Daphne-Zacharenia Kounali

Maternal Depression During Pregnancy and the Postnatal Period: Risks and Possible Mechanisms for Offspring Depression at Age 18 Years

IMPORTANCE Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention. OBJECTIVE To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. DESIGN, SETTING, AND PARTICIPANTS Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring. MAIN OUTCOMES AND MEASURES Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision. RESULTS Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. CONCLUSIONS AND RELEVANCE The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Psychotic Experiences and Psychotic Disorders at Age 18 in Relation to Psychotic Experiences at Age 12 in a Longitudinal Population-Based Cohort Study

OBJECTIVE The authors examined the development of psychotic experiences and psychotic disorders in a large population-based sample of young adults and explored their relationship to psychotic phenomena earlier in childhood. METHOD The authors conducted a longitudinal birth cohort study of individuals assessed with the semistructured Psychosis-Like Symptom Interviews at ages 12 and 18 years. RESULTS Of the 4,724 individuals interviewed at age 18, 433 (9.2%) had either suspected (N=203 [4.3%]) or definite (N=230 [4.9%]) psychotic experiences. Of these, 79 (1.7%) met criteria for a psychotic disorder, and of those, only 50% sought professional help. All psychotic outcomes were more likely in young women and in those from socioeconomically disadvantaged backgrounds. Of the participants who had psychotic experiences at age 12, 78.7% had remitted by age 18. The risk of psychotic disorders at age 18 was greater in those with suspected (odds ratio=5.6, 95% CI=2.6-12.1) and especially in those with definite (odds ratio=12.7, 95% CI=6.2-26.1) psychotic experiences at age 12, and also among those with psychotic experiences at age 12 attributed to sleep or fever or with nonpsychotic experiences such as depersonalization. The positive predictive values for increasing frequency of experiences at age 12 predicting psychotic disorders at age 18 ranged from 5.5% to 22.8%. CONCLUSIONS Despite evidence for a continuum of psychotic experiences from as early as age 12, positive predictive values for predicting psychotic disorders were too low to offer real potential for targeted interventions. Psychotic disorders in young adults are relatively uncommon, but they constitute an important unmet need for care given that half of the individuals in this study who met criteria for a psychiatric disorder had not sought help for these problems despite high levels of associated distress and impairment.

Minimal clinically important difference on the Beck Depression Inventory - II according to the patient's perspective

Background The Beck Depression Inventory, 2nd edition (BDI-II) is widely used in research on depression. However, the minimal clinically important difference (MCID) is unknown. MCID can be estimated in several ways. Here we take a patient-centred approach, anchoring the change on the BDI-II to the patients global report of improvement. Method We used data collected (n = 1039) from three randomized controlled trials for the management of depression. Improvement on a ‘global rating of change’ question was compared with changes in BDI-II scores using general linear modelling to explore baseline dependency, assessing whether MCID is best measured in absolute terms (i.e. difference) or as percent reduction in scores from baseline (i.e. ratio), and receiver operator characteristics (ROC) to estimate MCID according to the optimal threshold above which individuals report feeling ‘better’. Results Improvement in BDI-II scores associated with reporting feeling ‘better’ depended on initial depression severity, and statistical modelling indicated that MCID is best measured on a ratio scale as a percentage reduction of score. We estimated a MCID of a 17.5% reduction in scores from baseline from ROC analyses. The corresponding estimate for individuals with longer duration depression who had not responded to antidepressants was higher at 32%. Conclusions MCID on the BDI-II is dependent on baseline severity, is best measured on a ratio scale, and the MCID for treatment-resistant depression is larger than that for more typical depression. This has important implications for clinical trials and practice.

Modelling measurement errors and category misclassifications in multilevel models.

Models are developed to adjust for measurement errors in normally distributed predictor and response variables and categorical predictors with misclassification errors. The models allow for a hierarchical data structure and for correlations among the errors and misclassifications. Markov Chain Monte Carlo (MCMC) estimation is used and implemented in a set of MATLAB macros.

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence

Background An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes. Method We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress–adversity, emotional–behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation. Results Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs. Conclusions The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

Longitudinal associations between adolescent psychotic experiences and depressive symptoms

Background Psychotic experiences are prevalent in community samples and are highly correlated with depressive symptoms. This study aimed to investigate the longitudinal associations between psychotic experiences and depressive symptoms between adolescence and young adulthood. Method Prospective cohort study with a 6 year follow-up in a community sample of 7632 adolescents and young adults. Depressive symptoms were assessed with the Short Moods and Feelings Questionnaire and psychotic experiences with a semi-structured clinical interview at 12 and 18 years. Longitudinal and cross-sectional associations were investigated with regression and structural equation models. Results Depressive symptoms and psychotic experiences were associated at each time-point (12 years r = 0.486 [95% CI 0.457, 0.515]; 18 years r = 0.286 [95% CI 0.233, 0.339]) and there were longitudinal within-phenotype associations (depressive symptoms r = 0.252 [95% CI 0.205, 0.299]; psychotic experiences r = 0.662 [95% CI 0.595, 0.729]). There was an across-phenotype association between psychotic experiences at 12 and depressive symptoms at 18 r = 0.139 [95% CI 0.086, 0.192; p<0.001], but no association between depressive symptoms at 12 and psychotic experiences at 18 r = −0.022 [95% CI −0.032, 0.077; p = 0.891]. Conclusions Longitudinal across-phenotype associations were substantially weaker than cross-sectional associations or within-phenotype longitudinal associations. Whilst psychotic experiences at 12 years were associated with a small increase in depression at 18 years, depression at 12 years was not associated with psychotic experiences at 18 years once across-phenotype cross-sectional and within-phenotype longitudinal associations were accounted for. This suggests that the biological mechanisms underlying depression at this age do not increase subsequent risk of psychotic experiences once they resolve.

