Glutamate levels in the medial prefrontal cortex of healthy pregnant women compared to non-pregnant controls.

Very little is known about maternal cerebral changes during pregnancy. Since there is an increased risk for major depression during pregnancy and postpartum, it is important to understand the structural and neurochemical changes that occur in the brain during pregnancy. Using proton magnetic resonance spectroscopy (1H-MRS) (3 T field strength), glutamate (Glu) levels were measured in the medial prefrontal cortex (MPFC) of 21 healthy gravid subjects 2-3 weeks before their due date (6.74 ± 1.39), and in 14 non-pregnant healthy controls during their follicular phase (8.53 ± 1.55). Water quantified MPFC Glu levels were decreased in pregnant women (p < 0.01). We also observed a 13.9% decrease in percentage grey matter (%GM) (p < 0.01) in our MPFC voxel. As Glu is mostly found in GM, we repeated the statistical analysis after adjustment for %GM and found that the difference in Glu levels was no longer statistically significant when adjusted for %GM (p = 0.10). This investigation is the only systematic direct investigation of brain tissue composition and Glu levels in pregnant women. The main finding of this investigation is the decreased %GM in healthy pregnant women compared to non-pregnant women. These findings of decreased %GM in pregnancy may be responsible for the frequent complaints by pregnant women of cognitive difficulties also described as pregnesia.

Long-term course and outcome in schizophrenia: a 34-year follow-up study in Alberta, Canada.

BACKGROUND: The aim of this study was to extend an earlier retrospective cohort study of schizophrenia via a prospective study to a follow-up of 34 years, with an emphasis on describing the life-course of the illness. METHOD: Subjects were 128 first-ever admissions for schizophrenia in 1963 to either of two mental hospital in Alberta, Canada. Follow-up continued until death or 1997. A symptom severity scale, with scores ranging from 0 (no symptoms) to 3 (hospitalized), was used to collect time-series data on each subject and create life-course curves. Indices were constructed to summarize the information in each curve. Information on social functioning was also collected. RESULTS: Results were similar for men and women. The life-course curves showed marked variability of symptom severity across subjects and over time. The average score over the entire period of follow-up for the cohort indicated 'moderate' symptoms, and the change in average score from beginning to end of follow-up demonstrated a slight worsening of symptoms. The measures of social functioning indicated that only about one quarter of the patients had a good to excellent outcome. CONCLUSIONS: The long-term course in schizophrenia is one of varying symptom severity, and for many patients, there is a poor overall outcome.

A multivariate study of predictors of repeat parasuicide.

OBJECTIVE: To identify variables which differentiate future repeaters of parasuicide from non-repeaters in a multivariate analysis. METHOD: Interviews were conducted with 507 parasuicide cases; data were collected on precipitating factors for the index parasuicide, psychiatric and medical history, stressful life events, prior history of parasuicide, hopelessness, anger, self-esteem and social adjustment. Individuals were followed for 1-2 years to determine if a repeat parasuicide occurred. RESULTS: A logistic regression model identified four significant predictors of repeat parasuicide: prior history of parasuicide, a history of depression, a history of schizophrenia and poor physical health. A risk factor scale constructed from these four variables showed that the risk of repeat parasuicide increases as the number of risk factors increases. CONCLUSION: This study identifies four key predictors of repeat parasuicide, and provides evidence that the risk of repeat parasuicide increases when multiple risk factors are present.

Spouse similarity for antisocial behaviour in the general population.

