Genetic questions for environmental studies. Differential parenting and psychopathology in adolescence.

BACKGROUND: Recent genetic evidence suggests that the most important environmental influences on normal and pathologic development are those that are not shared by siblings in the same family. We sought to determine the relationship between differences in parenting styles and depressive symptoms and antisocial behavior in adolescence, and to compare the influence of these nonshared experiences with genetic influences. METHODS: We studied 708 families with at least two same-sexed adolescent siblings who were monozygotic twins (93 families), dizygotic twins (99 families), ordinary siblings (95 families), full siblings in step families (181 families), half siblings in step families (110 families), and genetically unrelated siblings in step families (130 families). Data on parenting style were collected by questionnaire and by video recording of interaction between parents and children. RESULTS: Almost 60% of variance in adolescent antisocial behavior and 37% of variance in depressive symptoms could be accounted for by conflictual and negative parental behavior directed specifically at the adolescent. In contrast, when a parent directed harsh, aggressive, explosive, and inconsistent parenting toward the sibling, we found less psychopathologic outcome in the adolescent. CONCLUSIONS: Parenting behavior directed specifically at each child in the family is a major correlate of symptoms in adolescents. Furthermore, harsh parental behavior directed at a sibling may have protective effects for adolescents, a phenomenon we call the "siblin barricade."

Determining disability due to mental impairment: APA's evaluation of Social Security Administration guidelines.

OBJECTIVE: APA evaluated the Social Security Administration's (SSA's) medical standards and guidelines for determining disability due to mental impairment to determine how well the standards and guidelines operationalize the statutory definition of disability in a manner consistent with current psychiatric practice. METHOD: Seventy-two psychiatrists were trained in one of two procedures: those in the sequential evaluation condition were trained in the process and forms used by the SSA's reviewing medical consultants, and those in the statutory definition condition were trained in the statutory definition of disability and application of clinical judgment according to this standard. Decisions regarding claimant's ability or inability to work were recorded on an instrument designed for the study. Each condition consisted of 12 panels of three members. They reviewed 732 actual claims for disability benefits. The panelists reviewed claims independently, then rendered panel judgments. Each claim was reviewed by one panel in each condition. RESULTS: The proportion of agreement between conditions for panel decisions (0.77) was higher than chance agreement (kappa = 0.46). The high level of agreement on claims judged to have good medical evidence and on which confident decisions were made (proportion of agreement = 0.96, kappa = 0.78) suggests that disagreements largely reflected ambiguities in application of the standards and guidelines to more complex cases or those with inadequate information. CONCLUSIONS: The SSA's revised medical standards and guidelines reflect clinical decisions about ability to work based on the statute and, with procedural modifications, should be retained. The SSA should be involved in further systematic studies to develop a field of scientific inquiry into disability and psychiatric disorders.

Incidence of Candida parapsilosis colonization in an intensive care nursery population and its association with invasive fungal disease.

We have studied 82 consecutive intensive care nursery admissions to determine rates of colonization and incidence of fungal sepsis. Cultures were obtained from stool, gastric aspirate and skin at three different times. Infants studied ranged in gestational age from 23 to 38 weeks (mean +/- SEM 29 +/- 0.4 weeks). Nineteen percent of all infants were colonized with Candida sp.; stools were more frequently culture-positive than skin or gastric aspirates. Colonized infants began enteral feeds at a later time compared with noncolonized neonates. Five of the study infants developed fungal sepsis. One had congenital Candida albicans sepsis and died at 10 days of age; the other four had Candida parapsilosis sepsis and survived. The development of C. parapsilosis sepsis was significantly associated with gastrointestinal colonization. Our results suggest that early initiation of enteral feeds decreases gastrointestinal colonization with C. parapsilosis. Gastrointestinal colonization was strongly associated with the subsequent development of C. parapsilosis sepsis in this group of high risk neonates.

The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumors and other neoplasms in rats.

