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Vidar M Steen

Publications and source records attributed to Vidar M Steen.

14 recordsLinked to original sources
PubMed2006

Associations between cod liver oil use and symptoms of depression: the Hordaland Health Study.

BACKGROUND: Clinical trials suggest that omega-3 fatty acids improve the outcome of depression. This study aimed to evaluate the association between intake of cod liver oil, rich in omega-3 fatty acids, and high levels of symptoms of depression and anxiety in the general population. METHODS: We used data from the "The Hordaland Health Study '97-'99" (HUSK), a population based cross-sectional health survey from Norway including 21,835 subjects aged 40-49 and 70-74 years. Symptoms of depression and anxiety were measured by The Hospital Anxiety and Depression Scale (HADS). We used logistic regression to study associations. RESULTS: Among the participants, 8.9% used cod liver oil daily. A total of 3.6% had high levels of depressive symptoms. The prevalence of such depressive symptoms among the subjects who used cod liver oil daily was 2.5%, as compared to 3.8% in the rest of the population. The users of cod liver oil were significantly less likely to have depressive symptoms than non-users after adjusting for multiple possible confounding factors (odds ratio=0.71, 95% confidence interval 0.52 to 0.97). These factors included age, gender, smoking habits, coffee consumption, alcohol consumption, physical activity, and education. In addition, we found that the prevalence of high levels of depressive symptoms decreased with increasing duration (0-12 months) of cod liver oil use (multivariate adjusted test for trend, P=0.04). We were only able to study this latter association in a subset of the population aged 40-46 years. LIMITATIONS: Data are cross sectional. CONCLUSIONS: The findings indicate that regular use of cod liver oil is negatively associated with high levels of depressive symptoms in the general population.

Adult↗
PubMed2006

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs.

BACKGROUND: The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1) in four CNS-relevant human cell lines. RESULTS: There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. CONCLUSION: Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

Antipsychotic Agents↗
PubMed2006

[Pharmacogenetics and tailored drug treatment in schizophrenia].

BACKGROUND: Medical treatment of psychiatric disorders is often characterised by trial and error. Psychotropic drugs show a large variation in response and side effects. Molecular genetic techniques seem to have a potential for identifying biological predictors of drug response and side effects, and help to establish tailored drug treatment. MATERIAL AND METHODS: Based on relevant literature and own research, this article gives a short overview of some pharmacogenetic aspects related to pharmacological treatment of schizophrenia. RESULTS: Antipsychotic and antidepressive drugs are metabolized by many different enzymes in the cytochrome P450 system. The rate of the drug-metabolism depends to some extent on genetic variants, and several gene-variants affect the serum level of the drugs, which may cause side effects or non-response. Several pharmacogenetic studies have indicated that both the therapeutic response and the level of motor and metabolic side effects of antipsychotic drug treatment of schizophrenia are related to polymorphisms in the serotonine and dopamine receptor genes, but there are conflicting findings. INTERPRETATION: However, most of these data remain preliminary, and so far pharmacogenetics has been of little practical help for clinical psychiatry. Due to the progress in molecular genetics and improved quality of clinical studies, there is a hope that a new generation of psychiatric pharmacogenetic studies will provide us with more useful information for drug treatment of schizophrenia and other psychiatric conditions.

Antidepressive Agents↗
PubMed2006

SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects?

Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

Animals↗
PubMed2006

Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo.

Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced synaptic consolidation in the adult brain in vivo.

Animals↗
PubMed2006

Obesity, dyslipidemia, and diabetes with selective serotonin reuptake inhibitors: the Hordaland Health Study.

