Platelet cytosolic calcium responses to serotonin in depressed patients and controls: relationship to symptomatology and medication.

BACKGROUND: Serotonin produces an exaggerated rise in platelet cytosolic calcium (delta [Ca++]i) in patients with mood disorders. Studies on patients with bipolar disorder consistently demonstrate calcium abnormalities. By comparison, data on patients with major depression are more variable. METHODS: To determine causes of variability, we utilized Fura-2 loaded platelets to compare changes in platelet intracellular calcium levels (delta [Ca++]i) following serotonin stimulation in 24 patients with major depression and in 20 controls. We also sought relationships between the delta [Ca++]i responses and scores on clinical depression and anxiety scales. RESULTS: We found positive correlations between delta [Ca++]i responses and the clinical scales across all subjects. Furthermore, depressed patients with high anxiety had significantly increased delta [Ca++]i responses compared to depressed patients with low anxiety. In addition, patients receiving selective-serotonin reuptake inhibitors (SSRIs) demonstrated reduced delta [Ca++]i responses compared to patients not on SSRIs. CONCLUSIONS: Since elevations in [Ca++]i mediate platelet aggregation and secretion cascades, the enhanced responsivity observed in depressed, and in particular anxious, depressed patients may contribute to their increased risk for vascular disease.

Platelet cytosolic calcium hyperresponsivity to serotonin in patients with hypertension and depressive symptoms.

BACKGROUND: Data from recent studies indicate that the presence of depression is an independent risk factor for cardiovascular and cerebrovascular events. The mechanism by which depression increases the morbidity and mortality risks in patients with comorbid vascular disease is currently the object of considerable research interest. Platelets may be involved in this pathological process. Although many investigators have extensively evaluated platelet biochemistry in depressed patients, there currently exists very little information regarding how the biochemical alterations might relate to an increased risk of cardiovascular events. In this study, we examined the responsivity of platelet cytosolic calcium concentrations ([Ca++]i) to serotonin stimulation in populations of hypertensive patients with or without comorbid depressive symptoms. METHODS: We utilized Fura-2 loaded platelets to compare changes in intracellular calcium levels (delta [Ca++]i) following serotonin stimulation among 48 patients with hypertension and varying degrees of depressive symptomatology. RESULTS: We found that those patients with higher scores on standardized depression rating scales showed significantly greater [Ca++]i (82.82 +/- 15.88 mmol/L) increase compared with [Ca++]i (60.10 +/- 22.65 mmol/L) patients with lower depression scores. CONCLUSIONS: The results of this study support the hypothesis that the enhanced platelet reactivity seen in patients with depressive symptoms may mediate the deleterious effects of depression on cardiovascular disease.

Platelet paroxetine binding and fluoxetine pharmacotherapy in posttraumatic stress disorder: preliminary observations on a possible predictor of clinical treatment response.

Recent open clinical trials have found the selective serotonin reuptake inhibitor (SSRI) fluoxetine to be beneficial in the treatment of posttraumatic stress disorder (PTSD) symptoms. We have reported previously that the binding of a newer SSRI, paroxetine, to blood platelets is decreased in PTSD patients compared to normal control subjects. In the current study, pretreatment platelet paroxetine binding data were analyzed for ten Vietnam combat veterans who were treated clinically with fluoxetine for PTSD, diagnosed on the basis of the Structured Clinical Interview for DSM-III-R. Specific binding of 3H-paroxetine is reported in terms of the dissociation constant (Kd) and the maximum density of binding sites (Bmax). Based on our previous findings we hypothesized that decreased platelet 3H-paroxetine binding would be associated with positive therapeutic response to subsequent treatment with fluoxetine. Global clinical improvement ratings, conducted blind to the biochemical data, were used to separate patients into five maximal responders and five partial responders. The results indicated that maximal responders had lower pretreatment Kd values (p = .016) and a trend toward lower pretreatment Bmax values (p = .075) than the partial responders. These preliminary findings may warrant further study of platelet SSRI binding as a possible predictor of SSRI treatment response in PTSD patients.

Hypodensity of platelet serotonin uptake sites in posttraumatic stress disorder: associated clinical features.

We have previously reported that binding to blood platelets of paroxetine, a selective serotonin (5-HT) reuptake inhibitor which binds to 5-HT uptake sites, is decreased in patients with posttraumatic stress disorder (PTSD). Specifically, we found a lower number of platelet 3H-paroxetine binding sites (Bmax) and a lower dissociation constant (Kd) for 3H-paroxetine binding in combat veterans with PTSD compared to normal control subjects. In the current study we assessed the relationship of platelet 3H-paroxetine binding to clinical features in 41 Vietnam combat veterans with SCID-diagnosed PTSD. The results indicated that Bmax of platelet 3H-paroxetine binding was negatively correlated with both state and trait anxiety, as well as with depressive and overall PTSD symptoms. However, there was no evidence that platelet 3H-paroxetine binding differed as a function of comorbid psychiatric diagnoses including major depression, other anxiety disorders, and substance abuse in these patients.

The in vitro differential binding of benzoylecgonine to pigmented human hair samples.

Only fragmentary information on the relationship between hair pigmentation (melanin) and the cocaine/benzoylecgonine content of hair samples is available. The in vitro incorporation of benzoylecgonine into the shafts of black, brown, and blond samples of human hair was accomplished. Post digestion analysis and wash samples demonstrate the relative incorporated ions of benzoylecgonine to be black > brown > blond. Melanin content seems to be important. Lightly pigmented blond hairs may be less appropriate samples for benzoylecgonine and cocaine analysis.

Cocaine and metabolites in human graying hair: pigmentary relationship.

OBJECTIVE: To assess differences in the binding of cocaine, cocaethylene, and benzoylecgonine among pigmented and senile white hairs of the graying human cocaine abuser. DESIGN: A sheath of graying hair in the region around the apex of the head was gathered between the thumb and index finger then cut and removed about 2 mm proximal to the scalp. The graying hair was divided into pigmented and senile white of equal weights and lengths and then analyzed by gas chromatography/mass spectrometry chemical ionization. Twenty-nine such pairs were analyzed. SUBJECTS: Male cocaine abusers, ages 33-55 years hospitalized for substance abuse. Informed consent was obtained and confidentiality assured. MAIN OUTCOME MEASURES: Concentrations of cocaine, cocaethylene and benzoylecgonine in ng were assessed for each of 29 paired hair samples by gas chromatography/mass spectrometry chemical ionization. RESULTS: There were statistically significant differences between pigmented and senile white sections of paired samples. Cocaine (ng/mg hair, mean +/- SD) was 31.5 +/- 30.2 for pigmented hair vs 14.9 +/- 19.8 for senile white portions; (p < 0.0001). Cocaethylene (ng/mg hair, mean +/- SD) 3.22 +/- 5.0 (pigmented) vs 0.52 +/- 0.88 (senile white); (p < 0.0016). Benzoylecgonine (ng/mg hair, mean +/- SD) 5.1 +/- 5.3 (pigmented) vs 3.9 +/- 4.8 (senile white); (p < 0.005). CONCLUSION: Melaninated pigmented hair seems to bind more cocaine, cocaethylene and benzoylecgonine than white hair in the same subject.