Binding of 3H-spiperone to human lymphocytes: A biological marker in schizophrenia?

Bondy, Brigitta; Ackenheil, Manfred; Elbers, Rembert; Fröhler, M.

doi:10.1016/0165-1781(85)90038-1

Cited by 48 publications

(18 citation statements)

References 16 publications

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“…Although the significance of dopamine receptors, as well as of other neurotransmitter receptors, in lymphocytes is still not clear, it has been suggested that they may reflect corresponding brain receptors. Several studies have demonstrated the increased binding of dopamine antagonists in lymphocytes of schizophrenic patients as compared with healthy individuals (11,12). In addition, a previous study carried out in our lab has demonstrated that spiperone (a D2 antagonist) binding in peripheral blood lymphocytes is higher in neuroleptic responders as compared with treatment-resistant schizophrenic patients (13).…”

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confidence: 91%

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes

Ilani¹

2001

Proceedings of the National Academy of Sciences

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Dopamine is a major neurotransmitter in the central nervous system, and its receptors are associated with a number of neuropathological disorders such as Parkinson's disease and schizophrenia. Although the precise pathophysiology of schizophrenia remains unknown, the dopaminergic hypothesis of the illness assumes that the illness results from excessive activity at dopamine synapses in the brain. Because, at present, the diagnosis of schizophrenia relies on descriptive behavioral and symptomatic information, a peripheral measurable marker may enable a simpler, more rapid, and more accurate diagnosis and monitoring. In recent years, human peripheral blood lymphocytes have been found to express several dopamine receptors (D3, D4, and D5) by using molecular biology techniques and binding assays. It has been suggested that these dopamine receptors found on lymphocytes may reflect receptors found in the brain. Here we demonstrate a correlation between the D3 dopamine receptor on lymphocytes and schizophrenia and show a significant elevation of at least 2-fold in the mRNA level of the D3, but not of the D4, dopamine receptor in schizophrenic patients. This increase is not affected by different antipsychotic drug treatments (typical or atypical). Moreover, nonmedicated patients exhibit the same pattern, indicating that this change is not a result of medical treatment. We propose the D 3 receptor mRNA on blood lymphocytes as a marker for identification and followup of schizophrenia. S chizophrenia is a neuropsychiatric disorder afflicting about one percent of the population. Although its exact pathogenesis is still not known precisely, a common belief is that excessive activity at dopaminergic synapses in the brain plays a prominent role (1). To date, a definitive diagnosis of schizophrenia requires a 6-month duration of symptomatology and relies on heterogeneous symptoms. Because there is neither an effective biological marker for identifying schizophrenia (2, 3), nor an accurate and rapid diagnosis to ensure more optimal management at an early stage in the illness (4), there remains a vital need for a convenient assay for diagnosis and followup of schizophrenia.Most of the drugs used to treat schizophrenia act to control symptoms by neuroreceptor antagonism. Moreover, the dopaminergic basis of schizophrenia is strongly supported by the close correlation between clinical efficacy of antipsychotic medications and their potency to antagonize the binding of dopamine to its receptors (5).Dopamine receptors are divided into two subclasses, D1 and D2. The D1 subclass contains the D 1 and D 5 receptor subtypes, and the D2 subclass contains the D 2 , D 3 , and D 4 subtypes (6). The dopamine hypothesis of schizophrenia specifically relates to the D2 subclass. Notably, most drugs effective in treating schizophrenia exhibit D2 receptor antagonistic activity, and administration of a selective D1-like antagonist has been reported to result in the worsening of symptoms (7). The D 3 receptor, one among the three in the D2 subclass, is...

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confidence: 91%

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes

Ilani¹

2001

Proceedings of the National Academy of Sciences

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“…Nevertheless, one group has consistently reported quantitative detection of D3, D4 and D5, but not D1 or D2 receptors on human lymphocytes (Ricci and Amenta, 1994; Ricci et al, 1995, 1997–1999; Amenta et al, 1999). Despite controversy in the results of binding studies with lymphocytes, there have been attempts to apply the receptor binding assay (RBA) in clinical studies of schizophrenia, migraine, Alzheimer’s disease and Parkinson’s disease (Le Fur et al, 1980,1983; Rotstein et al, 1983; Bondy et al, 1985; Bondy and Ackenheil, 1987; Halbach and Henning, 1989; Barbanti et al, 1999, 2000a, b). Some of these RBA findings were supported by RT-PCR results (Nagai et al, 1996; Ilani et al, 2001; Kwak et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Dopamine receptors in human lymphocytes: Radioligand binding and quantitative RT-PCR assays

Kirillova

Hrutkay

Shurin

et al. 2008

Journal of Neuroscience Methods

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Analysis of dopamine receptors (DR) in lymphocytes of the human peripheral blood mononuclear cell (PBMC) fraction is an attractive tool for evaluation of functional properties of dopaminergic function underlying variation in complex psychological/psychopathological traits. Receptor binding assays (RBA) with selective radioligands, which are widely used in CNS studies, have not produced consistent results when applied to isolated PBMC. We tested the assay conditions that could be essential for detection of DR in human PBMC and their membrane preparations. Using [3H]SCH23390, a dopamine D1-like receptor antagonist, we demonstrated the presence of two binding sites in PBMC-derived membrane fraction. One of them is characterized by the Kd value consistent with that reported for D5 dopamine receptors in human lymphocytes, whereas the other Kd value possibly corresponds to serotonin receptor(s). Although D5 receptor binding sites in PBMC membranes could be characterized by binding assays, the low protein expression and the large volume of blood needed for membrane preparation render the binding method impracticable for individual phenotyping. In contrast, real-time RT-PCR may be used for this purpose, contingent on the relationship between DR expression in the brain and in lymphocytes. The expression of the DRD2-DRD5 genes, as detected by this method, varied widely among samples, whereas the DRD1 expression was not detected. The expression levels were comparable with those in the brain for DRD3 and DRD4, and were significantly lower for DRD2 and DRD5.

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“…A number of dopaminergic markers have been evaluated in blood from people with Sz, including DA receptors (i.e., DRD2, DRD3, and DRD4 [70] ), DA transporter (DAT), and other molecules associated with the dopaminergic system [i.e., tyrosine hydroxylase (TH)]. Both mRNA expression and receptor binding of DRD2 were increased in lymphocytes from people with Sz who were drugnaive [71,72] , however the upregulation of DRD2 mRNA was not replicated [73,74] . The levels of lymphocyte DRD3 mRNA was reported to be elevated in both people with chronic Sz [73,75] and people with Sz who were drugnaïve [76] .…”

Section: Monoamine Pathwaysmentioning

confidence: 99%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

140

108

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Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood World Journal of Psychiatry W J P oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

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Binding of 3H-spiperone to human lymphocytes: A biological marker in schizophrenia?

Cited by 48 publications

References 16 publications

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes

Dopamine receptors in human lymphocytes: Radioligand binding and quantitative RT-PCR assays

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

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