Sprague-Dawley rats were irradiated with a continuous- wave (CW) or a pulsed-wave (P) radiofrequency (RF) for 6 h/day, 5 days/week from 2 up to 24 months of age. The RFs emanated from dipole antennas (1 W average output) 2.0 +/- 0.5 cm from the tip of each rat's nose. The RFs had an 860 MHz frequency, and the specific absorption rate was 1.0 W/ kg averaged over the brain. Fifteen groups of 60 rats (900 total) were formed from offspring of females injected i.v. with 0 (groups 1, 2, 9, 10, 13), 2.5 (groups 5, 6, 7, 8, 11, 12, 14) or 10 mg/kg (groups 3, 4, 15) ethylnitrosourea (ENU) to induce brain tumors. Groups 1, 3, 5 and 7 received the PRF, and groups 9 and 11 the CWRF; groups 2, 4, 6, 8, 10 and 12 were sham-irradiated, and groups 13-15 were cage controls. All rats but 2, totaling 898, were necropsied, and major tissues were studied histopathologically. There was no statistically significant evidence that the PRF or CWRF induced neoplasia in any tissues. Additionally, there was no significant evidence of promotion of cranial or spinal nerve or spinal cord tumors. The PRF or CWRF had no statistically significant effect on the number, volume, location, multiplicity, histological type, malignancy or fatality of brain tumors. There was a trend for the group that received a high dose of ENU and was exposed to the PRF to develop fatal brain tumors at a higher rate than its sham group; however, the result was not significant using the log-rank test (P = 0.14, 2-tailed). No statistically significant differences were related to the PRF or CWRF compared to controls in the low- or zero-dose groups regarding tumors of any kind.

Young adolescents' comfort with discussion about sexual problems with their physician.

OBJECTIVE: To identify factors associated with young adolescents' sense of comfort about discussing sexual problems with their physician. DESIGN: Confidential, assisted self-report questionnaires on physician-adolescent communication developed by the investigators and completed by participants at visits for general health examinations. SETTING: Five primary care pediatric practices at health maintenance organizations in Washington, DC. PATIENTS: A consecutive sample of all adolescents 12 to 15 years old who received a general health examination. Of 412 eligible patients, 221 received parental consent and participated. MAIN OUTCOME MEASURE: Adolescents' sense of comfort about talking to their physician about a sexually transmitted disease or some other sexual problem. This outcome was chosen for a substudy of a larger longitudinal prevention trial. RESULTS: Most adolescents valued their physicians' opinions about sex (89%) and said it was easy to talk to the physician during their visit (99%), but about half said they would be uncomfortable talking to the physician if they had a sexually transmitted disease or some other sexual problem (43%) [corrected]. Adolescents' sense of comfort was greater when physicians discussed sexual issues in the general health examination, adolescents perceived their personal risk of sexually transmitted disease to be high, adolescents had high self-esteem, and physicians were adolescents' usual physicians. CONCLUSIONS: This study emphasizes the need for physicians to discuss sexual risks with young adolescents and suggests ways physicians can help young adolescents feel more comfortable talking with them about sexual concerns.

Ability to measure sensitive adolescent behaviors via telephone.

INTRODUCTION: Difficulty in measuring sensitive behaviors in 12-15-year-old adolescents is a barrier to research. This study determined whether early adolescents reported substance use and sexual activity similarly in assisted paper-and-pencil versus touch-tone telephone responses. METHODS: Adolescents 12-15 years old completed confidential, interviewer-assisted questionnaires first in a physician office by paper-and-pencil and then at home by touch-tone approximately 3 months later. Adolescents were from a high-risk urban area, 71% were minority, and all had parent consent to participate. RESULTS: The follow-up participation rate was 94% (follow-up n = 207). Test-retest stability was generally poor for low-frequency behaviors such as injection drug use, anal intercourse, and sexual behaviors in 12-13-year-olds. Test-retest stability was fair to good for common substance use items. Test-retest stability was generally good among females and 14-15-year-old adolescents, and poor to fair among males and 12-13-year-olds, for common sexual experiences in the last 3 months. Test-retest stability was generally good to excellent for all lifetime sexual experiences except among 12-13-year-olds in which it was generally poor. Internal consistency of the self-esteem scale was high using both response technologies. Both response technologies reproduced correlations between substance use and lifetime sexual experience. CONCLUSION: A high participation rate and reliable data capture were achieved when assessing sensitive behaviors of 14-15-year-olds using touch-tone telephone response. Sexual behaviors were more reliably captured using a "lifetime" versus "last 3-month" reference period. Low prevalence contributed to poor reliability in 12-13-year-olds.

