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ABSTRACT: The effect of clozapine and typical neuroleptic drug treatment on platelet serotonin2 (5-HT2) binding kinetic constants (Kd, Bmax) was studied in schizophrenic patients. Both treatments increased Bmax by a comparable amount, indicating increased numbers of 5-HT2 sites, although not all typical neuroleptic drugs were effective in this regard. Clozapine, but not typical neuroleptic drugs, increased Kd, indicating a lower affinity of the 5-HT2 sites for 5-HT. In a multiple regression model, low Bmax at baseline predicted poor outcome on Brief Psychiatric Rating Scale measures in the clozapine-treated patients but not the neuroleptic-treated patients.
Neuropsychopharmacology 05/1994; 10(2):109-14. · 7.99 Impact Factor
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ABSTRACT: Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and tryptophan (TRP) were determined in the frontal cortex of individuals who died by suicide, homicide, accident, or the result of physical diseases. Females had significantly higher tryptophan concentrations than males. There was a significant correlation HVA and the interval between death to refrigeration of the body. Mean HVA levels were higher from noon to 5 PM. Suicide and homicide victims had significantly higher cortical HVA concentrations than those who died of physical disease but not accident victims. This was not accounted for by gender, age, postmortem interval from death to refrigeration of the body or to autopsy, specimen storage time, or drug effects. The ratio of HVA/5-HIAA was also significantly higher in suicides compared with those who died of physical disease. No differences in cortical 5-HIAA or tryptophan concentrations between the four groups were found. There were no differences in the levels of the three substances in violent and nonviolent suicides. There were no significant correlations between 5-HIAA, HVA and TRP concentrations in all subjects or any of the four subgroups. The implications of these findings for the role of serotonin and dopamine in suicide and violence are discussed.
Biological Psychiatry 08/1992; 32(1):57-71. · 8.28 Impact Factor
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ABSTRACT: Kinetic constants of platelet imipramine binding were determined in youths with major depression, and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (Bmax) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (Kd) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/- 0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups. Although actively depressed females' Bmax was significantly lower than recovering depressed and nondepressed males, neither age, Tannner stage, nor circannual rhythms influenced Bmax, but suicidality may be associated with low Bmax. A decrease in Bmax may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history.
Journal of the American Academy of Child & Adolescent Psychiatry 04/1992; 31(2):298-305. · 6.44 Impact Factor
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ABSTRACT: We determined serotonin (5-HT) uptake in the blood platelets of Alzheimer's disease (AD) patients and comparable age-matched normal controls. The maximum number of 5-HT uptake sites (Vmax) was significantly increased in mild and moderate AD patients, and a trend toward decreased V max was observed in severe AD patients as compared with normal controls. The Km of 5-HT uptake was negatively correlated with the Face-Hand Test (FHT) score of severely ill AD patients, whereas Vmax was correlated with the FHT score and the Mental Status Questionnaire score in the entire AD sample.
Neurology 09/1991; 41(8):1307-9. · 8.31 Impact Factor
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ABSTRACT: 14C-Serotonin (5-HT) uptake and 3H-imipramine binding (IB) were studied in the blood platelets of 20 obsessive-compulsive disorder (OCD) patients, 53 normal controls (5-HT uptake) and 32 normal controls (IB binding). The maximum number of binding sites (Bmax) was significantly decreased in OCD patients compared to normal controls, but there was no difference in the affinity for 3H-imipramine (Kd). The affinity for 5-HT uptake (Km) was also decreased in the OCD patients but the maximum velocity of 5-HT uptake sites (Vmax) was not significantly different in OCD patients and normal volunteers. There were trends for the Slowness Subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI) to be positively correlated with the Km of 5-HT uptake (p = 0.094), whereas the Global Scale, Checking Subscale, and Doubting Conscientiousness Subscale of MOCI were negatively correlated with the Kd of IB (p = 0.066, p = 0.08, and p = 0.062, respectively). The results provide further evidence for the dysfunction of the serotonergic system in OCD.
Biological Psychiatry 08/1991; 30(2):131-9. · 8.28 Impact Factor
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ABSTRACT: Serotonin [5-hydroxytryptamine (5-HT)]-sensitive imipramine binding (IB) was determined in the left and right hemisphere of frontal cortex of suicide victims and nonpsychiatric controls who died due to myocardial infarction or accident. The Kd (an inverse measure of affinity of 3H-imipramine to its binding sites) was significantly higher in left hemisphere than right hemisphere in normal controls. There were no differences in Bmax and Kd or Bmax between left hemisphere and right hemisphere in normals and suicides, respectively. These results do not support the finding of hemispheric asymmetry of 5-HT uptake as measured by IB (Bmax) in postmortem tissue from controls and suicide victims.
Biological Psychiatry 06/1991; 29(10):1016-22. · 8.28 Impact Factor
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ABSTRACT: The density of 5-HT1A binding using 3H-8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (Bmax) or Kd (an inverse measure of affinity) of 5-HT1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher Bmax (22-25%) compared to both controls and violent suicides. A negative correlation between age and Bmax of 5-HT1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60.
Acta Neurovegetativa 02/1991; 85(3):181-94. · 2.73 Impact Factor
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ABSTRACT: Serotonin2 (5-HT2) receptor binding was studied, using 3H-spiperone as the ligand, in post-mortem brain specimens obtained from schizophrenic patients (N = 11) and non-psychiatric controls (N = 11). The maximum number of binding sites (Bmax) was significantly decreased in schizophrenic patients as compared to normal controls. This difference did not appear to be due to neuroleptic treatment. No difference in Kd (an inverse measure of the affinity of 3H-spiperone to its binding sites) was observed between the two groups. However, studies with unmedicated schizophrenic patients are needed to draw any definite conclusion. The role of serotonergic processes in the psychobiology of schizophrenia is discussed.
