Leaf proteome alterations in the context of physiological and morphological responses to drought and heat stress in barley (Hordeum vulgare L.).

The objective of this study was to identify barley leaf proteins differentially regulated in response to drought and heat and the combined stresses in context of the morphological and physiological changes that also occur. The Syrian landrace Arta and the Australian cultivar Keel were subjected to drought, high temperature, or a combination of both treatments starting at heading. Changes in the leaf proteome were identified using differential gel electrophoresis and mass spectrometry. The drought treatment caused strong reductions of biomass and yield, while photosynthetic performance and the proteome were not significantly changed. In contrast, the heat treatment and the combination of heat and drought reduced photosynthetic performance and caused changes of the leaf proteome. The proteomic analysis identified 99 protein spots differentially regulated in response to heat treatment, 14 of which were regulated in a genotype-specific manner. Differentially regulated proteins predominantly had functions in photosynthesis, but also in detoxification, energy metabolism, and protein biosynthesis. The analysis indicated that de novo protein biosynthesis, protein quality control mediated by chaperones and proteases, and the use of alternative energy resources, i.e. glycolysis, play important roles in adaptation to heat stress. In addition, genetic variation identified in the proteome, in plant growth and photosynthetic performance in response to drought and heat represent stress adaption mechanisms to be exploited in future crop breeding efforts.

Variation at the vernalisation genes Vrn-H1 and Vrn-H2 determines growth and yield stability in barley (Hordeum vulgare) grown under dryland conditions in Syria.

KEY MESSAGE: Spring growth in barley controlled by natural variation at Vrn-H1 and Vrn-H2 improved yield stability in marginal Syrian environments. The objective of the present study was to identify QTL influencing agronomic performance in rain-fed Mediterranean environments in a recombinant inbred line (RIL) population, ARKE derived from the Syrian barley landrace, Arta and the Australian feed cultivar, Keel. The population was field tested for agronomic performance at two locations in Syria for 4 years with two sowing dates, in autumn and winter. Genotypic variability in yield of the RIL population was mainly affected by year-to-year variation presumably caused by inter-annual differences in rainfall distribution. The spring growth habit and early flowering inherited from the Australian cultivar Keel increased plant height and biomass and improved yield stability in Syrian environments. QTL for yield and biomass coincided with the map location of flowering time genes, in particular the vernalisation genes Vrn-H1 and Vrn-H2. In marginal environments with terminal drought, the Vrn-H1 allele inherited from Keel improved final biomass and yield. Under changing climate conditions, such as shorter winters, reduced rainfall, and early summer drought, spring barley might thus outperform the traditional vernalisation-sensitive Syrian landraces. We present the ARKE population as a valuable genetic resource to further elucidate the genetics of drought adaptation of barley in the field.

Advanced backcross-QTL analysis in spring barley (H. vulgare ssp. spontaneum) comparing a REML versus a Bayesian model in multi-environmental field trials.

A common difficulty in mapping quantitative trait loci (QTLs) is that QTL effects may show environment specificity and thus differ across environments. Furthermore, quantitative traits are likely to be influenced by multiple QTLs or genes having different effect sizes. There is currently a need for efficient mapping strategies to account for both multiple QTLs and marker-by-environment interactions. Thus, the objective of our study was to develop a Bayesian multi-locus multi-environmental method of QTL analysis. This strategy is compared to (1) Bayesian multi-locus mapping, where each environment is analysed separately, (2) Restricted Maximum Likelihood (REML) single-locus method using a mixed hierarchical model, and (3) REML forward selection applying a mixed hierarchical model. For this study, we used data on multi-environmental field trials of 301 BC(2)DH lines derived from a cross between the spring barley elite cultivar Scarlett and the wild donor ISR42-8 from Israel. The lines were genotyped by 98 SSR markers and measured for the agronomic traits "ears per m(2)," "days until heading," "plant height," "thousand grain weight," and "grain yield". Additionally, a simulation study was performed to verify the QTL results obtained in the spring barley population. In general, the results of Bayesian QTL mapping are in accordance with REML methods. In this study, Bayesian multi-locus multi-environmental analysis is a valuable method that is particularly suitable if lines are cultivated in multi-environmental field trials.

Obesity and mental disorders in the general population: results from the world mental health surveys.

