Limitations of diagnostic criteria and assessment instruments for mental disorders. Implications for research and policy.

During the past 2 decades, psychiatric epidemiological studies have contributed a rapidly growing body of scientific knowledge on the scope and risk factors associated with mental disorders in communities. Technological advances in diagnostic criteria specificity and community case-identification interview methods, which made such progress feasible, now face new challenges. Standardized methods are needed to reduce apparent discrepancies in prevalence rates between similar population surveys and to differentiate clinically important disorders in need of treatment from less severe syndromes. Reports of some significant differences in mental disorder rates from 2 large community surveys conducted in the United States--the Epidemiologic Catchment Area study and the National Comorbidity Survey--provide the basis for examining the stability of methods in this field. We discuss the health policy implications of discrepant and/or high prevalence rates for determining treatment need in the context of managed care definitions of "medical necessity."

Education and change in cognitive function. The Epidemiologic Catchment Area Study.

The association between educational attainment and decline in cognitive function over an interval of 1 year was examined for 14,883 subjects 18 years and older in the National Institute of Mental Health Epidemiologic Catchment Area Study. Cognitive function was assessed at both time points by the Mini-Mental State Examination (MMSE); cognitive decline was coded as a dichotomous variable and was defined as 1 if the subject's score had declined 3 or more points from the baseline MMSE score at the 1-year follow-up interview and as 0 otherwise. The association between educational attainment and decline in cognitive function over 1 year was examined in logistic regression models that were stratified by age group (< 65 years, > or = 65 years) and by baseline MMSE level (MMSE > 23, MMSE < or = 23). Covariates included age, baseline MMSE score, ethnicity, residence, lifetime diagnosis of abuse of alcohol or other drugs, and gender. In those with baseline MMSE > 23, education was a significant predictor of cognitive decline, not only in the elderly but also in younger subjects. Among those with baseline MMSE < or = 23, education was not a significant predictor of cognitive decline. The fact that education provides protection against cognitive decline even in those younger than 65 years, in whom the prevalence and incidence of dementia are very low, would seem to indicate that education or its correlates provides protection against processes other than dementia that might produce a decline in test performance in young persons.

Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study.

The relation of longitudinally measured blood pressure to cognitive performance in the absence of clinically diagnosed cerebrovascular disease was investigated in the Framingham Study. In 1976-1978, neuropsychologic testing was administered to 1993 participants aged 55-89 years. Performance on an education-adjusted composite of these tests was examined in relation to measures of chronicity of hypertension as well as the average systolic and average diastolic blood pressure. All analyses were stratified by antihypertensive medication use during the 2 years prior to cognitive testing and adjusted for age, sex, occupation, alcohol consumption, and participation rate in prior examination cycles. Among subjects on drug therapy for hypertension, there was no association between cognitive performance and longitudinally measured blood pressure. The proportion of cycles in which hypertension was present and average systolic and diastolic blood pressure had a significant inverse relation with cognitive performance only in the group not on antihypertensive drug therapy. However, among subjects on antihypertensive medication at earlier cycles, there was a highly significant graded relation between cognitive impairment and the probability of being off medication at the time of testing. These results suggest that hypertension-related subclinical vascular disease is not an important cause of cognitive impairment in the elderly. Cognitive impairment may, however, be associated with a reduced adherence to drug treatment regimens.

Anthropometric indicators and hip fracture. The NHANES I epidemiologic follow-up study.

A cohort of 3,595 white women aged 40-77 years was followed for an average of 10 years during which 84 new cases of hip fracture were identified. Triceps skinfold thickness and arm muscle area measured at baseline were examined as possible risk factors for hip fracture controlling for physical activity, height, menopausal status, calcium consumption, and smoking. Of these variables only arm muscle area, triceps skinfold thickness, and activity in recreation were independent predictors of hip fracture incidence using the Cox proportional hazards model. After adjustment, the estimated relative risk of hip fracture was approximately two for an increment of each anthropometric indicator (adjusted for the other) equivalent to comparing those at the 25th percentile to those at the 75th percentile (maximum width of 95% confidence intervals, 1.2-2.9). Risk of hip fracture was approximately two-fold for persons who reported little recreational exercise compared to persons who reported much recreational exercise (95% confidence interval, 1.2-3.2). Our findings are the first evidence from a prospective study that anthropometric indicators besides body mass index may have an independent relationship to risk of hip fracture.

Acquired word deafness, and the temporal grain of sound representation in the primary auditory cortex.

