Highlights
IN THIS ISSUE
- CRAIG MORGAN
-
- Published online by Cambridge University Press:
- 16 October 2006, pp. 1499-1500
-
- Article
-
- You have access Access
- Export citation
-
This issue contains two reviews, one on the findings from high-risk studies of schizophrenia, and one comparing two psychological interventions for post-traumatic stress disorder (PTSD). Other sets of papers examine various aspects of PTSD, psychosis, personality disorder, and common mental disorders, and four individual papers examine a variety of topics.
Invited Review
Precursors and prodromata of schizophrenia: findings from the Edinburgh High Risk Study and their literature context
- D. G. CUNNINGHAM OWENS, EVE C. JOHNSTONE
-
- Published online by Cambridge University Press:
- 03 July 2006, pp. 1501-1514
-
- Article
- Export citation
-
Background. In schizophrenia research, ‘high risk’ traditionally referred to studies of the offspring of schizophrenic parents at genetically enhanced risk of illness development. Sixteen major high-risk studies have been undertaken although only six followed through to formal illness so data on prediction remain weak. Recently, ‘high risk’ has widened to encompass individuals considered ‘at risk’ by having ‘high risk mental states’, regardless of family history, in whom initiation of early treatment is postulated to improve outcome.
Method. The major familial high-risk studies are reviewed from the perspective of the Edinburgh High Risk Study of Schizophrenia (EHRS), with emphasis on prediction.
Results. Familial high-risk studies have established multiple biological markers, the most reproducible of which relate to neuromotor development and cognition, especially aspects of memory/learning. Although most are probably not specific, they support a neurodevelopmental hypothesis. Family and environmental variables point largely to secondary or indirect associations. Pre-illness, non-specific affective symptomatology may be of greater predictive power than most psychotic phenomena.
Conclusions. Traditional high-risk designs embody many problems but are able to distinguish non-specific markers from illness predictors, and are ideally suited to exploring the evolution of schizophrenia both clinically and biologically (especially with imaging techniques). The EHRS supports the view that greater specificity may accrue to cognitive domains as precursors of predictive utility.
Review Article
Comparing the efficacy of EMDR and trauma-focused cognitive-behavioral therapy in the treatment of PTSD: a meta-analytic study
- GUENTER H. SEIDLER, FRANK E. WAGNER
-
- Published online by Cambridge University Press:
- 02 June 2006, pp. 1515-1522
-
- Article
- Export citation
-
Background. Eye movement desensitization and reprocessing (EMDR) and trauma-focused cognitive-behavioral therapy (CBT) are both widely used in the treatment of post-traumatic stress disorder (PTSD). There has, however, been debate regarding the advantages of one approach over the other. This study sought to determine whether there was any evidence that one treatment was superior to the other.
Method. We performed a systematic review of the literature dating from 1989 to 2005 and identified eight publications describing treatment outcomes of EMDR and CBT in active–active comparisons. Seven of these studies were investigated meta-analytically.
Results. The superiority of one treatment over the other could not be demonstrated. Trauma-focused CBT and EMDR tend to be equally efficacious. Differences between the two forms of treatment are probably not of clinical significance. While the data indicate that moderator variables influence treatment efficacy, we argue that because of the small number of original studies, little benefit is to be gained from a closer examination of these variables. Further research is needed within the framework of randomized controlled trials.
Conclusions. Our results suggest that in the treatment of PTSD, both therapy methods tend to be equally efficacious. We suggest that future research should not restrict its focus to the efficacy, effectiveness and efficiency of these therapy methods but should also attempt to establish which trauma patients are more likely to benefit from one method or the other. What remains unclear is the contribution of the eye movement component in EMDR to treatment outcome.
