Preventing early infant sleep and crying problems and postnatal depression: a randomized trial

Objective
To evaluate a prevention program for infant sleep and cry problems and postnatal depression.

Methods
Randomized controlled trial with 781 infants born at 32 weeks or later in 42 well-child centers, Melbourne, Australia. Follow-up occurred at infant age 4 and 6 months. The intervention including supplying information about normal infant sleep and cry patterns, settling techniques, medical causes of crying and parent self-care, delivered via booklet and DVD (at infant age 4 weeks), telephone consultation (8 weeks), and parent group (13 weeks) versus well-child care. Outcomes included caregiver-reported infant night sleep problem (primary outcome), infant daytime sleep, cry and feeding problems, crying and sleep duration, caregiver depression symptoms, attendance at night wakings, and formula changes.

Results
Infant outcomes were similar between groups. Relative to control caregivers, intervention caregivers at 6 months were less likely to score >9 on the Edinburgh Postnatal Depression Scale (7.9%, vs 12.9%, adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.34 to 0.94), spend >20 minutes attending infant wakings (41% vs 51%, adjusted OR 0.66, 95% CI 0.46 to 0.95), or change formula (13% vs 23%, P < .05). Infant frequent feeders (>11 feeds/24 hours) in the intervention group were less likely to have daytime sleep (OR 0.13, 95% CI 0.03 to 0.54) or cry problems (OR 0.27, 95% CI 0.08 to 0.86) at 4 months.

Conclusions
An education program reduces postnatal depression symptoms, as well as sleep and cry problems in infants who are frequent feeders. The program may be best targeted to frequent feeders.

Role of immune-inflammatory and oxidative and nitrosative stress pathways in the etiology of depression: therapeutic implications

Accumulating data have led to a re-conceptualization of depression that emphasizes the role of immuneinflammatory processes, coupled to oxidative and nitrosative stress (O&NS). These in turn drive the production of neuroregulatory tryptophan catabolites (TRYCATs), driving tryptophan away from serotonin, melatonin, and Nacetylserotonin production, and contributing to central dysregulation. This revised perspective better encompasses the diverse range of biological changes occurring in depression and in doing so provides novel and readily attainable treatment targets, as well as potential screening investigations prior to treatment initiation. We briefly review the role that immune-inflammatory, O&NS, and TRYCAT pathways play in the etiology, course, and treatment of depression. We then discuss the pharmacological treatment implications arising from this, including the potentiation of currently available antidepressants by the adjunctive use of immune- and O&NS- targeted therapies. The use of such a frame of reference and the treatment benefits attained are likely to have wider implications and utility for depression-associated conditions, including the neuroinflammatory and (neuro)degenerative disorders.

Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression

Background: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.

Methods/Design: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression.

Study eligibility criteria: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias.

Data sources: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.  The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results.

Discussion: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.