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Article ; Online: Preliminary Study of White Matter Abnormalities and Associations With the Metabotropic Glutamate Receptor 5 to Distinguish Bipolar and Major Depressive Disorders.

Fan, Siyan / Asch, Ruth H / Davis, Margaret T / DellaGioia, Nicole / Cool, Ryan / Blumberg, Hilary P / Esterlis, Irina

Chronic stress (Thousand Oaks, Calif.)

2024 Volume 8, Page(s) 24705470231225320

Abstract: Background: Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion- ... ...

Abstract	Background: Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion-weighted MRI studies have suggested some common frontotemporal corticolimbic system white matter (WM) abnormalities across the disorders. However, critical to the development of more precise diagnosis and treatment is identifying distinguishing abnormalities. Promising candidates include more prominent frontotemporal WM abnormalities observed in BD in the uncinate fasciculus (UF) that have been associated with frontal-amygdala functional dysconnectivity, and with suicide that is especially high in BD. Prior work also showed differentiation in metabotropic glutamate receptor 5 (mGlu5) abnormalities in BD versus MDD, which could be a mechanism affected in the frontotemporal system. However, associations between WM and mGlu5 have not been examined previously as a differentiator of BD. Using a multimodal neuroimaging approach, we examined WM integrity alterations in the disorders and their associations with mGluR5 levels. Methods: Individuals with BD ( Results: FA corticolimbic reductions were observed in both disorders and altered UF WM integrity was observed only in BD. In BD, lower UF FA was associated with lower amygdala mGlu5 availability ( Conclusions: These novel preliminary findings suggest important associations between lower UF FA and lower amygdala mGlu5 levels that could represent a disorder-specific neural mechanism in which mGluR5 is associated with the frontotemporal dysconnectivity of the disorder.
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ISSN	2470-5470
ISSN (online)	2470-5470
DOI	10.1177/24705470231225320
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Article ; Online: Nicotine Use and Metabotropic Glutamate Receptor 5 in Individuals With Major Depressive and Posttraumatic Stress Disorders.

Baldassarri, Stephen R / Asch, Ruth H / Hillmer, Ansel T / Pietrzak, Robert H / DellaGioia, Nicole / Esterlis, Irina / Davis, Margaret T

Chronic stress (Thousand Oaks, Calif.)

2023 Volume 7, Page(s) 24705470231154842

Abstract: Metabotropic glutamate receptor 5 (mGluR5) dysregulation has been implicated in the pathophysiology of many psychiatric disorders, as well as nicotine use and dependence. We used positron emission tomography with [ ...

Abstract	Metabotropic glutamate receptor 5 (mGluR5) dysregulation has been implicated in the pathophysiology of many psychiatric disorders, as well as nicotine use and dependence. We used positron emission tomography with [
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2470-5470
ISSN (online)	2470-5470
DOI	10.1177/24705470231154842
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Article ; Online: Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder.

Holmes, Sophie E / Asch, Ruth H / Davis, Margaret T / DellaGioia, Nicole / Pashankar, Neha / Gallezot, Jean-Dominique / Nabulsi, Nabeel / Matuskey, David / Sanacora, Gerard / Carson, Richard E / Blumberg, Hilary P / Esterlis, Irina

Biological psychiatry

2022 Volume 93, Issue 12, Page(s) 1099–1107

Abstract: 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 ... ...

Abstract	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. Methods: Individuals with BD (n = 17 depressed; n = 10 euthymic) or MDD (n = 17) and healthy control (HC) individuals (n = 18) underwent imaging with [ Results: Prefrontal cortex mGluR5 availability was significantly different across groups (F Conclusions: This work suggests that mGluR5 could be helpful in distinguishing BD and MDD as a possible treatment target for depressive symptoms in MDD and for cognitive alterations in both disorders. Further work is needed to confirm differentiating roles for mGluR5 in BD and MDD and to probe modulation of mGluR5 as a preventive/treatment strategy.
MeSH term(s)	Humans ; Depressive Disorder, Major ; Bipolar Disorder ; Receptor, Metabotropic Glutamate 5/metabolism ; Prefrontal Cortex/metabolism ; Positron-Emission Tomography/methods ; Magnetic Resonance Imaging
Chemical Substances	Receptor, Metabotropic Glutamate 5
Language	English
Publishing date	2022-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2022.10.018
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Zs.A 720: Show issues

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Article ; Online: A critical review of human endotoxin administration as an experimental paradigm of depression.