OBJECTIVE: This study aimed to examine whether subjects taking selective serotonin reuptake inhibitors (SSRIs) are more likely to have elements of the metabolic syndrome compared with those taking no psychotropic drugs. For comparison, we also studied subjects taking antipsychotic drugs. METHOD: We used data from The Hordaland Health Study '97-'99, a general community cross-sectional health survey including 25,315 subjects aged 40 to 49 and 70 to 74 years. For the groups studied, we estimated prevalence and odds ratios (ORs) for obesity, hypercholesterolemia, low high-density lipoprotein cholesterol, hyper-triglyceridemia, and diabetes. RESULTS: We observed an association between use of SSRIs as a group (N = 461) and abdominal obesity (OR = 1.40, 95% CI = 1.08 to 1.81) and hypercholesterolemia (OR = 1.36, 95% CI = 1.07 to 1.73) after adjusting for multiple possible confounders. There was also a trend toward an association between SSRI use and diabetes. In a subgroup analysis of subjects taking SSRIs, the use of paroxetine (N = 187) was markedly associated with both general and abdominal obesity but not with hypercholesterolemia. In contrast, the use of citalopram (N = 142) was not associated with any of the metabolic outcome variables, while the use of any other SSRI (sertraline, fluoxetine, or fluvoxamine) (N = 131) as a mixed subgroup was associated with both abdominal obesity and hypercholesterolemia. We also replicated the previously reported associations between use of antipsychotics and obesity and metabolic disturbances. CONCLUSION: We have shown that use of at least some SSRIs is associated with clinical and biochemical elements of the metabolic syndrome. Our data indicate differences in the metabolic side effect profile among various SSRI drugs, although treatment bias might have influenced these results. We suggest that patients taking SSRIs be carefully monitored for obesity and dyslipidemia.

Adult↗
PubMed2005

Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.

Dysfunction of glial lipid metabolism and abnormal myelination has recently been reported in both schizophrenia and bipolar disorder. Cholesterol is a major component of myelin, and glia-produced cholesterol serves as a glial growth factor in synaptogenesis. We have recently demonstrated that antipsychotic drugs activate the sterol regulatory element-binding protein (SREBP) transcription factors in human and rat glial cells, with subsequent up-regulation of numerous downstream genes involved in cholesterol and fatty acid biosynthesis. Since this stimulation of cellular lipogenesis could represent a new mechanism of action of psychotropic drugs, we investigated whether antidepressants and mood-stabilizers were able to induce a similar activation of SREBP-controlled lipid biosynthesis. Cultured human glioma cells (GaMg) were exposed to the antidepressant drugs imipramine, amitriptyline, clomipramine, citalopram, fluoxetine, mirtazapine and bupropion and the mood-stabilizers/antiepileptics lithium, valproate and carbamazepine. All antidepressant drugs activated the SREBP system with subsequent up-regulation of the downstream lipogenesis-related genes, although to a markedly different extent. The mood-stabilizers did not affect the SREBPs or the downstream genes. These results link antidepressant drugs, but not mood-stabilizers, to SREBP-mediated activation of cellular lipogenesis, and demonstrate a functional similarity between antipsychotic and antidepressant molecular drug action.

Antidepressive Agents↗
PubMed2005

The CYP2C19 genotype and the use of oral contraceptives influence the pharmacokinetics of carisoprodol in healthy human subjects.

AIMS: The aim of the present study was to investigate if subjects with one normal and one non-functional CYP2C19 allele (intermediate metabolizers; IMs) metabolized carisoprodol differently than individuals with two normal CYP2C19 alleles (extensive metabolizers; EMs) We also wanted to investigate whether the use of oral contraceptives influences the metabolism of carisoprodol in EMs and IMs. Impairing effects on psychomotor coordination and feelings of sedation were studied by comparing IMs with EMs following their ingestion of a single dose of 700 mg carisoprodol. METHODS: Thirty-seven healthy Caucasian volunteers participated in the study, of whom 25 were not using any drugs known to interact with CYP2C19, including two poor metabolizers (PMs) (CYP2C19 *2/*2 or CYP2C19 *2 /*4), 11 IMs (CYP2C19 *1/*2 or CYP2C19 *1/*4) and 12 EMs (CYP2C19 *1/*1); the remaining 12 participants were six EMs and six IMs using oral contraceptives. A single oral dose of 700 mg of carisoprodol was given, and blood drug concentrations were followed for 11 h and 45 min. During this time period, different pharmacodynamic measurements were made. RESULTS: IMs had a longer elimination half life (T(1/2)) (127 min; 95% confidence interval (CI) 95, 159) than EMs (96 min; 95% CI 84, 107) and a larger area under the concentration-time curve from 0 to infinity (AUC(0-infinity)) for carisoprodol (16.3 microg h ml(-1) ; 95% CI 11.9, 20.7) than EMs (11.3 microg h ml(-1) ; 95% CI 7.8, 14.8). The use of oral contraceptives was accompanied by larger AUC(0-infinity) for carisoprodol in both EMs (18.5 microg h ml(-1); 95% CI 10.7, 26.3) and IMs (26.0 microg h ml(-1) ; 95% CI 18.8, 33.2). EMs using oral contraceptives also had a longer T(1/2) (117 min; 95% CI 92, 143) and higher maximum carisoprodol concentration than EMs not using oral contraceptives. No significant differences in pharmacodynamic parameters were found between subjects in the different genotype groups or between users and non-users of oral contraceptives. CONCLUSIONS: Subsequent to a single-dose administration of carisoprodol, the carisoprodol AUC was approximately 45% larger in CYP2C19 IMs than in EMs. The use of oral contraceptives increased the AUC by approximately 60% in both EMs and IMs. Despite these pharmacokinetic effects, no significant differences with respect to the CYP2C19 IM and EM genotypes were observed in the acute impairing effects of a single dose of carisoprodol.