Original Article
Epidemiology of trauma, post-traumatic stress disorder (PTSD) and co-morbid disorders in Chile
- CARON ZLOTNICK, JENNIFER JOHNSON, ROBERT KOHN, BENJAMIN VICENTE, PEDRO RIOSECO, SANDRA SALDIVIA
-
- Published online by Cambridge University Press:
- 20 July 2006, pp. 1523-1533
-
- Article
- Export citation
-
Background. In this study we examined the prevalence rates of post-traumatic stress disorder (PTSD), types of trauma most often associated with PTSD, the co-morbidity of PTSD with other lifetime psychiatric disorders, which disorders preceded PTSD, and gender differences in PTSD and trauma exposure in a representative sample of Chileans.
Method. The DSM-III-R PTSD and antisocial personality disorder modules from the Diagnostic Interview Schedule (DIS) and modules for a range of DSM-III-R diagnoses from the Composite International Diagnostic Interview (CIDI) were administered to a representative sample of 2390 persons aged 15 to over 64 years in three cities in Chile.
Results. The lifetime prevalence of PTSD was 4·4% (2·5% for men and 6·2% for women). Among persons exposed to trauma, rape was most strongly associated with PTSD. Onset of PTSD significantly increased the risk of developing each of the 10 other tested disorders. Among those exposed to trauma, women were significantly more likely to develop PTSD, after controlling for assaultive violence.
Conclusions. This study highlights the importance of investigating the prevalence of PTSD, patterns of co-morbidity of PTSD, and gender differences in PTSD in non-English-speaking countries.
Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach
- ERIC Q. WU, LIZHENG SHI, HOWARD BIRNBAUM, TERESA HUDSON, RONALD KESSLER
-
- Published online by Cambridge University Press:
- 15 August 2006, pp. 1535-1540
-
- Article
- Export citation
-
Background. Schizophrenia is a debilitating chronic mental illness. However, the annual prevalence of schizophrenia is not well understood because of under-representation of schizophrenia patients in epidemiological surveys. This study used multiple administrative claims databases to estimate the annual prevalence of diagnosed schizophrenia in the USA.
Method. The annual prevalence of diagnosed schizophrenia in the USA was estimated for different health insurance coverage groups. The prevalence for privately insured individuals was calculated from an administrative claims database of approximately 3 million privately insured beneficiaries covering the period 1999–2003. The prevalence for Medicaid enrollees was calculated from California Medicaid claims covering the period 2000–2002. The prevalence for Medicare and Medicaid/Medicare dual eligibles was estimated using a combination of both databases. Published statistics were used to estimate the prevalence of schizophrenia in the uninsured and veteran populations and to weight the prevalence rates obtained to the population of the USA.
Results. The 12-month prevalence of diagnosed schizophrenia in the USA in 2002 was estimated at 5·1 per 1000 lives. The Medicaid population was identified with the highest prevalence rate among the populations studied. Sensitivity analyses taking into consideration the Veterans Affairs population only changed the estimate slightly to 5·3 per 1000 lives.
Conclusion. Analyses of administrative claims data contribute to the understanding of the prevalence of diagnosed schizophrenia.
Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study
- PAUL FEARON, JAMES B. KIRKBRIDE, CRAIG MORGAN, PAOLA DAZZAN, KEVIN MORGAN, TUHINA LLOYD, GERARD HUTCHINSON, JANE TARRANT, WAI LUN ALAN FUNG, JOHN HOLLOWAY, ROSEMARIE MALLETT, GLYNN HARRISON, JULIAN LEFF, PETER B. JONES, ROBIN M. MURRAY
-
- Published online by Cambridge University Press:
- 29 August 2006, pp. 1541-1550
-
- Article
- Export citation
-
Background. The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk.
Method. We identified all people (n=568) aged 16–64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated.
Results. We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9·1, manic psychosis 8·0) and Black Africans (schizophrenia 5·8, manic psychosis 6·2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study.
Conclusions. Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.
Remission and relapse in psychosis: operational definitions based on case-note data
- PAUL E. BEBBINGTON, TOM CRAIG, PHILIPPA GARETY, DAVID FOWLER, GRAHAM DUNN, SUSANNAH COLBERT, MIRIAM FORNELLS-AMBROJO, ELIZABETH KUIPERS
-
- Published online by Cambridge University Press:
- 16 August 2006, pp. 1551-1562
-
- Article
- Export citation
-
Background. In psychosis, the prime indicator of outcome has been relapse, but hospital readmission can no longer be used for this purpose. Researchers now require methods for assessing relapse that are objective, blind, reliable and valid. We describe the reliability and validity of such a technique using case-notes.
