Beverly J. Insel

Is There More to Complicated Grief Than Depression and Posttraumatic Stress Disorder? A Test of Incremental Validity

There is growing interest in complicated grief reactions as a possible new diagnostic category for inclusion in the Diagnostic and Statistical Manual of Mental Disorders. However, no research has yet shown that complicated grief has incremental validity (i.e., predicts unique variance in functioning). The authors addressed this issue in 2 studies by comparing grief, depression, and posttraumatic stress disorder (PTSD) symptoms with different measures of functioning (interviewer ratings, friend ratings, self-report, and autonomic arousal). The 1st study (N = 73) used longitudinal data collected at 4 and 18 months postloss, and the 2nd study (N = 447) used cross-sectional data collected 2.5-3.5 years postloss. With depression and PTSD controlled, grief emerged as a unique predictor of functioning, both cross-sectionally and prospectively. The findings provide convergent support for the incremental validity of complicated grief as an independent marker of bereavement-related psychopathology.

Maternal Iron Deficiency and the Risk of Schizophrenia in Offspring

CONTEXT Iron is essential for brain development and functioning. Emerging evidence suggests that iron deficiency in early life leads to long-lasting neural and behavioral deficits in infants and children. Adopting a life course perspective, we examined the effects of early iron deficiency on the risk of schizophrenia in adulthood. OBJECTIVE To determine whether maternal iron deficiency, assessed by maternal hemoglobin concentration during pregnancy, increases the susceptibility to schizophrenia spectrum disorders (SSDs) among offspring. DESIGN Data were drawn from a population-based cohort born from 1959 through 1967 and followed up for development of SSD from 1981 through 1997. PARTICIPANTS Of 6872 offspring for whom maternal hemoglobin concentration was available, 57 had SSDs (0.8%) and 6815 did not (99.2%). MAIN OUTCOME MEASURE Prospectively assayed, the mean value of maternal hemoglobin concentration was the primary exposure. Hemoglobin concentration was analyzed as a continuous and a categorical variable. RESULTS A mean maternal hemoglobin concentration of 10.0 g/dL or less was associated with a nearly 4-fold statistically significant increased rate of SSDs (adjusted rate ratio, 3.73; 95% confidence interval, 1.41-9.81; P = .008) compared with a mean maternal hemoglobin concentration of 12.0 g/dL or higher, adjusting for maternal education and ethnicity. For every 1-g/dL increase in mean maternal hemoglobin concentration, a 27% decrease in the rate of SSDs was observed (95% confidence interval, 0.55-0.96; P = .02). CONCLUSIONS The findings suggest that maternal iron deficiency may be a risk factor for SSDs among offspring. Given that this hypothesis offers the potential for reducing the risk for SSDs, further investigation in independent samples is warranted.

Impact of Modeling on Adolescent Suicidal Behavior

The evidence to date suggests that suicide modeling is a real phenomenon, although of a smaller effect size than other psychiatric and psychosocial risk factors for adolescent suicide. Multiple lines of inquiry provide converging evidence, including studies on suicide clusters, media influence on suicide (particularly coverage of nonfictional suicides), and peer influence on suicidality. Despite variations in study setting and methodology, the body of literature is consistent with a modeling hypothesis. Although advances in documentation of suicide modeling have been made over the past decade, we are still confronted by unresolved issues regarding the underlying mechanisms. Prevention and postvention strategies can be optimized to avert modeling of suicidal behavior only once research addresses the complexities and uncertainties of this phenomenon.

Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years

Background Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age. Methods In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ). Results Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = −2.69 (95% confidence interval [CI] = −4.33, −1.05) and b = −2.69 (95% CI = −4.22, −1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4) and 7.6 (95% CI = 3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning. Conclusion Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children’s intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.

