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Article ; Online: Constance E. Lieber, Theodore R. Stanley, and the Enduring Impact of Philanthropy on Psychiatry Research.

Krystal, John H / Abi-Dargham, Anissa / Akbarian, Schahram / Arnsten, Amy F T / Barch, Deanna M / Bearden, Carrie E / Braff, David L / Brown, E Sherwood / Bullmore, Edward T / Carlezon, William A / Carter, Cameron S / Cook, Edwin H / Daskalakis, Zafiris Jeff / DiLeone, Ralph J / Duman, Ronald S / Grace, Anthony A / Hariri, Ahmad R / Harrison, Paul J / Hiroi, Noboru /

Kenny, Paul J / Kleinman, Joel E / Krystal, Andrew D / Lewis, David A / Lipska, Barbara K / Marder, Stephen R / Mason, Graeme F / Mathalon, Daniel H / McClung, Colleen A / McDougle, Christopher J / McIntosh, Andrew M / McMahon, Francis J / Mirnics, Károly / Monteggia, Lisa M / Narendran, Rajesh / Nestler, Eric J / Neumeister, Alexander / O'Donovan, Michael C / Öngür, Dost / Pariante, Carmine M / Paulus, Martin P / Pearlson, Godfrey / Phillips, Mary L / Pine, Daniel S / Pizzagalli, Diego A / Pletnikov, Mikhail V / Ragland, J Daniel / Rapoport, Judith L / Ressler, Kerry J / Russo, Scott J / Sanacora, Gerard / Sawa, Akira / Schatzberg, Alan F / Shaham, Yavin / Shamay-Tsoory, Simone G / Sklar, Pamela / State, Matthew W / Stein, Murray B / Strakowski, Stephen M / Taylor, Stephan F / Turecki, Gustavo / Turetsky, Bruce I / Weissman, Myrna M / Zachariou, Venetia / Zarate, Carlos A / Zubieta, Jon-Kar

Biological psychiatry

2016 Volume 80, Issue 2, Page(s) 84–86

Language	English
Publishing date	2016-02-23
Publishing country	United States
Document type	Journal Article ; 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.2016.05.004
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Article ; Online: Aspirin and celecoxib may help to rectify a neurotransmission imbalance in bipolar disorder.

Rapoport, Stanley I

Medical hypotheses

2021 Volume 149, Page(s) 110536

Abstract: Background: Mood stabilizers with disparate chemical structures are approved for treating bipolar disorder, but their mechanisms of action are not agreed on. However, when administered to unanesthetized rats at clinically relevant doses, they modulate ... ...

Abstract	Background: Mood stabilizers with disparate chemical structures are approved for treating bipolar disorder, but their mechanisms of action are not agreed on. However, when administered to unanesthetized rats at clinically relevant doses, they modulate neurotransmission involving arachidonic acid and brain activity of COX-2, which oxidizes arachidonic acid within the arachidonic acid metabolic cascade. Hypothesis: Inhibiting COX-2 directly might enhance mood stabilizer effects in bipolar disorder patients. Observations: This paper reviews randomized controlled trials that showed that celecoxib, a selective COX-2 inhibitor, or low-dose aspirin, which inhibits COX-1 and inhibits/acetylates COX-2, reduced bipolar symptoms in patients on mood stabilizers. More convincing are two population based pharmacoepidemiological studies that each demonstrated that chronic low dose aspirin reduced bipolar severity markers in patients on mood stabilizers. Conclusions: This clinical evidence is consistent with the hypothesis that low-dose chronic aspirin and celecoxib, which can inhibit COX-2 and enter brain, can be repurposed in bipolar disorder to enhance mood stabilizer effects on arachidonic acid metabolism and neurotransmission.
MeSH term(s)	Animals ; Antimanic Agents/therapeutic use ; Aspirin/therapeutic use ; Bipolar Disorder/drug therapy ; Celecoxib/therapeutic use ; Humans ; Rats ; Synaptic Transmission
Chemical Substances	Antimanic Agents ; Celecoxib (JCX84Q7J1L) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2021-02-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2021.110536
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Article ; Online: THERAPEUTIC TARGETING OF BRAIN ARACHIDONIC ACID CASCADE IN BIPOLAR DISORDER BY LOW DOSE ASPIRIN AND CELECOXIB.

Rapoport, Stanley I / Hibbeln, Joseph R

Prostaglandins, leukotrienes, and essential fatty acids

2020 Volume 159, Page(s) 102118

Abstract: Background: Studies in unanesthetized rats suggest that mood stabilizers approved for treating bipolar disorder downregulate brain arachidonic acid (AA) metabolism. AA plays a role in neurotransmission and neuroinflammation, among other processes. Other ...

