Antidepressants prevent hierarchy destabilization induced by lipopolysaccharide administration in mice: a neurobiological approach to depression

In spite of the high prevalence and negative impact of depression, little is known about its pathophysiology. Basic research on depression needs new animal models in order to increase knowledge of the disease and search for new therapies. The work presented here aims to provide a neurobiologically validated model for investigating the relationships among sickness behavior, antidepressants treatment, and social dominance behavior. For this purpose, dominant individuals from dyads of male Swiss mice were treated with the bacterial endotoxin lipopolysaccharide (LPS) to induce social hierarchy destabilization. Two groups were treated with the antidepressants imipramine and fluoxetine prior to LPS administration. In these groups, antidepressant treatment prevented the occurrence of social destabilization. These results indicate that this model could be useful in providing new insights into the understanding of the brain systems involved in depression.

Lifetime prevalence estimates of major depression: An indirect estimation method and a quantification of recall bias

The measurement of lifetime prevalence of depression in cross-sectional surveys is biased by recall problems. We estimated it indirectly for two countries using modelling, and quantified the underestimation in the empirical estimate for one. A microsimulation model was used to generate population-based epidemiological measures of depression. We fitted the model to 1-and 12-month prevalence data from the Netherlands Mental Health Survey and Incidence Study (NEMESIS) and the Australian Adult Mental Health and Wellbeing Survey. The lowest proportion of cases ever having an episode in their life is 30% of men and 40% of women, for both countries. This corresponds to a lifetime prevalence of 20 and 30%, respectively, in a cross-sectional setting (aged 15-65). The NEMESIS data were 38% lower than these estimates. We conclude that modelling enabled us to estimate lifetime prevalence of depression indirectly. This method is useful in the absence of direct measurement, but also showed that direct estimates are underestimated by recall bias and by the cross-sectional setting.

Aplicación práctica de los modelos de Mercer y Beck en las especialidades de enfermería

El vínculo afectivo es la atracción que un individuo siente por otro. La conducta de apego busca la unión emocional y seguridad del bebé hacia su madre. Distintas especialidades de enfermería indican la importancia de trabajar el vínculo afectivo, las relaciones familiares y utilizar el proceso enfermero partiendo de modelos conceptuales. Los modelos conceptuales de Mercer y Beck estudian factores a considerar en la formación y desarrollo de vínculos afectivos entre madres e hijos. Este estudio pretende desarrollar conocimientos, habilidades y actitudes que permitan una atención óptima al bebé y su familia. Analizando los elementos comunes y diferenciadores de ambos modelos y justificando la necesidad de prestar especial atención a la formación y mantenimiento del vínculo maternofilial desde la perspectiva de las diferentes especialidades de enfermería, se utiliza el proceso enfermero para la detección y resolución de problemas que afecten al vínculo afectivo y a las relaciones familiares.

Checking Assumptions in Latent Class Regression Models via a Markov Chain Monte Carlo Estimation Approach: An Application to Depression and Socio-Economic Status

Latent class regression models are useful tools for assessing associations between covariates and latent variables. However, evaluation of key model assumptions cannot be performed using methods from standard regression models due to the unobserved nature of latent outcome variables. This paper presents graphical diagnostic tools to evaluate whether or not latent class regression models adhere to standard assumptions of the model: conditional independence and non-differential measurement. An integral part of these methods is the use of a Markov Chain Monte Carlo estimation procedure. Unlike standard maximum likelihood implementations for latent class regression model estimation, the MCMC approach allows us to calculate posterior distributions and point estimates of any functions of parameters. It is this convenience that allows us to provide the diagnostic methods that we introduce. As a motivating example we present an analysis focusing on the association between depression and socioeconomic status, using data from the Epidemiologic Catchment Area study. We consider a latent class regression analysis investigating the association between depression and socioeconomic status measures, where the latent variable depression is regressed on education and income indicators, in addition to age, gender, and marital status variables. While the fitted latent class regression model yields interesting results, the model parameters are found to be invalid due to the violation of model assumptions. The violation of these assumptions is clearly identified by the presented diagnostic plots. These methods can be applied to standard latent class and latent class regression models, and the general principle can be extended to evaluate model assumptions in other types of models.

