Differential G protein measures in mononuclear leukocytes of patients with bipolar mood disorder are state dependent

Avissar, Sofia; Nechamkin, Yakov; Barki‐Harrington, Liza; Roitman, Gregori; Schreiber, Gabriel

doi:10.1016/s0165-0327(96)01400-0

Cited by 65 publications

(36 citation statements)

References 38 publications

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“…As shown in Table 2, the increased levels obtained for the 14 patients ranged from 1.59 to 7.73 (average increase 3.64 Ϯ 2.09). This increase in D 3 receptor mRNA in schizophrenic patients is significantly higher than the reported increases in binding levels and other recently suggested peripheral markers for schizophrenia (15). Furthermore, the increase in D 3 receptor RNA was unaffected by different drug treatments.…”

Section: Resultscontrasting

confidence: 64%

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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Section: Resultscontrasting

confidence: 64%

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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“…The increases of peripheral immunoreactive levels of G as and/or G ai are not peculiar of patients with AN or BN, since similar alterations have been reported in subjects with bipolar disorder, 3,4 major depression 27 and schizophrenia, 10 in men at high risk for alcoholism 28 and in opioid addicts. 29 Therefore, the major challenge for future studies will be to elucidate the mechanisms by which shared peripheral abnormalities of G proteins might be involved in the pathophysiology of different psychiatric disorders.…”

Section: Discussionsupporting

confidence: 63%

“…[3][4][5][6][7] Similarly, modifications in the various subunits of G proteins have been demonstrated in both the periphery and the CNS of schizophrenic patients, [8][9][10] whereas no change has been detected in patients with panic disorder. 11 An increasing body of evidence also suggests that psychotropic drugs, upon chronic administration, may exert effects at postreceptor sites, in particular, at the level of G proteins.…”

mentioning

confidence: 99%

Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa

et al. 2003

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Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G as , G ai , G aq/11 and G b protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G ai and G b proteins, while bulimic patients had significantly increased levels of G as , G ai and G b proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.

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“…In the same context, the -adrenoceptor and cholinergic muscarinic stimulated binding of [ 3 H]GppNHp was found elevated in the manic episodes, but decreased in depressive episodes [12]. State markers correlating with the severity of the bipolar disorder have been described according to the increased levels obtained in the density of Antidepressant abbreviations: amtp, amitriptyline; clg, clorgyline; clo, clomipramine; dsp; desipramine; ECS, electroconvulsive shock; flx; fluoxetine; imi, imipramine; iprl, iprindole; TCA, tricyclic antidepressants; trn; tranylcypromine.…”

Section: Studies In Peripheral Tissue Of Depressive Patientsmentioning

confidence: 75%

“…Mammals have more than twenty different described G subunits, encoded in seventeen different genes [168]. They are classified in four families according to their homology in their primary structure: G s , G i , G q , G 12 , each family with several subtypes. These G protein subtypes are extremely conserved in evolution.…”

Section: Heterotrimeric G Proteinsmentioning

confidence: 99%

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

González-Maeso

Meana²

2006

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Mood disorders such as major depression and bipolar disorder are common, severe, chronic and often lifethreatening illnesses. Suicide is estimated to be the cause of death in up to approximately 10-15% of individuals with mood disorders. Alterations in the signal transduction through G protein-coupled receptor (GPCR) pathways have been reported in the etiopathology of mood disorders and the suicidal behavior. In this regard, the implication of certain GPCR subtypes such as 2A -adrenoceptor has been repeatedly described using different approaches. However, several discrepancies have been recently reported in density and functional status of the heterotrimeric G proteins both in major depression and bipolar disorder. A compilation of the most relevant research topics about the implication of heterotrimeric G proteins in the etiology of mood disorders (i.e., animal models of mood disorders, studies in peripheral tissue of depressive patients, and studies in postmortem human brain of suicide victims with mood disorders) will provide a broad perspective of this potential therapeutic target field. Proposed causes of the discrepancies reported at the level of G proteins in postmortem human brain of suicide victims will be discussed.

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Differential G protein measures in mononuclear leukocytes of patients with bipolar mood disorder are state dependent

Cited by 65 publications

References 38 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

Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

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