Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Individual variability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources
PubMed1994

Importance of cholinergic, GABAergic, serotonergic and other neurons in the medial medullary reticular formation for sleep-wake states studied by cytotoxic lesions in the cat.

Previous evidence has suggested that neurons in the medial medullary reticular formation play a critical role in the modulation of forebrain and spinal cord activity that occurs during the sleep-waking cycle and particularly in association with the state of paradoxical sleep. The importance of these neurons, including cholinergic, serotonergic and GABAergic cells [Holmes C. J. et al. (1994) Neuroscience 62, 1155-1178] for sleep-wake states was investigated after their destruction with the neurotoxin quisqualic acid injected into the medullary gigantocellular and magnocellular tegmental fields in cats. To assess the effects of the neuronal loss, polygraphic recording and behavioural observations were performed in baseline and for three weeks after the lesion, and the changes in these measures were correlated with the volume of destruction of medullary regions and the numbers of chemically identified cells within those regions. Following the cytotoxic lesions, which affected approximately 60% of the medullary gigantocellular and magnocellular tegmental fields, there was a significant reduction in the amount of paradoxical sleep (to a mean of 64% of baseline) during the first postlesion week, that recovered variably across cats in the second and third weeks. There was little to no change in the amount or organization of waking and slow wave sleep. The individually variable amounts of postlesion paradoxical sleep were correlated positively with the number of surviving cholinergic cells, negatively with the number of surviving serotonergic cells and positively with the ratio of surviving cholinergic or GABAergic cells to serotonergic cells. The most marked effect of the lesion was a substantial increase in the amplitude of the nuchal electromyogram during slow wave sleep (to 198%) and paradoxical sleep (to 378% of baseline in the first postlesion week). The increase in muscle tone was associated with movements of the head, neck or limbs during paradoxical sleep. Although, in some cats, the abnormal neck muscle tone decreased with time, limb movements continued to occur during paradoxical sleep for the duration of the experiment. The ratio of the total number of remaining cholinergic or GABAergic cells to serotonergic cells correlated negatively with the increased muscle tone and/or movements. It was concluded that the neurons of the medial medullary reticular formation contribute to, but are not necessary for, the generation of paradoxical sleep, and have particular importance for the regulation of muscle tone and inhibition of movement during this state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Reliability of ultrasound fetometry in estimating gestational age in the second trimester.

The reliability of ultrasound fetometry for estimating gestational age (GA) in the second trimester was evaluated, using the fetal variables: biparietal diameter (BPD), occipitofrontal diameter (OFD), mean abdominal diameter (AD), and femur length (FL), each value being taken as the mean of five measurements. Of the individual variables, BPD gave the best precision, with a standard deviation (SD) from true GA of 3.2 days. Using a combination of all four variables, GA could be estimated with a SD of 2.2 days, which was not significantly better than the formula, GA = BPD X 1.2 + FL X 1.0 + 49, which gave results with a SD of 2.4 days. Equations obtained from regression analysis of the variables against true GA were tested in 44 cases where the precise date of conception was known, GA being estimated by BPD with a SD of 3.2 days, and by the combination of BPD and FL with a SD of 2.7 days; the maximum difference between GA estimated by BPD and by FL was 7 days. Using a combination of BPD and FL to estimate GA in the total population, the number of post-term deliveries was only marginally less than when using BPD alone.

Anthropometry↗
PubMed2003

Sequence variability during hypopharyngeal bolus transit.

The pharyngeal phase of deglutition is considered to occur in a reflexive, preprogrammed fashion. Previous studies have determined a general sequence of events based on the mean timing of bolus transit and swallowing gestures. Individual variability has not been studied, however. The purpose of this study was to determine the amount of sequence variability that normally occurs during the hypopharyngeal phase of deglutition. Dynamic swallow studies from 60 normal volunteers were evaluated and event sequence variability was determined for 12 two-event sequences during swallowing of three bolus sizes. There was found to be some variability in event sequences for almost all events evaluated except for the following: (1) arytenoid cartilage elevation always began prior to opening of the upper esophageal sphincter, (2) the sphincter always opened prior to the arrival of the bolus at the sphincter, (3) larynx-to-hyoid approximation always occurred after the onset of upper esophageal sphincter opening, and (4) maximum pharyngeal constriction always occurred after maximal distension of the upper esophageal sphincter. Variability was more common during swallowing of the smallest bolus size. This information may be helpful in evaluating event coordination in patients with dysphagia.

