Comparative assessment of Vibrio virulence in marine fish larvae.

Vibrionaceae infections are a major obstacle for marine larviculture; however, little is known about virulence differences of Vibrio strains. The virulence of Vibrio strains, mostly isolated from vibriosis outbreaks in farmed fish, was tested in larval challenge trials with cod (Gadus morhua), turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus) using a multiwell dish assays with single-egg/larvae cultures. The strains differed significantly in virulence as some caused a high mortality of larva reaching 100% mortality after a few days, while others had no or only marginal effects on survival. Some Vibrio strains were pathogenic in all of the larva species, while some caused disease only in one of the species. Twenty-nine of the Vibrio anguillarum strains increased the mortality of larvae from at least one fish species; however, pathogenicity of the strains differed markedly. Other Vibrio species had no or less pronounced effects on larval mortalities. Iron uptake has been related to V. anguillarum virulence; however, the presence or absence of the plasmid pJM1 encoding anguibactin did not correlate with virulence. The genomes of V. anguillarum were compared (D. Castillo, P.W. D'Alvise, M. Middelboe & L. Gram, unpublished data) and most of the high-virulent strains had acquired virulence genes from other pathogenic Vibrio.

Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7).

INTRODUCTION: Electroconvulsive treatment (ECT) is an effective treatment for severe depression but carries a risk of relapse in the following months. METHODS: Major depressive disorder patients in a current episode attaining remission from ECT (17-item Hamilton Depression Rating Scale (HAM-D17) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during the study period, and one third completed. DISCUSSION: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier: NCT00660062.

Biofilm formation is not a prerequisite for production of the antibacterial compound tropodithietic acid in Phaeobacter inhibens DSM17395.

AIMS: The goal of this study was to investigate if biofilm formation on population level is a physiological requirement for antagonism in Phaeobacter inhibens DSM17395, since the antibiotic compound tropodithietic acid (TDA) is produced by several Roseobacter clade species during growth as multicellular aggregates or biofilms at the air-liquid interface and is induced on single cell level upon attachment. METHODS AND RESULTS: A mutant library was created by Tn5 transposon insertion and 22 TDA-positive (brown) mutants with decreased biofilm formation or adhesion, and eight TDA-negative (white) mutants with increased biofilm formation or adhesion were selected. None of the selected biofilm-overproducing white mutants showed any antibiotic activity, while all brown mutants with reduced or disabled biofilm formation produced the antibacterial compound. Sequencing analysis indicated that genes that are likely involved in EPS/LPS production, motility and chemotaxis, and redox regulation play a role in biofilm formation and/or adhesion in P. inhibens DSM17395. CONCLUSIONS: Cell aggregation and biofilm formation are not physiological prerequisites for TDA production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to the understanding of TDA production in P. inhibens, which has great potential as a probiotic in marine larviculture.

Disruption of cell-to-cell signaling does not abolish the antagonism of Phaeobacter gallaeciensis toward the fish pathogen Vibrio anguillarum in algal systems.

Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobacter and QS inhibitors is a feasible strategy for aquaculture disease control.

Physicochemical characterization of fish protein adlayers with bacteria repelling properties.

Materials coated with aqueous fish protein extracts can reduce bacterial adhesion, but the mechanism behind the observed effect is not fully understood. In this study we explore the physicochemical properties of fish muscle protein adlayers on four substrates: gold, stainless steel, polystyrene and silicon dioxide. The aims were (i) to determine if the anti-adhesive effect is independent of the underlying substrate chemistry, (ii) to link the physicochemical properties of the adlayer to its ability to repel bacteria, and (iii) to elucidate the mechanism behind this effect. The main proteins on all surfaces were the muscle proteins troponin, tropomyosin, and myosin, and the lipid binding protein apolipoprotein. The quantity, viscoelasticity, and hydration of the protein adlayers varied greatly on the different substrates, but this variation did not affect the bacterial repelling properties. Our results imply that these proteins adsorb to all substrates and provide a steric barrier towards bacterial adhesion, potentially providing a universal antifouling solution.

Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco-2 cell invasion.

