A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. PATIENTS AND METHODS: The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. RESULTS: The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more frequently normal weight compared to carriers of other BDNF genotypesBDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more frequently normal weight compared to carriers of other BDNF genotypes. CONCLUSIONS: BDNF rs6265 polymorphism is associated with BMI categories, and the BDNF Met/Met genotype has a protective role in obesity in healthy subjects, while this effect was not present in patients with CHD.

Spleen volume changes during adrenergic stimulation with low doses of epinephrine.

It is generally accepted that the spleen contraction is a consequence of humoral stimulation but recent data suggest a role of neural mechanisms. This study tested the hypothesis that the reduction in spleen size in response to low dose epinephrine infusion is a consequence of neurally mediated unloading of baroreceptors. Continuous ultrasonic measurements of spleen volume in response to intravenous infusion of low doses of epinephrine (0.06 µg/kg/min for 6 minutes, followed 0.12 µg/kg/min for 3 minutes) were performed with simultaneous continuous noninvasive measurements of cardiovascular parameters in thirteen subjects. In subgroup of six subjects we also continuously measured muscle sympathetic nerve activity (MSNA) as an index of peripheral sympathetic activation. Significant spleen contraction (≈30%, p=0.008) was observed early after the onset of epinephrine infusion and was preceded by a decrease in total peripheral resistance (41%, p=0.001) and mean arterial pressure (6.2%, p=0.02) and an increase in heart rate (27%, p=0.001) and total MSNA (120%, p=0.02). Our results demonstrate rapid spleen contraction induced by low-dose epinephrine infusion in conditions of decreased blood pressure and increased MSNA suggesting that the spleen may represent a constitutive part of the sympathetic nervous system under stressful situations.

The role of the serotonergic system at the interface of aggression and suicide.

Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the multifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homoeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and identify new effective therapies for these conditions.

The analgesic and anticonvulsant effects of piperine in mice.

Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

The association between catechol-O-methyl-transferase Val108/158Met polymorphism and suicide.

One of the candidate genes for suicide is also a gene in the pathway for catecholamine degradation encoding an enzyme catechol-O-methyl-transferase (COMT). It harbors a common functional polymorphism, a G to A nucleotide transition resulting in amino acid substitution from valine (Val) to methionine (Met) at position 158 (COMT Val(108/158) Met; rs4680), that has been associated with psychiatric disorders characterized with an increased risk of suicidal behavior. We have performed the first study on Caucasian population examining the association between completed suicide and the COMT Val(108/158) Met polymorphism. The study population consisted of 356 suicide victims and 198 control subjects. Significant difference in COMT Val(108/158) Met variants' (genotypes, alleles and Val carriers) distribution was found only in male groups, between controls and suicide victims (P = 0.018, P = 0.031, P = 0.005), and between controls and violent suicide victims (P = 0.026, P = 0.042, P = 0.010). The r value from the standardized residuals showed that the Met/Met genotype (r = 2.03) in the control group contributed to these significant differences. In contrast to male subjects, no significant differences in the frequency of the COMT Val(108/158) Met variants were detected between female control and female suicide groups; however, the power of calculation (range 0.161-0.680) was below the desired 0.800. In addition, the logistic regression analysis confirmed these significant differences. In conclusion, our results showed the overpresentation of the Met/Met genotype in male control subjects compared with male suicide victims, suggesting that this genotype of the COMT Val(108/158) Met might be a protective factor against suicide.

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study.

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.

Platelet serotonin concentration in dialysis patients with somatic symptoms of depression.

Platelet serotonin (5-HT) concentration was measured in 65 male and 45 female chronic renal patients on hemodialysis (HD) with different somatic symptoms of depression (crying spells, irritability, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation and loss of libido), to find out the relationship between the severity of symptoms and platelet 5-HT concentration. Male and female patients had significantly lower platelet 5-HT concentration than 62 male and 38 female healthy subjects. Gender-differences in platelet 5-HT values observed in healthy subjects were not found in patients. Platelet 5-HT concentration differed in the groups of patients with the different scores of particular somatic symptoms (loss of appetite and loss of libido), but was similar in patients with other somatic symptoms. There was no relationship between platelet 5-HT concentration and the severity of somatic symptoms, or between platelet 5-HT concentration and age of the patients. Gender-related differences in the occurrence of somatic symptoms were detected in patients with the different degrees of weight loss, somatic preoccupation and loss of libido. Our results suggest that platelet 5-HT concentration could not be used as a biological marker for the severity of somatic symptoms in chronic renal patients on HD.