Chlamydia trachomatis Pgp3 Antibody Persists and Correlates with Self-Reported Infection and Behavioural Risks in a Blinded Cohort Study

Chlamydia trachomatis (Ct) serological studies in populations could help monitor changes in lifetime cumulative risk of infection. We developed a double-antigen sandwich ELISA based on the Ct-specific Pgp3 antigen, then tested blind stored sera from over 800 participants in a New Zealand birth cohort from Dunedin at ages 26, 32 and 38. The double-antigen sandwich ELISA was more sensitive than our previously characterised indirect Pgp3 ELISA. Pgp3 antibody was detected more often in women compared to men and correlated with increasing numbers of sexual partners, self-reported Ct, and younger age at sexual debut in both women and men. At age 26, 24.1% (99/411) of women were Pgp3 seropositive, as were 79.5% (35/44) of those reporting Ct infection; Pgp3 antibody persisted to age 38 in 96.5% (83/86). In men at age 26, the figures were 10.7% (47/442) and 25.0% (6/24), respectively, with high (83.9%) antibody persistence to age 38. At age 38, among those Pgp3 seropositive, 63.3% of women and 83.1% of men had not reported Ct infection. Thus, Ct-specific Pgp3 antibody was detected in most women reporting Ct infection and correlated with risk of infection in those who did not, with most infections remaining undetected. As this antibody persisted for at least twelve years in 96% of these women, serology could be used to evaluate Ct prevention programmes among women.

Simultaneous Multioutcome Synthesis and Mapping of Treatment Effects to a Common Scale

Objectives A new method is presented for both synthesizing treatment effects on multiple outcomes subject to measurement error and estimating coherent mapping coefficients between all outcomes. It can be applied to sets of trials reporting different combinations of patient- or clinician-reported outcomes, including both disease-specific measures and generic health-related quality-of-life measures. It is underpinned by a structural equation model that includes measurement error and latent common treatment effect factor. Treatment effects can be expressed on any of the test instruments that have been used. Methods This is illustrated in a synthesis of eight placebo-controlled trials of TNF-α inhibitors in ankylosing spondylitis, each reporting treatment effects on between two and five of a total six test instruments. Results The method has advantages over other methods for synthesis of multiple outcome data, including standardization and multivariate normal synthesis. Unlike standardization, it allows synthesis of treatment effect information from test instruments sensitive to different underlying constructs. It represents a special case of previously proposed multivariate normal models for evidence synthesis, but unlike the former, it also estimates mappings. Combining synthesis and mapping as a single operation makes more efficient use of available data than do current mapping methods and generates treatment effects that are consistent with the mappings. A limitation, however, is that it can only generate mappings to and from those instruments on which some trial data exist. Conclusions The method should be assessed in a wide range of data sets on different clinical conditions, before it can be used routinely in health technology assessment.

Simultaneous Synthesis of Treatment Effects and Mapping to a Common Scale: An Alternative to Standardisation.

Objective Trials often may report several similar outcomes measured on different test instruments. We explored a method for synthesising treatment effect information both within and between trials and for reporting treatment effects on a common scale as an alternative to standardisation Study design We applied a procedure that simultaneously estimates a pooled treatment effect and the “mapping” ratios between the treatment effects on test instruments in a connected network. Standardised and non-standardised treatment effects were compared. The methods were illustrated in a dataset of 22 trials of selective serotonin reuptake inhibitors against placebo for social anxiety disorder, each reporting treatment effects on between one and six of a total nine test instruments. Results Ratios of treatment effects on different test instruments varied from trial to trial, with a coefficient of variation of 18% (95% credible interval 11–29%). Standardised effect models fitted the data less well, and standardised treatment effects were estimated with less relative precision than non-standardised effects and with greater relative heterogeneity. Conclusion Simultaneous synthesis of treatment effects and mapping to a common scale make fewer assumptions than standardising by dividing effects by the sample standard deviation, allow results to be reported on a common scale, and deliver estimates with superior relative precision.

Proportion of Tubal Factor Infertility due to Chlamydia: Finite Mixture Modeling of Serum Antibody Titers

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michaels Hospital in Bristol, United Kingdom, during the period 1985–1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis. Further studies using modern assays in contemporary, representative populations should be undertaken.