OBJECTIVES: (1) To investigate whether there is an association between obesity and mental disorders in the general populations of diverse countries, and (2) to establish whether demographic variables (sex, age, education) moderate any associations observed. DESIGN: Thirteen cross-sectional, general population surveys conducted as part of the World Mental Health Surveys initiative. SUBJECTS: Household residing adults, 18 years and over (n=62 277). MEASUREMENTS: DSM-IV mental disorders (anxiety disorders, depressive disorders, alcohol use disorders) were assessed with the Composite International Diagnostic Interview (CIDI 3.0), a fully structured diagnostic interview. Obesity was defined as a body mass index (BMI) of 30 kg/m(2) or greater; severe obesity as BMI 35+. Persons with BMI less than 18.5 were excluded from analysis. Height and weight were self-reported. RESULTS: Statistically significant, albeit modest associations (odds ratios generally in the range of 1.2-1.5) were observed between obesity and depressive disorders, and between obesity and anxiety disorders, in pooled data across countries. These associations were concentrated among those with severe obesity, and among females. Age and education had variable effects across depressive and anxiety disorders. CONCLUSIONS: The findings are suggestive of a modest relationship between obesity (particularly severe obesity) and emotional disorders among women in the general population. The study is limited by the self-report of BMI and cannot clarify the direction or nature of the relationship observed, but it may indicate a need for a research and clinical focus on the psychological heterogeneity of the obese population.

Association of perceived stigma and mood and anxiety disorders: results from the World Mental Health Surveys.

OBJECTIVE: We assessed the prevalence of perceived stigma among persons with mental disorders and chronic physical conditions in an international study. METHOD: Perceived stigma (reporting health-related embarrassment and discrimination) was assessed among adults reporting significant disability. Mental disorders were assessed with Composite International Diagnostic Interview (CIDI) 3.0. Chronic conditions were ascertained by self-report. Household-residing adults (80,737) participated in 17 population surveys in 16 countries. RESULTS: Perceived stigma was present in 13.5% (22.1% in developing and 11.7% in developed countries). Suffering from a depressive or an anxiety disorder (vs. no mental disorder) was associated with about a twofold increase in the likelihood of stigma, while comorbid depression and anxiety was even more strongly associated (OR 3.4, 95%CI 2.7-4.2). Chronic physical conditions showed a much lower association. CONCLUSION: Perceived stigma is frequent and strongly associated with mental disorders worldwide. Efforts to alleviate stigma among individuals with comorbid depression and anxiety are needed.

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).

Depression-anxiety relationships with chronic physical conditions: results from the World Mental Health Surveys.

BACKGROUND: Prior research on the association between affective disorders and physical conditions has been carried out in developed countries, usually in clinical populations, on a limited range of mental disorders and physical conditions, and has seldom taken into account the comorbidity between depressive and anxiety disorders. METHODS: Eighteen general population surveys were carried out among adults in 17 countries as part of the World Mental Health Surveys initiative (N=42, 249). DSM-IV depressive and anxiety disorders were assessed using face-to-face interviews with the Composite International Diagnostic Interview (CIDI 3.0). Chronic physical conditions were ascertained via a standard checklist. The relationship between mental disorders and physical conditions was assessed by considering depressive and anxiety disorders independently (depression without anxiety; anxiety without depression) and conjointly (depression plus anxiety). RESULTS: All physical conditions were significantly associated with depressive and/or anxiety disorders but there was variation in the strength of association (ORs 1.2-4.5). Non-comorbid depressive and anxiety disorders were associated in equal degree with physical conditions. Comorbid depressive-anxiety disorder was more strongly associated with several physical conditions than were single mental disorders. LIMITATIONS: Physical conditions were ascertained via self report, though for a number of conditions this was self-report of diagnosis by a physician. CONCLUSIONS: Given the prevalence and clinical consequences of the co-occurrence of mental and physical disorders, attention to their comorbidity should remain a clinical and research priority.

Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.