TCH-346 (Novartis).

TCH-346, an anti-apoptotic compound, is under development by Novartis for the potential treatment of Parkinson's disease (PD) and motor neuron disease [271447,342937]. By September 1999, phase I clinical trials for PD were underway [342937]. The compound was discovered in a screen for molecules with both norepinephrine uptake and MAO inhibiting properties but, although it had anti-apoptotic properties, it did not inhibit MAOA or MAO-B [333136,332004]. The compound increases lifespan in the progressive motorneuropathy mouse model and prevents ischemia in models of ischemia and seizure [288893]. In vivo, it shows neurorescuing and anti-apoptotic properties in PC12 cells and cerebellar granule cells, among others, at concentrations of 0.1 pM to 10 microM, suggesting that its action might prove potentially useful against Alzheimer's and/or Parkinson's disease [332004]. The compound has also shown neurorescuing properties in rat pups after axotomy, rat hippocampal CA1 neurons after transient ischemia/hypoxia and mouse nigral dopaminergic (DA) neurons after treatment with MPTP in doses ranging between 0.0003 and 0.1 mg/kg po or sc, depending on the model [333136]. Data presented by the University of Nijmengen and the Free University of Amsterdam show that TCH-346 improves the behavioral and enzymatic outcome in the rat 6-OH-dopamine model of Parkinson's disease. TCH-346 (0.0014 mg/kg sc bid) prevented abnormal stepping (open field test) and prevented increases in fore and hind-paw retraction time. TCH-346 also improved acquisition in the Morris water maze task and, at doses between 0.0014 and 0.14 mg/kg, prevented reduction in tyrosine hydroxylase immunoreactivity [345259]. Affinity binding studies with TCH-346 showed that GAPDH is the target [294902,283200]. Differential display RT-PCR also showed that protein-isoaspartyl-methyl transferase is induced by the drug [283200].

Sex differences, season of birth and platelet 5-HT levels in schizophrenic patients.

Similar occurrence of schizophrenia was observed in men and women independent of their season of birth. Platelet 5-HT concentration was determined in 116 healthy control subjects (61 male and 55 female) and 152 patients with schizophrenia (96 male and 56 female). Platelet 5-HT concentration was significantly higher in male than in female healthy persons and schizophrenic patients. Male and female healthy subjects born in different seasons had similar platelet 5-HT concentrations, whereas schizophrenic patients with different birth-seasons had significantly different platelet 5-HT concentrations. The highest platelet 5-HT levels were observed in both male and female schizophrenic patients born in winter when compared to matched healthy controls. Male schizophrenic patients born in winter had higher platelet 5-HT levels than schizophrenic men born in spring and summer. Female schizophrenic patients born in winter had higher platelet 5-HT than schizophrenic women born in all other seasons. These results indicated sex differences in platelet 5-HT levels in healthy persons and schizophrenic patients. The relationship between season of the birth and platelet 5-HT concentration observed only in schizophrenic patients added further support to the presumption that schizophrenia is connected with a disturbance in the central serotoninergic system.

Platelet serotonin, plasma cortisol, and dexamethasone suppression test in schizophrenic patients.

BACKGROUND: Serotonin (5-HT) regulates hypothalamic-pituitary-adrenal (HPA) axis activity. Abnormal response to the dexamethasone suppression test (DST) and altered platelet 5-HT concentration have been shown in some schizophrenic patients. METHODS: Platelet 5-HT and plasma cortisol concentrations were determined simultaneously in 86 male schizophrenic patients before and after DST. Basal plasma cortisol and platelet 5-HT levels were also determined in 69 healthy male persons. RESULTS: Schizophrenic patients had higher plasma cortisol and platelet 5-HT concentrations than healthy persons. An abnormal escape from dexamethasone suppression was observed in 50% of patients. In these patients predexamethasone cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. CONCLUSIONS: This study demonstrates that schizophrenic patients have the HPA axis dysregulation that could be connected with a disturbance in the 5-HT system.

EPHAR 99--Second European Congress of Pharmacology. 3-7 July 1999, Budapest, Hungary.