Rejecting the patient: preliminary validation of a self-report scale.

The authors describe an easily administered scale being developed to assess the rejecting feelings of family respondents toward former mental patients who return to live with their families. Based upon a sample of 133 discharged mental patients and family members, the scale demonstrates a moderately high reliability (alpha = .78) and test-retest correlation (r = .72). Data are presented for evaluating the construct validity of the scale.

Pharmacotherapy response and diagnostic validity in atypical depression.

BACKGROUND: The validity of diagnostic criteria and the efficacy of tricyclic antidepressant pharmacotherapy for atypical depression were studied in the NIMH Treatment of Depression Collaborative Research Program. METHODS: Outpatients with major depressive disorder (N = 239) entered a 16-week clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive behavior therapy, and imipramine or placebo with clinical management. Features of atypical depression were rated on the SADS and ISI and clinical outcome was measured on the HRSD and GAS. RESULTS: Atypical features of mood reactivity and at least one reversed vegetative symptom of hypersomnia, hyperphagia or weight gain (25.2% patients) were predictive of pharmacotherapy non-responsiveness with imipramine compared to placebo. The additional features of diurnal mood variation, 'leaden paralysis', and 'rejection sensitivity' did not further distinguish animipramine non-responsive subgroup. Imipramine did show significant effectiveness compared to placebo among non-atypical patients on measures of depressive symptom change. LIMITATIONS: The predictive influence of atypical features was not accounted for on the basis of depression severity. CONCLUSIONS: This study provides evidence for the predictive validity of atypical features of major depressive disorder, including mood reactivity and at least one reversed vegetative symptom of either hypersomnia, hyperphagia, or weight gain, supporting the inclusion of atypical depressive features, with these criteria, in the DSM-IV.

Negative affectivity, restriction of emotions, and site of metastases predict mortality in recurrent breast cancer.

OBJECTIVE: To assess whether negative affectivity and restriction of emotions predict survival time with recurrent breast cancer. METHODS: Thirty-two patients with recurrent breast cancer, diagnosed 6-19 months earlier and stabilized using surgical, medical and/or radiation therapies, were enrolled. Cox regression survival analyses, including initial severity of metastases (RR=4.3 [1.3-14.3]; p=0.02), were used to explore the association of psychological variables with survival. RESULTS: Low chronic anxiety in the context of low emotional constraint predicted low mortality (RR 0.07 [0.01-0.52]; p=0.007). However, patients with low chronic anxiety scores but with high constraint had higher mortality (RR=3.7 [1.2-11.5; p=0.02). High chronic anxiety, with or without high constraint, also predicted earlier death, as did high control of feelings. CONCLUSION: An integrated model of negative affectivity in the context of restriction of emotions appears to strengthen the prediction of survival based on severity of breast cancer metastases.

Use of human milk in the intensive care nursery decreases the incidence of nosocomial sepsis.

OBJECTIVES: This study compares stool colonization and incidence of sepsis in human milk-fed (HM) and formula-fed (FF) intensive care nursery (ICN) patients. STUDY DESIGN: Infants recruited prospectively were fed HM based on the decision of their mothers (59 HM and 114 FF). The incidence of sepsis was determined during the following three intervals: period 1, first 10 days of life; period 2, 11 to 24 days; and period 3, 25 to 38 days. RESULTS: Frequency of Escherichia coli and Enterococcus sp. colonization was increased in HM infants. The incidence of sepsis was 9.5% in period 1 (5% in HM vs 10% in FF), 17.2% in period 2 (9% in HM vs 20% in FF), and 12.5% in period 3 (0% in HM vs 15% in FF). The odds ratio for sepsis in HM infants was 0.4, the 95% limits 0.15 to 0.95, p = 0.04. CONCLUSIONS: HM feeding in the ICN has a protective effect against nosocomial sepsis, which is unrelated to its influence on gastrointestinal (GI) flora.

