The effects of latent variables in the development of comorbidity among common mental disorders

Background: Although numerous studies have examined the role of latent predispositions to internalizing and externalizing disorders in the structure of comorbidity among common mental disorders, none examined latent predispositions in predicting development of comorbidity. Methods: A novel method was used to study the role of latent variables in the development of comorbidity among lifetime DSM-IV disorders in the National Comorbidity Surveys. Broad preliminary findings are briefly presented to describe the method. The method used survival analysis to estimate time-lagged associations among 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders. A novel estimation approach examined the extent to which these predictive associations could be explained by latent canonical variables representing internalizing and externalizing disorders. Results: Consistently significant positive associations were found between temporally primary and secondary disorders. Within-domain time-lagged associations were generally stronger than between-domain associations. The vast majority of associations were explained by a model that assumed mediating effects of latent internalizing and externalizing variables, although the complexity of this model differed across samples. A number of intriguing residual associations emerged that warrant further investigation. Conclusions: The good fit of the canonical model suggests that common causal pathways account for most comorbidity among the disorders considered. These common pathways should be the focus of future research on the development of comorbidity. However, the existence of several important residual associations shows that more is involved than simple mediation. The method developed to carry out these analyses provides a unique way to pinpoint these significant residual associations for subsequent focused study. Depression and Anxiety, 2011. (c) 2011 Wiley-Liss, Inc

Thrombolysis in very elderly people: controlled comparison of SITS international stroke thrombolysis registry and virtual international stroke trials archive

<p>Objective To assess effect of age on response to alteplase in acute ischaemic stroke.</p> <p>Design Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.</p> <p>Setting Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).</p> <p>Participants 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 (“elderly,” mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity.</p> <p>Main outcome measures Functional outcomes at 90 days measured by score on modified Rankin scale.</p> <p>Results Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.</p> <p>Conclusions Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.</p&gt

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study

BACKGROUND: Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. METHODS: A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. CONCLUSIONS: This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure

Predictors of response to cognitive-behavioral therapy for body dysmorphic disorder

Body dysmorphic disorder (BDD) is a common and distressing or impairing preoccupation with a perceived defect in physical appearance. Individuals with BDD engage in time-consuming rituals to check, hide, or "fix" their appearance or alleviate distress. BDD is associated with substantial psychosocial impairment and high rates of depression, hospitalization, and suicidality. Cognitive-behavioral therapy (CBT) is the treatment of choice for BDD, but not everyone benefits. We examined predictors of CBT-related improvement, an important topic that has received very limited investigation. Treatment was delivered in weekly individual sessions over 18-22 weeks. Results indicated that greater motivation/readiness to change (University of Rhode Island Change Assessment Questionnaire), greater treatment expectancy (Treatment Credibility/Expectancy Questionnaire), and better baseline BDD-related insight (Brown Assessment of Beliefs Scale) significantly predicted better CBT response at posttreatment. Baseline BDD symptom severity and depression did not predict outcome, suggesting that even patients with more severe BDD and depressive symptoms can benefit from CBT for BDD. Efforts should be aimed at enhancing readiness to change and confidence in the treatment at treatment onset as well as addressing the poor insight that often characterizes BDD.R34 MH070490 - NIMH NIH HHSAccepted manuscrip

Tourette-like behaviors in the normal population are associated with hyperactive/impulsive ADHD-like behaviors but do not relate to deficits in conditioned inhibition or response inhibition

Attention-Deficit Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) present as distinct conditions clinically; however, comorbidity and inhibitory control deficits have been proposed for both. Whilst such deficits have been studied widely within clinical populations, findings are mixed — partly due to comorbidity and/or medication effects — and studies have rarely distinguished between subtypes of the disorders. Studies in the general population are sparse. Using a continuity approach, the present study examined (i) the relationships between inattentive and hyperactive/impulsive aspects of ADHD and TS-like behaviors in the general population, and (ii) their unique associations with automatic and executive inhibitory control, as well as (iii) yawning (a proposed behavioural model of TS). One hundred and thirty-eight participants completed self-report measures for ADHD and TS-like behaviors as well as yawning, and aconditioned inhibition task to assess automatic inhibition

Hypothesis exploration with visualization of variance.

BackgroundThe Consortium for Neuropsychiatric Phenomics (CNP) at UCLA was an investigation into the biological bases of traits such as memory and response inhibition phenotypes-to explore whether they are linked to syndromes including ADHD, Bipolar disorder, and Schizophrenia. An aim of the consortium was in moving from traditional categorical approaches for psychiatric syndromes towards more quantitative approaches based on large-scale analysis of the space of human variation. It represented an application of phenomics-wide-scale, systematic study of phenotypes-to neuropsychiatry research.ResultsThis paper reports on a system for exploration of hypotheses in data obtained from the LA2K, LA3C, and LA5C studies in CNP. ViVA is a system for exploratory data analysis using novel mathematical models and methods for visualization of variance. An example of these methods is called VISOVA, a combination of visualization and analysis of variance, with the flavor of exploration associated with ANOVA in biomedical hypothesis generation. It permits visual identification of phenotype profiles-patterns of values across phenotypes-that characterize groups. Visualization enables screening and refinement of hypotheses about variance structure of sets of phenotypes.ConclusionsThe ViVA system was designed for exploration of neuropsychiatric hypotheses by interdisciplinary teams. Automated visualization in ViVA supports 'natural selection' on a pool of hypotheses, and permits deeper understanding of the statistical architecture of the data. Large-scale perspective of this kind could lead to better neuropsychiatric diagnostics

Decline in Telomere Length by Age and Effect Modification by Gender, Allostatic Load and Comorbidities in National Health and Nutrition Examination Survey (1999-2002)

Background: This study aims to assess the decline in telomere length (TL) with age and evaluate effect modification by gender, chronic stress, and comorbidity in a representative sample of the US population. Methods: Cross-sectional data on 7826 adults with a TL measurement, were included from the National Health and Nutrition Examination Survey, years 1999–2002. The population rate of decline in TL across 10-year age categories was estimated using crude and adjusted regression. Results: In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20–29 (β = -0.0172, 95% CI: -0.0342, -0.0002), 50–59 (β = -0.0182, 95% CI: -0.0311, -0.0054) and 70–79 (β = -0.0170, 95% CI: -0.0329, -0.0011) years. The population rate of decline in TL with age was significantly greater for males and those with high allostatic load and a history of comorbidities. When the population rate of decline in TL was analyzed by gender in 10-year age bins, a fairly consistent yet statistically non-significant decline for males was observed; however, a trough in the rate was observed for females in the age categories 20–29 years (β = -0.0284, 95% CI: -0.0464, -0.0103) and 50–59 years (β = -0.0211, 95% CI: -0.0391, -0.0032). To further elucidate the gender difference observed in the primary analyses, secondary analyses were conducted with reproductive and hormonal status; a significant inverse association was found between TL and parity, menopause, and age at menopause. Conclusions: TL was shorter with increasing age and this decline was modified by gender, chronic stress and comorbidities; individuals with chronic morbidity and/or chronic stress and females in their twenties and fifties experienced greater decline. Female reproductive factors, i.e., parity and menopause, were associated with TL