Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys.

BACKGROUND: To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). METHOD: Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: 45.7% of respondents with lifetime MDD (32.0-46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8-54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9-47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ 2 1 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ 2 1 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ 2 1 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ 2 1 = 11.7, p < 0.001). CONCLUSIONS: Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6-74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.

The effects of temporally secondary co-morbid mental disorders on the associations of DSM-IV ADHD with adverse outcomes in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A).

BACKGROUND: Although DSM-IV attention deficit hyperactivity disorder (ADHD) is known to be associated with numerous adverse outcomes, uncertainties exist about how much these associations are mediated temporally by secondary co-morbid disorders. METHOD: The US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13-17 years (n = 6483 adolescent-parent pairs), assessed DSM-IV disorders with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Statistical decomposition was used to compare direct effects of ADHD with indirect effects of ADHD through temporally secondary mental disorders (anxiety, mood, disruptive behavior, substance disorders) in predicting poor educational performance (suspension, repeating a grade, below-average grades), suicidality (ideation, plans, attempts) and parent perceptions of adolescent functioning (physical and mental health, interference with role functioning and distress due to emotional problems). RESULTS: ADHD had significant gross associations with all outcomes. Direct effects of ADHD explained most (51.9-67.6%) of these associations with repeating a grade in school, perceived physical and mental health (only girls), interference with role functioning and distress, and significant components (34.5-44.6%) of the associations with school suspension and perceived mental health (only boys). Indirect effects of ADHD on educational outcomes were predominantly through disruptive behavior disorders (26.9-52.5%) whereas indirect effects on suicidality were predominantly through mood disorders (42.8-59.1%). Indirect effects on most other outcomes were through both mood (19.8-31.2%) and disruptive behavior (20.1-24.5%) disorders, with anxiety and substance disorders less consistently important. Most associations were comparable for girls and boys. CONCLUSIONS: Interventions aimed at reducing the adverse effects of ADHD might profitably target prevention or treatment of temporally secondary co-morbid disorders.

A comparative analysis of role attainment and impairment in binge-eating disorder and bulimia nervosa: results from the WHO World Mental Health Surveys.

Background. Cross-national population data from the WHO World Mental Health surveys are used to compare role attainments and role impairments associated with binge-eating disorder (BED) and bulimia nervosa (BN). Methods. Community surveys assessed 23 000 adults across 12 countries for BED, BN and ten other DSM-IV mental disorders using the WHO Composite International Diagnostic Interview. Age-of-onset was assessed retrospectively. Ten physical disorders were assessed using standard conditions checklists. Analyses examined reciprocal time-lagged associations of eating disorders (EDs) with education, associations of early-onset (i.e., prior to completing education) EDs with subsequent adult role attainments and cross-sectional associations of current EDs with days of role impairment. Results. BED and BN predicted significantly increased education (females). Student status predicted increased risk of subsequent BED and BN (females). Early-onset BED predicted reduced odds of current (at time of interview) marriage (females) and reduced odds of current employment (males). Early-onset BN predicted increased odds of current work disability (females and males). Current BED and BN were both associated with significantly increased days of role impairment (females and males). Significant BED and BN effects on adult role attainments and impairments were explained by controls for comorbid disorders. Conclusions. Effects of BED on role attainments and impairments are comparable with those of BN. The most plausible interpretation of the fact that these associations are explained by comorbid disorders is that causal effects of EDs are mediated through secondary disorders. Controlled treatment effectiveness studies are needed to trace out long-term effects of BED-BN on secondary disorders.

Mental disorders as risk factors for later substance dependence: estimates of optimal prevention and treatment benefits.

BACKGROUND: Although mental disorders have been shown to predict subsequent substance disorders, it is not known whether substance disorders could be cost-effectively prevented by large-scale interventions aimed at prior mental disorders. Although experimental intervention is the only way to resolve this uncertainty, a logically prior question is whether the associations of mental disorders with subsequent substance disorders are strong enough to justify mounting such an intervention. We investigated this question in this study using simulations to estimate the number of substance disorders that might be prevented under several hypothetical intervention scenarios focused on mental disorders. METHOD: Data came from the National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey that retrospectively assessed lifetime history and age of onset of DSM-IV mental and substance disorders. Survival analysis using retrospective age-of-onset reports was used to estimate associations of mental disorders with subsequent substance dependence. Simulations based on the models estimated effect sizes in several hypothetical intervention scenarios. RESULTS: Although successful intervention aimed at mental disorders might prevent some proportion of substance dependence, the number of cases of mental disorder that would have to be treated to prevent a single case of substance dependence is estimated to be so high that this would not be a cost-effective way to prevent substance dependence (in the range 76-177 for anxiety-mood disorders and 40-47 for externalizing disorders). CONCLUSIONS: Treatment of prior mental disorders would not be a cost-effective way to prevent substance dependence. However, prevention of substance dependence might be considered an important secondary outcome of interventions for early-onset mental disorders.

Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern.

AIMS: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours. METHODS: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. RESULTS: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. CONCLUSION: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.

First measurement of the transverse spin asymmetries of the deuteron in semi-inclusive deep inelastic scattering.

First measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarized 6LiD target are presented. The data were taken in 2002 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out to be compatible with zero, as does the measured Sivers asymmetry within the present statistical errors.

Patterns and predictors of treatment seeking after onset of a substance use disorder.

BACKGROUND: We studied survey respondents aged 18 through 54 years to determine consistent predictors of treatment seeking after onset of a DSM-III-R substance use disorder. METHODS: Survey populations included a regional sample in Ontario (n = 6261), a national sample in the United States (n = 5388), and local samples in Fresno, Calif (n = 2874) and Mexico City, Mexico (n = 1734). The analysis examined the effects of demographics, symptoms, and types of substances on treatment seeking. RESULTS: Between 50% (Ontario) and 85% (Fresno) of people with substance use disorders seek treatment but the time lag between onset and treatment seeking averages a decade or more. Consistent predictors of treatment seeking include: (1) late onset of disorder (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.6-5.6 for late [> or =30 years] vs early [1-15 years] age at first symptom of disorder); (2) recency of cohort (OR, 3.4; 95% CI, 2.3-5.0 for most recent [aged 15-24 years at interview] vs earliest [aged > or =45 years] cohorts); (3) 4 specific dependence symptoms (using larger amounts than intended, unsuccessful attempts to cut down use, tolerance, and withdrawal symptoms), with ORs ranging between 1.6 (95% CI, 1.3-2.0) and 2.7 (95% CI, 2.1-3.6) for people with vs without these symptoms; and (4) use vs nonuse of cocaine (OR, 2.1; 95% CI, 1.6-2.7) and heroin (OR, 2.6; 95% CI, 1.1-6.0). CONCLUSIONS: Although most people with substance use disorders eventually seek treatment, treatment seeking often occurs a decade or more after the onset of symptoms of disorder. While treatment seeking has increased in recent years, it is not clear whether this is because of increased access, increased demand, increased societal pressures, or other factors.

Pollen and mold exposure impairs the work performance of employees with allergic rhinitis.

BACKGROUND: Although quality of life studies suggest that allergic rhinitis has a substantial impact on work impairment, national survey estimates of the magnitude of this impairment have varied widely. Retrospective recall bias is likely to be a major cause of this variability. OBJECTIVE: This study used a nationally representative daily diary sample to obtain prospective data that improve on previous estimates of the work impairment because of allergic rhinitis. METHODS: The MacArthur Foundation National Survey of Daily Experience is a daily diary survey that included a nationally representative subsample of 739 employed people, each of whom provided daily reports on work performance for 1 randomly assigned week of the calendar year. National Allergy Bureau monitoring station data were merged with the survey data to study the association of time-space variation in pollen/mold exposure with impaired daily work quality and quantity. RESULTS: National Allergy Bureau pollen/mold counts are significantly related to work impairments only among respondents with self-reported allergic rhinitis. The average estimated monthly salary-equivalent work impairment costs associated with pollen/mold exposure for each allergy sufferer is between $109 and $156, with an annualized national projection of between $5.4 billion and $7.7 billion. CONCLUSIONS: The extent to which these costs can be recovered by increasing the proportion of allergy sufferers who are successfully treated remains unknown and can only be evaluated definitively in effectiveness trials.

Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response.