BACKGROUND: In contrast with the large amount of research on the familial transmission of antisocial behaviour, few studies have investigated similarity between spouses for such behaviour. In addition, none of these studies have examined child conduct disorder (CCD) and adult antisocial behaviour (AAB) separately. METHOD: We studied 519 pairs of spouses who completed the Diagnostic Interview Schedule. In each pair, one spouse belonged to a random subsample of persons who had participated in a large population survey and was re-interviewed. Association between spouses for lifetime symptoms and DSM-III criteria of CCD, AAB, antisocial personality disorder and co-morbid psychiatric diagnoses was examined with bivariate and multivariate logistic regression analyses. RESULTS: We observed a moderate association between spouses for the presence of CCD (OR = 4.02, 95% CI = 2.03-7.96), and a strong association for the presence of AAB (OR = 20.1, 95 % CI = 5.97-67.5). This similarity for AAB was independent of the similarity for CCD and persisted after adjustment for spousal similarity for disorders co-morbid with AAB. An examination of the relationship between marital status and the presence of CCD and/or AAB in the general population sample (from which originated our sample of couples) suggested that the spousal similarity for AAB was more likely attributable to assortative mating rather than marital contamination. CONCLUSION: Our finding of a strong similarity between spouses for AAB has significant implications for both clinicians and researchers. It also suggests that adult antisocial behaviour should be considered as a distinct diagnostic entity, an approach which diverges from DSM-IV diagnostic criteria.

Prevalence and determinants of tuberculin reactivity among physicians in Edmonton, Canada: 1996-1997.

BACKGROUND: Health care workers (HCW) have historically borne a heavy burden of tuberculosis (TB) infection and disease. Unfortunately, physicians are rarely included in HCW surveys of tuberculin exposure and infection. METHODS: The prevalence and risk factors for tuberculin reactivity were determined for a sample of the 1732 licensed physicians in Edmonton. Stratified random sampling was used to select 554 specialists and 219 general practitioners. These physicians were contacted by means of an introductory letter and a follow-up telephone call to solicit participation. All eligible physicians were asked to complete a questionnaire and those with either no recorded positive tuberculin test or a previously negative result were two-step tuberculin skin tested. RESULTS: In total, 560 physicians (72.4 %) participated in the study. The overall tuberculin reactivity for this population was 45.9%. Using logistic regression analysis, we determined that risk factors for reactivity were aged over 45 years, of foreign-birth, previous Bacillus Calmette-Guérin (BCG) vaccination, foreign practice experience, and being a respiratory medicine specialist. CONCLUSION: The prevalence of tuberculin reactivity among physicians is considerably higher than estimates for the general Canadian population. This observed excess risk may be associated with factors linked to their medical practice. The high participation rate suggests physician willingness to participate in this type of research, and emphasizes the need to include them in routine HCW surveillance.

Mild dementia or cognitive impairment: the Modified Mini-Mental State examination (3MS) as a screen for dementia.

OBJECTIVE: To examine the Modified Mini-Mental State Examination (3MS) as a screen for dementia. METHOD: A group of 1092 elderly Edmonton community residents completed the 3MS and the Geriatric Mental State Examination (GMS). 3MS sensitivity and specificity were determined by comparing positive 3MS screens (score < or = 77) with those classified as GMS "organic" (severity level 3, equivalent to a clinical diagnosis). In the Canadian Study of Health and Aging (CSHA), 2914 subjects received the 3MS and a clinical examination. A group described as having "cognitive impairment but no dementia (CIND)" was identified. RESULTS: In Edmonton, the 3MS showed 88% sensitivity, 90% specificity, 29% positive predictive value (PPV), and 99% negative predictive value (NPV). In the CSHA, 30% of subjects receiving both the 3MS and a clinical examination were classified as CIND. One-half of these were classified as having "age associated memory impairment (AAMI)" or as "unspecified." CONCLUSIONS: The 3MS with a cutting score of 77/78 proved a reasonable screening instrument; 1 case in 3 screening "positive" has dementia, but few (0.64%) will be missed by screening "negative." CIND, accounting for 2 out of 3 cases screened positive by the 3MS in the Edmonton study, is a substantial, heterogeneous group that is not necessarily "predementia" but that in many cases merits further investigation.

Change in pain and function while waiting for major joint arthroplasty.