AIMS: Antibiotics can act as signal molecules and affect bacterial gene expression, physiology and virulence. The purpose of this study was to determine whether subinhibitory antibiotic concentrations alter gene expression and physiology of Listeria monocytogenes. METHODS AND RESULTS: Using an agar-based screening assay with promoter fusions, 14 of 16 antibiotics induced or repressed expression of one or more stress and/or virulence genes. Despite ampicillin-induced up-regulation of PinlA-lacZ expression, Caco-2 cell invasion was not affected. Subinhibitory concentrations of ampicillin and tetracycline caused up- and down-regulation of stress response genes, respectively, but both antibiotics caused increased sensitivity to acid stress. Six combinations of gene-antibiotic were quantified in broth cultures and five of the six resulted in the same expression pattern as the agar-based assay. CONCLUSIONS: Antibiotics affect virulence and/or stress gene expression; however, altered expression could not predict changes in phenotypic behaviour. Subinhibitory concentrations of antibiotics led to increased acid sensitivity, and we speculate that this is attributed to changes in cell envelope or reduced σ(B) -dependent gene expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Although subinhibitory concentrations of antibiotics affect gene expression in L. monocytogenes, the changes did not increase virulence but did enhance the acid sensitivity.

The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine.

OBJECTIVE: To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). METHODS: In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. RESULTS: PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. LIMITATIONS: The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. CONCLUSIONS: It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients.

Listeria monocytogenes survival of UV-C radiation is enhanced by presence of sodium chloride, organic food material and by bacterial biofilm formation.

The bactericidal effect on food processing surfaces of ceiling-mounted UV-C light (wavelength 254 nm) was determined in a fish smoke house after the routine cleaning and disinfection procedure. The total aerobic counts were reduced during UV-C light exposure (48 h) and the number of Listeria monocytogenes positive samples went from 30 (of 68) before exposure to 8 (of 68). We therefore in a laboratory model determined the L. monocytogenes reduction kinetics by UV-C light with the purpose of evaluating the influence of food production environmental variables, such as presence of NaCl, organic material and the time L. monocytogenes was allowed to adhere to steel before exposure. L. monocytogenes grown and attached in tryptone soy broth (TSB) with glucose were rapidly killed (after 2 min) by UV-C light. However, bacteria grown and adhered in TSB with glucose and 5% NaCl were more resistant and numbers declined with 4-5 log units during exposure of 8-10 min. Bacteria grown in juice prepared from cold-smoked salmon were protected and numbers were reduced with 2-3 log when UV-C light was used immediately after attachment whereas numbers did not change at all if bacteria had been allowed to form a biofilm for 7 days before exposure. It is not known if this enhanced survival is due to physiological changes in the attached bacterial cells, a physical protection of the cells in the food matrix or a combination. In conclusion, we demonstrate that UV-C light is a useful extra bacteriocidal step and that it, as all disinfecting procedures, is hampered by the presence of organic material.

Adhesion of food-borne bacteria to stainless steel is reduced by food conditioning films.

AIMS: Preconditioning of stainless steel with aqueous cod muscle extract significantly impedes subsequent bacterial adhesion most likely due to repelling effects of fish tropomyosin. The purpose of this study was to determine if other food conditioning films decrease or enhance bacterial adhesion to stainless steel. METHODS AND RESULTS: Attachment of Pseudomonas fluorescens AH2 to stainless steel coated with water-soluble coatings of animal origin was significantly reduced as compared with noncoated stainless steel or stainless steel coated with laboratory substrate or extracts of plant origin. Coating with animal extracts also decreases adhesion of other food-relevant bacteria. The manipulation of adhesion was not attributable to growth inhibitory effects. Chemical analysis revealed that the stainless steels were covered by homogenous layers of adsorbed proteins. The presence of tropomyocin was indicated by appearance of proteins with similar molecular weight based in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in several extracts that reduced adhesion but also extracts not containing this protein reduced bacterial adhesion, indicating that several molecular species may be involved in the phenomenon. CONCLUSIONS: It is a common perception that food materials facilitate bacterial adhesion to surfaces; however, this study demonstrates that aqueous coatings of food origin may actually reduce bacterial adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Compounds from food extracts may potentially be used as nontoxic coatings to reduce bacterial attachment to inert surfaces.

Real-time PCR detection and quantification of fish probiotic Phaeobacter strain 27-4 and fish pathogenic Vibrio in microalgae, rotifer, Artemia and first feeding turbot (Psetta maxima) larvae.