This paper explores the nature of the processing disorder which underlies the speech discrimination deficit in the syndrome of acquired word deafness following from pathology to the primary auditory cortex. A critical examination of the evidence on this disorder revealed the following. First, the most profound forms of the condition are expressed not only in an isolation of the cerebral linguistic processor from auditory input, but in a failure of even the perceptual elaboration of the relevant sounds. Second, in agreement with earlier studies, we conclude that the perceptual dimension disturbed in word deafness is a temporal one. We argue, however, that it is not a generalized disorder of auditory temporal processing, but one which is largely restricted to the processing of sounds with temporal content in the milliseconds to tens-of-milliseconds time frame. The perceptual elaboration of sounds with temporal content outside that range, in either direction, may survive the disorder. Third, we present neurophysiological evidence that the primary auditory cortex has a special role in the representation of auditory events in that time frame, but not in the representation of auditory events with temporal grains outside that range.

The evidence for a temporal processing deficit linked to dyslexia: A review.

The existence of a phonemic deficit that is predictive of, and probably causal to, many cases of reading difficulty is well established. Tallal (1984) has suggested that this phonemic deficit is in fact a symptom of an underlying auditory temporal processing deficit. Our purpose in this paper is to evaluate the plausibility of this hypothesis. The various components that might constitute sequential (or temporal) processing are described. Our review of the literature reveals considerable evidence for a deficit in dyslexics in stimulus individuation tasks (e.g., gap detection) and temporal order judgments in both the auditory and visual modalities. The possibility that a general temporal processing deficit is associated with dyslexia, as suggested by Tallal (1984), is explored, and possible etiologies for such a deficit are discussed. The possibility of a causal link between temporal processing deficits and some reading disabilities is demonstrated, and converging evidence from morphological studies is reviewed. It is concluded that a temporal processing deficit does appear to be present in many developmental dyslexics, and strategies are suggested for further research aimed at evaluating the hypothesis that this deficit may be the root cause of a number of cases of dyslexia itself.

Dyslexia and a temporal processing deficit: A reply to the commentaries.

A number of points and criticisms were raised in the commentaries on our review paper (Farmer & Klein, 1995), and in this reply we address the most pertinent and major of those points. First, we clarify and expand upon what we mean by a temporal processing deficit. We then address Studdert-Kennedy and Mody's (1995) major claims, which are confined to the auditory modality, that (1) a discriminative deficit underlies what they see as a rate of processing deficit, and (2) discriminative/rate deficits for speech and nonspeech materials are independent. We explain why we believe the first proposal is unlikely to provide an explanation of the temporal processing deficits that we reviewed, and we present a simple framework within which speech and nonspeech perceptual codes are viewed as higher level isolable subsystems that depend on a common, lower level, auditory input system. The speech and nonspeech systems may be influenced similarly by damage to, or impairments of, their common input system, but they can be selectively influenced by insults after the pathways diverge. Then we address some of the issues raised by Rayner, Pollatsek, and Bilsky (1995), relating to visual deficits and oculomotor behavior, and we point to the rapidly growing evidence to diminish skepticism about the occurrence of a transient system deficit in dyslexia. Next, while agreeing that case studies are valuable, we dispute Martin's (1995) endorsement of the case study as the preferred methodology for studying a heterogeneous deficit such as developmental dyslexia. Finally, we affirm our original conclusion that more research aimed at revealing the nature and generality of the visual and auditory temporal processing deficits is warranted, and we reiterate some of our suggestions for the types of study that might help elucidate if and how these deficits might be causally related to the dyslexia with which they are frequently associated.

The effects of conservation tillage practices on benthic invertebrate communities in headwater streams in southwestern Ontario, Canada.

Samples of benthic invertebrates from four pairs of streams in southwestern Ontario collected monthly from May through August 1991, and once during the subsequent autumn and winter, demonstrated that conservation tillage practices have a remedial effect on the water quality of adjacent streams as indicated by biotic, rather than physical or chemical, parameters. One stream of each pair drained a basin under conventional tillage (CONV, mainly mouldboard ploughing), the other primarily under conservation tillage (CONS). The paired drainage basins were otherwise similar to one another in type of crops grown, as well as size, topography, soils and hydrology. CONS streams yielded a greater variety of Insecta but fewer taxa of Mollusca, Annelida and Crustacea than did samples from CONV streams. Both kick-net and Surber samples from CONS streams yielded significantly more taxa, more kinds of Ephemeroptera, Plecoptera and Trichoptera, and lower Hilsenhoff Biotic Index scores than did samples from CONV streams. Kick samples from CONS streams were significantly more similar to expected reference communities in overall taxonomic composition. Surber samples from CONS streams contained significantly larger numbers of invertebrates. The relatively greater abundances of infaunal species, especially Tubificidae and Chironomini, in CONV streams suggest greater accumulation of fine sediment particles. Conditions during low flow appear to have the greatest influence on the composition of benthic invertebrate communities. The results of the study indicate that conservation tillage practices have a beneficial effect on the quality of surface waters.