Vectors based on Semliki Forest virus (SFV) have been widely used in vitro and in vivo to express heterologous genes in animal cells. In particular, the ability of recombinant SFV (rSFV) to elicit specific, protective immune responses in animal models suggests that rSFV may be used as a vaccine vehicle. In this study, we examined the distribution of rSFV in vivo by immunohistochemistry and RT-PCR after intravenous, intramuscular and subcutaneous injection of rSFV particles and related this to the degree of cytotoxic T lymphocyte (CTL) responses and frequency of specific T cells detected by MHC-I tetramers. We found that after i.v. injection, rSFV-RNA was distributed to a variety of different tissues, whereas it was confined locally after i.m. and s.c. injections. The persistence of the rSFV vector was transient, and no viral RNA could be detected 10 days after inoculation. All tested routes of immunization generated significant levels of antigen-specific CTL responses and increased numbers of specific CD8+ T cells, as detected by tetramer binding. The distribution of antigen-specific CTLs correlated with the in vivo distribution pattern of rSFV, with a highest frequency in the spleen or local lymph node, depending on the injection route.

Comparative immunization study using RNA and DNA constructs encoding a part of the Plasmodium falciparum antigen Pf332.

Development of nucleic acid-based vaccines against parasitic diseases shows great promise, although certain concerns about safety aspects of conventional DNA vaccines have been raised. This study presents a comparison of antibody responses induced in mice by DNA and RNA-based immunization with vectors encoding a part of the P. falciparum antigen Pf332. Two types of plasmids were used, one conventional DNA plasmid containing a cytomegalovirus promoter and one suicidal DNA plasmid encoding the Semliki Forest virus (SFV) replicase. RNA, encoding the SFV replicase and the relevant antigen, was delivered either as naked RNA or packaged in SFV suicide particles. In general, the antibody responses induced by the DNA plasmids were low and peaking after three injections, the conventional plasmid giving the highest responses. Also the RNA delivered in SFV particles consistently induced antibody responses, although comparatively low. Analyses of the ratio of immunoglobulin (Ig)G1/IgG2a subclasses in the responses indicated that all plasmids resulted in a bias for a Th2-type of response, while the SFV-particles elicited a Th1 type of response. Importantly, all these immunogens induced an immunological memory, which could be efficiently activated by a booster injection with the corresponding protein, with unchanged patterns of IgG subclasses.

Controlling lipase enantioselectivity for organic synthesis.

Lipases are used frequently as chiral catalysts in the synthesis of various fine chemicals and intermediates. The increasing need of compounds with high stereochemical purity requires catalysts with an improved and controlled performance. This overview emphasizes some important aspects for the control of lipase enantioselectivity and some examples where the enantioselectivity has been altered or reversed are highlighted. However, in several of these cases the complete explanation for the altered or reversed enantioselectivity remains unclear and needs to be solved. Three different strategies (engineering of the reaction medium, the substrate molecule, and the enzyme) for exploring lipase enantioselectivity at a molecular level are discussed and summarized. These three different approaches represent powerful tools for understanding the molecular basis for lipase enantioselective catalysis and can guide the rational improvement and tailoring of catalyst performance. By combining approaches from chemistry and biology much is learnt about the most important parameters controlling lipase enantioselectivity for organic synthesis.

Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki Forest virus and boosting with modified vaccinia virus Ankara.

The immunogenicity of two vector-based vaccines, either given alone or in a prime-boost regimen, was investigated. Cynomolgus macaques were immunised with modified vaccinia virus Ankara (MVA) expressing simian immunodeficiency virus (SIV)macJ5 env, gag-pol, nef, rev, and tat genes (MVA-SIVmac) or primed with a Semliki forest virus (SFV) vaccine expressing the same genes (SFV-SIVmac) and boosted with MVA-SIVmac. Generally, antibody responses, T-cell proliferative responses and cytotoxic T-cell responses remained low or undetectable in vaccinees receiving MVA-SIVmac or SFV-SIVmac alone. In contrast, monkeys who first received SFV-SIVmac twice and then were boosted with MVA-SIVmac showed increased antibody responses as well as high T-cell proliferative responses. Three of these vaccinees had cytotoxic T-lymphocytes directed against three or four of the gene products. No evidence of protection was seen against an intrarectal heterologous SIVsm challenge given 3 months after the last immunisation. The study demonstrates a prime-boost strategy that efficiently induces both humoral and cellular immune responses.

Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus.

In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses: influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model virus diseases.

The prevalence and correlates of untreated serious mental illness.

