Reduced Sensitivity of Lymphocyte Beta-Adrenergic Receptors in Patients with Endogenous Depression and Psychomotor Agitation

Mann, J. John; Brown, Richard P.; Halper, James P.; Sweeney, John A.; Kocsis, James H.; Stokes, Peter E.; Bilezikian, John P.

doi:10.1056/nejm198509193131202

Cited by 152 publications

(44 citation statements)

References 33 publications

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“…Indeed, reduced levels of the β-adrenergic receptor were previously extensively described in mononuclear leukocytes of patients with unipolar and bipolar depression (40)(41)(42)(43)(44). However, our functional measures, together with the complementary immunoblot studies, suggest also direct, quantitative, and functional reductions in G s protein in mononuclear leukocytes of depressed patients at the postreceptor level that are in accordance with functional findings of reduced β-adrenergic-receptor-coupled adenylate cyclase activity in patients with depression (40,41,(45)(46)(47). Most evidence suggests that muscarinic receptor characteristics are not altered in patients with affective disorder (37).…”

Section: Resultssupporting

confidence: 89%

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression

Avissar

Nechamkin²,

Roitman³

et al. 1997

AJP

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Section: Resultssupporting

confidence: 89%

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression

Avissar

Nechamkin²,

Roitman³

et al. 1997

AJP

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“…Impaired cAMP production has been reported in agitated depressives, not in retarded depressives (Mann et al 1985). Halper et al (1988) also reported that both basal cAMP and isoproterenol-stimulated cAMP levels are lower in hospitalized, depressed patients.…”

Section: Discussionmentioning

confidence: 96%

Psychological States and Lymphocyte β-Adrenergic Receptor Responsiveness

Dimsdale

Mills

1999

Neuropsychopharmacology

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There is a complex interplay between psychological states and biochemical factors. ␤ -Adrenergic receptor responsiveness is altered in some patients with depression and anxiety disorders, but the relation between various psychological states and receptor function in a normal population is unknown. We measured lymphocyte ␤ -adrenergic receptor density (B max ), sensitivity (cAMP ratio), the Profile of Mood States (POMS), and Spielberger State-TraitThere is a strong interplay between psychological states and physiology. This interplay has traditionally been studied extensively in terms of hormonal levels. More recently, investigators have begun to explain how such factors relate to receptor physiology. ␤ -Adrenergic receptor responsiveness may be altered in patients with such psychiatric diseases as depression (Pandey et al. 1987;Magliozzi et al. 1989) and panic disorder (Nesse et al. 1984;Brown et al. 1988;Aronson et al. 1989). In panic disorder, reduced ␤ -adrenergic receptor responsiveness has been noted in two ways, with both reduced receptor density and reduced responsivity to isoproterenol (Maddock et al. 1993).Adrenergic receptor regulation is closely related to psychological stressors (Graafsma et al. 1989). ␤ -Adrenergic receptor function is closely affected by numerous psychological stressors; for example, individuals with high life stress have lower ␤ -adrenergic receptor sensitivity (Dimsdale et al. 1994). Recently, hostility has been shown to be associated with ␤ -adrenergic receptor down-regulation in healthy young males (Suarez et al. 1997). All of these studies suggest that adrenergic receptors may be regarded as an important link between humoral signals influenced by psychological stressors and end organ responsiveness. However, normative information still needs to be acquired concerning the relationship between various psychological states and ␤ -adrenergic receptor responsiveness in a nonpsychiatric population.Human leukocytes offer a useful model for studying the role of ␤ -adrenergic receptor responsiveness in patients with medical or psychiatric illness (Pandey et al. . The use of lymphocyte ␤ -adrenergic receptors as a model for central ␤ -receptors is not as well established as the use of lymphocyte ␤ -receptors for such peripheral tissues as the heart and lung. Nonetheless, Mann et al. (1990) reported a normalization of blunted lymphocyte ␤ -receptors in depression following treatment. In addition, Brodde et al. (1986) reported that alterations in lymphocyte ␤ -adrenoceptors mirror changes in ␤ -adrenoceptors in other tissues less accessible in human studies. There are two major techniques for measuring ␤ -adrenergic receptor responsiveness in human leukocytes; measuring receptor density (B max ) and sensitivity. ␤ -Adrenergic receptor density in lymphocytes is defined as the number of receptors/cell for intact cells, and as pico-or femto-moles/mg protein for membranes. ␤ -Adrenergic receptor sensitivity is defined as the efficiency with which agonist binding translates into stimulation...

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“…The S/S genotype, which is considered to be slow for 5HT transport [30] , was found to be correlated with the severity of depression assessed by HAM-D, although the signifi cance of this observation remains to be determined, and results may be limited by the small number of patients included in the study. However, some studies in mononuclear leukocytes, such as the isoproterenol stimulation of cAMP, are negatively correlated with the severity of depression [33] or psychomotor activation [34] . Moreover, a signifi cant, positive correlation was reported for taurine levels in lymphocytes and the severity of a depressive disorder [35] , but no relationship between immune variables and the severity of the illness has been observed [36] .…”

Section: P42 C43 P44 P51 C52mentioning

confidence: 99%

Allelic Isoforms and Decrease in Serotonin Transporter mRNA in Lymphocytes of Patients with Major Depression

Lima

Mata

Urbina

2005

Neuroimmunomodulation

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Serotonin transporter, measured by the specific binding of [³H]paroxetine, has been reported to be reduced in circulating lymphocytes of patients with major depression. Due to this observation, the objective of the present report was to determine the levels of serotonin transporter mRNA in lymphocytes obtained from 29 major depression patients (4 men, age 33.10 ± 1.63 years) and from 30 subjects included as a control group (4 men, age 37.54 ± 2.18 years) using RT-PCR. The patients were diagnosed according to the criteria of the American Psychiatric Association, and had a severity of depression of 32.68 ± 1.55 determined by the Hamilton Rating Scale for Depression. The DNA was submitted to polymerase chain reaction with primers for the 5′ regulatory region of human serotonin transporter, which could show the long and the short allelic forms of the transporter gene for the 5HTTLPR polymorphism. Semiquantitative analysis was performed using β-actin as internal and external standard. Control subjects presented the two allelic forms in 9.09% and depressed patients in 8.69%. The long variant was present in 73% of controls and in 60% of patients, without significant differences. There was a significant reduction in mRNA in depressed patients expressing the long allele. The number of immunofluorescent lymphocytes, labeled with a specific antibody against serotonin transporter, was reduced in the patients, as well as CD3+ lymphocytes. Serotonin and 5-hydroxyindoleacetic acid in platelet-poor plasma or lymphocytes did not differ between depressed patients and controls. The reduction in lymphocyte serotonin transporter described in major depression might be due to a decrease in the level of its mRNA and in the number of cells expressing it. These observations might implicate that functional modifications are associated with nervous-immune interactions in depression.

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Reduced Sensitivity of Lymphocyte Beta-Adrenergic Receptors in Patients with Endogenous Depression and Psychomotor Agitation

Cited by 152 publications

References 33 publications

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression

Psychological States and Lymphocyte β-Adrenergic Receptor Responsiveness

Allelic Isoforms and Decrease in Serotonin Transporter mRNA in Lymphocytes of Patients with Major Depression

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