DellaGioia, Nicole / Hannestad, Jonas

Neuroscience and biobehavioral reviews

2009 Volume 34, Issue 1, Page(s) 130–143

Abstract: The syndrome called depression may represent the common final pathway at which different aetiopathogenic processes converge. One such aetiopathogenic process is innate immune system activation. Some depressed patients have increased levels of ... ...

Abstract	The syndrome called depression may represent the common final pathway at which different aetiopathogenic processes converge. One such aetiopathogenic process is innate immune system activation. Some depressed patients have increased levels of inflammatory cytokines and other immunologic abnormalities. It is not known whether immune system activation contributes to the pathogenesis of depressive symptoms. Supporting this possibility is the observation that in both rodents and humans, exogenous immune stimuli such as endotoxin can produce symptoms that resemble depression. A new approach to depression research would be to use immune stimuli to elicit depressive symptoms in humans. Here we review each of the symptoms elicited in humans by endotoxin administration, and compare this model to two other immune depression paradigms: interferon-alpha treatment and typhoid vaccine administration, to assess to what degree endotoxin administration represents a valid model of immune depression. We also review corresponding behavioral changes in rodents and the potential molecular pathways through which immune system activation produces each symptom.
MeSH term(s)	Animals ; Brain/immunology ; Brain/metabolism ; Depression/immunology ; Depression/metabolism ; Depressive Disorder/immunology ; Depressive Disorder/metabolism ; Endotoxins/metabolism ; Humans ; Inflammation/metabolism ; Models, Neurological
Chemical Substances	Endotoxins
Language	English
Publishing date	2009-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2009.07.014
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Zs.A 1371: Show issues

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Article ; Online: Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.

Holmes, Sophie E / Finnema, Sjoerd J / Naganawa, Mika / DellaGioia, Nicole / Holden, Daniel / Fowles, Krista / Davis, Margaret / Ropchan, Jim / Emory, Paul / Ye, Yunpeng / Nabulsi, Nabeel / Matuskey, David / Angarita, Gustavo A / Pietrzak, Robert H / Duman, Ronald S / Sanacora, Gerard / Krystal, John H / Carson, Richard E / Esterlis, Irina

Molecular psychiatry

2022 Volume 27, Issue 4, Page(s) 2273–2281

Abstract: The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic ... ...

Abstract	The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic connections. We investigated this hypothesis in humans for the first time using positron emission tomography (PET) and [
MeSH term(s)	Animals ; Antidepressive Agents/metabolism ; Antidepressive Agents/pharmacology ; Brain/diagnostic imaging ; Brain/metabolism ; Depressive Disorder, Major/drug therapy ; Depressive Disorder, Major/metabolism ; Humans ; Ketamine/metabolism ; Ketamine/pharmacology ; Macaca mulatta/metabolism ; Membrane Glycoproteins/metabolism ; Nerve Tissue Proteins/metabolism ; Positron-Emission Tomography/methods
Chemical Substances	Antidepressive Agents ; Membrane Glycoproteins ; Nerve Tissue Proteins ; SV2A protein, human (148845-93-6) ; Ketamine (690G0D6V8H)
Language	English
Publishing date	2022-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-022-01465-2
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Zs.A 4812: Show issues

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Article ; Online: Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [

Mecca, Adam P / Rogers, Kelly / Jacobs, Zachary / McDonald, Julia W / Michalak, Hannah R / DellaGioia, Nicole / Zhao, Wenzhen / Hillmer, Ansel T / Nabulsi, Nabeel / Lim, Keunpoong / Ropchan, Jim / Huang, Yiyun / Matuskey, David / Esterlis, Irina / Carson, Richard E / van Dyck, Christopher H

NeuroImage

2021 Volume 238, Page(s) 118217

Abstract: Objective: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability.: Methods: Cognitively ... ...