Adolescent↗
PubMed1992

Measurement of myocardium at risk by technetium-99m sestamibi: correlation with coronary angiography.

Previous studies have shown that tomographic perfusion imaging with technetium-99m sestamibi (RP-30A) can accurately measure the myocardium at risk during acute myocardial infarction. The ability of coronary angiography to predict the wide variability in myocardium at risk was studied in 21 patients with their first acute myocardial infarction. In blinded fashion, two experienced angiographers provided an overall "best estimate" of the percent of left ventricular myocardium at risk considering multiple angiographic variables--infarct-related artery, location of stenosis (proximal or nonproximal), vessel diameter, length, territory and the number and size of proximal branches and collateral vessels. Many of these individual variables showed a significant association with myocardium at risk. The most important angiographic variable was the mean best estimate of the two angiographers (r = 0.89, p less than 0.0001). However, the SEE was large (8.6% of the left ventricle) and angiography significantly (p less than 0.002) overestimated myocardium at risk. When patients with an anterior or an inferior infarct were considered separately, the angiographic best estimate had a weaker correlation with myocardium at risk measured by technetium-99m sestamibi in patients in both groups (anterior infarction r = 0.65, p = 0.04; inferior infarction r = 0.65, p = 0.04. Seven patients with an inferior infarct and myocardium at risk ranging from 7% to 32% of the left ventricle had identical angiographic best estimates. Although angiographic estimates correlate closely with measurements of myocardium at risk in groups of patients, their ability to predict the myocardium at risk in individual patients is limited.

Adult↗
PubMed1988

Effect of musical modelling on late auditory evoked potentials.

Late auditory evoked potentials were recorded in four subjects during musical tasks. A PDP 12 computer synchronized stimuli, which were produced by an integrated circuit, and recording with the help of a quartz time basis. The content of each experiment was different modelling of an ambiguous identical acoustic stimulus. In experiment 1, subjects had to model a 6-note melody according to the classic metric foot. In experiment 2, segmentation of an 8-note melody into 5- and 3- versus 3- and 5-tone motifs had to be performed. In experiment 1 an intra-individually reliable, but inter-individually variable neurophysiological correlate was detected during the heavy tone: (1) positivity, (2) negativity, (3) alpha blocking and (4) DC shift. Experiment 2 yielded an intra- and inter-individually reliable positive DC shift of about 4 microV between the two motifs. Myogenic, ocular, dermal, respiratory or electrocardiographic artefacts were excluded in each case. The results indicate that conclusions from evoked potentials to musical perception might be possible and that possible modelling mechanisms with subsequent undesirable influence on recordings have to be considered in any kind of evoked potential experimental design.

Adult↗
PubMed1998

Changes in nutritional status during the hospital stay: a predictor of long-term survival.

The objectives of this prospective observational study were to assess whether: 1) midarm circumference (MAC), previously shown to predict in-hospital mortality, maintains its prognostic implication after discharge; 2) in-hospital changes in aspecific indicators of the health status are predictors of long-term survival. The study population consisted of 249 patients from the general community [mean age 80 +/- 7 (70-99) years], consecutively discharged from geriatric and medical wards of an acute care hospital. Changes in health status during hospitalization were recorded (dynamic or delta variables) and health-related variables were collected at discharge (discharge variables). The relationship of both sets of variables to survival over a 3-year period was assessed by Cox's proportional hazards regression analysis. The discriminatory efficacy of predictive models was estimated by the Hanley and McNeil method. Survival curves were drawn with the patients alternatively grouped according to the presence or absence of each of the predictive variables. Serum albumin < 3.5 g/dL (hazard rate = 0.57, 95% confidence limits = 0.33-0.96) and dependency in at least one ADL (h.r. = 0.87, c.l. = 0.79-0.98) were found to be associated with increased mortality, and delta MAC (h.r. = 1.03, c.l. = 1.01-1.05), i.e., there was a positive change or no change in MAC from admission to discharge, with increased survival. A slightly weaker predictive model was obtained using only discharge variables. However, Hanley and McNeil's analysis showed that both models were far from achieving the optimal discrimination of high from low risk subjects. Effects on survival of individual variables varied in magnitude and dependency on time. We concluded that measuring in-hospital changes in nutritional status might improve prediction of long-term survival. Attempts should be made to identify variables having the strongest prognostic implications, and to tailor dynamic assessment to the needs of selected categories of patients.

