Faculty Bibliography

BACKGROUND: The central serotonergic system has been implicated in the pathophysiology of depression and in the mechanism of the action of antidepressant drugs. The human platelet has been proposed as a peripheral model of central serotonergic neurons. METHODS: Six peripheral serotonergic parameters were determined simultaneously in 27 patients with unipolar depression before and after 2, 4, and 12 weeks of clomipramine or fluoxetine treatment according to the psychiatrist. RESULTS: In patients with depression versus matched control subjects, platelet [3H]paroxetine binding sites were found to be significantly decreased (2.10 +/- 0.70 versus 3.88 +/- 0.77 fmol/10(9) platelets; P = .0001), platelet serotonin (5-HT) content was found to be significantly decreased (1.90 +/- 1.52 versus 2.74 +/- 1.12 nmol/10(9) platelets; P = .001), and platelet inositol triphosphate levels were found to be significantly increased (2.85 +/- 0.70 versus 1.85 +/- 0.77 fmol/10(9) platelets; P = .0001). No significant difference between patients and control subjects was found for platelet [3H]-lysergic acid diethylamide ([3H]LSD) binding sites, aggregation tests with 5-HT or adenosine diphosphate and plasma 5-HT levels. Treatment with both clomipramine and fluoxetine gradually further reduced the density of platelet [3H]paroxetine binding sites and induced a dramatic decrease in platelet and plasma 5-HT levels. With clomipramine, the decreased blood 5-HT levels are associated with increased platelet [3H]LSD binding sites and aggregation responses. After 12 weeks, nonresponders to both treatments had platelet inositol triphosphate levels that were still increased (2.81 +/- 0.75 fmol/10(9) platelets) when responders levels were not different from those of control subjects (1.41 +/- 0.45 versus 1.70 +/- 0.25 fmol/10(9) platelets). CONCLUSIONS: Drug-free patients with depression had simultaneously decreased 5-HT transporter (5-HTT) sites and overstimulated phosphoinositide signaling systems. Clomipramine and fluoxetine treatments, which further decreased the density of 5-HTT sites, allowed platelet inositol triphosphate levels to return to normal values only in responders

RATIONALE: Antidepressant treatments present a delayed onset of action. OBJECTIVE: The present study investigated whether plasma or serum serotonin, 5-hydroxytryptamine (5-HT), could predict clinical improvement. METHODS: Biological parameters were determined after a 4-week drug-free period (day 0) and 1, 14 and 28 days after the beginning of the treatment with fluoxetine 20 mg daily in depressed patients. Clinical evaluations were assessed on days 0, 14 and 28. RESULTS: One day after a single dose, the mean values of plasma 5-HT (5.4 +/- 2.6 nmol/l) and serum 5-HT (484 +/- 215 nmol/l) were not statistically different from basal mean values (4.5 +/- 2.5 nmol/l and 523 +/- 263 nmol/l, respectively). The repeated treatment significantly reduced serum 5-HT to 34% (P = 0.002) and 17% (P = 0.0004) of pretreatment values after 14 and 28 days of treatment, respectively; plasma 5-HT was also reduced significantly to 28% and 15% of pretreatment values (P < 0.05 in both cases). At day 28, four of the eight patients responded by showing a reduction in MADRS score of at least 50% of the baseline score. No correlation was found between pretreatment values of serum or plasma 5-HT and clinical evolution, even if a tendency (P < 0.07) to lower serum 5-HT pretreatment values was observed in responders. Plasma 5-HT after 1 day of treatment was significantly different between responders and non-responders: the plasma 5-HT concentration in responders was 3.4 +/- 1.7 nmol/l versus 7.4 +/- 1.6 nmol/l in non-responders (P = 0.02). Moreover, plasma 5-HT levels after 1 day of treatment were positively correlated to the final MADRS score (r = +0.89, n = 8, P = 0.003) and inversely correlated to its change from the initial score (r = -0.76, n = 8, P = 0.02). CONCLUSION: These preliminary data show that fluoxetine and norfluoxetine might influence 5-HT peripheral venous blood parameters and that plasma 5-HT after 1 day of treatment might be a biological predictor for antidepressant response

The SPECT (Single Photon Emission Computed Tomography), a new advance in medical imagery, allows the measure of cerebral blood flow and could be of interest in studying mental disorders. We report here a case of pseudo-dementia for which a SPECT has been performed before and after treatment. Mrs V., a 49 years old female, has been suffering from a dementia-like syndrome for several months. She is divorced, has two children, lives with a boy-friend, and has been working in a factory for 25 years. The first psychiatric disorders began three years ago with a gradual apragmatism and muteness. A neuroleptic treatment gave no result. One year later, without any reason, Mrs V. recovered a normal way of life. Nevertheless, from time to time, she had some periods of subexcitation. Few months later, she relapsed in her previous state of apragmatism and muteness. During a new hospitalization, neuroleptic treatment is tried again without any success. Mrs V. is then referred to us for medical screening of a dementia syndrome. In the Unit, it is difficult to communicate with her; she looks sad or amimic and has motor stereotypies (like rubbing her feet continuously against the floor). She has polidypsia and glutonny. Neurologic examination is normal, as well as EEG, X Scan, Nuclear Magnetic Resonance. The Folstein Mini Mental State score is 9/30.(ABSTRACT TRUNCATED AT 250 WORDS)