Biomedical subjects

Astrid Zobel

Publications and source records attributed to Astrid Zobel.

10 recordsLinked to original sources

PubMed2006

Schizophrenia and bipolar disorder: differences and overlaps.

PURPOSE OF REVIEW: Following the recent progress mainly in the fields of genetics and neurobiology, the validity of the diagnostic distinction between schizophrenia and bipolar disorder is increasingly challenged. RECENT FINDINGS: Evidence for basic neurobiological processes common for both disorders is expanding with regard to (a) susceptibility genes, (b) neurodevelopment (for example myelination), and (c) brain functions (for example sensory gating, visuospatial achievement). Recent epidemiological studies also stress communalities. SUMMARY: The diagnostic split between schizophrenia and bipolar disorder is unable to define distinct etiological and/or pathophysiological entities.

Bipolar Disorder↗

PubMed2006

Clinical impact of recently detected susceptibility genes for schizophrenia.

After years of frustration, the search for genes impacting on schizophrenia is now undergoing some exciting developments. Several proposals of susceptibility genes have been able to be supported by replications. Thus, there are now at least three very strong candidates: the gene for dysbindin (DTNBP1), the gene for neuregulin-1 (NRG1), and a less well-understood gene locus, G72/G30, which are likely to influence manifestations of schizophrenia. Other "hot" candidates such as the disrupted-in-schizophrenia 1 gene (DISC1) and the gene coding for protein kinase B (AKT1) might also prove to be susceptibility genes in the next future. The clinical implications of these findings are not yet fully visible. However, some first insights are possible: most of the genetic findings lack diagnostic specificity, and are also reproduced in bipolar disorder. Strong associations are also obtained on a symptomatic level, not only on a diagnostic level. The pathophysiological role of these hot candidate genes is currently under intensive study.

Animals↗

PubMed2006

Response-dependent differences in regional cerebral blood flow changes with citalopram in treatment of major depression.

UNLABELLED: Major depression (MD) is the most frequent psychiatric disorder with a predicted increase within the next decade. The understanding of the neurobiologic basis of its cause, antidepressive treatment effects, and identification of treatment outcome predictors is of crucial importance to warrant efficient medical care. The aim of our study was to investigate differences of regional cerebral blood flow (rCBF) in MD between responders and nonresponders in the beginning and differences during the course of treatment. METHODS: 99mTc-Labeled d,l-hexamethylpropyleneamine oxime brain scans under resting conditions were performed on 65 patients with MD. All patients were treated with citalopram as an antidepressive monotherapy. SPECT scans were performed 2 times, at the beginning (t1) and after 4 wk of medication (t2). Voxel-by-voxel analyses were performed using SPM. Unpaired t test, paired t test, and multigroup analysis were used on a significance threshold of P < 0.005 (uncorrected) to identify significant differences in rCBF between responders and nonresponders at t1, within both groups over time of treatment (t2-t1), as well as a group x time interactions. RESULTS: Thirty-five patients responded after 4 wk of treatment. Distinct differences between responders and nonresponders were found at the beginning of treatment and also relating to changes in rCBF during treatment. Responders showed a higher posterior cingulate activity at t1. Furthermore, an opposite direction of rCBF changes during treatment could be observed in this area. CONCLUSION: The differences in rCBF in responders and nonresponders in the posterior cingulate at t1 and the opposite directed changes in rCBF in both groups during treatment in this region suggest that the posterior cingulate function plays a key role in the pathophysiology of depression and may have a predictive value for antidepressive treatment outcome.

Adult↗

PubMed2005

Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach.

Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with (99m)Tc-hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.

Adult↗

PubMed2005

Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression.

BACKGROUND: Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results. METHODS: We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects). RESULTS: Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)n-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p = .00006, BPAD p = .0057, schizophrenia p = .016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p = .0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. CONCLUSIONS: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.

Adult↗

PubMed2005

The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.

BACKGROUND: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant. METHODS: We assessed a potential association between 5-HTTLPR and MDD, using the largest reported sample to date (466 patients, 836 control subjects). Individuals were all of German descent. Patients were systematically recruited from consecutive inpatient admissions. Control subjects were drawn from random lists of the local Census Bureau and screened for psychiatric disorders. RESULTS: The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26). CONCLUSIONS: These results support an involvement of 5-HTTLPR in the etiology of MDD. They also demonstrate that the detection of small genetic effects requires very large and homogenous samples.

Adult↗

PubMed2005

Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes?