Evaluation of ENU-induced gliomas in rats: nomenclature, immunochemistry, and malignancy.

Rats developed mixed gliomas, oligodendrogliomas, and a few astrocytomas in response to transplacental ethylnitrosourea. The neoplastic cell composition of mixed gliomas must be defined; this study required a 20-80% admixture of neoplastic astrocytes and oligodendroglia for the diagnosis of mixed glioma. A battery of immunoantibodies, including Leu-7, S-100, and vimentin, were helpful in classifying rat gliomas, and the histologic features of each tumor type are described. Other brain tumor characteristics that may decide the outcome of carcinogenicity studies include incidence, multiplicity, latency, fatality, size, and malignancy. The size of tumors was determined by measuring their 3-dimensional volumes. Brain tumor volume was found to be highly correlated with malignancy and fatality. Systematic evaluation of the malignancy of brain tumors is an important but often overlooked adjunct method of measuring the effectiveness of a carcinogen. A system to estimate malignancy, one that grades 9 tumor characteristics and weights, each according to clinical outcome, was developed. It was found that mixed gliomas grew larger, had a shorter latency, and were significantly more malignant than were other gliomas.

Continuous ambulatory peritoneal dialysis and survival of HIV infected patients with end-stage renal disease.

As the number of human immunodeficiency virus (HIV) infected patients has increased in the U.S., the number of infected patients treated for end-stage renal disease (ESRD) has stabilized at about 1 to 2% of the hemodialyzed population. Little has been written regarding the role of continuous ambulatory peritoneal dialysis (CAPD) in the treatment of HIV infected patients with ESRD. To evaluate the effectiveness of CAPD as a long term therapy for HIV infected patients with ESRD, we reviewed our ESRD program's experience. We entered 392 patients from its inception in February 1984 until April 1992. Thirty-one, or 7.9% of our population were HIV infected. Twenty, or 64.5% had stage IV infection. Patients were entered into our chronic hemodialysis (HD) or CAPD program according to standard clinical criteria. Eight HIV infected patients elected to start CAPD, while 23 patients were treated exclusively with HD. The proportion of stage IV infected patients was similar in both treatment modality groups. HIV infected ESRD patients were younger than non-HIV infected patients (37.5 +/- 9.7 vs. 49.8 +/- 15.7 years, respectively, P < 0.0001) at the start of treatment. We used Cox regression techniques to analyze survival data. Mean survival time for our entire non-HIV infected ESRD population (N = 361) was 44.0 +/- 33.9 months. Mean survival time for HIV infected patients with ESRD was 15.5 +/- 9.9 months. Median survival for HIV infected ESRD patients was 13 months compared to 38 months for the non-infected population. As expected, mean survival time in HIV infected ESRD patients was significantly diminished compared to non-infected ESRD patients (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Social Security Disability Evaluation Study.

Disability has continued to gain attention as a research topic in the mental health field. Both the SSA and the National Institute of Disability and Rehabilitation Research currently fund research aimed at understanding the vocational needs of severely mentally ill adults, particularly those in supportive employment programs. The National Institute of Mental Health funds research on disability and rehabilitation, particularly research on innovative approaches to increasing the individual's level of functioning and quality of life. All of these federal agencies anticipate continued funding of research on disability. This evaluation of the SSA's 1985 medical standards and guidelines by the APA is an example of the type of disability research that seeks to address issues related to individuals as well as important policy questions. In this evaluation, both the appropriateness and utility of the standards and guidelines were assessed, and the quality of disability decisions for severely mentally impaired applicants was studied.

Behavioral and biochemical indices of compliance in hemodialysis patients.