Abstract	Background: Studies in unanesthetized rats suggest that mood stabilizers approved for treating bipolar disorder downregulate brain arachidonic acid (AA) metabolism. AA plays a role in neurotransmission and neuroinflammation, among other processes. Other drugs that reduce brain AA metabolism may add to mood stabilizer action. Methods: We reviewed randomized controlled trials (RCTs) and population studies to examine whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, and acetylsalicylate (aspirin), a COX-1 and COX-2 inhibitor and acetylator, were useful in bipolar disorder patients on mood stabilizers. COX-1 and COX-2 metabolize AA to bioactive eicosanoids. Results: Celecoxib significantly enhanced mood stabilizer efficacy in two 6-week RCTs involving 86 manic bipolar inpatients, and in one 8-week RCT on 49 patients with treatment-resistant bipolar depression. With regard to aspirin, a Dutch pharmacoepidemiological study involving 5145 subjects taking lithium reported symptom reduction with added chronic low dose 30-80 mg/day aspirin, while a Danish study on 321,350 subjects taking chronic 75-150 mg/day aspirin found fewer manic episodes than in subjects not on aspirin. Finally, a recent 6-week RCT using low-dose aspirin and/or minocycline showed a specific positive effect of aspirin. Conclusions: Efficacy of both celecoxib and aspirin as adjuncts to mood stabilizers in the treatment of bipolar disorder is consistent with the AA hypothesis for mood stabilizer action in that disorder.
Language	English
Publishing date	2020-05-21
Publishing country	Scotland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	286714-x
ISSN	1532-2823 ; 0952-3278
ISSN (online)	1532-2823
ISSN	0952-3278
DOI	10.1016/j.plefa.2020.102118
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Article ; Online: Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade.

Rapoport, Stanley I

ACS chemical neuroscience

2014 Volume 5, Issue 6, Page(s) 459–467

Abstract: This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically ... ...

Abstract	This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically administered lithium, carbamazepine, valproate, or lamotrigine each downregulated brain AA metabolism, and it is consistent with reported upregulated AA cascade markers in post-mortem BD brain. In the rats, each mood stabilizer reduced AA turnover in brain phospholipids, cyclooxygenase-2 expression, and prostaglandin E2 concentration. Lithium and carbamazepine also reduced expression of cytosolic phospholipase A2 (cPLA2) IVA, which releases AA from membrane phospholipids, whereas valproate uncompetitively inhibited in vitro acyl-CoA synthetase-4, which recycles AA into phospholipid. Topiramate and gabapentin, proven ineffective in BD, changed rat brain AA metabolism minimally. On the other hand, the atypical antipsychotics olanzapine and clozapine, which show efficacy in BD, decreased rat brain AA metabolism by reducing plasma AA availability. Each of the four approved mood stabilizers also dampened brain AA signaling during glutamatergic NMDA and dopaminergic D2 receptor activation, while lithium enhanced the signal during cholinergic muscarinic receptor activation. In BD patients, such signaling effects might normalize the neurotransmission imbalance proposed to cause disease symptoms. Additionally, the antidepressants fluoxetine and imipramine, which tend to switch BD depression to mania, each increased AA turnover and cPLA2 IVA expression in rat brain, suggesting that brain AA metabolism is higher in BD mania than depression. The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients.
MeSH term(s)	Animals ; Arachidonic Acid/metabolism ; Bipolar Disorder/drug therapy ; Bipolar Disorder/metabolism ; Brain/drug effects ; Brain/metabolism ; Lithium Compounds/pharmacology ; Psychotropic Drugs/pharmacology ; Rats ; Signal Transduction/drug effects
Chemical Substances	Lithium Compounds ; Psychotropic Drugs ; Arachidonic Acid (27YG812J1I)
Language	English
Publishing date	2014-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/cn500058v
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Article: [Results of a comparative multi-center randomized clinical study of efficacy and safety of EFFEX Tribulus and Tribestan in patients with erectile dysfunction].

Spivak, L G / Platonova, D V / Enikeev, D V / Rapoport, L M / Vinarov, A Z / Demidko, Yu L

Urologiia (Moscow, Russia : 1999)

2018 , Issue 2, Page(s) 54–61

Abstract: ... herbal preparations (EFFEX Tribulus and Tribestan) based on Tribulus Terrestris herb dry extract in patients with ED ... group II) received EFFEX Tribulus and Tribestan, respectively. The mean age of patients was 42.2+/-11.5 ... Tribulus and Tribestan have a similar efficacy and safety profiles. ...