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

Mechanisms of improvement in treatment for depression : test of a self-efficacy and performance model

Tested D. J. Kavanagh's (1983) depression model's explanation of response to cognitive-behavioral treatment among 19 20–60 yr old Ss who received treatment and 24 age-matched Ss who were assigned to a waiting list. Measures included the Beck Depression Inventory and self-efficacy (SE) and self-monitoring scales. Rises in SE and self-monitored performance of targeted skills were closely associated with the improved depression scores of treated Ss. Improvements in the depression of waiting list Ss occurred through random, uncontrolled events rather than via a systematic increase in specific skills targeted in treatment. SE regarding assertion also predicted depression scores over a 12-wk follow-up.

The Alcohol Helplessness Scale and its prediction of depression among problem drinkers

Event-specific scales commonly have greater power than generalized scales in prediction of specific disorders and in testing mediator models for predicting such disorders. Therefore, in a preliminary study, a 6-item Alcohol Helplessness Scale was constructed and found to be reliable for a sample of 98 problem drinkers. Hierarchical multiple regression and its derivative path analysis were used to test whether helplessness and self-efficacy moderate or mediate the link between alcohol dependence and depression, A test of a moderation model was not supported, whereas a test of a mediation model was supported. Helplessness and self-efficacy both significantly and independently mediated between alcohol dependence and depression. Nevertheless, a significant direct effect of alcohol dependence on depression also remained.

Depression, anxiety and body image after treatment for invasive stage one epithelial ovarian cancer

Background: Diagnosis of epithelial ovarian cancer (EOC) in young women has major implications including those to their reproductive potential. We evaluated depression, anxiety and body image in patients with stage I EOC treated with fertility sparing surgery (FSS) or radical surgery (RS). We also investigated fertility outcomes after FSS.----- Methods: A retrospective study was undertaken in which 62 patients completed questionnaires related to anxiety, depression, body image and fertility outcomes. Additional information on adjuvant therapy after FSS and RS and demographic details were abstracted from medical records. Both bi and multivariate regression models were used to assess the relationship between demographic, clinical and pathological results and scores for anxiety, depression and body image.----- Results: Thirty-nine patients underwent RS and the rest, FSS. The percentage of patients reporting elevated anxiety and depression (subscores ≥ 11) were 27 % and 5% respectively. The median (inter quartile range) score for body image scale (BIS) was 6 (3-15). None of the demographic or clinical factors examined showed significant association with anxiety and BIS with the exception of ‘time since diagnosis’. For depression, post-menopausal status was the only independent predictor. Among those 23 patients treated by FSS, 14 patients tried to conceive (7 successful), resulting in 7 live births, one termination of pregnancy and one miscarriage.----- Conclusion: This study shows that psychological issues are common in women treated for stage I EOC. Reproduction after FSS is feasible and lead to the birth of healthy babies in about half of patients who wished to have another child. Further prospective studies with standardised instruments are required.