The objective of this study was to examine the change in pain and physical function that occurs while waiting for major arthroplasty. Data were collected prospectively from a cohort of 313 patients who were waiting > 1 month for total hip arthroplasty or total knee arthroplasty. The WOMAC and the SF-36 health status instruments were administered at the time the patient was placed on the waiting list and again just before surgery. Minimal amounts of change in pain and physical and psychosocial function occurred for hip and knee arthroplasty patients while they waited. Overall, waiting time did not appear to have a negative impact on the amount of pain and dysfunction experienced.

Toward measuring the impact of ecological disintegrity on human health.

Ecological integrity refers to the ability of environmental life-support systems to sustain themselves in the face of human-induced impacts. We used a correlational, aggregate-data study design to explore whether life expectancy, as a general measure of population health, is linked to large-scale declines in ecological integrity. Most of the data were obtained from World Resources Institute publications. Selected surrogate measures of ecological integrity and gross domestic product (GDP) per capita (as a socioeconomic confounder) were modeled, for the first time, using linear regression techniques with life expectancy as the health outcome. We found a modest relation between ecological integrity and life expectancy, but the direction of the association was inconsistent. When GDP per capita was controlled, the relation between ecological integrity and life expectancy was lost. GDP per capita was the overwhelming predictor of health. Any relation between ecological integrity and health may be mediated by socioeconomic factors. The effect of declines in ecological integrity may be cushioned by the exploitation of ecological capital, preventing a direct association between measures of exposure and outcome. In addition, life expectancy may be too insensitive a measure of health impacts related to ecological decline, and more sensitive measures may need to be developed.

Clinical survival predictors in patients with advanced cancer.

BACKGROUND: The clinical and epidemiological relevance of different prognostic factors for survival in patients with advanced or terminal cancer remains controversial. PURPOSES: To establish the survival of patients with cancer after diagnosis of terminal disease and to determine the predictors of survival. METHODS: An inception cohort of 227 consecutive patients aged 18 years or older with terminal cancer of the lung, breast, and gastrointestinal tract were observed from July 1, 1996, through December 31, 1998. Tumor- and treatment-specific, clinical, laboratory, demographic, and socioeconomic variables were recorded at baseline. The relationships between these characteristics and survival time were examined using univariate Kaplan-Meier and multivariate Cox regression analyses. RESULTS: At the time of data analysis, 208 patients (91.6%) had died; the overall median survival for the sample was 15.3 weeks. Shorter survival was independently associated (P< or =.05) with a primary tumor of the lung (vs breast and gastrointestinal tract combined), liver metastases, moderate to-severe comorbidity levels (vs absent-to-mild levels), weight loss of greater than 8.1 kg in the previous 6 months, serum albumin levels of less than 35 g/L, lymphocyte counts of less than 1 X 10(9)/L, serum lactate dehydrogenase levels of greater than 618 U/L, and clinical estimation of survival by the treating physician of less than 2 months (vs 2-6 and >6 months). Performance status, symptoms other than nausea and vomiting, tumor burden, and socioeconomic characteristics such as social support and education and income levels did not appear to be independently associated with survival after adjusting for the effect of prognostic factors. CONCLUSIONS: Simple clinical and laboratory assessments are useful aids in the prediction of survival in patients with solid malignant neoplasms at the onset of terminal stages. Methodological improvements in the design and implementation of survival studies may reduce prognostic uncertainty and ultimately provide better care for the terminally ill patients and their families.

An iterative method of estimating excess death rates and mortality ratios.

OBJECTIVES: To present a method of comparative mortality analysis of published data that can be applied when age- and sex-specific mortality rates for the study population are not available. METHODS: The quantitative method is described and illustrated using data from the SHEP study. A comparison is made with the results of Singer.

Antidepressant use in the elderly population in Canada: results from a national survey.