BACKGROUND: Studies suggest that the positive predictive value of the Rome II criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red flags for detecting organic diseases in patients diagnosed irritable bowel syndrome by their physicians. METHODS: Systematic chart reviews were completed in 1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal pain, diarrhoea or constipation, who also completed questionnaires to identify Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome). Red flags were reported by 84% of the sample. The positive predictive value of individual red flags for identifying organic disease was 7-9%. Excluding any patient with a red flag improved the agreement between Rome II and clinical diagnosis by a modest 5%, but left 84% of patients who were diagnosed with irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS: Red flags may be useful for identifying patients who require additional diagnostic evaluation, but incorporating them into the Rome criteria would not improve sensitivity and would result in too many missed irritable bowel syndrome diagnoses.

Multiple pains and psychiatric disturbance. An epidemiologic investigation.

We assessed multiple pain conditions and their association with affective disturbance, somatization, and psychological distress based on questionnaire data from a probability sample of 1016 enrollees of a large health maintenance organization. Respondents were asked about the presence of five pain conditions and were classified empirically in terms of dysfunctional chronic pain status based on pain severity, pain persistence, and pain-related disability days. Logistic regression analyses revealed a highly significant association between number of pain conditions reported and elevated levels of somatization as measured by the Symptom Checklist 90-Revised. Individuals with two or more pain conditions were at elevated risk of an algorithm diagnosis of major depression, while persons with a single pain condition did not differ from persons with no current pain conditions. Number of pain conditions reported was a better predictor of major depression than were important measures of pain experience, including pain severity and pain persistence.

Disability and depression among high utilizers of health care. A longitudinal analysis.

We evaluated, among depressed medical patients who are high utilizers of health care, whether improved vs unimproved depression is associated with differences in the course of functional disability. At baseline, 6 months, and 12 months, depression and disability were assessed among a sample of enrollees in health maintenance organizations (N = 145) in the top decile of users of ambulatory health care who exceeded the 70th percentile of health maintenance organization population norms for depression. Improved depression was defined as a reduction of at least one third in depressive symptoms averaged across the two follow-up times. At the 12-month follow-up, persons with severe-improved depression experienced a 36% reduction in disability days (79 days per year to 51 days per year) and a 45% reduction in disability score. Persons with moderate-improved depression experienced a 72% reduction in disability days (62 days per year to 18 days per year) and a 40% reduction in disability score. In contrast, persons with severe-unimproved depression reported 134 disability days per year at baseline, while persons with moderate-unimproved depression reported 77 disability days per year at baseline. Neither group with unimproved depression showed improvement in either disability days or disability score during the 1-year follow-up period. High utilizers of health care with severe-unimproved depression were more likely to have current major depression and to be unemployed. Improved (relative to unimproved) depression was associated with borderline differences in the severity of physical disease and in the percent married. We conclude that depression and disability showed synchrony in change over time. However, depression and disability may show synchrony in change with disability because both depression and disability are controlled by some other factor that influences the chronicity of depression (eg, chronic disease or personality disorder). The finding of synchronous change of depression and disability provides a rationale for randomized controlled trials of depression treatments among depressed and disabled medical patients to determine whether psychiatric intervention might improve functional status in such patients. Such research is needed to determine whether there is a causal relationship between depression offset and reductions in functional disability.

A multifaceted intervention to improve treatment of depression in primary care.

BACKGROUND: This research study evaluates the effectiveness of a multifaceted intervention program to improve the management of depression in primary care. METHODS: One hundred fifty-three primary care patients with current depression were entered into a randomized controlled trial. Intervention patients received a structured depression treatment program in the primary care setting that included both behavioral treatment to increase use of adaptive coping strategies and counseling to improve medication adherence. Control patients received "usual" care by their primary care physicians. Outcome measures included adherence to antidepressant medication, satisfaction with care of depression and with antidepressant treatment, and reduction of depressive symptoms over time. RESULTS: At 4-month follow-up, significantly more intervention patients with major and minor depression than usual care patients adhered to antidepressant medication and rated the quality of care they received for depression as good to excellent. Intervention patients with major depression demonstrated a significantly greater decrease in depression severity over time compared with usual care patients on all 4 outcome analyses. Intervention patients with minor depression were found to have a significant decrease over time in depression severity on only 1 of 4 study outcome analyses compared with usual care patients. CONCLUSION: A multifaceted primary care intervention improved adherence to antidepressant regimens and satisfaction with care in patients with major and minor depression. The intervention consistently resulted in more favorable depression outcomes among patients with major depression, while outcome effects were ambiguous among patients with minor depression.