Maternal–fetal blood incompatibility and the risk of schizophrenia in offspring

OBJECTIVE Predicated on a maternal immune response to paternally inherited foreign fetal blood antigens, we hypothesized that maternal-fetal blood incompatibility increases susceptibility to schizophrenia in the offspring. The relation between schizophrenia and maternal-fetal blood incompatibility, arising from the D antigen of the Rhesus (Rh) and the ABO blood group antigens, was examined in a cohort of live-births. METHOD The data were drawn from the Prenatal Determinants of Schizophrenia Study, a cohort of births occurring between 1959 and 1967 to women enrolled in a Kaiser Permanente Plan-Northern California Region (KP). Adult offspring belonging to the KP from 1981 to 1997 were followed for the incidence of schizophrenia spectrum disorder (SSD). Cox proportional hazards regression was the primary analytic technique. RESULTS Among second and later born offspring, the adjusted incidence rate ratio (RR(adj)) of SSD was 1.80 (95% CI=0.71-4.58) for the Rh incompatible offspring compared with the Rh compatible offspring; with the males exhibiting higher rate ratio (RR(adj)=2.37; 95% CI=0.82-6.86) than the females (RR(adj)=0.93 95% CI=0.12-7.01). Among all offspring, the RR(adj) for ABO incompatibility was lower and the elevated rate ratio was similarly limited to the males (RR(adj)=1.68; 95% CI=0.76-3.70). For Rh and/or ABO incompatibility, the RR(adj) was 1.57 (95% CI=0.87-2.82). A statistically significant result was detected only for the male offspring (RR(adj)=2.22; 95% CI=1.10-4.47). CONCLUSION Although the results should be interpreted with caution given the few events of SSD, the findings extend the line of evidence that maternal-fetal blood incompatibility is a risk factor for schizophrenia spectrum disorder; with the strongest evidence to date implicating that the susceptibility pertains only to male offspring.

Adolescent Varicocele: Influence of Tanner Stage at Presentation on the Presence, Development, Worsening and/or Improvement of Testicular Hypotrophy Without Surgical Intervention

PURPOSE Testicular asymmetry in adolescents with varicocele can worsen, remain unchanged or decrease on followup. We determined the incidence of testicular asymmetry at presentation by Tanner stage and the correlation between Tanner stage at presentation and subsequent changes in percent asymmetry (ability for catch-up growth or progressive asymmetry) without surgical intervention. MATERIALS AND METHODS We retrospectively studied the records of 115 boys with a mean age of 14.1 years (range 9.2 to 20.0) with grade 2 or 3 left varicocele who underwent testicular volume measurement at 2 visits at least that were a minimum of 6 months apart. Of the patients 92% and 8% underwent Doppler duplex ultrasound and orchidometry, respectively. Patients were divided into 2 groups, including those with less than 15% and those with 15% or greater asymmetry. Catch-up growth was defined as less than 15% asymmetry at any subsequent visit. RESULTS At presentation 58%, 64%, 67%, 35% and 39% of Tanner 1 to 5 cases showed 15% or greater testicular asymmetry, respectively. When Tanner 1 to 3 cases were combined and compared with Tanner 4 and 5 cases, the difference in initial asymmetry was significant (64% vs 38%, p = 0.007). Although it was not statistically significant, there was a trend toward more catch-up growth for the later Tanner stages, including 27% for Tanner 1 to 3 vs 53% for Tanner 4 and 5 (p = 0.06). CONCLUSIONS Slightly more than 50% of children and adolescents referred with varicocele have 15% or greater testicular asymmetry at presentation. Initial asymmetry is statistically more common in cases of earlier Tanner stages (1 to 3). Adolescents with 15% or greater testicular asymmetry who present at higher Tanner stages (4 and 5) show a trend toward a higher incidence of catch-up growth, although it is not significant.

Suicide reporting content analysis: abstract development and reliability

Despite substantial research on media influences and the development of media guidelines on suicide reporting, research on the specifics of media stories that facilitate suicide contagion has been limited. The goal of the present study was to develop a content analytic strategy to code features in media suicide reports presumed to be influential in suicide contagion and determine the interrater reliability of the qualitative characteristics abstracted from newspaper stories. A random subset of 151 articles from a database of 1851 newspaper suicide stories published during 1988 through 1996, which were collected as part of a national study in the United States to identify factors associated with the initiation of youth suicide clusters, were evaluated. Using a well-defined content-analysis procedure, the agreement between raters in scoring key concepts of suicide reports from the headline, the pictorial presentation, and the text were evaluated. The results show that while the majority of variables in the content analysis were very reliable, assessed using the kappa statistic, and obtained excellent percentages of agreement, the reliability of complicated constructs, such as sensationalizing, glorifying, or romanticizing the suicide, was comparatively low. The data emphasize that before effective guidelines and responsible suicide reporting can ensue, further explication of suicide story constructs is necessary to ensure the implementation and compliance of responsible reporting on behalf of the media.