This meeting was chaired by Dr ES Vizi (Chairman of the Hungarian Pharmacological Society) and was attended by approximately 1600 delegates from 62 countries, including the USA, Canada, Israel, Japan and various parts of Europe. The opening ceremony was honored by the plenary lecture of a Nobel prize winner, Dr J Axelrod. The conference consisted of plenary sessions, 57 symposia and poster sessions. Each day the program included seven morning and seven afternoon symposia, simultaneously held, and a large poster section. The symposia focused on the neurotransmitter receptors as targets for the action of new drugs, new trends in the treatment of diabetes, Alzheimer's and Parkinson's diseases, psychiatric disorders, cardiac and gastrointestinal diseases and neuronal damage. All abstracts (more than 1200) were published in Fundamental and Clinical Pharmacology (1999) 13(Suppl 1). This year's meeting was substantially larger than the first EPHAR congress held in Milan, Italy, in 1995. It was generally well organized and served to introduce new basic and clinical knowledge in pharmacology.

Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.

In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

QT interval as a marker of venous reactivity in dialysis patients.

Fourteen patients (7 females and 7 males, mean age 51.9 +/- 11.6 years) were studied to find out whether there is a connection between the QTc interval (a diagnostic tool for evaluating autonomic neuropathy) and venous reactivity in uremics on chronic hemodialysis. The QT interval was measured using standard lead II as reference, corrected for heart rate, and designed QTc. Venous reactivity was measured by the so-called venoconstriction test. Pressure changes inside the vein were obtained by injection of 2 micrograms of noradrenaline, and expressed in venoconstrictive units (VCU). The mean QTc was 445.7 +/- 36.9 ms. The mean venous tone response was 2130.9 +/- 1435.5 VCU. There was a significant correlation between the QTc interval and venous reactivity to catecholamine (r = 0.565, P = 0.03). It is concluded that the QTc interval may be used as a marker of venous tone reactivity, suitable for everyday clinical practice. Furthermore, the magnitude of this reactivity possibly represents either the end-organ or peripheral sympathetic impairment.

Platelet 5-HT and plasma cortisol concentrations after dexamethasone suppression test in patients with different time course of schizophrenia.

Platelet 5-HT and plasma cortisol concentrations were determined in 59 schizophrenic patients with different time course of illness before and after dexamethasone suppression test (DST). An abnormal DST (nonsuppression) was observed in 51% of patients. In these patients basal cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. After DST, plasma cortisol levels were higher in nonsuppressors with intermittent and intermittent-chronic time course, whereas platelet 5-HT concentrations were increased in nonsuppressors with intermittent-chronic time course. The results suggest that schizophrenic patients have dysregulated hypothalamic-pituitary-adrenal axis as shown by a high rate of DST nonsuppression, and that nonsuppressors showed hypercortisolemia and hyperserotonemia independent of the time course of schizophrenia. No significant association between DST and time course of the illness was found.

Seasonal influence on platelet 5-HT levels in patients with recurrent major depression and schizophrenia.

The influence of seasons on platelet serotonin (5-HT) concentration was determined in 88 unipolar depressed and 117 schizophrenic male inpatients, and 90 normal male controls. Platelet 5-HT concentrations showed moderate, but insignificant intragroup seasonal variations in healthy controls and in the groups of depressed (psychotic and nonpsychotic) and schizophrenic (positive and negative) patients. In spring, platelet 5-HT concentrations were higher in schizophrenic patients than in normal controls or in depressed patients, while in other seasons platelet 5-HT concentrations were not significantly different between the groups. Higher platelet 5-HT concentrations were detected in psychotic when compared to nonpsychotic depressed patients in summer, fall, and winter. Increased platelet 5-HT concentrations observed in schizophrenic patients with positive symptoms clearly separated these patients from patients with negative schizophrenia, especially in spring, summer, and fall. Our results indicate the necessity to match patients with regard to the season of the sampling, and to divide depressed and schizophrenic patients into subtypes.

[Occurrence of thromboembolic complications in patients with dilated cardiomyopathy. Retrospective-prospective study]. / Ucestalost tromboembolijskih komplikacija u bolesnika s dilatacijskom kardiomiopatijom. Retrospektivno-prospektivna studija.