Treatment process and outcomes for managed care patients receiving new antidepressant prescriptions from psychiatrists and primary care physicians.

BACKGROUND: While many studies describe deficiencies in primary care antidepressant treatment, little research has applied similar standards to psychiatric practice. This study compares baseline characteristics, process of care, and outcomes for managed care patients who received new antidepressant prescriptions from psychiatrists and primary care physicians. METHODS: At a prepaid health plan in Washington State, patients receiving initial antidepressant prescriptions from psychiatrists (n = 165) and primary care physicians (n = 204) completed a baseline assessment, including the Structured Clinical Interview for DSM-IV depression module, a 20-item depression assessment from the Symptom Checklist-90, and the Medical Outcomes Survey 36-Item Short-Form Health Survey functional status questionnaire. All measures were repeated after 2 and 6 months. Computerized data were used to assess antidepressant refills and follow-up visits over 6 months. RESULTS: At baseline, psychiatrists' patients reported slightly higher levels of functional impairment and greater prior use of specialty mental health care. During follow-up, psychiatrists' patients made more frequent follow-up visits, and the proportion making 3 or more visits in 90 days was 57% vs 26% for primary care physicians' patients. The proportion receiving antidepressant medication at an adequate dose for 90 days or more was similar (49% vs 48%). The 2 groups showed similar rates of improvement in all measures of symptom severity and functioning. CONCLUSIONS: In this sample, clinical differences between patients treated by psychiatrists and primary care physicians were modest. Shortcomings in depression treatment frequently noted in primary care (inadequate follow-up care and high rates of inadequate antidepressant treatment) were also common in specialty practice. Possible selection bias limits any conclusions about relative effectiveness or cost-effectiveness.

Anxiety and depression in a primary care clinic. Comparison of Diagnostic Interview Schedule, General Health Questionnaire, and practitioner assessments.

Over one half of all persons seen in a primary care clinic were identified as having anxiety or depressive disorder by the primary care provider, the General Health Questionnaire (GHQ), or the Diagnostic Interview Schedule (DIS). In only about 5% of all patients were findings positive on all three assessments concurrently. Both the GHQ and the practitioners identified over 30% of all patients as having a disorder, while about 8% had one or more of five DIS anxiety or depressive disorders (major depression, dysthymia, panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder). Of the patients with DIS disorders 83% had positive GHQ scores, and 73% were identified by the practitioner as having a mental disorder.

An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'.

This article describes a large longitudinal multicenter collaborative study that investigated the form, frequency, course, and outcome of psychological problems that were seen in primary health care settings in 15 different sites around the world. The research employed a two-stage sampling design in which the 12-item General Health Questionnaire was administered to 26,422 persons aged 18 to 65 years who were consulting health care services. Of these persons, 5604 were selected for detailed examinations using standardized instruments and were followed up at 3 months and 1 year to provide information on course and outcome. All assessment instruments have been translated into 13 different languages. The project has produced a database that allows for the exploration of the nature of psychological disorders experienced by patients in general medical care and their association with physical illness, illness behavior, and disability over time.

Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial.

BACKGROUND: Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects, many patients treated with antidepressant medications by primary care physicians have persistent symptoms. METHODS: A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were randomized to a collaborative care intervention (n = 114) or usual care (n = 114) by the primary care physician. Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment. Follow-up assessments were completed at 1, 3, and 6 months by a telephone survey team blinded to randomization status. RESULTS: Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls. Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months. CONCLUSIONS: A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants, satisfaction with care, and depressive outcomes compared with usual care.

A randomized trial of relapse prevention of depression in primary care.

BACKGROUND: Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment. We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care. METHODS: Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were randomized to a relapse prevention program (n = 194) or usual primary care (n = 192). Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aimed at enhancing adherence to antidepressant medication, recognition of prodromal symptoms, monitoring of symptoms, and development of a written relapse prevention plan. Follow-up assessments were completed at 3, 6, 9, and 12 months by a telephone survey team blinded to randomization status. RESULTS: Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls. Intervention patients had significantly fewer depressive symptoms, but not fewer episodes of relapse/recurrence over the 12-month follow-up period. CONCLUSIONS: A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes.

Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis. Experience in eastern Baltimore.

We studied DSM-III diagnoses made by the lay Diagnostic Interview Schedule (DIS) method in relation to a standardized DSM-III diagnosis by psychiatrists in the two-stage Baltimore Epidemiologic Catchment Area mental morbidity survey. Generally, prevalence estimates based on the DIS one-month diagnoses were significantly different from those based on the psychiatric diagnoses. Subjects identified as cases by each method were often different subjects. Measured in terms of kappa, the chance-corrected degree of agreement between the DIS and psychiatrists' one-month diagnoses was moderate for DSM-III alcohol-use disorder (abuse and dependence combined), and lower for other mental disorder categories. The unreliability of either the DIS or psychiatric diagnoses is one potential explanation for the observed disagreements. Others include the following: insufficient or inadequate information (on which to base a diagnosis); recency of disorder; incomplete criterion coverage; overinclusive DIS questions; and degree of reliance on subject symptom reports. Further study of the nature and sources of these discrepancies is underway. This work should produce a more complete understanding of obstacles to mental disorder case ascertainment by lay interview and clinical examination methods in the context of a field survey.

The design of the Epidemiologic Catchment Area surveys. The control and measurement of error.

Several methods are used to minimize and measure error in the NIMH Epidemiologic Catchment Area program. Sampling methods involve the inclusion of group quarters such as prisons, nursing homes, and mental hospitals in the sample frame and the use of probability sampling throughout. Interviewing, methods include use of identical diagnostic interview protocols, centralized training of interview supervisors, standard instructions to interviewers, and reinterview of a subsample by clinicians. In the area of completion, the methods include a 75% to 80% respondent completion rate, a 95% or greater completion rate for individual questions, use of informant interviews where necessary, and statistical adjustments to correct for low completion rates in some subgroups. Analytic methods include use of a computerized diagnostic algorithm, common estimation formulas on identically formatted data files, and estimation of exact variances that take account of the multistage sample design.

Utilization of health and mental health services. Three Epidemiologic Catchment Area sites.

Utilization of health and mental health services by non-institutionalized persons aged 18 years and older is examined based on interviews with probability samples of 3,000 to 3,500 persons in each of three sites of the National Institute of Mental Health Epidemiologic Catchment Area (ECA) program: New Haven, Conn, Baltimore, and St Louis. In all three ECAs, 6% to 7% of the adults made a visit during the prior six months for mental health reasons; proportions were considerably higher among persons with recent DSM-III disorders covered by the Diagnostic Interview Schedule (DIS) or severe cognitive impairment. Between 24% and 38% of all ambulatory visits by persons with DIS disorders were to mental health specialists. In seeking mental health services, men were more likely to turn to the specialty sector than to the generalist; women used both sectors about equally. The aged infrequently received care from mental health specialists. Visits for mental health reasons varied considerably depending on specific types of DIS disorder.

Somatization: a spectrum of severity.

OBJECTIVE: The DSM-III-R diagnosis of somatization disorder requires that a patient have a specific number of medically unexplained somatic symptoms. This number of symptoms was developed by committee consensus, and it is not clear whether patients with this specific number of symptoms can be differentiated from patients with lower but still substantial numbers of somatic symptoms. METHOD: Fifty-one percent of 767 high utilizers of two primary care clinics were identified as distressed by an elevated SCL anxiety, depression, or somatization scale score or by their primary care physician. The Diagnostic Interview Schedule (DIS) was completed on 119 distressed high utilizers who were randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The 119 distressed high utilizers were separated into four categories according to the number of unexplained somatic symptoms found on the DIS and were compared on demographic, psychiatric distress, disability, medical, and health utilization variables. RESULTS: The data suggest that many clinical and behavioral features of somatization are significantly more common in patients with four to 12 medically unexplained somatic symptoms rather than changing dramatically at the diagnostic threshold for somatization disorder. The data also showed that patients who meet the DSM-III-R criteria for somatization disorder are severely ill and have a high burden of psychiatric illness and disability. CONCLUSIONS: The results suggest that the DSM-IV somatoform disorders section should include somatization disorder, an abridged definition of somatization disorder often associated with anxiety and depression, as well as a type of somatization associated with an adjustment disorder.