Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: A randomized, double-blind, placebo-controlled study

Sumiyoshi, Tomiki; Park, Sohee; Jayathilake, Karu; Roy, Aditi; Ertuğrul, Aygün; Meltzer, Herbert Y.

doi:10.1016/j.schres.2007.06.008

Cited by 128 publications

(86 citation statements)

References 65 publications

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“…Improvements were observed in all 6 subjects for digit symbol coding, which were robust in magnitude, [8][9][10] and in 5 subjects for global cognition. Digit symbol coding is a measure of processing speed not associated with specific brain regions or functional neurocircuitry, 11 and greater impairments predict poorer prognosis and functional disability.…”

Section: J Clin Psychiatry 77:2 February 2016mentioning

confidence: 78%

An Open-Label, Pilot Trial of Adjunctive Tocilizumab in Schizophrenia

Miller¹,

Dias²,

Lemos³

et al. 2016

J. Clin. Psychiatry

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To the Editor: Interest and enthusiasm for research on the immunology of schizophrenia has, arguably, taken a prominent role in the field. Adjunctive antiinflammatory treatment may be associated with improvement in psychopathology and cognition in some patients with schizophrenia. 1,2 Interleukin-6 (IL-6) is an inflammatory cytokine produced by blood leukocytes and central nervous system microglia and astrocytes. IL-6 levels are elevated and associated with psychopathology, smaller hippocampal volume, and poorer cognition in schizophrenia. [3][4][5] We hypothesized that adjunctive tocilizumab-a humanized IL-6 receptor monoclonal antibody-would improve cognition in schizophrenia, an important determinant of quality of life and functioning. Method. With Institutional Review Board approval and anInvestigational New Drug waiver from the US Food and Drug Administration (FDA), we conducted an 8-week open-label trial of adjunctive tocilizumab in schizophrenia (ClinicalTrials.gov Identifier NCT01696929). All subjects provided written informed consent, and a Data Safety Monitoring Board, which included a psychiatrist and rheumatologist, provided study oversight.Tocilizumab is FDA approved for adults with rheumatoid arthritis and juvenile idiopathic arthritis and is administered as an intravenous infusion every 4 weeks. Subjects were aged 18-55 years, had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, were taking a non-clozapine antipsychotic, had no psychiatric hospitalizations in the past 3 months, and were on stable psychotropic medications for ≥ 1 month.Exclusion criteria were taking scheduled immunomodulatory agents; having a history of immune disorder; using an illicit drug in the past month; having unstable medical conditions; having active or chronic infections; and being pregnant, breastfeeding, or being a reproductive-age female not using contraception.After screening, subjects received 4 mg/kg of tocilizumab at baseline and 4 weeks. Psychopathology (Positive and Negative Syndrome Scale 6 [PANSS], cognition (Brief Assessment of Cognition in Schizophrenia 7 [BACS], alternate forms of testing) and fasting serum high-sensitivity C-reactive protein (hsCRP) and cytokine levels were assessed at baseline and weeks 2, 4, and 8. Changes in psychopathology and cognition were analyzed using a paired t test, 2-sided, using a last-observation carried forward approach; P values were considered statistically significant at the α = .05 level. It is illegal to post this copyrighted PDF on any website. J Clin Psychiatry 77:2, February 2016Letters to the Editor Results. Eight subjects were enrolled; 2 were excluded after screening. Although 6 subjects entered the trial, 1 was removed after the first infusion because psychosocial stressors required psychiatric hospitalization. All week-4 study assessments were completed by the subject; however, a second infusion was not administered. Thus, 5 subjects completed the trial. Demographic and clinical characteristics are presented in Table 1. Infusions were well tolera...

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Section: J Clin Psychiatry 77:2 February 2016mentioning

confidence: 78%

An Open-Label, Pilot Trial of Adjunctive Tocilizumab in Schizophrenia

Miller¹,

Dias²,

Lemos³

et al. 2016

J. Clin. Psychiatry

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“…Among the subtypes of 5-HT receptors (Fig. 4), 5-HT 1A , 5-HT 2A , 5-HT 6 , and 5-HT 7 receptors have been shown to be associated with cognitive effects of AAPDs, suggesting pivotal roles for the serotonergic system in cognitive symptoms of schizophrenia (Sumiyoshi T. et al 2007a, Meltzer and Sumiyoshi 2008. Fig.…”

Section: -Ht Receptors and Cognitive Functionmentioning

confidence: 99%

“…summarizes the mode of actions (agonism or antagonism) and specific compounds related to the above-mentioned 5-HT receptor subtypes. Among them, 5-HT 1A receptor stimulation is currently considered as the most promising approach (Llado-Pelfort et al 2011, Newman-Tancredi and Kleven 2011, Newman-Tancredi and Albert in press, Sumiyoshi C. et al 2006, Sumiyoshi T. et al 2007a, Sumiyoshi T. et al 2000, Sumiyoshi T. et al 2007b, Sumiyoshi T. et al 2001a, Sumiyoshi T. et al 2001b), as discussed in the next section. This is followed by 5-HT 2A antagonism, as elicited by certain (although not satisfactory) efficacy of a series of AAPDs whose principal pharmacologic feature is blockade of 5-HT 2A receptors (Meltzer et al 1989, Meltzer and Massey 2011, Stockmeier et al 1993, Sumiyoshi T. et al 1995.…”

Section: -Ht Receptors and Cognitive Functionmentioning

confidence: 99%

Serotonin-1A Receptors and Cognitive Enhancement in Schizophrenia: Role for Brain Energy Metabolism

Sumiyoshi¹,

Uehara²

2012

Schizophrenia in the 21st Century

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“…In support of this hypothesis, Sumiyoshi et al (Sumiyoshi et al, 2001a(Sumiyoshi et al, , 2001b reported that chronic administration of the selective 5-HT 1A receptor agonist tandospirone as a co-therapy with typical antipsychotics enhance verbal memory and executive functions in schizophrenia patients. In contrast, chronic co-administration of the 5-HT 1A receptor partial agonist buspirone with atypical antipsychotics improved psychomotor speed but not memory or executive function in schizophrenia patients (Sumiyoshi et al, 2007). On the other hand, tandospirone exerted negative effects on memory function in demented patients (Yasuno et al, 2003), and the potent 5-HT 1A agonist NAE-086 induced hallucinations and nightmares in healthy volunteers after repeated doses (Renyi et al, 2001).…”

Section: Role Of Other 5-ht Receptorsmentioning

confidence: 99%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

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Although the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades. Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin. Serotonin and Schizophrenia AbstractAlthough the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades.Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin.3

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Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: A randomized, double-blind, placebo-controlled study

Cited by 128 publications

References 65 publications

An Open-Label, Pilot Trial of Adjunctive Tocilizumab in Schizophrenia

An Open-Label, Pilot Trial of Adjunctive Tocilizumab in Schizophrenia

Serotonin-1A Receptors and Cognitive Enhancement in Schizophrenia: Role for Brain Energy Metabolism

Serotonin and Schizophrenia

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