AIMS: To develop a SYBR Green quantitative real-time PCR protocol enabling detection and quantification of a fish probiotic and two turbot pathogenic Vibrio spp. in microcosms. METHODS AND RESULTS: Phaeobacter 27-4, Vibrio anguillarum 90-11-287 and Vibrio splendidus DMC-1 were quantified as pure and mixed cultures and in presence of microalgae (Isochrysis galbana), rotifers (Brachionus plicatilis), Artemia nauplii or turbot (Psetta maxima) larvae by real-time PCR based on primers directed at genetic loci coding for antagonistic and virulence-related functions respectively. The optimized protocol was used to study bioencapsulation and maintenance of the probiont and pathogens in rotifers and for the detection and quantification of Phaeobacter and V. anguillarum in turbot larvae fed rotifers loaded with the different bacteria in a challenge trial. CONCLUSIONS: Our real-time PCR protocol is reproducible and specific. The method requires separate standard curve for each host organism and can be used to detect and quantify probiotic Phaeobacter and pathogenic Vibrio bioencapsulated in rotifers and in turbot larvae. SIGNIFICANCE AND IMPACT OF THE STUDY: Our method allows monitoring and quantification of a turbot larvae probiotic bacteria and turbot pathogenic vibrios in in vivo trials and will be useful tools for detecting the bacteria in industrial rearing units.

Model systems allowing quantification of sensitivity to disinfectants and comparison of disinfectant susceptibility of persistent and presumed nonpersistent Listeria monocytogenes.

AIMS: To determine if Listeria monocytogenes persistent strains differ from presumed nonpersistent strains in disinfection susceptibility and to examine the influence of attachment and NaCl on susceptibility. METHODS AND RESULTS: Two model-systems that allowed quantitative inter-strain comparison of disinfectant sensitivity were developed. Persistent L. monocytogenes were not more tolerant to the disinfectants Incimaxx DES and Triquart SUPER than presumed nonpersistent isolates. When calibrating the systems with respect to presence of biological material and cell density, attached bacteria were as sensitive to disinfectants as were planktonic bacteria. Growth with 5% NaCl increased the tolerance of planktonic cells to Incimaxx DES. All strains of spot inoculated L. monocytogenes survived well 20 h of drying when protected by growth media and 5% NaCl, but were not protected by NaCl against disinfection. CONCLUSIONS: Persistent strains of L. monocytogenes are as susceptible to disinfectants as are presumed nonpersistent strains and attachment does not render the strains more tolerant to disinfectants. Growth with NaCl affected the susceptibility of the planktonic L. monocytogenes to Incimaxx DES and protected spot inoculated cells during drying. SIGNIFICANCE AND IMPACT OF THE STUDY: Attachment to surfaces does not per se offer protection to L. monocytogenes against disinfectants and disinfection tolerances do not appear to influence the ability of a strain to persist.

Acute and continuation therapy in unipolar depression: observations from the run-in phase of a maintenance trial.

OBJECTIVE: The aim of the study was to analyze treatments and outcome in depressed patients. METHOD: Patients with recurrent depressive disorder (n = 289), recruited for a prophylaxis study, were followed up in hospital settings for 6 months with diagnostic and depression ratings at baseline and monthly depression ratings. Data on psychotropic drugs were retrieved from hospital case records. Independent associations between baseline, treatment and outcome variables were examined by logistic regression models. RESULTS: Depressive symptoms subsided gradually. After 6 months, 21% had dropped out, 43% were rated as remitted (HAM-D-17 <8) and 8% had not responded (HAM-D-17 >15). Patients once remitted rarely relapsed (<5%). All patients received antidepressant drugs, half of them more than one (2-4) as well as other psychotropic drugs. Patients responding poorly received more frequently multiple antidepressants, tricyclic antidepressants, hypnosedatives, lithium and/or antipsychotics. CONCLUSION: The 6-month outcome was generally poor. Choice of treatment appeared at least partly to be determined by the therapeutic outcome.

Anti-adhesive properties of fish tropomyosins.

AIMS: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. METHODS AND RESULTS: The anti-adhesive activity was assayed against Escherchia coli K-12, and bacterial adhesion was quantified by crystal violet staining and sonication methods. Proteolytic digestion, elution and fractionation experiments revealed that the anti-adhesive activity of the extract was linked to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein adsorption profiles obtained from the various materials did not differ significantly, but elution was often incomplete making minor qualitative/quantitative differences indiscernible. CONCLUSIONS: The data highlights the significance of protein conditioning films on bacterial adhesion and emphasizes the importance of substratum's physiochemical properties and exposure time with regards to protein adsorption/elution efficiency and subsequent bacterial adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Fish tropomyosin-coatings could potentially offer a nontoxic and relatively inexpensive measure of reducing bacterial colonization of inert surfaces.