BACKGROUND: There are few epidemiologic studies of the rate of antidepressant use in the elderly population, especially for community residents. We report findings on antidepressant use in the elderly population using data from a national survey in Canada which drew samples from both the community and institutional settings. METHODS: Data for the present study came from the Canadian Study of Health and Aging (CSHA), a national prevalence study of dementia in which information was collected from 2914 elderly subjects on current drug use, place of residence (community, institution), depression, dementia, and self-reported health. Survey weights were constructed to reflect the national population and data were analyzed using the SUDAAN statistical software package. RESULTS: The rate of antidepressant use was 4.1% (community 3.1%, institution 16.5%). Of those who were depressed, 9.4% were taking an antidepressant (community 4.2%, institution 36.0%). A logistic regression analysis showed that female gender, living in an institution, the presence of dementia, and the presence of a chronic physical disease, but not depression, were associated with increased antidepressant use. CONCLUSIONS: Our findings on the rate of antidepressant use in the elderly population are consistent with and extend previously published reports. We found evidence of underutilization of antidepressants in the treatment of geriatric depression, especially for community residents. However, this evidence needs to be interpreted with caution as the CSHA data on depressive symptoms were incomplete.

Treatment seeking for depression: role of depressive symptoms and comorbid psychiatric diagnoses.

BACKGROUND: General population research has indicated that many persons with lifetime major depression report they have never sought medical help for their illness. We examined the role played by both depressive symptoms and comorbid psychiatric diagnoses in treatment seeking. METHODS: From standardized psychiatric interviews of 7214 Edmonton residents, we identified 1348 subjects with lifetime depressive illness; 866 subjects (64%) had sought medical treatment. RESULTS: Psychomotor retardation (odds ratio, OR = 1.4), suicidal ideation (OR = 1.4), comorbid mania (OR = 9.5), comorbid panic disorder (OR = 3.0), and comorbid drug abuse/dependence (OR = 0.6) were significantly associated with treatment seeking in multivariate analysis. CONCLUSION: The finding that only a few depressive symptoms were associated with treatment seeking underlines the importance of public health education to address the undertreatment of depression.

The prevalence of depression in Alzheimer's disease and vascular dementia in a population sample.

BACKGROUND: Previous studies have shown that depression is more prevalent in vascular dementia than Alzheimer's disease (AD). Subjects for these studies were either psychiatry or neurology patients, raising the issue of whether factors leading to treatment might have introduced sampling bias. METHODS: Data for the present study came from the Canadian Study of Health and Aging (CSHA, 1994), a population-based prevalence study of dementia. AD was diagnosed using NINCDS-ADRDA criteria (McKhann et al., 1984), vascular dementia was diagnosed using draft ICD-10 criteria (World Health Organization, 1987) and the Ischemic Scale (Hachinski et al., 1975), major depression was diagnosed using an algorithm based on DSM-III-R criteria (American Psychiatric Association, 1987). The sample for the present study consisted of 481 subjects with AD and 140 with vascular dementia. RESULTS: The weighted prevalence rate of major depression was 3.2% for AD and 21.2% for vascular dementia, giving a crude odds ratio of 8.2 (95% Confidence Interval: 1.7-40.2). This finding was confirmed by a logistic regression analysis which adjusted for age, sex, place of residence (community, institution), self-reported health, severity of cognitive impairment, and antidepressant or beta-blocker use. LIMITATIONS: Data on depressive symptoms were more often missing in subjects with dementia resulting in differential loss of potential study subjects. Data on depressive symptoms were not sufficiently detailed to permit DSM-III-R criteria to be implemented rigorously. The method of diagnosing vascular dementia was subject to misclassification. CONCLUSIONS: This study confirms in a population sample that depression is more prevalent in vascular dementia compared to AD.

Prevalence of suicide ideation and suicide attempts in nine countries.

BACKGROUND: There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data. METHODS: Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand. RESULTS: The lifetime prevalence rates/100 for suicide ideation ranged from 2.09 (Beirut) to 18.51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0.72 (Beirut) to 5.93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married. CONCLUSIONS: While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.

Prevalence of depression in an elderly community sample: a comparison of GMS-AGECAT and DSM-IV diagnostic criteria.