Physical activity, sitting and depression during pregnancy

Aims The aim of this cross sectional study is to explore levels of physical activity and sitting behaviour amongst a sample of pregnant Australian women (n = 81), and investigate whether reported levels of physical activity and/or time spent sitting were associated with depressive symptom scores after controlling for potential covariates. Methods Study participants were women who attended the antenatal clinic of a large Brisbane maternity hospital between October and November 2006. Data relating to participants. current levels of physical activity, sitting behaviour, depressive symptoms, demographic characteristics and exposure to known risk factors for depression during pregnancy were collected; via on-site survey, follow-up telephone interview (approximately one week later) and post delivery access to participant hospital records. Results Participants were aged 29.5 (¡¾ 5.6) years and mostly partnered (86.4%) with a gross household income above $26,000 per annum (88.9%). Levels of physical activity were generally low, with only 28.4 % of participants reporting sufficient total activity and 16% of participants reporting sufficient planned (leisure-time) activity. The sample mean for depressive symptom scores measured by the Hospital Anxiety and Depression Scale (HADS-D) was 6.38 (¡¾ 2.55). The mean depressive symptom scores for participants who reported total moderate-to-vigorous activity levels of sufficient, insufficient, and none, were 5.43 (¡¾ 1.56), 5.82 (¡¾ 1.77) and 7.63 (¡¾ 3.25), respectively. Hierarchical multivariable linear regression modelling indicated that after controlling for covariates, a statistically significant difference of 1.09 points was observed between mean depressive symptom scores of participants who reported sufficient total physical activity, compared with participants who reported they were engaging in no moderate-to-vigorous activity in a typical week (p = 0.05) but this did not reach the criteria for a clinically meaningful difference. Total physical activity was contributed 2.2% to the total 30.3% of explained variance within this model. The other main contributors to explained variance in multivariable regression models were anxiety symptom scores and the number of existing children. Further, a trend was observed between higher levels of planned sitting behaviour and higher depressive symptom scores (p = 0.06); this correlation was not clinically meaningful. Planned sitting contributed 3.2% to the total 31.3 % of explained variance. The number of regression covariates and limited sample size led to a less than ideal ratio of covariates to participants, probably attenuating this relationship. Specific information about the sitting-based activities in which participants engaged may have provided greater insight about the relationship between planned sitting and depressive symptoms, but these data were not captured by the present study. Conclusions The finding that higher levels of physical activity were associated with lower levels of depressive symptoms is consistent with the current body of existing literature in pregnant women, and with a larger body of evidence based in general population samples. Although this result was not considered clinically meaningful, the criterion for a clinically meaningful result was an a priori decision based on quality of life literature in non-pregnant populations and may not truly reflect a difference in symptoms that is meaningful to pregnant women. Further investigation to establish clinically meaningful criteria for continuous depressive symptom data in pregnant women is required. This result may have implications relating to prevention and management options for depression during pregnancy. The observed trend between planned sitting and depressive symptom scores is consistent with literature based on leisure-time sitting behaviour in general population samples, and suggests that further research in this area, with larger samples of pregnant women and more specific sitting data is required to explore potential associations between activities such as television viewing and depressive symptoms, as this may be an area of behaviour that is amenable to modification.

What explains the association between socioeconomic status and depression among Vietnamese adults?

Background Depression is a major public health problem worldwide and is currently ranked second to heart disease for years lost due to disability. For many decades, international research has found that depressive symptoms occur more frequently among low socioeconomic (SES) individuals than their more-advantaged peers. However, the reasons as to why those of low socioeconomic groups suffer more depressive symptoms are not well understood. Studies investigating the prevalence of depression and its association with SES emanate largely from developed countries, with little research among developing countries. In particular, there is a serious dearth of research on depression and no investigation of its association with SES in Vietnam. The aims of the research presented in this Thesis are to: estimate the prevalence of depressive symptoms among Vietnamese adults, examine the nature and extent of the association between SES and depression and to elucidate causal pathways linking SES to depressive symptoms Methods The research was conducted between September 2008 and November 2009 in Hue city in central Vietnam and used a combination of qualitative (in-depth interviews) and quantitative (survey) data collection methods. The qualitative study contributed to the development of the theoretical model and to the refinement of culturally-appropriate data collection instruments for the quantitative study. The main survey comprised a cross-sectional population–based survey with randomised cluster sampling. A sample of 1976 respondents aged between 25-55 years from ten randomly-selected residential zones (quarters) of Hue city completed the questionnaire (response rate 95.5%). Measures SES was classified using three indicators: education, occupation and income. The Center for Epidemiologic Studies-Depression (CES-D) scale was used to measure depressive symptoms (range0-51, mean=11.0, SD=8.5). Three cut-off points for the CES-D scores were applied: ‘at risk for clinical depression’ (16 or above), ‘depressive symptoms’ (above 21) and ‘depression’ (above 25). Six psychosocial indicators: life time trauma, chronic stress, recent life events, social support, self esteem, and mastery were hypothesized to mediate the association between SES and depressive symptoms. Analyses The prevalence of depressive symptoms were analysed using bivariate analyses. The multivariable analytic phase comprised of ordinary least squares regression, in accordance with Baron and Kenny’s three-step framework for mediation modeling. All analyses were adjusted for a range of confounders, including age, marital status, smoking, drinking and chronic diseases and the mediation models were stratified by gender. Results Among these Vietnamese adults, 24.3% were at or above the cut-off for being ‘at risk for clinical depression’, 11.9% were classified as having depressive symptoms and 6.8% were categorised as having depression. SES was inversely related to depressive symptoms: the least educated those with low occupational status or with the lowest incomes reported more depressive symptoms. Socioeconomicallydisadvantaged individuals were more likely to report experiencing stress (life time trauma, chronic stress or recent life events), perceived less social support and reported fewer personal resources (self esteem and mastery) than their moreadvantaged counterparts. These psychosocial resources were all significantly associated with depressive symptoms independent of SES. Each psychosocial factor showed a significant mediating effect on the association between SES and depressive symptoms. This was found for all measures of SES, and for males and females. In particular, personal resources (mastery, self esteem) and chronic stress accounted for a substantial proportion of the variation in depressive symptoms between socioeconomic groups. Social support and recent life events contributed modestly to socioeconomic differences in depressive symptoms, whereas lifetime trauma contributed the least to these inequalities. Conclusion This is the first known study in Vietnam or any developing country to systematically examine the extent to which psychosocial factors mediate the relationship between SES and depression. The study contributes new evidence regarding the burden of depression in Vietnam. The findings have practical relevance for advocacy, for mental health promotion and health-care services, and point to the need for programs that focus on building a sense of personal mastery and self esteem. More broadly, the work presented in this Thesis contributes to the international scientific literature on the social determinants of depression.