Method. Information from routine clinical notes of participants in the Lambeth Early Onset (LEO) study (less all references that would unblind the assessor) were recorded on a form divided into 1-month sections. Operational definitions of remission and relapse enabled clinicians to identify remissions and relapses blindly from the summary information. We calculated reliability regarding both the fact and the timing of remission and relapse. PANSS ratings at 6 and 18 months provided a measure of validity.
Results. The kappa value for the identification of remission by individuals ranged from 0·64 to 0·82, while that for consensus between paired raters was 0·56. The corresponding values for relapse were 0·57–0·59 and 0·71. Intra-class correlations for time to remission and to relapse were very high. Raters guessed correctly whether the participants came from the intervention or control group on 60–75% of occasions. Independent PANSS ratings were strongly related to the remission/relapse status of participants.
Conclusions. The reliability of the technique described here was moderate to good, its validity was good, and it provides a useful and timely addition to methods of evaluating remission and relapse in psychosis. On the basis of our experience, we recommend consensus rather than individual ratings.
Face affect recognition deficits in personality-disordered offenders: association with psychopathy
- MAIREAD DOLAN, RACHAEL FULLAM
-
- Published online by Cambridge University Press:
- 08 August 2006, pp. 1563-1569
-
- Article
- Export citation
-
Background. There is a limited literature examining face affect recognition in offenders. In line with the Integrated Emotion Systems (IES) model, existing studies suggest a psychopathy-related deficit in sad/fear recognition. However, many of these studies have small samples, and few include a healthy control group in order to examine the contribution of criminality.
Method. We compared the performance of male criminals with dissocial (antisocial) personality disorder (PD group) and healthy male IQ-matched controls, on a morphed face affect-processing task and examined the relationship between psychopathy (assessed using the Psychopathy Checklist: Screening Version, PCL: SV), score and performance on this task in the PD sample.
Results. The PD group had a specific deficit in the recognition of sad facial affect that was present even at 100% expression intensity. This deficit could not be attributed to impulsive responding as the PD group generally had longer mean reaction times than healthy controls. Within the PD group, those with high scores on the PCL: SV were less accurate than low scorers at classifying sad facial affect. There was also a significant negative correlation between total psychopathy score and sad affect recognition accuracy. There were no specific relationships between affect recognition and the subcomponents of psychopathy.
Conclusions. The findings suggest that criminality/antisocial personality may be associated with a deficit in the recognition of aversive cues in others, and that this deficit is more severe in psychopathic offenders. The findings lend further support to the IES model.
Is antisocial personality disorder continuous or categorical? A taxometric analysis
- DAVID K. MARCUS, SCOTT O. LILIENFELD, JOHN F. EDENS, NORMAN G. POYTHRESS
-
- Published online by Cambridge University Press:
- 12 July 2006, pp. 1571-1581
-
- Article
- Export citation
-
Background. Although the DSM-IV-TR is organized into discrete disorders, the question of whether a given disorder possesses a dimensional or a categorical latent structure is an empirical one that can be examined using taxometric methods. The objective of this study was to ascertain the latent structure of antisocial personality disorder (ASPD).
Method. Participants were 1146 male offenders incarcerated in state prisons (n=569), or court-ordered to residential drug treatment (n=577). Participants were interviewed using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) to assess ASPD symptoms; they also completed the Personality Diagnostic Questionnaire-4 (PDQ-4) ASPD scale. Taxometric analyses were performed to examine whether ASPD is underpinned by a discrete category or a dimensional construct.
Results. Multiple taxometric procedures using two different sets of indicators provided no evidence that ASPD has a taxonic latent structure. Instead, the results were far more consistent with the proposition that ASPD exists on a continuum, regardless of whether it is assessed using a structured interview or a self-report measure.