Cognitive deficits related to major organ failure: the potential role of neuropsychological testing.

Until recently, little attention has been paid to the possibility of cognitive deficits in patients with disease or failure of major organs such as the liver, kidney, or heart. However, there is a growing awareness that major organ failure often has neuropsychological sequelae. These sequelae may at times be quite subtle and not detectable under gross examination. Nevertheless, even subtle deficits may have a major impact on adherence to medical regimens, psychosocial adjustment, and quality of life of patients. Neuropsychological assessment has a potentially valuable role to play both in research and in clinical work. It can be useful in adding to our knowledge of the cognitive effects of various types, severity and duration of major organ disease, as well as sequelae associated with treatment. It also is a potentially valuable clinical tool for identifying cognitive deficits that will affect the quality of life and probability of survival for organ failure patients.

Absence of menopausal effect on hip fracture occurrence in white females.

The rate of hip fracture among White females rises sharply between ages 40 and 44 and then continues at a constant rate of acceleration doubling every five to six years throughout life with no deviation during, or in the years immediately following, menopause. We suggest that the important role of sex hormones and other factors in osteoporosis commences prior to menopause. A premenopause prevention strategy which postpones the onset of the osteoporotic process by five or six years would be expected to reduce the risk of hip fracture by 50 per cent throughout the remainder of a woman's life.

Ultrastructural comparison of ion beam and radiofrequency plasma etching effects on biological tissue sections.

Three dry etching techniques (Ar+ ion beam, O2+ ion beam, O2 radiofrequency electrodeless discharge) were compared with respect to preferential etching and damage to the ultrastructure of glutaraldehyde-fixed Epon-embedded frog skeletal muscle sections. SEM and TEM studies were performed on both unstained and stained (osmium tetroxide, uranyl acetate) sections. Etching effects were observed to differ for the various ion beam or plasma etching techniques. Whereas selective retention of electron dense structures (e.g. Z lines, nuclear heterochromatin) was observed for oxygen plasma etching, preferential etching of these components was observed using O2+ ion beam bombardment. Selectively etched Z lines and etch-resistant nucleoli were observed for both reactive (O2+) and inert (Ar+) ion beam sputtering after sufficiently high ion doses. The above suggest that selective etching under keV ion beam irradiation is related more to physical sputtering processes (momentum transfer) than to the chemical reactivity of the incident ion. Heavy metal post-fixation and staining had no qualitative effect on the nature of the selective etching phenomena. The above findings are significant in that they potentially influence both electron and ion microprobe measurements of etched biological specimens.

Ion beam etching effects in biological microanalysis.

Oxygen ion beam sputter etching used in SIMS has been shown to produce morphologic effects which have similarities and differences in comparison to rf plasma etching of biological specimens. For example, selective retention of nuclear and plasma membranes is observed in both cases, however, heterochromatin is preferentially sputtered by O2+ bombardment in SIMS and preferentially preserved during O2 plasma etching. Sputter yield variations resulting from structural microheterogeneity are illustrated (e.g. etch-resistant nucleoli in preferentially etched nuclei), including their impact upon ion image formation in an ion microanalyzer. These image artifacts must be evaluated before secondary ion images revealing subcellular organelles can be related quantitatively to elemental localization in cells or tissues. To minimize gross surface roughness effects such as cone formation induced by ion bombardment, ion imaging studies of thin sections using low primary ion doses are indicated.

Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis.

In the post-genomic era, the laboratory mouse will excel as a premier mammalian system to study normal and disordered biological processes, in part because of low cost, but largely because of the rich opportunities that exist for exploiting genetic tools and technologies in the mouse to systematically determine mammalian gene function. Many robust models of human disease may therefore be developed, and these in turn will provide critical clues to understanding gene function. The full potential of the mouse for understanding many of the neural and behavioral phenotypes of relevance to neuroscientists has yet to be realized. With the full anatomy of the mouse genome at hand, researchers for the first time will be able to move beyond traditional gene-by-gene approaches and take a global view of gene expression patterns crucial for neurobiological processes. In response to an action plan for mouse genomics developed on the basis of recommendations from the scientific community, seven institutes of the National Institutes of Health (NIH) initiated in 1999 a mouse genetics research program that specifically focused on neurobiology and complex behavior. The specific goals of these neuroscience initiatives are to develop high-throughput phenotyping assays and to initiate genome-wide mutagenesis projects to identify hundreds of mutant strains with heritable abnormalities of high relevance to neuroscientists. Assays and mutants generated in these efforts will be made widely available to the scientific community, and such resources will provide neuroscientists unprecedented opportunities to elucidate the molecular mechanisms of neural function and complex behavior. Such research tools ultimately will permit the manipulation and analysis of the mouse genome, as a means of gaining insight into the genetic bases of the mammalian nervous system and its complex disorders.

