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Biomedical subjects

R Uebelhack

Publications and source records attributed to R Uebelhack.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects.

BACKGROUND: A robust association between "suicidality" and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. METHODS: In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT(2A) receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. RESULTS: Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls. Mean V(max) of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients. Mean K(D) for the platelet 5HT(2A) receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls. The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher V(max) of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. CONCLUSIONS: In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

Adult↗
PubMed2006

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM.

We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [(123)I]-ADAM SPECT. The midbrain SERT availability (SERT V(3)'') was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 +/- 0.27 vs. 0.71 +/- 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.

Adult↗
PubMed2003

Effect of piracetam on cognitive performance in patients undergoing bypass surgery.

In this study, the protective effect of piracetam on select aspects of cognitive function in patients undergoing bypass surgery was investigated. Male patients (n = 64) with an indication for a surgical revascularization using artificial extracorporal circuits were randomly assigned in a double-blind fashion to receive a single challenge of 12-g piracetam infusion or placebo (sterile saline) prior to the bypass surgery. A brief battery of neuropsychological tests for verbal and non-verbal short-term memory and attention was administered 1 day before and 3 days after the surgical intervention. There was a significant difference in short-term memory and attention, with the piracetam-treated patients producing a better level of performance 3 days after surgery compared to the placebo group. The overall postoperative cognitive function (z-transformation of all 6 test results) was more significantly (p < 0.001) reduced in the placebo group than in the piracetam group (z = -1.19 +/- 0.72 vs. -0.46 +/- 0.58, respectively). A single challenge of 12-g piracetam infusion prior to surgical intervention might offer a short-term neuroprotective effect for patients undergoing cardiac bypass surgery. Whether this effect persists for a longer period of time requires further investigation.

Adult↗
PubMed2003

Predictors of therapeutic effects in amitriptyline treatment--1. Plasma drug levels.

OBJECTIVE: To analyze the spectrum of relationships between clinical effects of amitriptyline (At) treatment after 2 and 4 weeks (wks) and plasma levels of At, nortriptyline (Nt), At+Nt, demethylation rate of At, treatment modalities, age, and gender. METHODS: Patients with major depression (ICD 10: F31-F33) and a HAMD-21 total score of 15-41 received At on a dosage schedule chosen by the doctor for at least 4 wks. Plasma drug levels were assessed at baseline and at wks 2 and 4. RESULTS: Of the 58 patients enrolled in the study, 47 (15males, 32 females) were eligible for statistical analysis. An early response by wk 2 (decrease in HAMD-21 score of at least 50 % from baseline) was observed in 34.0 % of patients, and after 4 wks, the response rate was 63.8 % (males 86.6 %, females 53.1 %). There was a low, negative, and significant correlation between percent reduction in HAMD and steady state At concentration only at wk 2 (n = 47 r Sp. = -0.306 p < 0.05). However, the correlation was dependent on the degree of At demethylation and treatment modalities. A ratio of Nt/At >1 was observed in 23 patients; of these, 11 (47.8 %) were non-responders by wk 4. A low rate of demethylation (Nt/At </= 1) in 24 patients was associated with a lower frequency of non-response (6/24 = 25.0 %). In the latter subgroup, the 2-wk At plasma concentration varied between 20 and 240 ng/ml, and all patients with </= 110 ng At /ml were responders by wk 4. On the other hand, in the Nt/At >1 group, the non-responders were distributed in the whole range of observed At plasma concentrations (20-150 ng/ml). Only in patients with Nt/At </= 1 and constant doses from wk 1 to wk 4 (n = 14) was a strong, linear, and negative correlation between percent reduction in HAMD and plasma At, Nt, or At+Nt concentrations found for the 2-wk data (r Sp. = -0.754, -0.716, and -0.732, respectively), but not after 4 wks. CONCLUSIONS: The frequently assumed dependence of clinical effects on plasma drug levels is not a simple function. There most likely exist different patterns of relationships with partially unknown backgrounds. The ratio Nt/At may become a discriminating variable in future studies on the nature of plasma level-therapeutic effect relationship in At treatment of major depression.

Adult↗
PubMed2002

[Psychopharmacotherapy of bipolar affective diseases].

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Antidepressive Agents↗
PubMed2001

Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia.

The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to schizophrenia or may serve as predictors of therapeutic response. We therefore analyzed these polymorphisms as susceptibility factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587 healthy controls. We furthermore compared the therapeutic outcome of schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective patients were more frequently homozygous for the 44-bp insertion allele (Odds ratio, OR: 1.6, 95% confidence interval, CI: 1.1--2.3, P < 0.03) than were all other schizophrenic patients and controls. The 17-bp VNTR alleles found were: STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence motifs with an invariable arrangement. Patients with schizo-paranoid schizophrenia were more frequently homozygous for the STin2.12 allele than were controls (OR: 1.4, CI: 1.1--1.8, P < 0.007) and all other schizophrenic patients (OR: 1.6, CI: 1.2--2.3). The STin2.9 allele represented a risk factor for the residual subtype of schizophrenia (OR: 6.4, CI: 2.5--16.2, P < 0.001). On the basis of global clinical impressions, as well as measurements with the positive and negative syndrome scale we found no association of the polymorphisms with therapeutic response. In conclusion, the 44-bp polymorphism may be associated with the schizo-affective and the 17-bp VNTR with the residual and schizo-paranoid subtype of schizophrenia, findings which require further biochemical and epidemiological confirmation.