Activities of Daily Living↗
PubMed2004

Individual variation in plasma estradiol-17beta and androgen levels during egg formation in the European starling Sturnus vulgaris: implications for regulation of yolk steroids.

While it is clear that maternal transfer of steroids to egg yolk can have significant effects on offspring phenotype, an unresolved question is whether females can facultatively adjust yolk hormone levels independently of their own plasma levels or whether yolk steroid levels are simply a direct consequence of temporal variation in the female's hormonal status. In part, this is because we lack detailed information about the day-to-day pattern of changes in plasma hormone levels during the laying cycle for non-domesticated birds. Here, we describe changes in plasma estradiol-17beta (E2) and androgens, throughout laying in relation to specific stages of ovarian follicular development in the European starling (Sturnus vulgaris). Plasma E2 levels increased rapidly from the onset of rapid yolk development (RYD) to reach maximum levels in birds with a complete follicle hierarchy (> or = 4 yolky follicles). However, levels decreased linearly throughout the later stages of follicle development returning to pre-breeding values before the final yolky follicle was ovulated. In females with > or = 4 yolky follicles there was 10-fold variation in plasma E2 levels among individual females, but this was not related to plasma levels of the main yolk precursor vitellogenin or to the total mass of yolky follicles developing at the time of blood sampling. In contrast to E2, plasma androgen levels showed only a very gradual linear decline throughout the laying cycle from pre-RYD to clutch completion. Furthermore, androgen levels showed less individual variability: 4-fold variation among females with > or = 4 yolky follicles, although this was also independent of our measures of reproductive function. Data on inter- and intra-individual variation in female hormone levels are important to set-up a priori predictions for, and interpretation of, studies of yolk hormone levels.

Androgens↗
PubMed1999

Variability and sequential order of consonant normalization in children with speech delay.

A source of discrepancy among attempts to establish a rank order in the development of English consonants has been the inability to cope concurrently with principled generalization and individual variability. This problem may be surmounted by survival analytic techniques. From the conversational speech of 24 children with speech delay (SD) recorded over 2 years, a Kaplan-Meier (KM) survival analysis provided a rank order of acquisition for all probabilities above .75. The rank ordering by chronological age uncovered an alignment by place and manner of articulation comparable to, but not identical with, the predictions of Jakobson (1941, 1968). When the derived normalization probabilities for the speech delayed children were lagged according to the strong delay hypothesis (Shriberg, Gruber, & Kwiatkowski, 1994), they were shown to converge with previous normative studies and the age of speech-sound determinations (Prather, Hedrick, & Kern, 1975; Sander, 1972). The convergence of results is interpreted both as an argument for generalizability and as support for the strong delay hypothesis.

Age Factors↗
PubMed1999

High-resolution gametic map of the sheep callipyge region: linkage heterogeneity among rams detected by sperm typing.

The callipyge locus (CLPG) causing muscular hypertrophy in domestic sheep has previously been mapped to the distal part of ovine chromosome 18. In this study, an accurate multipoint linkage map consisting of six microsatellite markers in this chromosomal region was constructed based on the analysis of 1145 single sperm cells. The best supported order of markers was OARHH47-ILSTS54-MCM38-CSSM18-IDVGA30-BM S1561. The log odds against the second most likely order, which has a reversal of the closely linked markers CSSM18 and IDVGA30, was 5.026. Sperm typing can be used to examine a large number of meioses in single individuals, and therefore, was exploited to study individual variability of recombination rate in rams of different callipyge genotypes. The results revealed statistically significant linkage heterogeneity among rams (P < 0.05) for marker interval OARHH47-CSSM18, with individual recombination fractions varying from 0.209 to 0.357.