Acta Neurovegetativa 02/1991; 85(1):19-29. · 2.73 Impact Factor
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ABSTRACT: The authors determined serotonin2 (5-HT2) binding in the frontal cortex of 32 suicide victims and 37 subjects who died from nonpsychiatric causes. The maximum number of binding sites (Bmax) and the affinity (Kd) were significantly higher in subjects who had committed suicide than in control subjects. However, there was no difference in Kd between these two groups after the influence of age, race, sex, and postmortem delay was covaried. The Bmax of subjects who had committed violent suicide was significantly greater than that of control subjects.
American Journal of Psychiatry 07/1989; 146(6):730-6. · 12.54 Impact Factor
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ABSTRACT: Platelet serotonin (5HT) uptake was studied in 13 pairs of monozygotic (MZ) twins, 13 pairs of dizygotic (DZ) twins, and 14 pairs of unrelated normal volunteers. Significant intraclass correlations (ICC) in the affinity (Km) of 5HT uptake in the blood platelets of MZ and DZ twins and unrelated pairs were found. However, the ICC for maximum velocity (Vmax) was significant only in MZ and DZ twins. The ICC of the Vmax of 5HT uptake of MZ twins was significantly greater than that of DZ twins and unrelated pairs. This suggests that the Vmax of 5HT uptake in blood platelets is, in part, heritable. Thus, low platelet 5HT uptake (Vmax) in major depression and other disorders may be genetically determined.
Psychiatry Research 07/1988; 24(3):263-9. · 2.52 Impact Factor
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ABSTRACT: Platelet imipramine binding (IB) was studied in depressed patients before and after treatment with desipramine for 17-28 days. Administration of desipramine was associated with a significant increase in Bmax. There was a trend for an increase in Kd, but it did not reach statistical significance. The net result of the changes in Bmax and Kd was an increase in IB. There were significant correlations between the change in depression ratings and pretreatment Kd, as well as the change in Kd during treatment. These results suggest that decreased IB is not a trait-dependent marker, but a state-dependent marker for depression.
Biological Psychiatry 03/1988; 23(4):397-404. · 8.28 Impact Factor
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ABSTRACT: Imipramine binding (IB) was studied in the blood platelets from normal controls and depressed patients over a 4-year period (1981-1984) to determine if seasonal variation was present in Bmax or KD. Bimonthly variation in the Bmax of IB was found in normal controls studied longitudinally. No such variation was found when individual values from normal controls were examined on a monthly or seasonal basis. Bmax in depressed patients showed a significant seasonal, but not monthly, variation. KD of IB varied in normal controls using monthly or seasonal data, but not in the probably more reliable bimonthly data. These results suggest that IB studies comparing groups of subjects should match groups for season of the year or, for greater accuracy, month of the year.
Biological Psychiatry 03/1988; 23(3):217-26. · 8.28 Impact Factor
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ABSTRACT: 3H-imipramine binding was studied in the blood platelets of 80 normal controls and 50 depressed (psychotic and nonpsychotic) patients. Protein concentration in the incubation mixture, and Kd and Bmax values were correlated in normal controls and depressed patients. A small but significant correlation between protein in the incubation mixture and Bmax was observed in normal controls and depressed patients. There was also a significant correlation between protein and Kd of imipramine binding in the blood platelets of unipolar psychotic depressed patients. However, analysis of covariance to remove the effect of protein on Kd and Bmax did not change the basic finding of decreased Bmax in the blood platelets of psychotic depressed patients.
Biological Psychiatry 02/1985; 20(1):116-9. · 8.28 Impact Factor
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Biological Psychiatry 12/1984; 19(11):1579-84. · 8.28 Impact Factor
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ABSTRACT: Serotonin (5-HT) uptake in blood platelets from depressed patients and normal controls were studied over a 2-year period to determine if seasonal variations were present. Vmax, a measure of the number of 5-HT uptake sites in normal controls and depressed patients, was significantly higher in fall and winter than in spring and summer; Vmax in the depressed patients was lower than in normal controls throughout the year. Normal controls showed lower Vmax in April and June. A similar trend was present in the depressed patients but the lowest values were found in the month of December. The necessity of considering seasonal variations in this and other putative biological markers is emphasized.
Biological Psychiatry 07/1984; 19(6):795-804. · 8.28 Impact Factor
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ABSTRACT: Imipramine binding was studied in platelet membranes isolated with different proportions of heavy (young) and light (old) platelets. The Bmax, a measure of the number of binding sites, was greater in the heavier platelets than in the light platelets. However, the dissociation constant Kd (a reflection of the affinity of imipramine binding) was greater in the lighter platelets compared to the heavy platelets. These results indicate that differences in Kd and Bmax in particular membrane preparation, could be due to the differences in the relative proportion of heavy and light platelets.
Biological Psychiatry 03/1984; 19(2):257-62. · 8.28 Impact Factor
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ABSTRACT: Serotonin uptake was studied in platelet-rich plasma with different proportions of heavy (young) and light (old) platelets. The maximum velocity of serotonin uptake, a measure of the number of uptake sites (Vmax), was greater in the heavy platelets than in the light platelets. However, the uptake sites in the lighter platelets had an increased affinity (Km) for serotonin compared to the heavy platelets, which could compensate for the decreased number of uptake sites. These results indicate differences in Vmax of 5-HT uptake in particular populations could be due to differences in the relative proportions of heavy and light platelets.
Biological Psychiatry 11/1982; 17(10):1157-62. · 8.28 Impact Factor