Well-known quorum sensing inhibitors do not affect bacterial quorum sensing-regulated bean sprout spoilage.

AIM: To investigate the potential of quorum sensing inhibitors (QSI) as food preservative agents in a food product, where bacterial spoilage is controlled by quorum sensing (QS). METHODS AND RESULTS: The effects of well-known QSI were tested on spoilage phenotypes and on QS-regulated genes of a bean sprout spoiling bacterial isolate (Pectobacterium A2JM) in laboratory substrates and in a bean sprout model system. The acylated homoserine lactones (AHL) analogues PenS-AHL and HepS-AHL decreased the specific protease activity of Pectobacterium A2JM in broth but did not reduce the expression of a QS-regulated secretion protein, and were without effect on soft rot of bean sprouts. The QSI ProS-AHL, furanone C-30, patulin, penicillic acid and 4-nitropyridine-N-oxide did not have any effect on protease activity, on gene expression or bean sprout appearance at nongrowth inhibitory concentrations. Extracts from garlic and bean sprouts induced the QS system of Pectobacterium in bean sprouts and a broth system, respectively. CONCLUSIONS: Among the several well-known QSI compounds, only PenS-AHL and HepS-AHL, inhibited QS-regulated protease activity of Pectobacterium A2JM in broth cultures, but had no effect on bean sprout spoilage. SIGNIFICANCE AND IMPACT OF THE STUDY: The QSI compounds must be selected in the specific system in which they are to function and they cannot easily be transferred from one QS system to another.

Profiling acylated homoserine lactones in Yersinia ruckeri and influence of exogenous acyl homoserine lactones and known quorum-sensing inhibitors on protease production.

AIMS: To profile the quorum-sensing (QS) signals in Yersinia ruckeri and to examine the possible regulatory link between QS signals and a typical QS-regulated virulence phenotype, a protease. METHODS AND RESULTS: Liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) showed that Y. ruckeri produced at least eight different acylated homoserine lactones (AHLs) with N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL) being the dominant molecule. Also, some uncommon AHL, N-(3-oxoheptanoyl)-L-homoserine lactone (3-oxo-C7-HSL) and N-(3-oxononanoyl)-L-homoserine lactone (3-oxo-C9-HSL), were produced. 3-oxo-C8-HSL was detected in organs from fish infected with Y. ruckeri. Protease production was significantly lower at temperatures above 23 degrees C than below although growth was faster at the higher temperatures. Neither addition of sterile filtered high-density Y. ruckeri culture supernatant nor the addition of pure exogenous AHLs induced protease production. Furthermore, three QS inhibitors (QSIs), sulfur-containing AHL analogues, did not inhibit protease production in Y. ruckeri. CONCLUSIONS: Exogenous AHL or sulfur-containing AHL analogues did not influence the protease production indicating that protease production may not be QS regulated in Y. ruckeri. SIGNIFICANCE AND IMPACT OF THE STUDY: The array of different AHLs produced indicates that the QS system of Y. ruckeri is complex and could involve several regulatory systems. In this case, neither AHLs nor QSI would be likely to directly affect a QS-regulated phenotype.

Nonbioluminescent strains of Photobacterium phosphoreum produce the cell-to-cell communication signal N-(3-Hydroxyoctanoyl)homoserine lactone.

Bioluminescence is a common phenotype in marine bacteria, such as Vibrio and Photobacterium species, and can be quorum regulated by N-acylated homoserine lactones (AHLs). We extracted a molecule that induced a bacterial AHL monitor (Agrobacterium tumefaciens NT1 [pZLR4]) from packed cod fillets, which spoil due to growth of Photobacterium phosphoreum. Interestingly, AHLs were produced by 13 nonbioluminescent strains of P. phosphoreum isolated from the product. Of 177 strains of P. phosphoreum (including 18 isolates from this study), none of 74 bioluminescent strains elicited a reaction in the AHL monitor, whereas 48 of 103 nonbioluminescent strains did produce AHLs. AHLs were also detected in Aeromonas spp., but not in Shewanella strains. Thin-layer chromatographic profiles of cod extracts and P. phosphoreum culture supernatants identified a molecule similar in relative mobility (Rf value) and shape to N-(3-hydroxyoctanoyl)homoserine lactone, and the presence of this molecule in culture supernatants from a nonbioluminescent strain of P. phosphoreum was confirmed by high-performance liquid chromatography-positive electrospray high-resolution mass spectrometry. Bioluminescence (in a non-AHL-producing strain of P. phosphoreum) was strongly up-regulated during growth, whereas AHL production in a nonbioluminescent strain of P. phosphoreum appeared constitutive. AHLs apparently did not influence bioluminescence, as the addition of neither synthetic AHLs nor supernatants delayed or reduced this phenotype in luminescent strains of P. phosphoreum. The phenotypes of nonbioluminescent P. phosphoreum strains regulated by AHLs remains to be elucidated.