Animals↗
PubMed2003

Neurophysiological factors in human information processing capacity.

What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of information processing have been identified, as well as sequences of events in the brain. The neurophysiological substrate of human information processing capacity, i.e. the amount that can be processed simultaneously, is, however, unresolved, as is the basis of inter-individual variability in capacity. Automatization of cognitive functions is known to increase capacity to process additional tasks, but behavioural indices of automatization are poor predictors of processing capacity in individuals. Automatization also leads to a decline of brain activity in the working memory system. In this study, we test the hypothesis that processing capacity is closely related to the way that the brain adjusts to practice of a single cognitive task, i.e. to the changes in neuronal activity that accompany automatization as measured with functional MRI (fMRI). Using a task that taxes the working memory system, and is sensitive to automatization, performance improved while activity in the network declined, as expected. The key finding is that the magnitude of automatization-induced reduction of activity in this system was a strong predictor for the ability to perform two different working memory tasks simultaneously (after scanning). It explained 60% of the variation in information processing capacity across individuals. In contrast, the behavioural measures of automatization did not predict this. We postulate that automatization involves at least two partially independent neurophysiological mechanisms, i.e. (i) streamlining of neuronal communication which improves performance on a single task; and (ii) functional trimming of neuronal ensembles which enhances the capacity to accommodate processing of additional tasks, potentially by facilitating rapid switching of instruction sets or contexts. Finally, this study shows that fMRI can provide information that predicts behavioural output, which is not provided by overt behavioural measures.

Adult↗
PubMed1997

Risk assessment and risk stratification in sudden cardiac death: a biostatistician's view.

Determining individual probabilities of developing lethal arrhythmia over time (risk assessment) and grouping individuals by that probability (risk stratification) are similar to, yet differ in purpose from, screening, diagnosis, risk factor identification, and prognostic staging. Methods of handling bias, use of multiple predictors, and evaluation of results provide challenges. A key purpose of risk assessment and stratification is examined. The role of operational definitions of predictors and events and of methods that account for multiple predictors and known confounding factors is analyzed. Constructed examples illustrate potential pitfalls in assessment and how multivariate techniques can deal with multiple predictors. A trial design to evaluate risk stratification for the identified purpose is elaborated and potential results are interpreted. Bias from predictors regressing to the mean can be minimized either by averaging a number of measurements or by equalizing the bias in comparison groups. An analysis of two predictors and two risk strata illustrates how the discrimination of combined predictors may be greater than the sum of the individual variables' discrimination. Risk stratification can be evaluated in trials that randomize competing interventions within different risk strata. Results of such trials indicate whether the risk strata adequately distinguish individuals by their responsiveness to particular intervention. Potential pitfalls, not easily recognized in risk stratification, can be avoided in the methods and in studies for evaluating those methods. Multivariate techniques maximize the discrimination of multiple predictors, but may increase complexity. Randomized trials of treatment provide evidence for utility of risk stratification.

Arrhythmias, Cardiac↗
PubMed2003

Drug interactions of paclitaxel metabolism in human liver microsomes.