Conclusions. Evidence that ASPD is dimensional suggests that it is best studied using continuous measures and that dichotomizing individuals into ASPD versus non-ASPD groups will typically result in decreased statistical power. The findings are also consistent with a multifactorial etiology for ASPD and with recent attempts to conceptualize ASPD within the framework of extant dimensional models of personality.
Dimensional representations of DSM-IV Cluster A personality disorders in a population-based sample of Norwegian twins: a multivariate study
- KENNETH S. KENDLER, NIKOLAI CZAJKOWSKI, KRISTIAN TAMBS, SVENN TORGERSEN, STEVEN H. AGGEN, MICHAEL C. NEALE, TED REICHBORN-KJENNERUD
-
- Published online by Cambridge University Press:
- 08 August 2006, pp. 1583-1591
-
- Article
- Export citation
-
Background. The ‘odd’ or ‘Cluster A’ personality disorders (PDs) – paranoid, schizoid and schizotypal PDs – were created in DSM-III with little empirical foundation. We have examined the relationship between the genetic and environmental risk factors for dimensional representations of these three personality disorders.
Method. These personality disorders were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel. Using Mx, a single-factor independent pathway twin model was fitted to the number of endorsed criteria for the three disorders.
Results. The best-fit model included genetic and unique environmental common factors and genetic and unique environmental effects specific to each personality disorder. Total heritability was modest for these personality disorders and ranged from 21% to 28%. Loadings on the common genetic and unique environmental factors were substantially higher for schizotypal than for paranoid or schizoid PD. The proportion of genetic liability shared with all Cluster A disorders was estimated at 100, 43 and 26% respectively for schizotypal, paranoid and schizoid PDs.
Conclusion. In support of the validity of the Cluster A construct, dimensional representations of schizotypal, paranoid and schizoid PD are all modestly heritable and share a portion of their genetic and environmental risk factors. No evidence was found for shared environmental or sex effects for these PDs. Schizotypal PD most closely reflects the genetic and environmental liability common to all three Cluster A disorders. These results should be interpreted in the context of the limited power of this sample.
The structure of common DSM-IV and ICD-10 mental disorders in the Australian general population
- TIM SLADE, DAVID WATSON
-
- Published online by Cambridge University Press:
- 02 August 2006, pp. 1593-1600
-
- Article
- Export citation
-
Background. Patterns of co-occurrence among the common mental disorders may provide information about underlying dimensions of psychopathology. The aim of the current study was to determine which of four models best fits the pattern of co-occurrence between 10 common DSM-IV and 11 common ICD-10 mental disorders.
Method. Data were from the Australian National Survey of Mental Health and Well-Being (NSMHWB), a large-scale community epidemiological survey of mental disorders. Participants consisted of a random population-based sample of 10641 community volunteers, representing a response rate of 78%. DSM-IV and ICD-10 mental disorder diagnoses were obtained using the Composite International Diagnostic Interview (CIDI), version 2.0. Confirmatory factor analysis (CFA) was used to assess the relative fit of competing models.
Results. A hierarchical three-factor variation of a two-factor model demonstrated the best fit to the correlations among the mental disorders. This model included a distress factor with high loadings on major depression, dysthymia, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) and neurasthenia (ICD-10 only); a fear factor with high loadings on social phobia, panic disorder, agoraphobia and obsessive–compulsive disorder (OCD); and an externalizing factor with high loadings on alcohol and drug dependence. The distress and fear factors were best conceptualized as subfactors of a higher order internalizing factor.
Conclusions. A greater focus on underlying dimensions of distress, fear and externalization is warranted.