Race and sex differences in hip fracture incidence.

Incidence rates for hip fracture in the United States were estimated using non-federal hospital discharges from the National Hospital Discharge Survey for the years 1974-1979. Age-specific incidence curves for women and for men showed similar patterns of increase in risk with age, with risks approximately doubling every five years after age 50. Age-specific rates by five-year age groups were compared among the four race-sex groups. No significant differences were observed between Black females, Black males, and White males. In contrast, rates for White females were one and one-half to four times those for Black females after age 40 and were approximately double those for White males after age 50. Analysis based on an independent data source of non-federal hospital discharges in Washington, DC confirmed these relationships. In the Washington study, White women were at twice the risk for hip fracture (controlled for age) compared with Black women and at 2.7 times the risk for hip fracture (controlled for age) compared to White men. No significant differences were observed between Black women and Black men.

Physical activity and depressive symptoms: the NHANES I Epidemiologic Follow-up Study.

The relation between self-reported physical activity and depressive symptoms was analyzed for 1,900 healthy subjects aged 25-77 years in the Epidemiologic Follow-up Study (1982-1984) to the first National Health and Nutrition Examination Survey (NHANES I). Depressive symptomatology as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) was examined by sex and race in relation to recreational physical activity and physical activity apart from recreation, controlling for age, education, income, employment status, and chronic conditions. Little or no recreational physical activity and little or no physical activity apart from recreation were cross-sectionally associated with depressive symptoms in whites and in blacks. After exclusion of those with depressive symptoms at baseline, recreational physical activity was an independent predictor of depressive symptoms an average of eight years later in white women. The adjusted odds of depressive symptoms at follow-up were approximately 2 for women with little or no recreational physical activity compared with women with much or moderate recreational physical activity (95% confidence interval 1.1-3.2). These findings are the first indication from a prospective study of a large community sample that physical inactivity may be a risk factor for depressive symptoms.

Blood pressure and cognitive performance. The Framingham Study.

In 1976-1978, a battery of eight neuropsychologic tests were administered to 2,123 participants in the Framingham Study who were aged 55-89 years. Performance on each test was examined in relation to concurrently measured systolic and diastolic blood pressure while controlling for age, sex, education, antihypertensive medication, alcohol consumption, and smoking. Those with a diagnosis of stroke were excluded from the analysis. In the remaining sample of 2,032, neither blood pressure nor antihypertensive treatment was significantly associated with cognitive performance. Even after excluding persons on antihypertensive medication, blood pressure was still unrelated to cognitive performance. In contrast to other studies, the authors found no consistent relation between blood pressure and cognitive performance.

Methodological issues in screening for dementia: the problem of education adjustment.

The methodological problems of developing efficient and unbiased screening methods for population-based studies of dementia have received scant attention. The potential advantages of education-adjusted screening methods are discussed. The implications for adjustment techniques of a negative correlation of educational attainment with age are emphasized. Two education adjustment methods, a stratified regression method and a nonparametric method, which take the age-education correlation into account are described, compared, and illustrated.

One-month prevalence of mental disorders in the United States and sociodemographic characteristics: the Epidemiologic Catchment Area study.

The associations between the one-month prevalence rates of mental disorders and sociodemographic characteristics were investigated for 18,571 people interviewed in the first-wave community samples of all 5 sites in the US National Institute of Mental Health (NIMH) Epidemiologic Catchment Area program. Men were found to have a significantly higher rate of cognitive impairment than women after controlling for the effects of age, race or ethnicity, marital status and socioeconomic status. Marital status was one of the most powerful correlates of mental disorder risk: the odds of separated or divorced people having any NIMH Diagnostic Interview Schedule disorder were twice that of married people after controlling for age, gender, race or ethnicity and socioeconomic status. The odds of those in the lowest socioeconomic status group having any Diagnostic Interview Schedule disorder was about 2.5 times that of those in the highest socioeconomic status group, controlling for age, gender, race or ethnicity and marital status. For all disorders except cognitive impairment, race or ethnicity did not remain statistically significant after controlling for age, gender, marital status and socioeconomic status.