaging and depressive behaviours.

Meyer, Jeffrey H

Current topics in behavioral neurosciences

2013 Volume 14, Page(s) 101–134

Abstract: Neurochemical imaging is frequently applied to measure markers of pathological change so as to understand mechanisms that create symptoms of major depressive disorder. For example, indices of greater monoamine oxidase A(MAO-A) level, particularly in the ... ...

Abstract	Neurochemical imaging is frequently applied to measure markers of pathological change so as to understand mechanisms that create symptoms of major depressive disorder. For example, indices of greater monoamine oxidase A(MAO-A) level, particularly in the prefrontal and anterior cingulate cortex, are associated with depressed mood states, and high-risk states for onset of major depressive episodes. MAO-A metabolises monoamines, and greater metabolism of monoamines occurs when MAO-A is elevated in brain. Lower extracellular serotonin is associated with greater pessimism in humans and chronic serotonin deficiency is associated with upregulation of 5-HT2A (serotonin2A) receptors in cortex. During major depressive episodes when pessimism is more severe, greater 5-HT2A BPND, an index of density occurs in prefrontal and anterior cingulate cortex. These results argue for a mechanism of lowering extracellular serotonin in the prefrontal and anterior cingulate cortex, consequent to elevated MAO-A level. The relationship between elevated 5-HTT BPND and greater pessimism during major depressive episodes suggests that greater 5-HTT density in the context of elevated MAO-A level further contributes to serotonin deficiency in these brain regions. A similar mechanism may explain the association between neuroimaging indices of greater dorsal striatal D2 density, DAT density and symptoms of motor retardation: Greater MAO-A level and relatively greater DAT density lower extracellular dopamine in the dorsal striatum, leading to motor retardation. Indices of greater 5-HT1A density, particularly in the cingulate cortex, have been associated with major depressive disorder, and well as anxiety disorders, suggesting that this abnormality is mechanistically related to presence of anxiety symptoms. To date, abnormalities of Glx a measure reflecting glutamate and glutamine levels have been most strongly associated with presence of major depressive episodes, with greater levels in occipital cortex, and reduced levels in prefrontal cortex. Ultimately, the future for neurochemical imaging is to better understand the mechanisms that predispose toward onset of MDE so as to create biologically informed, novel, methods of prevention, and superior, more symptom-targeted treatments.
MeSH term(s)	Animals ; Depressive Disorder/diagnostic imaging ; Depressive Disorder/metabolism ; Humans ; Neuroimaging/methods ; Radionuclide Imaging
Language	English
Publishing date	2013
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2012_219
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Article ; Online: In vivo imaging translocator protein (TSPO) in autism spectrum disorder.

Simpson, Dominic / Gharehgazlou, Avideh / Da Silva, Tania / Labrie-Cleary, Charlotte / Wilson, Alan A / Meyer, Jeffrey H / Mizrahi, Romina / Rusjan, Pablo M

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2022 Volume 47, Issue 7, Page(s) 1421–1427

Abstract: Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia ... ...

Abstract	Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [
MeSH term(s)	Adult ; Anilides/metabolism ; Autism Spectrum Disorder/diagnostic imaging ; Autism Spectrum Disorder/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Depressive Disorder, Major/metabolism ; Female ; Humans ; Male ; Positron-Emission Tomography ; Pyridines ; Receptors, GABA/genetics ; Receptors, GABA/metabolism ; Young Adult
Chemical Substances	Anilides ; Pyridines ; Receptors, GABA ; TSPO protein, human
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-022-01306-4
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Article: Applying neuroimaging ligands to study major depressive disorder.

Meyer, Jeffrey H

Seminars in nuclear medicine

2008 Volume 38, Issue 4, Page(s) 287–304

Abstract: The recent increase in radioligands available for neuroimaging major depressive disorder has led to advancements in our understanding of the pathophysiology of this illness and improved antidepressant development. Major depressive disorder can be defined ...

Abstract	The recent increase in radioligands available for neuroimaging major depressive disorder has led to advancements in our understanding of the pathophysiology of this illness and improved antidepressant development. Major depressive disorder can be defined as an illness of recurrent major depressive episodes of persistently low mood, dysregulated sleep, appetite and weight, anhedonia, cognitive impairment, and suicidality. The main target sites investigated with radioligand neuroimaging include receptor sites that regulate in response to lowered monoamine levels, targets related to removal of monoamines, uptake of ligands related to regional brain function, and target sites of antidepressants.
MeSH term(s)	Brain/diagnostic imaging ; Brain/metabolism ; Depressive Disorder, Major/diagnostic imaging ; Depressive Disorder, Major/metabolism ; Humans ; Image Enhancement/methods ; Ligands ; Positron-Emission Tomography/trends ; Radioisotopes/pharmacokinetics ; Radiopharmaceuticals ; Tomography, Emission-Computed, Single-Photon/trends
Chemical Substances	Ligands ; Radioisotopes ; Radiopharmaceuticals
Language	English
Publishing date	2008-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120248-0
ISSN	0001-2998
ISSN	0001-2998
DOI	10.1053/j.semnuclmed.2008.02.007
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Article ; Online: Astrogliosis marker 11C-SL25.1188 PET in traumatic brain injury with persistent symptoms.

Koshimori, Yuko / Cusimano, Michael D / Vieira, Erica L / Rusjan, Pablo M / Kish, Stephen J / Vasdev, Neil / Moriguchi, Sho / Boileau, Isabelle / Chao, Thomas / Nasser, Zahra / Ishrat Husain, M / Faiz, Khunsa / Braga, Joeffre / Meyer, Jeffrey H

Brain : a journal of neurology

2023 Volume 146, Issue 11, Page(s) 4469–4475

Abstract: Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in ... ...

Abstract	Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume (11C-SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with 11C-SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC 11C-SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. 11C-SL25.1188 VT was greater in TBI in PFC (P = 0.00064) and cortex (P = 0.00038). PFC 11C-SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r = -0.48, P = 0.01). In participants scanned within 2 years of last TBI, PFC 11C-SL25.1188 VT correlated with serum glial fibrillary acid protein (r = 0.51, P = 0.037) and total tau (r = 0.74, P = 0.001). Elevated 11C-SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.
MeSH term(s)	Humans ; Aged ; Carbon Radioisotopes/metabolism ; Gliosis/diagnostic imaging ; Positron-Emission Tomography ; Brain/metabolism ; Brain Injuries, Traumatic/diagnostic imaging ; Brain Injuries, Traumatic/metabolism ; Monoamine Oxidase/metabolism
Chemical Substances	SL25.1188 ; Carbon-11 ; Carbon Radioisotopes ; Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2023-08-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awad279
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