Area Under Curve↗
PubMed2004

Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes.

BACKGROUND: The aims of the study were to quantify the drug exposure in breastfed infants of antidepressant-treated mothers, to identify possible adverse events, and to correlate these variables to maternal and infant drug metabolism-relevant genotypes and milk triglyceride content. METHOD: The study included 25 lactating women treated with citalopram (N = 9), sertraline (N = 6), paroxetine (N = 6), fluoxetine (N = 1), or venlafaxine (N = 3) and their 26 breastfed infants. Drug concentrations in maternal and infant serum and milk were analyzed using liquid chromotography mass spectrometry methods; milk triglyceride levels were measured with a commercial kit. Cytochrome P450 (CYP) 2D6 and CYP2C19 activity was determined by polymerase chain reaction-based genotyping of the mothers and infants. An infant adverse event questionnaire was completed by the medication-treated mothers as well as by a control group of medication-free breastfeeding mothers of 68 infants. RESULTS: Sertraline and paroxetine were not detected in any of the drug-exposed infants. The infant serum level of citalopram was either undetectable (N = 4) or low (N = 6). All venlafaxine-exposed infants had measurable drug concentrations. We identified a paroxetine-treated mother and her infant who were both CYP2D6 poor metabolizers, as well as a citalopram-treated mother with CYP2C19 poor metabolizer status, but the serum drug levels of their infants were still either undetectable (paroxetine) or low (citalopram). There was no evidence of adverse events in the drug-exposed infants. CONCLUSION: Serum drug levels in breastfed infants of antidepressant-treated mothers were undetectable or low. This study adds further evidence to previously published data indicating that breastfeeding should not be generally discouraged in women using serotonin reuptake inhibitor anti-depressants.

Adult↗
PubMed2003

Evaluation of five different cDNA labeling methods for microarrays using spike controls.

BACKGROUND: Several different cDNA labeling methods have been developed for microarray based gene expression analysis. We have examined the accuracy and reproducibility of such five commercially available methods in detection of predetermined ratio values from target spike mRNAs (A. thaliana) in a background of total RNA. The five different labeling methods were: direct labeling (CyScribe), indirect labeling (FairPlay--aminoallyl), two protocols with dendrimer technology (3DNA Array 50 and 3DNA submicro), and hapten-antibody enzymatic labeling (Micromax TSA). Ten spike controls were mixed to give expected Cy5/Cy3 ratios in the range 0.125 to 6.0. The amounts of total RNA used in the labeling reactions ranged from 5-50 microg. RESULTS: The 3DNA array 50 and CyScribe labeling methods performed best with respect to relative deviation from the expected values (16% and 17% respectively). These two methods also displayed the best overall accuracy and reproducibility. The FairPlay method had the lowest total experimental variation (22%), but the estimated values were consistently higher than the expected values (36%). TSA had both the largest experimental variation and the largest deviation from the expected values (45% and 48% respectively). CONCLUSION: We demonstrate the usefulness of spike controls in validation and comparison of cDNA labeling methods for microarray experiments.

Arabidopsis↗
PubMed2003

Association between blood carisoprodol:meprobamate concentration ratios and CYP2C19 genotype in carisoprodol-drugged drivers: decreased metabolic capacity in heterozygous CYP2C19*1/CYP2C19*2 subjects?