Effect of environmental and physiological factors on the antibacterial activity of Curvularia haloperoxidase system against Escherichia coli.

AIMS: The aim of this study was to investigate the influence of environmental and physiological factors on the susceptibility of Escherichia coli to the Curvularia haloperoxidase system. METHODS AND RESULTS: The Curvularia haloperoxidase system is a novel enzyme system that produces reactive oxygen species which have an antimicrobial effect. Escherichia coli MG1655 was exposed to the Curvularia haloperoxidase system under different temperatures and NaCl concentrations and after exposure to different stress factors. Temperature clearly affected enzymatic activity with increasing antibacterial effect at increasing temperature. The presence of NaCl interfered with the enzyme system and in the presence of 1% NaCl, no antibacterial effect could be observed at pH 7. Cells grown at pH 8.0 were in one experiment more resistant than cells grown at pH 6.5, whereas cells grown in the presence of 2% NaCl were more susceptible to the Curvularia haloperoxidase system. CONCLUSIONS: Environmental and physiological factors can affect the antibacterial activity of the Curvularia haloperoxidase system. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates a systematic approach in assessing the effect of environmental and physiological factors on microbial susceptibility to biocides. Such information is crucial for prediction of application as well as potential side-effects.

Growth inhibition of Listeria monocytogenes by a nonbacteriocinogenic Carnobacterium piscicola.

AIMS: This study elucidates the mechanisms by which a nonbacteriocinogenic Carnobacterium piscicola inhibits growth of Listeria monocytogenes. METHODS AND RESULTS: Listeria monocytogenes was exposed to live cultures of a bacteriocin-negative variant of C. piscicola A9b in co-culture, in a diffusion chamber system, and to a cell-free supernatant. Suppression of maximum cell density (0-3.5 log units) of L. monocytogenes was proportional to initial levels of C. pisciola (10(3)-10(7) CFU ml(-1)). Cell-to-cell contact was not required to cause inhibition. The cell-free C. piscicola supernatant caused a decrease in L. monocytogenes maximum cell density, which was abolished by glucose addition but not by amino acid, vitamin or mineral addition. The fermentate also gave rise to a longer lag phase and a reduction in growth rate. These effects were independent of glucose and may have been caused by acetate production by C. piscicola. 2D gel-electrophoretic patterns of L. monocytogenes exposed to C. piscicola or to L. monocytogenes fermentate did not differ. Treatment with C. piscicola fermentate resulted in down-regulation (twofold) of genes involved in purine- or pyrimidine metabolism, and up-regulation (twofold) of genes from the regulon for vitamin B12 biosynthesis and propanediol and ethanolamine utilization. CONCLUSIONS: A nonbacteriocinogenic C. piscicola reduced growth of L. monocytogenes partly by glucose depletion. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanism of microbial interaction enhances prediction of growth in mixed communities as well as use of bioprotective principles for food preservation.

Socio-economic inequalities in first-time use of antidepressants: a population-based study.

OBJECTIVE: To analyse whether first-time use of antidepressants (incidence) and selection of TCAs (tricyclic antidepressants) versus new-generation drugs are associated with socio-economic status and psychiatric history. METHOD: We conducted a population-based cohort study using registry data covering Funen County, Denmark. A total of 305,953 adult residents without antidepressant prescriptions 5 years prior to the study period (1998) were included. RESULTS: The 1-year incidence rate of antidepressant prescription (1.7%) increased with age. It was higher in people who were female, less educated, unemployed, those receiving old-age or disability pension, low-income groups, and singles. The proportion prescribed new-generation antidepressants (82%) showed no difference according to socio-economic variables (education, annual income and socio-economic group), but was higher among the young and single. Admission to psychiatric hospital within 4 years prior to the study period was associated with high-incidence rate of antidepressant prescription and overall a preference for the new-generation antidepressants. CONCLUSION: Socio-economic status did not seem to influence the selection of TCAs versus new-generation antidepressants. Compatible with the general epidemiology of depression, low socio-economic status was associated with a high number of first-time users of antidepressants in the population, and the incidence rate increased with age.