OBJECTIVE: To identify the number of people in the United States with untreated serious mental illness (SMI) and the reasons for their lack of treatment. DATA SOURCE/STUDY DESIGN: The National Comorbidity Survey; cross-sectional, nationally representative household survey. DATA COLLECTION: An operationalization of the SMI definition set forth in the Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act identified individuals with SMI in the 12 months prior to the interview. The presence of SMI then was related to the use of mental health services in the past 12 months. PRINCIPAL FINDINGS: Of the 6.2 percent of respondents who had SMI in the year prior to interview, fewer than 40 percent received stable treatment. Young adults and those living in nonrural areas were more likely to have unmet needs for treatment. The majority of those who received no treatment felt that they did not have an emotional problem requiring treatment. Among those who did recognize this need, 52 percent reported situational barriers, 46 percent reported financial barriers, and 45 percent reported perceived lack of effectiveness as reasons for not seeking treatment. The most commonly reported reason both for failing to seek treatment (72 percent) and for treatment dropout (58 percent) was wanting to solve the problem on their own. CONCLUSIONS: Although changes in the financing of services are important, they are unlikely by themselves to eradicate unmet need for treatment of SMI. Efforts to increase both self-recognition of need for treatment and the patient centeredness of care also are needed.

A vaccine strategy utilizing a combination of three different chimeric vectors which share specific vaccine antigens.

A large number of recombinant of viral and bacterial systems have been engineered as vectors to express foreign genes for vaccination and/or gene therapy. A common problem is the immune response to the vector itself. The presence of anti-vector immune responses may preclude sufficient 'priming' or immunogenicity if pre-existing immune responses are present, or they may impair optimal 'boosting' upon repeated immunization or delivery with the same vector. To circumvent this problem we developed a strategy using different chimeric vectors which share only the expression of common specific antigens desired for immunization. This approach not only has the advantage of avoiding increased anti-vector responses, but allows the use of combinations of vectors which could subsequently present the same or related antigen differently to the immune system as well as at alternative sites to induce the optimal type of immunity against the pathogen of interest.

Emergence of CD8+ T cells expressing NK cell receptors in influenza A virus-infected mice.

Both innate and adaptive immune responses play an important role in the recovery of the host from viral infections. In the present report, a subset of cells coexpressing CD8 and NKR-P1C (NK1.1) was found in the lungs of mice infected with influenza A virus. These cells were detected at low numbers in the lungs of uninfected mice, but represented up to 10% of the total CD8(+) T cell population at day 10 postinfection. Almost all of the CD8(+)NK1.1(+) cells were CD8alphabeta(+)CD3(+)TCRalphabeta(+) and a proportion of these cells also expressed the NK cell-associated Ly49 receptors. Interestingly, up to 30% of these cells were virus-specific T cells as determined by MHC class I tetramer staining and by intracellular staining of IFN-gamma after viral peptide stimulation. Moreover, these cells were distinct from conventional NKT cells as they were also found at increased numbers in influenza-infected CD1(-/-) mice. These results demonstrate that a significant proportion of CD8(+) T cells acquire NK1.1 and other NK cell-associated molecules, and suggests that these receptors may possibly regulate CD8(+) T cell effector functions during viral infection.

Recent care of common mental disorders in the United States : prevalence and conformance with evidence-based recommendations.

OBJECTIVE: To relate the presence of recent mental disorders to use of mental health services. DESIGN: Cross-sectional survey. STUDY POPULATION: The study population was 3,032 respondents to the Midlife Development in the United States (MIDUS) survey, a nationally representative telephone-and-mail survey conducted in 1996. Twelve-month diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised, Third Edition, of major depressive episode, panic disorder, generalized anxiety disorder, and serious mental illness were made using a structured assessment. Information was obtained on 12-month treatment for mental health problems in the general medical, mental health specialty, human services, and self-help sectors. Definitions of treatments consistent with evidence-based recommendations were developed using available practice guidelines. MEASUREMENTS AND MAIN RESULTS: Crude and adjusted likelihoods of receiving any mental health care and guideline-concordant care were measured. Although 53. 8% of respondents with at least one 12-month mental disorder received any mental health care in the previous year, only 14.3% received care that could be considered consistent with evidence-based treatment recommendations. Even among those with the most serious and impairing mental illness, only 25% received guideline-concordant treatment. Predictors of receiving guideline-concordant care included being white, female, severely ill, and having mental health insurance coverage. CONCLUSIONS: An epidemic of untreated and poorly treated mental disorders exists in the United States, especially among vulnerable groups such as African Americans and the underinsured. Cost-effective interventions are needed to improve both access to and quality of treatment.