Abstract	Relevance: Erectile dysfunction (ED) is a common condition. Pharmacological management of ED involves medications produced by chemical synthesis. Despite high efficiency, their use is often accompanied by some side effects. Considering this, herbal preparations with sufficient efficacy and greater safety have received much attention. Aim: To compare the efficacy and safety of two herbal preparations (EFFEX Tribulus and Tribestan) based on Tribulus Terrestris herb dry extract in patients with ED. Materials and methods: A total of 173 patients were enrolled in the study, of whom 87 (group I) and 86 (group II) received EFFEX Tribulus and Tribestan, respectively. The mean age of patients was 42.2+/-11.5 years in group I and 42.8+/-11.2 years in group II. One hundred fifty two patients completed the study. The follow-up was 13 weeks (the herbal preparation dose was titrated at week five after the treatment initiation). The effectiveness of treatment was assessed on five follow-up visits using the IIEF, AMS, MSF, GAQ questionnaires, and a complex of diagnostic and laboratory studies. Results: At visit five compared to visit 1, the mean IIEF erectile function domain score increased by 5.7+/-4.6 and 5.2+/-4.3 points in group I and II, respectively. In both groups, all other IIEF domain scores demonstrated a statistically significant increase. The AMS scores decreased from 32.93+/-10.04 to 25.02+/-7.62 points in group I and 31.78+/-10.37 to 24.55+/-7.31 points in group II. The SMF scores increased from 22.36+/-4.85 to 27.16+/-4.80 points in group I and from 22.13+/-3.69 to 26.10+/-5.69 points in group II. Besides, the use of the herbal preparations was associated with a decrease in the serum cholesterol level, more pronounced with increasing patient age (correlation coefficient -0.06, p=0.41). Conclusion: The herbal preparations EFFEX Tribulus and Tribestan have a similar efficacy and safety profiles.
MeSH term(s)	Adult ; Erectile Dysfunction/drug therapy ; Erectile Dysfunction/physiopathology ; Humans ; Male ; Middle Aged ; Phytotherapy ; Plant Extracts/administration & dosage ; Plant Preparations/administration & dosage ; Saponins/administration & dosage ; Tribulus/chemistry
Chemical Substances	Plant Extracts ; Plant Preparations ; Saponins ; tribestan (83047-17-0)
Language	Russian
Publishing date	2018-06-14
Publishing country	Russia (Federation)
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	43204-0
ISSN	1728-2985 ; 0042-1154
ISSN	1728-2985 ; 0042-1154
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Zs.B 1177: Show issues

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Book ; Conference proceedings: Imaging, cerebral topography and Alzheimer's disease

Rapoport, Stanley I.

[proceedings of the Fifth Colloque Médecine et Recherche ... Lille on October 16, 1989]

(Research and perspectives in Alzheimer's disease)

1990

Institution	Fondation IPSEN pour la recherche thérapeutique
Event/congress	Colloque Médecine et Recherche (5, 1989, Lille)
Author's details	S. R. Rapoport ... (eds.). Fondation IPSEN pour la Recherche Thérapeutique
Series title	Research and perspectives in Alzheimer's disease
Keywords	Alzheimer Disease / diagnosis / congresses ; Brain / pathology / congresses ; Diagnostic Imaging / congresses ; Alzheimerkrankheit ; Hirnschädigung ; Topografische Anatomie ; Bildgebendes Verfahren
Subject	Alzheimer-Krankheit ; Alzheimersche Krankheit ; Alzheimer-Demenz ; Morbus Alzheimer ; Greisenblödsinn ; Alzheimer's Disease ; Topographische Anatomie ; Medizinische Topographie ; Medizinische Topografie ; Medizin ; Cerebralschädigung ; Gehirn ; Hirnschaden ; Hirnläsion ; Zerebralschädigung ; Bildgebendes Diagnoseverfahren ; Diagnostik ; Bilddiagnostik ; Bildgebende Methode ; Medical Imaging ; Medizinische Bildgebung ; Bildgebende Diagnostik ; Bildgebende Verfahren ; Imaging
Size	XIII, 176 S. : Ill., graph. Darst.
Publisher	Springer
Publishing place	Berlin u.a.
Document type	Book ; Conference proceedings
HBZ-ID	HT003581388
ISBN	3-540-52552-1 ; 0-387-52552-1 ; 978-3-540-52552-3 ; 978-0-387-52552-5
Database	Catalogue ZB MED Medicine, Health

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1990 A 6785	order for loan	Magazin

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Article ; Online: Translational studies on regulation of brain docosahexaenoic acid (DHA) metabolism in vivo.