Abstract	Objective: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability. Methods: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [ Results: In the primary analysis, older age was associated with lower [ Conclusion: Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/metabolism ; Brain Chemistry ; Female ; Fluorine Radioisotopes/pharmacokinetics ; Fluorodeoxyglucose F18/pharmacokinetics ; Gray Matter/chemistry ; Hippocampus/chemistry ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuroimaging ; Organ Size ; Positron-Emission Tomography ; Radiopharmaceuticals/pharmacokinetics ; Receptor, Metabotropic Glutamate 5/analysis ; Young Adult
Chemical Substances	Fluorine Radioisotopes ; GRM5 protein, human ; Radiopharmaceuticals ; Receptor, Metabotropic Glutamate 5 ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Fluorine-18 (GZ5I74KB8G)
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2021.118217
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Zs.A 3664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 7: Show issues

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Article ; Online: The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis.

Hannestad, Jonas / DellaGioia, Nicole / Bloch, Michael

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2011 Volume 36, Issue 12, Page(s) 2452–2459

Abstract: Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of ...

Abstract	Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.
MeSH term(s)	Antidepressive Agents/therapeutic use ; Biomarkers/blood ; Clinical Trials as Topic/methods ; Cytokines/blood ; Depressive Disorder, Major/blood ; Depressive Disorder, Major/drug therapy ; Humans ; Inflammation Mediators/blood ; Treatment Outcome
Chemical Substances	Antidepressive Agents ; Biomarkers ; Cytokines ; Inflammation Mediators
Language	English
Publishing date	2011-07-27
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; 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/npp.2011.132
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Zs.A 2379: Show issues

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Article ; Online: Bupropion pre-treatment of endotoxin-induced depressive symptoms.

DellaGioia, Nicole / Devine, Lesley / Pittman, Brian / Hannestad, Jonas

Brain, behavior, and immunity

2013 Volume 31, Page(s) 197–204

Abstract: Increased levels of inflammatory cytokines may play a role in depression. Depressive symptoms can be induced in humans with administration of low-dose lipopolysaccharide (LPS; endotoxin), which activates the innate immune system and causes release of ... ...

Abstract	Increased levels of inflammatory cytokines may play a role in depression. Depressive symptoms can be induced in humans with administration of low-dose lipopolysaccharide (LPS; endotoxin), which activates the innate immune system and causes release of inflammatory cytokines. We previously found that pre-treatment with the serotonin reuptake inhibitor citalopram reduced LPS-induced fatigue and anhedonia. This is a follow-up study to determine whether LPS-induced symptoms could be reduced by pre-treatment with bupropion, a norepinephrine and dopamine reuptake inhibitor. In this double-blind, randomized, placebo-controlled, cross-over study, 10 healthy subjects received intravenous LPS (0.8 ng/kg) after oral pre-treatment with bupropion (75 mg twice a day) or placebo for 7 days. The Montgomery-Åsberg Depression Rating Scale (MADRS), the Profile of Mood States (POMS), and a visual analog scale (VAS) were used to measure depressive symptoms. Serum levels of inflammatory cytokines and chemokines were measured with electrochemiluminescence assays. The results of this study, which must be considered preliminary, showed that LPS administration was associated with (1) increase in serum levels of all cytokines and chemokines assayed; (2) increase in total MADRS score, mostly due to items 7 (lassitude) and 8 (anhedonia); (3) increase in fatigue; (4) decrease in vigor; and (5) decrease in social interest. Bupropion pre-treatment had no statistically significant effect on the innate immune response to LPS or on LPS-induced behavioral changes, suggesting that 1-week pre-treatment with bupropion does not inhibit LPS-induced fatigue and anhedonia, contrary to what was found previously with citalopram.
MeSH term(s)	Adult ; Antidepressive Agents, Second-Generation/therapeutic use ; Blood Pressure ; Bupropion/therapeutic use ; Chemokines/blood ; Cross-Over Studies ; Cytokines/blood ; Depression/blood ; Depression/chemically induced ; Depression/diagnosis ; Depression/drug therapy ; Double-Blind Method ; Female ; Heart Rate ; Humans ; Lipopolysaccharides ; Male ; Treatment Outcome
Chemical Substances	Antidepressive Agents, Second-Generation ; Chemokines ; Cytokines ; Lipopolysaccharides ; Bupropion (01ZG3TPX31)
Language	English
Publishing date	2013-07
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2012.10.008
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Article ; Online: In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.