The purpose of the present study was to determine the prevalence of thromboembolic events in patients with primary and secondary (ischemic) dilated cardiomyopathy (DC), with regard to basic rhythm, sinus or atrial fibrillation. Retrospectively, over three years, from January 1, 1989 to December 31, 1991, the case histories of 75 inpatients with DC, mean age 56.2 +/- 14.1 years, 41 in sinus rhythm and 34 in atrial fibrillation from Clinic Hospital Split were analyzed and compared to those of 75 controls (heart failure with no DC). The incidence of thrombi, embolisms and mortality in both subgroups was similar, while the prevalence of thromboembolic events was significantly higher in the analyzed than in the control group (decompensated patients with ischemic cardiomyopathy and without cardiomegaly) (9/75:1/75, p < 0.05). Prospectively, between 9 and 22 months, from December 1, 1991 to September 30, 1993 51 consecutive decompensated outpatients with DC, in NYHA class II and III, mean age 54.2 +/- 15 years, were followed-up. Bilirubin, lactic dehydrogenase, prothrombin time and activated partial thromboplastin time were determined. 1-D and 2-D transthoracic echocardiographic exam was performed and clinical status was assessed. There were 24 patients in sinus rhythm and 27 patients in atrial fibrillation. The prevalence of thromboembolic events, thrombi and mortality in both subgroups was similar. The laboratory findings, indicators of possible thrombogenesis or thrombolysis, did not show any significant difference in both subgroups. The incidence of thrombi in both parts of this study was low, amounted to only 9.5% (12/126) with no clear signs of thromboembolism (these patients were anticoagulated!). Altogether 12.6% (16/126) patients suffered thromboembolic events, 9 in retrospective and 7 in prospective part of the trial (more patients were anticoagulated in prospective then in retrospective study, 5 versus 19; p < 0.05). We conclude that thromboembolism in patients with decompensated DC are rare, but appear at significantly higher rate than in decompensated patients with ischemic cardiomyopathy and no cardiomegaly. The beneficial effects of anticoagulant therapy are to be expected in these patients regardless of the basal rhythm. This hypothesis must, however, be assessed in a prospective, multicentric trial.

Platelet 5-HT levels and hypothalamic-pituitary-adrenal axis activity in schizophrenic patients with positive and negative symptoms.

Hypothalamic-pituitary-adrenal (HPA) axis activity and platelet 5-HT concentrations were determined before dexamethasone suppression test (DST) in 80 male schizophrenic patients with predominantly positive or negative symptoms. Significant differences in platelet 5-HT and no differences in baseline plasma cortisol concentrations among schizophrenic suppressors and nonsuppressors were found. A similar rate of nonsuppression (56% positive and 53% negative schizophrenic patients) was detected. Platelet 5-HT, but not plasma cortisol concentrations, could be used to differentiate positive and negative symptoms of schizophrenia.

Hypothalamic-pituitary-adrenal axis function and platelet serotonin concentrations in depressed patients.

Plasma cortisol and platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations were determined in 39 male psychotic and 39 male non-psychotic depressed inpatients, and in 69 male healthy control subjects. Psychotic or non-psychotic depressed patients had higher predexamethasone plasma cortisol levels than found in the control group. After the dexamethasone suppression test (DST), psychotic and non-psychotic depressed patients were subdivided into suppressors and non-suppressors. Psychotic and non-psychotic patients had significantly different platelet 5-HT concentrations among themselves and compared with the control group. However, there was no significant correlation between plasma cortisol levels and platelet 5-HT concentrations. Dexamethasone administration did not affect platelet 5-HT concentrations within subtypes of depressed patients. Abnormal cortisol suppression after the DST occurred more frequently in psychotic than in non-psychotic patients. Platelet 5-HT and plasma cortisol concentrations were decreased in patients with pronounced suicidal behaviour. Our results suggest that plasma cortisol and platelet 5-HT concentrations might serve as independent biological markers for different subtypes of depression.

Platelet 5-HT concentrations and suicidal behaviour in recurrent major depression.

Platelet 5-HT concentrations were determined in 84 male and 82 female psychotic and non-psychotic depressed inpatients with various degrees of suicidal behaviour, and in 175 healthy controls. Psychotic patients had higher platelet 5-HT concentrations than non-psychotic depressed patients and healthy controls. A sex difference, i.e., lower platelet 5-HT concentrations in females was found in healthy controls, depressed patients, non-psychotic patients and non-suicidal depressed patients. A negative relationship was shown between platelet 5-HT concentrations and suicidal behaviour. The lowest platelet 5-HT concentrations were associated with the most pronounced suicidal behaviour (with suicidal attempts and with the acts of suicide). The results suggest that the differences in platelet 5-HT concentrations found in depressed patients might be used as a biological marker for suicidal behaviour.