Rapoport, Stanley I

Prostaglandins, leukotrienes, and essential fatty acids

2012 Volume 88, Issue 1, Page(s) 79–85

Abstract: One goal in the field of brain polyunsaturated fatty acid (PUFA) metabolism is to translate the many studies that have been conducted in vitro and in animal models to the clinical setting. Doing so should elucidate the role of PUFAs in the human brain, ... ...

Abstract	One goal in the field of brain polyunsaturated fatty acid (PUFA) metabolism is to translate the many studies that have been conducted in vitro and in animal models to the clinical setting. Doing so should elucidate the role of PUFAs in the human brain, and effects of diet, drugs, disease and genetics on this role. This review discusses new in vivo radiotracer kinetic and neuroimaging techniques that allow us to do this, with a focus on docosahexaenoic acid (DHA). We illustrate how brain PUFA metabolism is influenced by graded reductions in dietary n-3 PUFA content in unanesthetized rats. We also show how kinetic tracer techniques in rodents have helped to identify mechanisms of action of mood stabilizers used in bipolar disorder, how DHA participates in neurotransmission, and how brain DHA metabolism is regulated by calcium-independent iPLA₂β. In humans, regional rates of brain DHA metabolism can be quantitatively imaged with positron emission tomography following intravenous injection of [1-¹¹C]DHA.
MeSH term(s)	Animals ; Biological Transport ; Biomarkers/blood ; Blood-Brain Barrier/metabolism ; Brain/physiology ; Brain Mapping ; Docosahexaenoic Acids/blood ; Docosahexaenoic Acids/metabolism ; Fatty Acids, Nonesterified/blood ; Humans ; Kinetics ; Neurons/metabolism ; Phospholipases A2/metabolism ; Phospholipids/metabolism ; Translational Research, Biomedical/trends
Chemical Substances	Biomarkers ; Fatty Acids, Nonesterified ; Phospholipids ; Docosahexaenoic Acids (25167-62-8) ; Phospholipases A2 (EC 3.1.1.4)
Language	English
Publishing date	2012-07-04
Publishing country	Scotland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	286714-x
ISSN	1532-2823 ; 0952-3278
ISSN (online)	1532-2823
ISSN	0952-3278
DOI	10.1016/j.plefa.2012.05.003
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Article ; Online: Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 a and AP-2 b in Frontal Cortex of Rats Treated with Lithium for 6 Weeks.

Rao, Jagadeesh S / Rapoport, Stanley I / Bosetti, Francesca

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2017 Volume 43, Issue 2, Page(s) 456

Abstract: This corrects the article DOI: 10.1038/ajg.2016.125. ...

Abstract	This corrects the article DOI: 10.1038/ajg.2016.125.
Language	English
Publishing date	2017-12-11
Publishing country	England
Document type	Journal Article ; Retraction of Publication
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2017.237
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Article ; Online: Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

Yuan, Zhi-Xin / Rapoport, Stanley I

Prostaglandins, leukotrienes, and essential fatty acids

2015 Volume 101, Page(s) 9–14

Abstract: Background: Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption ... ...

Abstract	Background: Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Hypothesis: Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Methods: Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Results: Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Conclusions: Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation.
MeSH term(s)	Animals ; Animals, Newborn ; Arachidonic Acids/analysis ; Behavior, Animal/drug effects ; Brain Chemistry/drug effects ; Fluoxetine/administration & dosage ; Fluoxetine/pharmacology ; Hydroxyeicosatetraenoic Acids/analysis ; Injections, Intraperitoneal ; Lipoxins/analysis ; Male ; Mice ; Serotonin Uptake Inhibitors/administration & dosage ; Serotonin Uptake Inhibitors/pharmacology
Chemical Substances	Arachidonic Acids ; Hydroxyeicosatetraenoic Acids ; Lipoxins ; Serotonin Uptake Inhibitors ; lipoxin A4 ; Fluoxetine (01K63SUP8D) ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3)
Language	English
Publishing date	2015-07-20
Publishing country	Scotland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	286714-x
ISSN	1532-2823 ; 0952-3278
ISSN (online)	1532-2823
ISSN	0952-3278
DOI	10.1016/j.plefa.2015.07.002
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Article ; Online: Retraction Note: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Wang, Shaowei / Li, Boyang / Solomon, Victoria / Fonteh, Alfred / Rapoport, Stanley I / Bennett, David A / Arvanitakis, Zoe / Chui, Helena C / Miller, Carol / Sullivan, Patrick M / Wang, Hoau-Yan / Yassine, Hussein N

Molecular neurodegeneration

2022 Volume 17, Issue 1, Page(s) 14

Language	English
Publishing date	2022-02-04
Publishing country	England
Document type	Journal Article ; Retraction of Publication
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-022-00519-x
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