Uptake and Patterns of Use of Gemcitabine for Metastatic Pancreatic Cancer: A Population-Based Study

Gemcitabine was approved for advanced pancreatic cancer in 1996. We investigated uptake and predictors of its use. We identified 3,231 individuals > 65 years in the SEER-Medicare database with stage IV pancreatic adenocarcinoma, diagnosed between 1998–2005, who survived >30 days. Of these, 54% received chemotherapy, 93% with gemcitabine. Gemcitabine nonreceipt was associated with advanced age and unmarried (OR: 0.65, 95% CI: 0.55–0.76). Diagnosis in 2004–2005 versus 1998–2000 was more likely to receive gemcitabine (OR: 1.51, 95% CI: 1.23–1.84) as were higher SES patients (highest versus lowest quintile, OR: 2.14, 95% CI: 1.60–2.85). Gemcitabine was rapidly adopted among elderly advanced pancreatic cancer patients; several factors are associated with use.

Phthalates and thyroid function in preschool age children: Sex specific associations

BACKGROUND Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive. METHODS In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3years. We measured childrens serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) at age 3. Linear regression models were used to investigate the associations between phthalate metabolites, measured in maternal urine during late pregnancy and measured in child urine at age 3 and thyroid function measured at age 3. RESULTS Mean concentrations (ranges) were 1.42ng/dL (1.02-2.24) for FT4, and 2.62uIU/mL (0.61-11.67) for TSH. In the children at age 3, among girls, FT4 decreased with increasing loge mono-n-butyl phthalate [estimated b=-0.06; 95% CI: (-0.09, -0.02)], loge mono-isobutyl phthalate [b=-0.05; 95% CI: (-0.09, -0.01)], loge monoethyl phthalate [b=-0.04; 95% CI: (-0.07, -0.01)], and loge mono(2-ethyl-5-hydroxyhexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.003)] and loge mono(2-ethyl-5-oxy-hexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.004)]. In contrast, among boys, we observed no associations between FT4 and child phthalate metabolites at age 3. On the other hand, in late gestation, FT4 increased with increasing loge mono-(2-ethylhexyl) phthalate [estimated b=0.04; 95% CI: (0.02, 0.06)] and no sex difference was observed. We found no associations between phthalate biomarkers measured in either the child or prenatal samples and TSH at age 3. CONCLUSIONS The data show inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and thyroid function in preschool children. These results may provide evidence for the hypothesis that reductions in thyroid hormones mediate associations between early life phthalate exposure and child cognitive outcomes.

Split dose and MiraLAX-based purgatives to enhance bowel preparation quality becoming common recommendations in the US

Objectives: Rates of suboptimal bowel preparation up to 30% have been reported. Liberalized precolonoscopy diet, split dose purgative, and the use of MiraLAX-based bowel preparation (MBBP) prior to colonoscopy are recently developed measures to improve bowel preparation quality but little is known about the utilization prevalence of these measures. We examined the patterns of utilization of these newer approaches to improve precolonoscopy bowel preparation quality among American gastroenterologists. Methods: Surveys were distributed to a random sample of members of the American College of Gastroenterologists. Participants were queried regarding demographics, practice characteristics, and bowel preparation recommendations including recommendations for liberal dietary restrictions, split dose purgative, and the use of MBBP. Approaches were evaluated individually and in combination. Results: Of the 999 eligible participants, 288 responded; 15.2% recommended a liberal diet, 60.0% split dose purgative, and 37.4% MBBP. Diet recommendations varied geographically with gastroenterologists in the West more likely to recommend a restrictive diet (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.16–7.67) and physicians in the Northeast more likely to recommend a liberal diet more likely. Older physicians more often recommended split dosing (OR 1.04, 95% CI 1.04–2.97). Use of MBBP was more common in suburban settings (OR 2.14, 95% CI 1.23–3.73). Evidence suggests that physicians in private practice were more likely to prescribe split dosing (p = 0.03) and less often recommended MBBP (p = 0.02). Likelihood of prescribing MBBP increased as weekly volume of colonoscopy increased (p = 0.03). Conclusions: To enhance bowel preparation quality American gastroenterologists commonly use purgative split dosing. The use of MBBP is becoming more prevalent while a liberalized diet is infrequently recommended. Utilization of these newer approaches to improve bowel preparation quality varies by physician and practice characteristics. Further evaluation of the patterns of usage of these measures is indicated.