The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development.

Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut–brain pathways

The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut–brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when “comorbid” with depression.

Does reverse causality explain the relationship between diet and depression?

BACKGROUND: Observational studies have repeatedly demonstrated relationships between habitual diet quality and depression. However, whilst reverse causality has not been the identified mechanism for these associations in prospective studies, the relationship between diet and depression is likely complex and bidirectional. Thus explicit investigation of the reverse causality hypothesis is warranted. METHODS: Data were drawn from the Personality and Total Health (PATH) Through Life Study, a longitudinal community survey following three age cohorts from Australia. Analyses evaluated the relationships between past depression and treatment, current depressive symptoms and dietary patterns. RESULTS: Individuals with current depression had lower scores on a healthy dietary pattern; however, those who had been previously depressed and sought treatment had higher scores on the healthy dietary pattern at the later baseline assessment. Moreover, those who had reported prior, but not current, depression also had lower scores on the western dietary pattern than those without prior depression, regardless of whether they had been previously treated for their symptoms. LIMITATIONS: Self-report data and possible recall bias limit our conclusions. CONCLUSIONS: In this study, prior depression was associated with better quality diets at the later time point. Thus, while current depression is associated with poorer dietary habits, a history of depression may prompt healthier dietary behaviours in the long term. Given the demonstrated relationships between diet quality and depressive illness, clinicians should advocate dietary improvement for their patients with depression and should not be pessimistic about the likelihood of adherence to such recommendations.

An examination of the influence of maternal depression trajectories on child cognitive development and adolescent psychotic experiences

 This thesis investigated trajectories of maternal depression over time, and their influence on offspring's cognitive development in childhood and subsequent risk of psychotic experiences in early adolescence. Offspring’s IQ was also examined as a potential mediator of the relationship between maternal depression and offspring’s risk of psychotic experiences.

Peripheral vascular endothelial growth factor as a novel depression biomarker: a meta-analysis

BACKGROUND: The neurotrophic hypothesis of major depressive disorder (MDD) postulates that the pathology of this illness incorporates a down-regulation of neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless, emerging evidence has implicated the multi-competent angiogenic and neurogenic molecule - vascular endothelial growth factor (VEGF) - in hippocampal neurogenesis and depression pathophysiology. OBJECTIVE: To compare peripheral levels of VEGF between individuals with MDD and healthy controls. METHODS: We performed a systematic review and meta-analysis of original studies measuring peripheral levels of VEGF in participants with MDD compared to healthy controls. We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies published in any language through December 16th, 2014. RESULTS: Fourteen studies met eligibility criteria (N=1633). VEGF levels were significantly elevated in individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI: 0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide evidence of publication bias. A significant degree of heterogeneity was observed (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta-regression and subgroup analyses. Overall methodological quality, sample for assay (plasma versus serum), as well as the matching of MDD and control samples for age and gender emerged as significant sources of heterogeneity. CONCLUSIONS: Taken together, extant data indicate that VEGF shows promise as a biomarker for MDD, and supports that this mediator may be involved in neuroplasticity mechanisms underlying the pathophysiology of MDD.

The Influence of preconception depression and postpartum depression upon parent-Infant bonding

 Depression occurring during adolescence can predict poorer emotional bonding between parent and infant many years later for both Men and Women. However, postpartum depression continues to have the largest impact on parent-infant bonding for both Mothers and Fathers, over and above depression occurring at any other time.

Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin

AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.

Antidepressant medication may moderate the effect of depression duration on hippocampus volume

Abstract.
Hippocampus volume has been frequently, but not universally reported to be reduced in people with major depression relative to age-matched healthy controls. Among the potential reasons for this discrepancy in finding across studies is the effect of antidepressant medication. Hippocampus volume was determined by MRI (1.5 Tesla) for 10 people diagnosed with major depression for who detailed history of depression and antidepressant treatment history were known, and 10 age-matched healthy controls with no history of depression. Left, but not right, hippocampus volumes were significantly smaller in the patient group compared to the controls. Furthermore, there was a significant correlation such that left hippocampus volume was smaller with increasing lifetime duration of depression. However, this relationship was moderated by a significant correlation such that greater lifetime duration of antidepressant medication was associated with larger left hippocampus volume.
The findings support the contention that antidepressant medication may act to normalize hippocampus volume.

Daily goals, cognititions and depression in Australia and Iran

 A new scale, the Daily Goals Scale was developed and validated as a measure of propensity to set and achieve small daily goals in three independent, follow-up studies among Australian, Iranian, and Iranian-Australian community samples. It demonstrated adequate psychometric properties as an easy-to-use self-report measure.

Falls and depression in men: a population-based study

The link between falls and depression has been researched in the elderly; however, little information is available on this association in younger adults, particularly men. This study sought to investigate the link between major depressive disorder (MDD) and falls in a population-based sample of 952 men (24-97 years). MDD was diagnosed utilizing the Structured Clinical Interview for DSM-IV-TR Research Version, Non-Patient edition, and categorized as 12-month/past/never. Body mass index and gait were measured; falls, smoking status, psychotropic medication use, and alcohol intake were self-reported as part of the Geelong Osteoporosis Study 5-year follow-up assessment. Thirty-four (3.6%) men met criteria for 12-month MDD, and 110 (11.6%) for past MDD. Of the 952 men, 175 (18.4%) reported falling at least once during the past 12 months. Fallers were older (66 [interquartile range: 48-79] vs. 59 [45-72] years, p = .001) and more likely to have uneven gait (n = 16, 10% vs. n = 31, 4%, p = .003) than nonfallers. Participants with 12-month MDD had more than twice the odds of falling (age-adjusted odds ratio: 2.22, 95% confidence interval [1.03, 4.80]). The odds of falling were not associated with past depression (p = .4). Further adjustments for psychotropic drug use, gait, body mass index, smoking status, blood pressure, and alcohol did not explain these associations. Given the 2.2-fold greater likelihood of falling associated with depression was not explained by age or psychotropic drug use, further research is warranted.

Symptoms of depression and difficulty initiating sleep from early adolescence to early adulthood: a longitudinal study

STUDY OBJECTIVES: To assess the direction of the relationship and degree of shared associations between symptoms of depression and difficulty initiating sleep (DIS) from early adolescence to early adulthood. DESIGN: Cross-sectional and longitudinal assessment of the symptoms of depression-DIS association from early adolescence (age 13 y) to early adulthood (age 23 y). SETTING: Hordaland, Norway. PARTICIPANTS: There were 1,105 individuals (55% male) who took part in the Norwegian Longitudinal Health Behaviour Study (NLHB) and participated at least once across seven data collection waves during the years 1990-2000. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Characteristic data were obtained during the first assessment. Symptoms of depression and instances of DIS were assessed during each data collection wave. Symptoms of depression and DIS were associated in all data waves, and one-step cross-lagged bivariate correlations were significant and comparatively high for both factors. Structural equation modelling indicated that DIS and symptoms of depression at wave 1 remain relatively stable across waves (all P < 0.001), and a significant and consistent unidirectional cross-lagged effect was noted running from symptoms of depression to DIS from early adolescence to early adulthood. DIS is only marginally and inconsistently associated with the lagged symptoms of depression score across waves. CONCLUSIONS: These results suggest that symptoms of depression established in early adolescence are a moderate predictor of difficulty initiating sleep (DIS) in early adulthood, whereas the reverse association of DIS predicting depression was not convincingly supported. These findings are in contrast to previous findings that suggest sleep problems as a risk factor for the later development of depression.