Postnatal depression in Central Vietnam

Postnatal depression (PND) is a significant global health issue, which not only impacts maternal wellbeing, but also infant development and family structures. Mental health disorders represent approximately 14% of global burden of disease and disability, including low and middle-income countries (LMIC), and PND has direct relevance to the Millennium Development Goals of reducing child mortality, improving maternal health, and creating global partnerships (United Nations, 2012; Guiseppe, Becker & Farmer, 2011). Emerging evidence suggests that PND in LMIC is similar to, or higher than in high-income countries (HIC), however, less than 10% of LMIC have prevalence data available (Fisher, Cabral de Mello, & Izutsu 2009; Lund et al., 2011). Whilst a small number of studies on maternal mental disorders have been published in Vietnam, only one specifically focuses on PND in a hospital-based sample. Also, community based mental health studies and information on mental health in rural areas of Vietnam is still scarce. The purpose of this study was to determine the prevalence of PND, and its associated social determinants in postnatal women in Thua Thien Hue Province, Central Vietnam. In order to identify social determinants relevant to the Central Vietnamese context, two qualitative studies and one community survey were undertaken. Associations between maternal mental health and infant health outcomes were also explored. The study was comprised of three phases. Firstly, iterative, qualitative interviews with Vietnamese health professionals (n = 17) and postpartum women (n = 15) were conducted and analysed using Kleinman's theory of explanatory models to identify narratives surrounding PND in the Vietnamese context (Kleinman, 1978). Secondly, a participatory concept mapping exercise was undertaken with two groups of health professionals (n = 12) to explore perceived risk and protective factors for postnatal mental health. Qualitative phases of the research elucidated narratives surrounding maternal mental health in the Vietnamese context such as son preference, use of traditional medicines, and the popularity of confinement practices such as having one to three months of complete rest. The qualitative research also revealed the construct of depression was not widely recognised. Rather, postpartum changes in mood were conceptualised as a loss of 'vital strength' following childbirth or 'disappointment'. Most women managed postpartum changes in mood within the family although some sought help from traditional medicine practitioners or biomedical doctors. Thirdly, a cross-sectional study of twelve randomly selected communes (six urban, six rural) in Thua Thien Hue Province was then conducted. Overall, 465 women with infants between 4 weeks and six months old participated, and 431 questionnaires were analysed. Women from urban (n = 216) and rural (n = 215) areas participated. All eligible women completed a structured interview about their health, basic demographics, and social circumstances. Maternal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) as a continuous variable. Multivariate generalised linear regression was conducted using PASW Statistics version 18.0 (2009). When using the conventional EPDS threshold for probable depression (EPDS score ~ 13) 18.1% (n = 78) of women were depressed (Gibson, McKenzie-McHarg, Shakespeare, Price & Gray, 2009). Interestingly, 20.4% of urban women (n = 44) had EPDS scores~ 13, which was a higher proportion than rural women, where 15.8% (n = 34) had EPDS scores ~ 13, although this difference was not statistically significant: t(429) = -0.689, p = 0.491. Whilst qualitative narratives identified infant gender and family composition, and traditional confinement practices as relevant to postnatal mood, these were not statistically significant in multivariate analysis. Rather, poverty, food security, being frightened of your husband or family members, experiences of intimate partner violence and breastfeeding difficulties had strong statistical associations. PND was also associated with having an infant with diarrhoea in the past two weeks, but not infant malnutrition or acute respiratory infections. This study is the first to explore maternal mental health in Central Vietnam, and provides further evidence that PND is a universally experienced phenomenon. The independent social risk factors of depressive symptoms identified such as poverty, food insecurity, experiences of violence and powerlessness, and relationship adversity points to women in a context of social suffering which is relevant throughout the world (Kleinman, Das & Lock, 1997). The culturally specific risk factors explored such as infant gender were not statistically significant when included in a multivariable model. However, they feature prominently in qualitative narratives surrounding PND in Vietnam, both in this study and previous literature. It appears that whilst infant gender may not be associated with PND per se, the reactions of close relatives to the gender of the baby can adversely affect maternal wellbeing. This study used a community based participatory research approach (CBPR) (Israel.2005). This approach encourages the knowledge produced to be used for public health interventions and workforce training in the community in which the research was conducted, and such work has commenced. These results suggest that packages of interventions for LMIC devised to address maternal mental health and infant wellbeing could be applied in Central Vietnam. Such interventions could include training lay workers to follow up postpartum women, and incorporating mental health screening and referral into primary maternal and child health care (Pate! et al., 2011; Rahman, Malik, Sikander & Roberts, 2008). Addressing the underlying social determinants of PND through poverty reduction and violence elimination programs is also recommended.