The human liver metabolism of paclitaxel (Taxol), an anticancer drug, leads to three metabolites: 6alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6alpha,3'-p-dihydroxypaclitaxel. The inter-individual variability of paclitaxel metabolism was investigated first in vitro using 22 human liver microsomes. Three metabolites have been detected by HPLC. This preliminary work revealed marked inter-individual differences in paclitaxel metabolism. The amount of major metabolite 6alpha-hydroxypaclitaxel formed varied 16-fold (0.7 to 11.5 nmol/mg/h). We next studied the effect of 29 compounds (antineoplastics, antiemetics, histamine-2 receptor antagonist, antalgics, antifungals, antivirals, psychotropics, antibiotic, corticoid, antiarrhythmic, calcium channel blocker) on paclitaxel metabolism in human liver microsomes. Among the compounds studied, quercetin, antifungal drugs such as ketoconazole and miconazole, and the antineoplastic drug doxorubicin inhibited formation of 6alpha-hydroxypaclitaxel. Dixon plots indicated that quercetin and doxorubicin inhibited 6alpha-hydroxypaclitaxel formation through a competitive mechanism with a Ki of 10.1 microM and 64.8 microM, respectively. The inhibition of this metabolite by ketoconazole was through a noncompetitive mechanism with a Ki of 11.8 microM. Our data thus suggest that special attention should be paid when these drugs are combined in clinical practice.

Adult↗
PubMed1979

The effects of season and temperature on D-lactate dehydrogenase, pyruvate kinase and arginine kinase in the foot of Helix pomatia L.

The effects of pH, season, environmental and experimental temperatures on the activities and kinetic parameters of D-lactate dehydrogenase, pyruvate kinase and arginine kinase from the foot of the pulmonate snail Helix pomatia were analyzed. Both in phosphate and Tris buffers D-lactate dehydrogenase was the enzyme with the most acid maximum, arginine kinase that with the most alkaline, whilst pyruvate kinase occupied an intermediate position. Pyruvate kinase activity, measured at 20 degrees C, was positively correlated with the environmental temperature at the moment of collecting the animal, whereas neither arginine kinase nor D-lactate dehydrogenase showed such a relationship. A seasonal study based on approximately 100 specimens established that arginine kinase activity remained the same throughout the year. Pyruvate kinase activity was slightly lower, and D-lactate dehydrogenase activity significantly higher, in winter than in summer animals. Snails subjected in spring to a short warm-up period before enzyme extraction showed extreme variability and some extraordinarily high values of pyruvate kinase activity, suggesting that either season or elevated temperature may have an immediate effect on the activity of this enzyme. Individual variability of all three enzymes ranges from 300 to 400%. The activities of pyruvate kinase and D-lactate dehydrogenase are strongly correlated in summer, forming a "constant-proportion-group", whereas in winter, with D-lactate dehydrogenase activity increasing and pyruvate kinase activity decreasing these two enzymes become "uncoupled". The Km value of pyruvate kinase is independent of experimental temperature between 10 and 25 degrees C, whereas that of D-lactate dehydrogenase and arginine kinase increases about three-fold within this range. Thus the temperature relationship of a single enzymic reaction cannot be used as an arguemnt for or against the occurrence of temperature compensation of whole animal metabolism. The possibility of modulation of enzyme activity by environmental temperature is discussed.

Acclimatization↗
PubMed1994

Can fetal biophysical observations anticipate outcome in preterm labor or preterm rupture of membranes?

OBJECTIVE: To evaluate fetal biophysical testing as a predictor of preterm delivery after preterm labor or preterm rupture of the membranes (PROM). METHODS: We studied 50 women with suspected preterm labor and intact membranes and 25 women with PROM but not in labor between 28 and 36 weeks' gestation. Before treatment, each subject had cervical Bishop scoring and 1-hour ultrasound observation of fetal heart rate, breathing, body movements, and flexion-extensions. Data were compared with t tests, chi 2 tests, or receiver operating curves. RESULTS: The mean gestational age at entry was similar in both groups. Twenty (80%) PROM and ten (18%) preterm labor patients delivered within 72 hours of admission; two (8%) PROM and 38 (76%) preterm labor patients delivered more than 7 days after admission. Absent breathing and body movements had high positive predictive values (100%) but moderate sensitivities (less than 55%) for predicting delivery within 72 hours or 7 days in the PROM and preterm labor groups. These sensitivities increased to nearly 70% with the addition of Bishop scores. The optimal diagnostic cutoffs for delivery within 72 hours or 7 days were a breathing incidence below 1% for the PROM group and a body movement incidence below 1% for the preterm labor group, and a breathing incidence of at most 5%. CONCLUSIONS: Complete absence of one biophysical variable confers limited sensitivity but high positive predictive value for early delivery in patients with preterm labor or PROM. The use of cutoff percentages for the incidence of individual variables improved sensitivity for both conditions. Cervical scoring added to biophysical monitoring by improving the sensitivity for early delivery of patients in preterm labor.