Carisoprodol is metabolized to meprobamate by the cytochrome P450 enzyme CYP2C19, encoded by the polymorphic CYP2C19 gene. Most studies on carisoprodol metabolism have been carried out on individuals phenotyped for CYP2C19 activity using the probe drug S-mephenytoin. We aimed to investigate whether the ratio of carisoprodol to meprobamate in a 'real life' setting could be predicted by CYP2C19 genotype or, more specifically, if high carisoprodol : meprobamate ratios in drugged drivers could be ascribed to the presence of mutant CYP2C19 alleles. From original material comprising 358 blood samples from apprehended drivers, two polarized groups were selected; a high-ratio group of 11 subjects where the carisoprodol : meprobamate ratio was >1 and a low-ratio control group of 23 subjects where the ratio was <0.31. Genotyping was carried out for the CYP2C19*2, CYP2C19*3 and CYP2C19*4 alleles. DNA samples from 94 healthy blood donors were used as reference material. The number of mutant alleles in the high-ratio and low-ratio groups was significantly higher and lower, respectively, than in the reference material. The increased number of mutant alleles in the high-ratio group was not due to the presence of many poor metabolizers, but to a high number of heterozygous individuals with the genotype CYP2C19*1/*2. This result indicates a gene dosage effect where the carisoprodol : meprobamate ratio reflects the number of active CYP2C19 alleles. The metabolism of carisoprodol to meprobamate is dependent on CYP2C19 genotype. Heterozygous individuals with the CYP2C19*1/*2 genotype have a reduced capacity for metabolizing carisoprodol, and should probably be regarded as intermediate metabolizers of this drug.

Adult↗
PubMed2002

[Schizophrenia and molecular genetics].

BACKGROUND: Schizophrenia is a severe mental disorder with a lifetime risk in the population of 1%. Despite extensive research, the underlying neurobiological mechanisms remain largely unknown. MATERIAL AND METHODS: Based on relevant research literature, an overview of the molecular genetics of schizophrenia is given. RESULTS AND INTERPRETATION: Family, twin and adoption studies have shown that schizophrenia has a high heritability, indicating a significant genetic component to its aetiology. There is positive linkage to chromosomal regions which probably contain susceptibility genes of moderate effect. Genetic variants in different candidate genes and different chromosome abnormalities are apparently associated with increased susceptibility to schizophrenia. However, the genetic mechanisms of schizophrenia are still largely unknown. As a result of recent advancements in molecular genetic knowledge and methods, high-throughput techniques are now available in functional genomic research that will enable genome-wide search for susceptibility genes. This has to be combined with a new clinical approach where schizophrenia is characterized based on symptoms and traits that might more directly reflect fundamental processes of relevance to the disorder.

Chromosome Mapping↗
PubMed2002

Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism.

Variability among individuals in their therapeutic response to psychotropic drugs and in susceptibility to adverse effects is considerable. Pharmacogenetics addresses the contribution of genetic factors to this variability. An important focus of interest in pharmacogenetics has been on candidate genes that play a role in susceptibility to the antipsychotic drug-induced adverse effect, tardive dyskinesia (TD). Four published studies have reported an association between a serine (ser) to glycine (gly) polymorphism in exon 1 of the dopamine D3 receptor gene (DRD3) and TD; three failed to replicate this finding and one found an insignificant trend. We examined the association in a pooled sample of 780 patients (317 with TD and 463 without TD) drawn from 6 research centers, who were divided into 8 groups based on their population origin. The analysis employed stepwise logistic regression so as to allow confounding effects of group, age, and gender to be taken into account. TD was significantly associated with DRD3 gly allele carrier status (x(2)=4.46, df 1, p =.04) and with DRD3 genotype (x(2)=6.62, df 2, p =.04) over and above the effect of group. Similar positive effects were observed when controlling for age and gender (x(2)=5.02, df 1, p =.02 for gly allele carrier status; x(2) = 7.51, df 2, p =.002 for genotype). Examining abnormal involuntary movement scores as a continuous variable, we found that patients homozygous for the gly allele had significantly higher scores than ser-gly heterozygotes (p =.006) or ser-ser homozygotes (p <.0001). We also performed a meta-analysis that included, besides the groups in the combined analysis, three other published studies on DRD3 and TD. The Mantel-Haenszel pooled odds ratio for DRD3 gly allele carrier status increasing susceptibility to TD was 1.33 (95% CI 1.04-1.70, p =.02); the cumulative pooled estimate showed an odds ratio of 1.52 (95% CI 1.08-1.68, p <.0001). These findings support a small but significant contribution of the DRD3 ser9gly polymorphism to TD susceptibility that is demonstrable over and above population effects and the effect of age and gender on the phenotype.

Adult↗