The association between socioeconomic status and depression in Vietnamese adults : pilot study

This study examined the prevalence of depressive symptoms and elucidated the causal pathway between socioeconomic status and depression in a community in the central region of Vietnam. The study used a combination of qualitative and quantitative research methods. Indepth interviews were applied with two local psychiatric experts and ten residents for qualitative research. A cross sectional survey with structured interview technique was implemented with 100 residents in the pilot quantitative survey. The Center for Epidemiological Studies-Depression Scale (CES-D) was applied to valuate depressive symptoms ( CES-D score over 21) and depression ( CESD core over 25). Ordinary Least Squares Regression following the three steps of Baron and Kenny’s framework was employed for testing mediation models. There was a strong social gradient with respect to depressive symptoms. People with higher education levels reported fewer depressive symptoms (lower CES-D scores). Incomes were also inversely associated with depressive symptoms, but only the ones at the bottom of the quartile income. Low level and unstable individuals in terms of occupation were associated with higher depressive symptoms compared with the highest occupation group. Employment status showed the strongest gradient with respect to its impact on the burden of depressive symptoms compared with other indicators of SES. Findings from this pilot study suggest a pattern on the negative association between socioeconomic status and depression in Vietnamese adults.

Co-morbidity of depression and anxiety in common age-related eye diseases : a population-based study of 662 adults

This study examined the prevalence of co-morbid age-related eye disease and symptoms of depression and anxiety in late life, and the relative roles of visual function and disease in explaining symptoms of depression and anxiety. A community-based sample of 662 individuals aged over 70 years was recruited through the electoral roll. Vision was measured using a battery of tests including high and low contrast visual acuity, contrast sensitivity, motion sensitivity, stereoacuity, Useful Field of View, and visual fields. Depression and anxiety symptoms were measured using the Goldberg scales. The prevalence of self-reported eye disease [cataract, glaucoma, or age-related macular degeneration (AMD)] in the sample was 43.4%, with 7.7% reporting more than one form of ocular pathology. Of those with no eye disease, 3.7% had clinically significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3% among those with glaucoma, and 10.5% for AMD. Generalized linear models adjusting for demographics, general health, treatment, and disability examined self-reported eye disease and visual function as correlates of depression and anxiety. Depressive symptoms were associated with cataract only, AMD, comorbid eye diseases and reduced low contrast visual acuity. Anxiety was significantly associated with self-reported cataract, and reduced low contrast visual acuity, motion sensitivity and contrast sensitivity. We found no evidence for elevated rates of depressive or anxiety symptoms associated with self-reported glaucoma. The results support previous findings of high rates of depression and anxiety in cataract and AMD, and in addition show that mood and anxiety are associated with objective measures of visual function independently of self-reported eye disease. The findings have implications for the assessment and treatment of mental health in the context of late-life visual impairment...