A scale to screen for DSM-IV Axis I disorders in psychiatric out-patients: performance of the Psychiatric Diagnostic Screening Questionnaire
- M. ZIMMERMAN, I. CHELMINSKI
-
- Published online by Cambridge University Press:
- 11 July 2006, pp. 1601-1611
-
- Article
- Export citation
-
Background. The Psychiatric Diagnostic Screening Questionnaire (PDSQ) is a reliable and valid self-report scale designed to screen for the most common DSM-IV Axis I disorders encountered in out-patient mental health settings. The present report is the second large-scale validation study of the PDSQ in psychiatric out-patients. Because some of the sizes of the diagnostic groups in the initial report were modest, it is important to determine whether the recommended cut-off scores to screen for psychiatric disorders remained the same in a replication study.
Method. Six hundred and seventy psychiatric out-patients presenting for treatment were evaluated with a semi-structured diagnostic interview after completing the PDSQ.
Results. Based on receiver operating curve analysis, the PDSQ performed as well in the replication sample as in the initial validation study. For nine of the 13 PDSQ subscales the recommended cut-off score in the replication study was the same as in the initial study. After combining the data from the two studies (n=1300) the mean sensitivity across the 13 PDSQ subscales was 87% and the mean negative predictive value was 97%.
Conclusions. The PDSQ is a diagnostic aid designed to improve the efficiency of conducting initial diagnostic evaluations. From a clinical perspective it is important that a screening tool have good sensitivity so that most cases are detected, and high negative predictive value so that most non-cases on the measure are indeed non-cases. The results of this second large validation study indicate that most of the PDSQ subscales achieved this goal.
Reaction time, inhibition, working memory and ‘delay aversion’ performance: genetic influences and their interpretation
- JONNA KUNTSI, HANNAH ROGERS, GREER SWINARD, NORBERT BÖRGER, JAAP van der MEERE, FRUHLING RIJSDIJK, PHILIP ASHERSON
-
- Published online by Cambridge University Press:
- 02 August 2006, pp. 1613-1624
-
- Article
- Export citation
-
Background. For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of theoretically driven cognitive-experimental tasks in a large twin sample. We further aimed to illustrate how test–retest reliability of the measures affects the estimates.
Method. Four-hundred 7- to 9-year-old twin pairs were assessed individually on tasks measuring reaction time, inhibition, working memory and ‘delay aversion’ performance. Test–retest reliability data on some of the key measures were available from a previous study.
Results. Several key measures of reaction time, inhibition and working-memory performance indicated a moderate degree of genetic influence. Combining data across theoretically related tasks increased the heritability estimates, as illustrated by the heritability estimates of 60% for mean reaction time and 50% for reaction-time variability. Psychometric properties (reliability or ceiling effects) had a substantial influence on the estimates for some measures.
Conclusions. The data support the usefulness of several of the variables for endophenotype studies that aim to link genes to cognitive and motivational processes. Importantly, the data also illustrate specific conditions under which the true extent of genetic influences may be underestimated and hence the usefulness for genetic mapping studies compromised, and suggest ways to address this.
Worry content across the lifespan: an analysis of 16- to 74-year-old participants in the British National Survey of Psychiatric Morbidity 2000
- JAMES LINDESAY, SARAH BAILLON, TRAOLACH BRUGHA, MICHAEL DENNIS, ROBERT STEWART, RICARDO ARAYA, HOWARD MELTZER
-
- Published online by Cambridge University Press:
- 25 July 2006, pp. 1625-1633
-
- Article
- Export citation
-
Background. Previous studies suggest that worry content and prevalence may vary as a function of age, but evidence is limited.
Method. Cross-sectional national survey of 8580 householders in Great Britain aged between 16 and 74 years. This analysis examined the relationship between age, worry content (relationships/family, financial/housing, work, health, miscellaneous), common mental disorders, and functional limitation, adjusting for other sociodemographic factors.
Results. Overall, the prevalence of worries declined with age. However, with the exception of worry about relationships, the strength of associations between worry types and mental disorder either remained constant or increased in the older age groups. Compared to the 16–24 years reference group, worries about relationships/family, finances/housing and work were lower in the 55–74 years age groups. Financial/housing worries were increased in the 25–44 years group, and health worries were increased in the 25–64 years groups. There were independent associations between all worry items and the categories of mental disorder. All worry types apart from miscellaneous worries were independently associated, positively or negatively, with functional limitation.
