Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.

Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 µm paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers.

[A trial for the complex risk assessment of repeated suicide predictors in patients after suicidal poisoning attempts, hospitalized in the Department of Clinical Toxicology CM UJ in Krakow. I. Influence of socio-demographic factors]. / Próba kompleksowej oceny predyktorów ryzyka ponowienia samobójstwa u pacjentów po samobójczym zatruciu lekami, hospitalizowanych w Klinice Toksykologii CM UJ w Krakowie. Czesc I. Wplyw czynników socjodemograficznych.

The study included 180 patients aged 18-79 (average 36) hospitalized for suicide attempts (drug intoxication) in Department of Clinical Toxicology CMUJ from March to December 2000. Examined group was composed of 49 men and 131 women. Structured investigation and medical documentation were used to estimate crucial socio-demographic risk factors of repeated suicide attempt. The following socio-demographic traits were taken into consideration in analysis: age, sex, marital status, place of living, education, employment, family background. We distinguished among patients under examinations: patients after first suicide attempt (I) and group after another suicidal attempt (II). The second group consisted of 15 men (27.8% of the total) and 39 women (72.2% of the total). Young people under 30 constituted 37.2% of the whole examined population. In population of women after repeated suicide attempt the percentage of divorced ones increased considerably (from 2.2% to 10.2%). Both in men and women after repeated suicide attempt the percentage of persons with only elementary education increased (from 34.1% to 53.7%). We observed high unemployment rate (from 26.6% to 29.6%) in both groups. Percentage of pensioners increased from 23.5% after first suicidal attempt to 33.3% after repeated suicidal attempt in men and from 25.5% to 35.9% in women. Men after repeated suicide attempt more often live with their parents, while women from the second group more often live alone with their children. It seems that some of the analysed predictors which are expression of social unadjustment may make risk factor for repeated suicidal attempts.

[A trial for the complex risk assessment of repeated suicide predictors in patients after suicidal poisoning attempts, hospitalized in the Department of Clinical Toxicology CM UJ in Krakow. II. Clinical predictors]. / Próba kompleksowej oceny predyktorów ryzyka ponowienia samobójstwa u pacjentów po samobójczym zatruciu lekami, hospitalizowanych w Klinice Toksykologii CM UJ w Krakowie. Czesc II. Predyktory kliniczne.

The study included 180 patients aged 18-79 (average 36) hospitalized for suicide attempts (drug intoxi-cations) in the Department of Clinical Toxicology CM UJ from March to December 2000. Examined group was composed of 49 men and 131 women. The following tests were used in this study: structured questionnaire, psychological tests: Beck Depression Inventory, Hamilton Depression Scale, Hopelessness Scale, Suicidal Intent Scale, Life Events Scale, SOC 29 (by Antonovsky). Besides, we used data from patients' history. The aim of our study is to analyse clinical data of suicidal attempters--after first and repeated suicidal attempts. We took into consideration the severity of coma, severity of intoxication, the kind of substances used in the attempt, the presence of alcohol, previous psychiatric treatment, cases of suicide among the patients' close friends or relatives and duration of hospitalization. Then the psychiatric diagnosis was stated. The analysis of severity of intoxication (divided into three stages: severe, moderate, and light according to the Poisoning Severity Score (PSS) indicated that in the group of repeated suicide attempters the percentage of severe intoxications was greater (9.2%) then in first time attempters. In the population of second time female attempters there is a greater percentage of persons who took neuroleptics (15.4%) compared to group first attempters (5.4%). In both groups the majority were taking anxiolytisc, sleep-inducing and mixed drugs. There was a greater percentage of persons drinking alcohol during the attempt among repeated suicidal attempters (38.8%) than among the first time attempters (26%). The percentage of persons with diagnosis of mental disease (treated in ambulatory or in hospital) is higher in the group of repeated suicide attempters (25.9%) then after first attempters (6.3%). In both groups a lot of persons had reactive depression, often associated with personality disorders, rarely endogenic depressions or psychosis. We observed that addiction to alcohol is often a problem in men who attempt suicide (I group--32.3%, II group--33.3%). The analysis of medical documentation indicated in the group of repeated suicide attempters a high percentage of people with cases of suicide among their close friends or relatives.

[The sense of coherence and risk of suicide attempt]. / Poziom poczucia koherencji a ryzyko próby samobójczej.

The analysis was based upon 79 patients hospitalized for suicide attempts (drug intoxication) in the Department of Clinical Toxicology CM UJ in Kraków from July to December 2000. The purpose of the study was to estimate the sense of coherence level (according to Antonovsky) as a potential suicide attempt predictor. The population of patients was divided into two groups: patients after first suicide attempt (I) and group after reattempting suicide (II). The examination was based on structure interview, analysis of medical documentation and a number of tests including SOC 29 (by Antonovsky), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), and Beck Hopelessness Scale (HS 20). The most important psychological and independent variable measured in the study was the sense of coherence, introduced first by Aaron Antonovsky as a significant predictor of mental health. The sense of coherence (measured by SOC 29 questionnaire) comprises comprehensibility, manageability and meaningfulness. Both in foreign and in polish studies the SOC 29 level was lower in clinical groups compared to healthy people. The norm in Polish population was 139 scores in SOC 29. In the present study the average total result (men and women) was 112 scores in the group of patients after first suicide attempt, and in the group of repeated suicide attempters the average total result was even lower--only 99 scores, which makes a statistically significant difference. We also observed a statistically significant dependence between the results of SOC 20 questionnaire, the level of depression measured by Beck Depression Inventory and Hamilton Depression Scale, and the level of hopelessness measured by Beck Hopelessness Scale. The above results indicate that the sense of coherence level may make significant risk factor for repeated suicide attempt.

[Significance of subjective evaluation of life events as risk factors for predicting future suicide attempts]. / Znaczenie subiektywnej oceny wydarzen zyciowych jako czynników wplywajacych na ponowienie próby samobójczej.

Among the total population of 180 patients undergoing medical examination between March and December 2000, hospitalized for suicide attempts (drug intoxication) in the Department of Clinical Toxicology CM UJ in Kraków, 159 persons were examined by means of modified questionnaire of life events based on a scale elaborated by Thomas Holmes and Richard Rache. The patients were divided into 2 groups--first group comprised patients after first suicide attempt and second group consisted of those who had reattempted suicide. In regard to sex and age there were no significant differences between these two groups and the total population of 180 patients. In order to obtain the patients' subjective evaluation of the influence of their course of life on their attempting suicide, we asked the patients to select from the list of life events those that had affected their mental and physical state during of whole their life. Objectivization of life events was based on the 'units of life change' by T. Holmes and R. Rache. The sum of units of life events was 373 scores (SD +/- 200, in the range of 39-1042 units). From the total list of life events (max. score--1513) we selected the events estimated at 40 and more units of life change. Those were; marriage, divorce, separation, marital reconciliation, patient's illness, change of behavior and illness of a close relative, death of a husband/wife, child, close relative, imprisonment, pregnancy, unemployment, retirement. In the patients' subjective evaluation part, the events most frequently selected by the patients as those that had affected their mental state were: death of a close relative (56.6%), illness of a relative (40.8%), patient's illness (37.7%). A high number of patients stated events testifying to a conflict in marriage--45.7% of patients stated marital separation, and reconciliation, and 27% of patients stated unemployment as a fact that had influenced their mental state. 30.6% of these patients belonged to the first group (after first suicide attempt) and only 18.7% belonged to the second group (after repeated attempt). The authors of the study have presented a discussion over the results of the analysis and demonstrated the need for cultural adaptation of so that it can be effectively used in General Practitioners' training.