Adolescent↗
PubMed2000

Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects: relationship between 5HT content and 5HT uptake.

The dependence of platelet-5HT content on apparent kinetic parameters of 5HT uptake was analyzed in 56 healthy subjects and 47 depressed patients, who had not been taking psychotropic medication for several months. There were no significant relationships between apparent Vmax or Km and platelet-5HT content in both groups. However, the ratio of Vmax to Km, as a measure of apparent 5HT uptake efficiency, significantly correlated with the platelet-5HT concentration in healthy subjects (r=0.627 p<0.001). Female controls showed a higher correlation coefficient (r=0.723) than male controls (r=0.457). A marked deviation from the linear relationship between 5HT content and the ratio Vmax/K was observed in female depressed patients (r=0.250 n.s.). In male depressed patients the correlation coefficient (r=0.485 p<0.05) was similar to male healthy subjects, but the regression equations differed significantly in slope and intercept. Dividing controls and patients in subgroups with low, median and high net uptake rates, it was found that the frequencies of these uptake rate classes were 24.6%, 33.3%, 42.1% in controls and 38.3%, 44.7%, 17.0% in patients respectively. Patients and controls with low net uptake rate showed very similar uptake kinetics and uptake efficiencies, but the lack of a significant correlation between 5HT content and the ratio Vmax/Km differentiated patients from controls. The status of the serotonergic system, expressed as relationship between 5HT content and uptake efficiency, was very similar in patients and controls in the range of medium net uptake rate. A trend toward higher values of uptake efficiency was apparent in patients with high net uptake rate but the platelet-5HT content was similar to corresponding controls. Mean scores on the HAMD scale (total score and psychic anxiety item) were significantly higher in the low net uptake rate group of patients than in those with a high net uptake rate.

Adult↗
PubMed1999

Abnormality in saccadic eye movement in dementia.

In a small (n = 15) clinically heterogeneous group of patients with dementia of the Alzheimer-type or vascular dementia, abnormally high frequency of saccadic intrusions during fixation was significantly correlated to the Mini-Mental-State-Examination (MMSE) scores. In addition, the latency of saccades and hypometric saccades also correlated significantly to MMSE-scores. The results point to the possible use of saccadic eye movement as a physiological marker of cognitive performance.

Aged↗
PubMed1998

Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava).

Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.

Amitriptyline↗
PubMed1992

Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients.

Motor asymmetries were investigated in 28 unmedicated schizophrenic in-patients and 32 healthy controls. Of the patients, who were assessed as right-handers by a handedness questionnaire, 46.4% changed their motor laterality in at least one part of the tapping test series, probably because of a decrease of functional hemispheric asymmetry. These patients were characterized by more pronounced psychotic symptoms than those who did not change motor laterality. According to the tapping frequency, two groups of patients could be distinguished: the high- and the low-frequency group. In both groups certain tapping data could be correlated with characteristic clinical features. While the findings in the high-frequency group point to an enhanced activation level of the right hemisphere and appear to be correlated with the onset of positive symptoms and better prognosis, the findings in the low-frequency group may be a reflection of a disturbed function of the left frontal region and seem to be correlated with a gradual chronic development of predominant negative symptoms with worse prognostic implications.

Adult↗
PubMed1991

Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A (A = androstenedione) ratio were increased before and after ACTH stimulation. Furthermore, highly significantly increased basal plasma levels of dehydroepiandrosterone sulfate were found in male-to-female transsexuals as compared to normal males, suggesting partial 3 beta-ol hydroxysteroid dehydrogenase deficiency to be a predisposing factor for the development of male-to-female transsexualism.

Environment↗
PubMed1988

Abnormality of gangliosides in erythrocyte membranes of schizophrenic patients.

The pattern of gangliosides in membranes of erythrocytes was examined in healthy donors, in acute schizophrenics without neuroleptic treatment and in alcohol-dependent patients. 7 different gangliosides could be detected. Healthy donors were characterized by the following ganglioside pattern: GX = 5.8%; GT1b = 6.7%; FucGD1b = 5.2%; GD1a = 12.6%, GD3 = 9.2%, SPG = 43.5%, and GM3 = 17.0%. In schizophrenic patients the GM3 and GD3 fractions were increased. No difference was found between the control group and the alcoholics.

Adolescent↗