Conclusions. Worry content in the general population varies as a function of age, gender, marital status, and educational attainment. All categories of worry are more prevalent in individuals with common mental disorders. The lower prevalence of worries and their stronger association with mental disorder in old age emphasize the clinical significance of these symptoms in this age group.
Fear of falling more important than pain and depression for functional recovery after surgery for hip fracture in older people
- RICHARD C. OUDE VOSHAAR, SUBE BANERJEE, MIKE HORAN, ROBERT BALDWIN, NEIL PENDLETON, REBEKAH PROCTOR, NICHOLAS TARRIER, YVONNE WOODWARD, ALISTAIR BURNS
-
- Published online by Cambridge University Press:
- 25 July 2006, pp. 1635-1645
-
- Article
- Export citation
-
Background. Depression and cognitive functioning have a negative impact on functional recovery after hip fracture surgery in older people, and the same has been suggested for pain and fear of falling. These variables, however, have never been studied together, nor has the timing of psychiatric assessment been taken into account.
Method. Two parallel, randomized controlled trials were undertaken aiming to prevent and treat depression after hip fracture surgery in older people. Multiple logistic regression analyses corrected for age and pre-morbid level of functioning were performed to evaluate the effect of depressive symptoms (15-item Geriatric Depression Scale, GDS), pain (Wong–Baker pain scale), cognitive functioning (Mini-mental State Examination, MMSE) and fear of falling (Modified Falls Efficacy Scale, MFES) within 2 weeks after surgery and 6 weeks later on functional recovery at 6 months. Main outcome measures were performance-based measures (up-and-go test, gait test, functional reach) and the self-report Sickness Impact Profile (SIP) questionnaire to assess the impact of the hip fracture on activities of daily living (ADL).
Results. Two hundred and ninety-one patients participated and outcome measures for 187 (64%) patients were available at 6 months. All mental health variables interfered with functional recovery. However, in the final multivariate model, cognitive functioning and fear of falling assessed 6 weeks after surgery consistently predicted functional recovery, whereas pain and depressive symptoms were no longer significant.
Conclusion. Fear of falling and cognitive functioning may be more important than pain and depression to predict functional recovery after hip fracture surgery. Rehabilitation strategies should take this into account.
Relationship between drug company funding and outcomes of clinical psychiatric research
- ROBERT E. KELLY, LISA J. COHEN, RANDYE J. SEMPLE, PHILIP BIALER, ADAM LAU, ALISON BODENHEIMER, ELANA NEUSTADTER, ARKADY BARENBOIM, IGOR I. GALYNKER
-
- Published online by Cambridge University Press:
- 08 August 2006, pp. 1647-1656
-
- Article
- Export citation
-
Background. Pharmaceutical industry funding of psychiatric research has increased significantly in recent decades, raising the question of a relationship between pharmaceutical company funding of clinical psychiatric studies and the outcomes of those studies. This study examines this relationship.
Method. Abstracts of articles from 1992 and 2002 in four peer-reviewed psychiatric journals were examined. Drug outcomes (n=542) for clinical studies were evaluated and then compared across sponsorship source. Outcome raters were blind to source of sponsorship. The percentage of these studies sponsored by drug companies in 2002 v. 1992 was also compared. In a secondary analysis, the contribution of a series of potentially mediating variables to the relationship between sponsorship source and study outcome was assessed via logistic regression.
Results. The percentage of studies sponsored by drug companies increased from 25% in 1992 to 57% in 2002. Favorable outcomes were significantly more common in studies sponsored by the drug manufacturer (78%) than in studies without industry sponsorship (48%) or sponsored by a competitor (28%). These relationships remained after controlling for the effects of journal, year, drug studied, time since FDA drug approval, diagnosis, sample size, and selected study design variables.
Conclusions. These data indicate an association between pharmaceutical industry funding of clinical studies and positive outcomes of those studies. Further research is needed to elucidate the mechanisms underlying this relationship.