Davis, Margaret T / Hillmer, Ansel / Holmes, Sophie E / Pietrzak, Robert H / DellaGioia, Nicole / Nabulsi, Nabeel / Matuskey, David / Angarita, Gustavo / Carson, Richard E / Krystal, John H / Esterlis, Irina

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 23, Page(s) 11490–11495

Abstract: Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [ ...

Abstract	Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [
MeSH term(s)	Adult ; Biomarkers/metabolism ; Brain/metabolism ; Depressive Disorder, Major/metabolism ; Female ; Humans ; Male ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/metabolism ; Receptor, Metabotropic Glutamate 5/metabolism ; Suicidal Ideation ; Suicide Prevention
Chemical Substances	Biomarkers ; GRM5 protein, human ; Radiopharmaceuticals ; Receptor, Metabotropic Glutamate 5
Language	English
Publishing date	2019-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1818871116
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Zs.A 1148: Show issues

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Article ; Online: Preliminary evidence concerning the pattern and magnitude of cognitive dysfunction in major depressive disorder using cogstate measures.

Davis, Margaret T / DellaGioia, Nicole / Matuskey, David / Harel, Brian / Maruff, Paul / Pietrzak, Robert H / Esterlis, Irina

Journal of affective disorders

2017 Volume 218, Page(s) 82–85

Abstract: Background: Cognitive deficits are common in individuals with major depressive disorder (MDD), and are associated with treatment non-responsiveness and poorer functional outcomes. Characterization of the nature and magnitude of deficits in this ... ...

Abstract	Background: Cognitive deficits are common in individuals with major depressive disorder (MDD), and are associated with treatment non-responsiveness and poorer functional outcomes. Characterization of the nature and magnitude of deficits in this population has been limited in part by lack of brief, practical, and well-validated assessment measures. The goal of this study was to use a brief, practical, and repeatable computerized cognitive test battery from Cogstate to examine differences in cognitive functioning between individuals with MDD and healthy controls. Methods: Forty participants (22 healthy controls (HCs), 18 with MDD) completed a battery of six cognitive measures, as well as measures of intellectual functioning (intellect) and depressive symptom severity. A multivariate analysis of covariance (MANCOVA) was conducted to compare cognitive test performance across groups while controlling for intellect. Results: Individuals with MDD had lower full-scale IQ scores on average, and performed worse on measures of visual attention (d=1.04), verbal learning (d=1.22) and memory (d=1.22), and visuospatial problem solving (d=0.80) than HCs after adjustment for differences in intellect. Psychomotor speed, visual memory, and working memory did not differ between groups. Conclusions: Cogstate measures appear to be sensitive in assessing deficits in attention, verbal learning and memory, and executive function in individuals with MDD. Further research will be useful in establishing the utility of Cogstate measures for standard use in research and clinical practice.
MeSH term(s)	Adult ; Attention ; Case-Control Studies ; Cognition ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Depressive Disorder, Major/psychology ; Executive Function ; Female ; Humans ; Male ; Memory, Short-Term ; Middle Aged ; Multivariate Analysis ; Neuropsychological Tests ; Problem Solving ; Reproducibility of Results ; Sensitivity and Specificity ; Verbal Learning
Language	English
Publishing date	2017-04-27
Publishing country	Netherlands
Document type	Evaluation Studies ; Journal Article
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2017.04.064
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