Chi-Square Distribution↗
PubMed2003

A critical evaluation of DNA adducts as biological markers for human exposure to polycyclic aromatic compounds.

The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention or chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria: i. adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined. iii. sources of interand intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAHexposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with nonexposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intraindividual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurements may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurements as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.

Animals↗
PubMed2006

Water and electrolyte needs for football training and match-play.

The high metabolic rates sustained by soccer players during training and match-play cause sweat to be produced in both warm and temperate environments. There is limited published information available on the effects of this sweat loss on performance in soccer. However, this limited information, together with knowledge of the effects of sweat loss in other sports with skill components as well as endurance and sprint components, suggests that the effects of sweating will be similar to the effects in these other activities. Therefore, the generalization that a body mass reduction equivalent to 2% should be the acceptable limit of sweat losses seems reasonable. This amount, or more, of sweat loss reflected in body mass loss is a common experience for some players. Sodium is the main electrolyte lost in sweat and the available data indicate considerable variability in sodium losses between players due to differences in sweating rate and sweat electrolyte concentration. Additionally, the extent of sodium loss is such that its replacement will be warranted for some of these players during training sessions and matches. Although soccer is a team sport, the great individual variability in sweat and electrolyte losses of players in the same training session or match dictates that individual monitoring to determine individual water and electrolyte requirements should be an essential part of a player's nutritional strategy.

Adolescent↗
PubMed1998

Relevance of pheno- and genotyping in clinical drug development.

Individual variability in the plasma concentration of a xenobiotic is a considerable problem in the clinical use as well as in the clinical development of a new drug. In clinics altered drug response and drug toxicity are predominant findings. In clinical development (especially in the early phases) problems with the interpretation of individual pharmacokinetics and appearance of unexpected drug reactions may occur. One major reason for the inter-and intraindividual variability is based on variations in the metabolism of the drug that are dependent on the genetic variations of the metabolising enzymes. However, while the first of these so-called polymorphisms has already been described in 1979 (for a review see [Daly 1995]) and knowledge of these polymorphisms are still growing, the impact on clinical practice as well on the selection and development of drug candidates in the pharmaceutical industry at present is still limited. This may change in the near future as recent advances in molecular biology and especially in the diagnosis of individual genomic characteristics will result in a better understanding of the basic principles of the polymorphisms. High throughput screening methods will reveal information on the distribution of these polymorphic alleles in the target population and enable the broad characterization of the drug candidate in in vitro systems. The early knowledge as to whether a polymorphic pathway is involved in drug metabolism/action and of its clinical relevance will lead to a reduction of time and costs in the development of a new drug.

Decision Trees↗
PubMed2003

Individualized medicine - implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders.

Antidepressant drug therapy is characterized by a high rate of therapeutic failure. There is increasing evidence that genetic factors are contributing to the inter-individual variability in antidepressant drug response. Genetic variability is described in both the pharmacokinetic part of drug action as well as in pharmacodynamic structures mediating drug effects. Genetic polymorphisms in drug metabolizing enzymes are well characterized and have large effects on oral clearances or elimination half-lives of antidepressant drugs. These differences can be compensated by adapting the individual dose to genotype in addition to other factors such as gender, weight, age, liver and kidney function. On the part of drug action, genetic variability is described in molecular structures of antidepressant effects. Several studies on response of antidepressants have revealed influences of polymorphisms in neurotransmitter receptors and transporters changing sensitivity of patients to treatment with antidepressants; however, results were often contradictory. A pharmacogenomic approach to individualize antidepressant drug treatment is recommended to be based on several levels: 1) identifying and validating the candidate genes involved in drug-response; 2) providing therapeutic guidelines; and 3) developing a pharmacogenetic test-system for bedside-genotyping.

Age Factors↗