BACKGROUND: Prevalence rates of depression based on the GMS-AGECAT system are markedly higher than rates of major depression diagnosed using DSM-III and DSM-III-R criteria. Interpreting this finding is difficult since AGECAT diagnostic criteria have not been published. METHODS: We conducted a survey in Edmonton, Canada, in which 1119 community residents aged 65 years or older were administered the Geriatric Mental State (GMS) questionnaire. Depression was diagnosed using AGECAT and also according to criteria for DSM-IV major depression and minor depression. We identified 57 items in the GMS relating to major and minor depression which were then grouped into dysphoric, somatic and cognitive categories. The relationship of these symptoms to AGECAT depression was investigated by recording symptoms to absent (nullifying) and recalculating the number of AGECAT cases. Data were weighted to reflect the underlying population. RESULTS: There were 143 cases of AGECAT depression (prevalence rate = 11.4%), 14 cases of major depression (prevalence rate = 0.86%) and 44 cases of minor depression (prevalence rate = 3.6%). Of the 154 subjects with either AGECAT or DSM-IV depression, only 47 (31%) were depressed according to both diagnostic systems. Nullifying all dysphoric symptoms reduced the number of AGECAT cases to eight, whereas nullifying somatic and cognitive symptoms reduced the numbers of cases only to 138 and 142, respectively. By themselves, dysphoric symptoms accounted for 77 of the 143 cases of AGECAT depression, while somatic and cognitive symtpoms alone accounted for no cases. CONCLUSIONS: AGECAT depression is more inclusive than DSM-IV major or minor depression and AGECAT case status is determined mainly by the proportion of dysphoric symptoms.

The prevalence of mental disorders in the elderly in Edmonton: a community survey using GMS-AGECAT. Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy.

OBJECTIVE: To estimate the current prevalence rate of Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) disorders in the elderly population in Edmonton, Alberta. To compare the prevalence rate of GMS-AGECAT depression with the prevalence rate of Diagnostic Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders (DIS-DSM-III) major depression based on an earlier survey in Edmonton. METHOD: A sample of 1119 community residents age 65 years and over was selected using the provincial health insurance database. Data on mental disorders were collected using the Geriatric Mental State questionnaire, and diagnoses were made with the Automated Geriatric Examination for Computer Assisted Taxonomy computer program. Prevalence rates, standard errors, and logistic regression coefficients were estimated using software designed to analyze survey data. RESULTS: The prevalence rates of GMS-AGECAT depression and organic disorder were 11.2% and 2.9% respectively. For depression there was a statistically significant difference in the prevalence rates for males (7.3%) and females (14.1%) (P = 0.003), and for organic disorder there was a statistically significant increasing trend across age-groups for females (P < 0.0001). The prevalence rate of GMS-AGECAT depression in Edmonton is comparable to rates reported from several European studies but is much higher than the 6-month prevalence rate of DIS-DSM-III major depression of 1.2% based on an earlier Edmonton survey. CONCLUSIONS: GMS-AGECAT depression is a depressive syndrome that has a larger prevalence rate than DIS-DSM-III major depression. Community surveys that measure only the prevalence rate of DSM-III major depression may be missing clinically significant cases of geriatric depression.

Incidence of mental disorders in Edmonton: estimates of rates and methodological issues.

An incidence study was conducted in Edmonton, Alberta, Canada, in which 3956 community residents were interviewed using the Diagnostic Interview Schedule (DIS) and a sample of 1964 subjects were reinterviewed with the DIS an average of 2.8 years later. Incidence rates, estimated for a range of DSM-III disorders, were surprisingly large, raising questions about the reliability of DIS data. We examined major depression in detail to uncover possible sources of unreliability. There were 138 'incident' cases of major depression, giving an annual incidence rate for both sexes of 27.9 (per 1000). However, based on reinterview data, 106 (80%) of the incident cases reported an age of onset prior to the initial interview. These findings appear to be the result of a difference between the DIS definition of age of onset and the one used in our analysis of incidence. A syndrome called depressive spell is defined and used to demonstrate that the large number of incident cases is likely due, at least in part, to incomplete recall of lifetime depressive symptoms. Despite these potential sources of bias, the possibility remains that incidence rates and lifetime risks in Edmonton are larger than has generally been reported in the literature.