An anti-HIV strategy combining chemotherapy and therapeutic vaccination.

Combination chemotherapy using potent anti-retroviral agents has led to significant advances in the clinical management of human immunodeficiency virus (HIV) disease. However, the emergence of multiple drug-resistant mutants, the high need for compliance to adhere to demanding drug-dosing schemes, and the remaining toxic side-effects of drugs make the perspective of life-long treatment unattractive and possibly unrealistic. Therefore, means must be sought to shorten the time span during which treatment is necessary. Such means could be to stimulate an efficient immune response during the period of low virus load and restored CD4 + cell levels, which might be capable of keeping the virus under long-lasting control after treatment is stopped. Here we tested this concept of combined chemotherapy/ therapeutic vaccination in a non-human primate model. Rhesus macaques chronically infected with the chimeric simian/human immunodeficiency virus (SHIV) containing the HIV type 1 (HIV-1) HXBc2 gene for reverse transcriptase (RT) in the genomic background of simian immunodeficiency virus (SIV)(mac239) (RT-SHIV) were treated with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a potent anti-HIV drug. When virus load had decreased significantly, we immunized with SIV genes env, gag/pol, rev, tat, and nef inserted in two different expression vector systems. Four weeks after the second immunization, drug treatment was stopped. Animals were monitored to determine if virus load stayed low or if it increased again to the original levels and if CD4+ T-cell levels remained stable. Humoral and cellular immune responses were also measured. This combined chemotherapy/ therapeutic vaccination regimen induced a significant reduction in the steady-state level of viremia in one out of two chronically infected rhesus macaques. Chemotherapeutic treatment alone did not achieve reduction of viremia in two chronically infected animals. The nature of the immune responses assumed to have been induced by vaccination in one out of the two monkeys remains to be elucidated.

Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys.

OBJECTIVE: Generalized anxiety disorder might be better conceptualized as a prodrome, residual, or severity marker of major depression or other comorbid disorders than as an independent diagnosis. The authors questioned whether generalized anxiety disorder itself is associated with role impairment or whether the impairment of patients with generalized anxiety disorder is due to depression or other comorbid disorders. METHOD: The authors assessed data from the National Comorbidity Survey and the Midlife Development in the United States Survey for generalized anxiety disorder and major depression at 12 months by using the DSM-III-R criteria with modified versions of the Composite International Diagnostic Interview. RESULTS: The prevalences of generalized anxiety disorder at 12 months were 3.1% and 3.3%, respectively, in the National Comorbidity Survey and the Midlife Development in the United States Survey; the prevalences of major depression at 12 months were 10.3% and 14.1%. The majority of respondents with generalized anxiety disorder at 12 months in the National Comorbidity Survey (58.1%) and the Midlife Development in the United States Survey (69.7%) also met the criteria for major depression at 12 months. Comparisons of respondents with one versus neither disorder showed that both disorders had statistically significant independent associations with impairment that were roughly equal in magnitude. These associations could not be explained by the other comorbid DSM-III-R disorders or by sociodemographic variables. CONCLUSIONS: These results show that a substantial amount of generalized anxiety disorder occurs independently of major depression and that the role impairment of generalized anxiety disorder is comparable to that of major depression.

Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice.

The replicon of Semliki Forest virus (SFV) offers the possibility to direct high-level, transient expression of heterologous proteins in vivo. We initiated studies to determine the possibility of employing the SFV expression system for recombinant vaccine purposes. Mice immunized with recombinant SFV encoding Influenza A nucleoprotein (NP) or E. coli LacZ developed long-lasting antigen-specific IgG levels and induction of cytotoxic T-cell (CTL) memory that persisted for over one year. Predominantly type 1 T-helper cells were induced as shown by IgG subclass ELISA. Humoral and cell-mediated immune responses could be induced upon delivery by several administration routes and mucosal immunizations induced secretory IgA in the respiratory tract. Development of immune responses against the vector itself did not inhibit boost responses by subsequent immunizations with recombinant SFV. Immunization of mice with vectors encoding the Influenza A virus antigens nucleoprotein (NP) and hemagglutinin (HA) resulted in immune responses that were protective against challenge infection with Influenza virus.