Noncompliance has been implicated in modifying morbidity and mortality in end stage renal disease patients; however, the data are conflicting, and measurement of compliance has been difficult. Traditional measurements of compliance include serum potassium (K) and phosphorus (P) concentrations, and interdialytic fluctuations in weight gain (IWG). This study correlated three indices: 1) Adequacy of dialysis (Kt/V); 2) protein ingestion (PCR); and 3) the percentage of time dialyzed compared with the total dialysis time prescribed (% Time) with the traditional measurements of compliance. Correlations were calculated among pre- and post-BUN (blood urea nitrogen), Kt/V, K and P, PCR, IWG, and % Time. As expected, BUN levels correlated with Kt/V, K, P, PCR, IWG, and % Time. Protein ingestion correlated with K and IWG, but not with % Time. Adequacy of dialysis correlated with P levels, but not with PCR, WG, or % Time. Phosphorus correlated with pre- and post-BUN, Kt/V, and % Time, but not with K. Potassium, P, and IWG did not correlate internally. The authors conclude that standard biochemical measures of compliance reflect different compliance behaviors (dietary selection and restriction, restriction of fluid and salt intake, and adherence to medication regimens). Percent time may be a powerful, independent measure of patient compliance with the dialysis regimen.

Staphylococcus epidermidis sepsis in the intensive care nursery: a characterization of risk associations in infants < 1,000 g.

We undertook to determine Staphylococcus epidermidis colonization patterns and risks of sepsis in a cohort of 82 consecutive intensive care nursery admissions (birth weight 1,285 +/- 57 g), with 24 infants weighing < 1,000 g at birth. Colonization was determined by skin and stool cultures collected at three time points. Multiple neonatal variables were classified into three intervals preceding the time of sample collection including the occurrence of S. epidermidis sepsis. 16 infants (20%) developed S. epidermidis sepsis. 81% of these episodes occurred in infants < 1,000 g. Skin colonization was nearly universal at all sampling points. Rectal colonization was 63.6% initially (10 +/- 0.4 days), then declined to 32% by the third sample (37 +/- 0.4 days). Neither prevalence of skin nor rectal colonization influenced the incidence of sepsis significantly. Statistically significant risk associations for sepsis for the entire intensive care nursery population included: low birth weight, gestational age, presence of a central line, and delayed feeding. For infants < 1,000 g the occurrence of sepsis during the second study time period (54% of the episodes) was associated with preceding steroid exposure. During the third study time period, birth weight and delayed attainment of full enteral feeds showed a statistically significant association with sepsis. We conclude that infants < 1,000 g are at an increased risk of S. epidermidis sepsis. Extreme immaturity, steroid therapy, and prolonged hyperalimentation are all significant risk associations.

Natural disaster and depression: a prospective investigation of reactions to the 1993 midwest floods.

A statewide sample of 1735 Iowa residents, approximately half of whom were victims of the 1993 Midwest Floods, participated in interviews 1 year prior to, and 30 to 90 days after, the disaster. Employing a rigorous methodology including both control-group comparisons and predisaster assessments, we performed a systematic evaluation of the disaster's impact. Overall, the disaster led to true but small rises in depressive symptoms and diagnoses 60-90 days postflood. The disaster-psychopathology effect was not moderated by predisaster depressive symptoms or diagnostically defined depression; rather, predisaster symptoms and diagnoses uniquely contributed to increases in postdisaster distress. However, increases in symptoms as a function of flood impact were slightly greater among respondents with the lowest incomes and among residents living in small rural communities, as opposed to on farms or in cities. Implications for individual- and community-level disaster response are discussed.

Depression, perception of illness and mortality in patients with end-stage renal disease.

A role of depression in affecting outcome in patients with end stage renal disease (ESRD) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospectively. To assess whether depression or perception of illness influences survival in patients treated for ESRD, we prospectively evaluated fifty-seven patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14). Patients were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity. A cognitive item subset of the BDI (CDI) was used as an additional measure of depression. One and two years later, records were examined to determine survival. When initial results of the assessment of survivors and non-survivors were compared, at one year follow-up, there were no differences in mean age, duration of dialysis, severity scores, BDI or IEQ scores. The initial mean CDI scores in the group of non-survivors, however, were significantly greater than the scores in the survivor group. At two year follow-up, CDI scores were significantly different between groups, and were significant in a hazards regression. Disease severity, age and duration of dialysis were also significantly related to mortality at two year follow-up. We conclude cognitive depression is an important, early, indicator of grave prognosis in patients treated for ESRD. Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients.