Spouse similarity for lifetime psychiatric history in the general population.

BACKGROUND: Most studies of spouse similarity for psychiatric disorders have focused on clinical samples and are thus limited by selection bias. This study is, to our knowledge, the first comprehensive investigation of spouse similarity for lifetime psychiatric history in a general population sample using standardized diagnostic criteria. METHODS: We studied 519 pairs of spouses residing in Edmonton, Canada who completed the Diagnostic Interview Schedule psychiatric interview. In each pair, one spouse belonged to a random subsample of persons who had participated in a large population survey and was re-interviewed. Association between spouses for lifetime DSM-III psychiatric disorders was analysed with bivariate and multivariate logistic regression analyses. RESULTS: We observed significant spousal association for lifetime presence of affective disorders and for the spectrum of antisocial personality and addiction disorders. Antisocial personality in one spouse was also associated with anxiety disorders in the other spouse, namely post-traumatic stress disorder in wives and phobia in husbands; similarly, drug abuse/dependence in wives was associated with generalized anxiety in husbands and male drug abuse/dependence was associated with female post-traumatic stress disorder. Dysthymia in wives was associated with generalized anxiety and post-traumatic stress disorder in husbands. CONCLUSIONS: The existence of associations between spouses for the presence of psychiatric disorders, either similar or different, has significant implications for both clinicians and researchers. Future research should aim at exploring the aetiological mechanisms of these associations.

Surgeon-related factors and outcome in rectal cancer.

OBJECTIVE: To determine whether surgical subspecialty training in colorectal surgery or frequency of rectal cancer resection by the surgeon are independent prognostic factors for local recurrence (LR) and survival. SUMMARY BACKGROUND DATA: Variation in patient outcome in rectal cancer has been shown among centers and among individual surgeons. However, the prognostic importance of surgeon-related factors is largely unknown. METHODS: All patients undergoing potentially curative low anterior resection or abdominoperineal resection for primary adenocarcinoma of the rectum between 1983 and 1990 at the five Edmonton general hospitals were reviewed in a historic-prospective study design. Preoperative, intraoperative, pathologic, adjuvant therapy, and outcome variables were obtained. Outcomes of interest included LR and disease-specific survival (DSS). To determine survival rates and to control both confounding and interaction, multivariate analysis was performed using Cox proportional hazards regression. RESULTS: The study included 683 patients involving 52 surgeons, with > 5-year follow-up obtained on 663 (97%) patients. There were five colorectal-trained surgeons who performed 109 (16%) of the operations. Independent of surgeon training, 323 operations (47%) were done by surgeons performing < 21 rectal cancer resections over the study period. Multivariate analysis showed that the risk of LR was increased in patients of both noncolorectal trained surgeons (hazard ratio (HR) = 2.5, p = 0.001) and those of surgeons performing < 21 resections (HR = 1.8, p < 0.001). Stage (p < 0.001), use of adjuvant therapy (p = 0.002), rectal perforation or tumor spill (p < 0.001), and vascular/neural invasion (p = 0.002) also were significant prognostic factors for LR. Similarly, decreased disease-specific survival was found to be independently associated with noncolorectal-trained surgeons (HR = 1.5, p = 0.03) and surgeons performing < 21 resections (HR = 1.4, p = 0.005). Stage (p < 0.001), grade (p = 0.02), age (p = 0.02), rectal perforation or tumor spill (p < 0.001), and vascular or neural invasion (p < 0.001) were other significant prognostic factors for DSS. CONCLUSION: Outcome is improved with both colorectal surgical subspecialty training and a higher frequency of rectal cancer surgery. Therefore, the surgical treatment of rectal cancer patients should rely exclusively on surgeons with such training or surgeons with more experience.