Schizophrenia and affective disorder have been considered to be nosologically and etiologically distinct disorders. This postulate is challenged by progress in new biological research. Both disorders are strongly influenced by genetic factors; thus genetic research is a main contributor to this discussion. We review current evidence of the genetic relationship between schizophrenia and affective disorders, mainly bipolar disorder (the various genetic research methods have been particularly applied to bipolar disorder). Recent family and twin studies reveal a growing consistency in demonstrating cosegregation between both disorders which is difficult to detect with certainty given the low base rates. Systematic molecular genetic search for specific genes impacting on either disorder has now identified one gene which is apparently involved in both disorders (G72/G30); other candidate genes reveal some evidence to present as susceptibility genes with very modest effects for each of both disorders, although not consistently so (e. g., COMT, BDNF). There is room for speculation about other common susceptibility genes, given the overlap between candidate regions for schizophrenia and those for bipolar disorder emerging from linkage studies.

Bipolar Disorder↗

PubMed2004

Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting.

OBJECTIVE: This evaluation focuses on polymorphisms of the cytochrome-P450 (CYP) isoenzymes 2C9, 2C19 and 2D6 and their association with plasma concentrations within a typical clinical setting. Side effects and treatment response were analysed in an exploratory approach in poor and ultra-rapid metabolisers. PATIENTS AND METHODS: We analysed 136 Caucasian depressed inpatients treated with amitriptyline, citalopram, clomipramine, doxepin, fluvoxamine, mirtazapine, paroxetine, sertraline and venlafaxine, who underwent weekly plasma concentration measurements, assessment of the severity of illness and side effects during their stay in the hospital. Patients were genotyped with respect to CYP2C9 alleles *1 and *2, the CYP2C19 alleles *1, *2 and *3 and the CYP2D6 alleles *1 to *9 and CYP2D6 gene duplication. RESULTS: CYP2D6 poor metaboliser genotype and co-medication with inhibitors of CYP2D6 were associated with higher plasma concentrations than the drug-specific median plasma concentration when normalised to dose; plasma concentrations of CYP2C19 extensive metabolisers and smokers were significantly lower than the drug-specific median. Five of the six CYP2D6 poor metabolisers experienced side effects. Response was not associated with plasma concentrations above or below the lower limit of a presumed therapeutic range. CONCLUSION: These data indicate a significant influence of the CYP2D6 genotype, minor influence of the CYP2C19 genotype and no influence of the CYP2C9 genotype on plasma concentrations of patients taking mainly second-generation antidepressants. Because of the good tolerability of the latter and the flat dose-response relationship, genotyping should only be considered in cases of suspected side effects.

Antidepressive Agents↗

PubMed2004

Population pharmacokinetic analysis of mirtazapine.

OBJECTIVE: Mirtazapine belongs to the new generation of antidepressants that is commonly used in clinical routine. Therefore, we feel it mandatory to control compliance in the context of non-response, adverse events or other clinical situations by means of plasma concentration measurements. While controlled clinical studies have evaluated the effect of individual covariates on the pharmacokinetics of mirtazapine, our analysis aims to identify covariates within a naturalistic clinical setting. METHODS: We performed non-linear mixed-effects modelling with data from 65 depressed inpatients whose plasma concentrations were measured weekly during their stay in hospital. Each patient's age, height, weight, co-medication, alcohol, coffee and cigarette consumption, weekly serum creatinine concentrations, liver enzyme activity, blood pressure and pulse was noted. From 49 patients, the genotype of cytochrome P450 (CYP) isoenzymes 2D6, 2C9 and 2C19 was analysed. RESULTS: The clearance of CYP2D6 intermediate metabolisers was reduced by 26% compared with extensive metabolisers. No other factor significantly influenced the clearance of these patients. CONCLUSION: The variability of mirtazapine plasma concentrations in clinical routine is caused to a relevant degree by CYP2D6. This should be taken into account when therapeutic drug monitoring is carried out to check treatment adherence or when a special clinical situation, such as co-morbidity and add-on medication, demands careful dosing of this drug.

Antidepressive Agents, Tricyclic↗

PubMed2004

Impairment of inhibitory control of the hypothalamic pituitary adrenocortical system in epilepsy.

Excess comorbidity between depression and epilepsy proposes common pathophysiological patterns in both disorders. Neuroendocrine abnormalities were often observed in depression as well as in epilepsy. Lack of inhibitory control of the hypothalamic pituitary adrenocortical (HPA) system is a core feature of depression; main relay stations of this system are located in the amygdala and hippocampus, which are key regions for both disorders. Therefore we explored the feedback mechanism of the HPA system in epilepsy. In order to control for the impact of depression we focused on epilepsies without depression. We compared patients with epilepsy (subdivided by medication with or without hepatic enzyme inducing antiepileptic medication) with 16 healthy controls and 16 patients with unipolar major depression but without epilepsy. We observed a lack of inhibitory control of the HPA system in patients with epilepsy, also in the absence of enzyme inducing medication. An impact of the temporal lobe location of the epileptic focus could not be observed. Thus, epilepsies share with depression the deficiencies in the feedback mechanism of the HPA system, proposing common pathophysiological features of up to now unknown nature.

Adrenocorticotropic Hormone↗