Bcl-2 protects neural cells from cyanide/aglycemia-induced lipid oxidation, mitochondrial injury, and loss of viability.

The protooncogene bcl-2 rescues cells from a wide variety of insults. Recent evidence suggests that the mechanism of action of Bcl-2 involves antioxidant activity. The involvement of free radicals in ischemia/reperfusion injury to neural cells has led us to investigate the effect of Bcl-2 in a model of delayed neural cell death. We have examined the survival of control and bcl-2 transfectants of a hypothalamic tumor cell line, GT1-7, exposed to potassium cyanide in the absence of glucose (chemical hypoxia/aglycemia). After 30 min of treatment, no loss of viability was evident in control or bcl-2 transfectants; however, Bcl-2-expressing cells were protected from delayed cell death measured following 24-72 h of reoxygenation. Under these conditions, the rate and extent of ATP depletion in response to treatment with cyanide in the absence of glucose and the rate of recovery of ATP during reenergization were similar in control and Bcl-2-expressing cells. Bcl-2-expressing cells were protected from oxidative damage resulting from this treatment, as indicated by significantly lower levels of oxidized lipids. Mitochondrial respiration in control but not Bcl-2-expressing cells was compromised immediately following hypoxic treatment. These results indicate that Bcl-2 can protect neural cells from delayed death resulting from chemical hypoxia and reenergization, and may do so by an antioxidant mechanism. The results thereby provide evidence that Bcl-2 or a Bcl-2 mimetic has potential therapeutic application in the treatment of neuropathologies involving oxidative stress, including focal and global cerebral ischemia.

Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients.

BACKGROUND: The medical risk factors associated with increased mortality in hemodialysis (HD) patients are well known, but the psychosocial factors that may affect outcome have not been clearly defined. One key psychosocial factor, depression, has been considered a predictor of mortality, but previous studies have provided equivocal results regarding the association. We sought to determine whether depressive affect is associated with mortality in a longitudinal study of end-stage renal disease (ESRD) patients treated with HD, using multiple assessments over time. METHODS: Two hundred ninety-five outpatients with ESRD treated with HD were recruited from three outpatient dialysis units in Washington D.C. to participate in a prospective cohort study with longitudinal follow-up. Patients were assessed every six months for up to two years using the Beck Depression Inventory (BDI), age, serum albumin concentration, Kt/V, and protein catabolic rate (PCR). A severity index, previously demonstrated to be a mortality marker, was used to grade medical comorbidity. The type of dialyzer with which the patient was treated was noted. Patient mortality status was tracked for a minimum of 20 and a maximum of 60 months after the first interview. Cox proportional hazards models, treating depression scores as time-varying covariates in a univariable analysis, and controlling for age, medical comorbidity, albumin concentration, and dialyzer type and site in multivariable models, were used to assess the relative mortality risk. RESULTS: The mean (+/- SD) age of our population at initial interview was 54.6 +/- 14.1 years. The mean PCR was 1.06 +/- 0.27 g/kg/day, and the mean Kt/V was 1.2 +/- 0.4 at baseline, suggesting that the patients were well nourished and dialyzed comparably to contemporary U.S. patients. The patients' mean BDI at enrollment was 11.4 +/- 8.1, in the range of mild depression. Patients' baseline level of depression was not a significant predictor of mortality at 38.6 months of follow-up. In contrast, when depression was treated as a time-varying covariate based on periodic follow-up assessments, the level of depressive affect was significantly associated with mortality in both single variable and multivariable analyses. CONCLUSIONS: Higher levels of depressive affect in ESRD patients treated with HD are associated with increased mortality. The effects of depression on patient survival are of the same order of magnitude as medical risk factors. Our findings using both controls for factors possibly confounded with depressive affect in patients with ESRD and time-varying covariate analyses may explain the inconsistent results of previous studies of depression and mortality in ESRD patients. Time-varying analyses in longitudinal studies may add power to defining and sensitivity to establishing the association of psychosocial factors and survival in ESRD patients. The mechanism underlying the relationship of depression and survival and the effect of interventions to improve depression in HD outpatients and general medical inpatients should be studied.