Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

Arora, Ramesh; Meltzer, Herbert Y.

doi:10.1038/npp.1994.12

Cited by 19 publications

(13 citation statements)

References 19 publications

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“…A few studies of platelet 5‐HT 2A receptors in suicidal patients have found increased platelet 5‐HT 2A receptors in suicidally depressed but not nonsuicidally depressed patients. Further, our studies 21 and the studies of Arora and Meltzer 25 indicate that platelet 5‐HT 2A receptors may be increased in suicidal patients independent of diagnosis. In summary, these studies indicate that platelet 5‐HT 2A receptors are increased in depression, that this increase may be related to suicidal behavior, and that the increase in platelet 5‐HT 2A receptors in suicidal patients appears to be independent of diagnosis and may be state related.…”

Section: Serotonin Studies In Plateletssupporting

confidence: 56%

“…did not find significant increases in suicidal patients, they reported that B max correlated with the medical damage of the suicide attempt. Arora and Meltzer 25 studied 5‐HT 2A receptors in schizophrenic and suicidal schizophrenic patients and reported an increase in suicidal schizophrenic patients compared to the control group.…”

Section: Serotonin Studies In Plateletsmentioning

confidence: 99%

“…5‐HT receptor subtypes using neuroendocrine probes, such as mCPP or ipsapirone, have been widely studied in patients with depression, 25,52,53,57 but apparently there are no reports comparing suicidal patients with control subjects.…”

Section: Neuroendocrine Studies Of Serotonin Functionmentioning

confidence: 99%

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Altered Serotonin Function in Suicide

Pandey¹

1997

Annals of the New York Academy of Sciences

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Significant progress has been made in understanding psychosocial, psychological, and environmental factors associated with suicide; however, it is only recently that attention has been paid to the understanding of the neurobiology of suicide. There are several studies that implicate the serotonin (5-HT) system in suicide. Initial evidence was obtained from observations of low 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of depressed patients with a previous history of suicide attempts. Several strategies have been used to examine the serotonergic system in suicidal behavior, which include the determination of serotonin and its metabolites in CSF and postmortem brain tissues as well as serotonin receptor subtypes in postmortem brain tissues, and in platelets of suicidal patients. The neuroendocrine strategy, often termed the "window to the brain," has been extensively used for studying the serotonergic system in suicide. This chapter will review the results obtained from neuroendocrine and serotonin studies in platelets. Initial studies in platelets focussed on determining serotonin uptake and serotonin transporter binding sites in platelets of depressed and suicidal patients. Whereas several studies have found decreased imipramine binding sites of platelets of depressed patients, imipramine binding sites in platelets of suicidal patients showed inconsistent results. Similarly, no consistent changes in 5-HT uptake have been observed in platelets obtained from suicidal patients compared to nonsuicidal patients. On the other hand, studies of platelet 5-HT2A receptors appear to be quite encouraging. Initially, several investigators indicated that they found an increase in platelet 5-HT2A receptors in depressed patients. Subsequently, it was shown that platelet 5-HT2A receptors in suicidally depressed patients were significantly higher compared to nonsuicidally depressed patients and normal control subjects. It has also been shown that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis, similar to platelets. 5-HT2A receptors have also been shown to be increased in the postmortem brain of suicide victims by several investigators, although some investigators do not find such an increase. The neuroendocrine strategy provides an important method for studying serotonin function in the central nervous system of depressed and suicidal patents. Using a serotonergic probe of 5-HT1A receptors, several investigators examined ipsapirone-induced prolactin release in suicidal patients and did not find it different that that of control subjects. On the other hand, fenfluramine, which causes release of serotonin and blocks serotonin uptake, causes a decreased release of prolactin in depressed patients compared to normal control subjects. Furthermore it has been shown by some investigators that fenfluramine-induced prolactin release is also decreased in suicidal patients compared to normal control subjects. In summary, platelet and neuroendocrine studies have provided initial evid...

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Section: Serotonin Studies In Plateletssupporting

confidence: 56%

Section: Serotonin Studies In Plateletsmentioning

confidence: 99%

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Altered Serotonin Function in Suicide

Pandey¹

1997

Annals of the New York Academy of Sciences

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“…Using 125 I-LSD, B max values of platelet 5HT 2 receptors were shown to be higher in schizophrenic patients than controls (Pandey et al, 1993). These ®ndings could not be replicated once the statistical corrections for platelet as a psychiatric illnessage and sex effects were made (Arora and Meltzer, 1993). Marazziti et al (1989) …”

Section: Platelet Receptor Studiesmentioning

confidence: 94%

The platelet as a peripheral marker in psychiatric illness

Plein

Berk

2001

Human Psychopharmacology

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The identification of peripheral markers of psychiatric illness is important if an improvement in the diagnosis and treatment of various diseases with overlapping symptomatology is desired. There are many disorders that not only have overlapping symptomatology, but also have similar biological disturbances. The functional capability of the neurons involved in the disease processes may be at the crux of the underlying pathology. The platelet intracellular calcium response to neurotransmitter stimulation has previously been used as a peripheral marker of psychiatric illness. This review discusses evidence in support of the extended use of the platelet as a peripheral marker. The use of the platelet intracellular calcium response to neurotransmitter stimulation as a state or trait marker in major depression, the specificity and selectivity of this response, and the possible use of the platelet as a peripheral marker in psychotic disorders such as schizophrenia, mania and psychotic depression are shown. Finally, a proposed mechanism for the association between certain psychiatric disorders and cardiovascular disease is discussed. Copyright 2001 John Wiley& Sons, Ltd.

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“…The direction of findings in the brain of suicides is consistent with some platelet findings in suicide attempters. For example, more platelet 5-HT 2A receptors are found in suicide attempters compared with non-attempters and healthy controls (Arora and Meltzer, 1993 ;Biegon et al, 1990 ;McBride et al, 1994 ;Pandey et al, 1990Pandey et al, , 1995Rao et al, 1998), and in individuals with suicidal ideation compared to non-suicidal psychiatric patients and controls (Alda and Hrdina, 2000 ;Bakish et al, 1997 ;Hrdina et al, 1997). Two studies observed no difference (Serres et al, 1999 ;Uchitomi et al, 2002).…”

Section: Introductionmentioning

confidence: 92%

Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients

2006

Int. J. Neuropsychopharm.

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In depressed patients, high-lethality suicidal acts are accompanied by serotonin system abnormalities analogous to those seen in completed suicides. We have previously reported greater platelet 5-HT2A receptor density, and impaired serotonin enhancement of ADP-induced platelet aggregation, an indirect measure of signal transduction, in high-lethality suicide attempters. We hypothesized that serotonin-activated phosphoinositide (PI) hydrolysis, a direct measure of platelet serotonin 5-HT2A receptor responsivity would be lower in depressed high-lethality suicide attempters. Twenty-three depressed in-patients that had previously made suicide attempts (low-lethality, n=6; high-lethality, n=17) had platelet 5-HT2A-mediated serotonin-simulated PI hydrolysis assayed. Platelet 5-HT2A receptor responsivity in high-lethality suicide attempters was 41% that of low-lethality suicide attempters (p<0.05). A seasonal effect was also observed. High-lethality suicidal acts are associated with more 5-HT2A receptors but impaired signal transduction.

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Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

Cited by 19 publications

References 19 publications

Altered Serotonin Function in Suicide

Altered Serotonin Function in Suicide

The platelet as a peripheral marker in psychiatric illness

Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients

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