When the brain is not engaged in goal-directed activities and at rest, there are still measureable patterns of activity. One resting-state network, the default mode network (DMN) is responsible for a self-referential introspective state. There are many factors that influence normal changes in brain activity. The purpose of this review is to summarize differences in DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type to characterize what is "normal." Studies were systematically selected up to August 2016. Two reviewers independently used predetermined inclusion and exclusion criteria to identify relevant studies. Studies that provided sufficient information were included in a subsequent voxel-wise meta-analysis. Strength of DMN functional connectivity follows an inverse U-shape, where it is strongest in adulthood and lowest in children and elderly. Cognitive function is positively correlated with DMN functional connectivity. Females exhibit stronger intranetwork connectivity compared with males. Effects of analysis type were inconclusive and more studies need to incorporate complementing techniques. The voxel-wise meta-analysis was only conducted for the age factor. Findings supported an immature network in children compared with adults and a stronger network in adults compared with elderly. This is the first study to review differences of DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type. Findings add to the understanding of normal variance. Furthermore, defining a normal comparative base may allow for the identification of DMN change into pathology. This is important since it may allow for the detection of an intermediate risk phenotype and could serve as a biomarker for treatment response.

Highlights d Cities possess a consistent ''core'' set of non-human microbes d Urban microbiomes echo important features of cities and city-life d Antimicrobial resistance genes are widespread in cities d Cities contain many novel bacterial and viral species

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The serotonin transporter polymorphism has been implicated in obsessive-compulsive disorder (OCD). However, molecular genetic association studies have yielded inconsistent results. Variation may be due to lack of OCD subtype classification. The goal of this systematic review is to investigate the association of the S-allele of the serotonin transporter polymorphism with OCD and OCD subtypes. A total of 69 studies were initially found through a systematic search of the literature but only 13 with sufficient information to compute odds ratios were suitable for review. A total of 1991 participants with OCD and their 5-HTTLPR allele status were examined. The primary outcome measures were allele frequency and OCD diagnosis. A full meta-analysis was completed comparing the L- and S-alleles using a random effects model in RevMan 5.2.1. Further, a secondary meta-analysis stratified by sex and late-onset was conducted for S- versus L-allele frequency. In the primary meta-analysis, OCD was not associated with the S-allele of the 5-HTTLPR polymorphism (Z = 0.07, p = 0.94). Moreover, late-onset OCD was not associated with the S-allele (Z = 1.45, p = 0.15). However, when stratified by sex, there is an emerging sex-specific relationship. There was a trending association between the S-allele and OCD status in females (Z = 1.62, p = 0.10) but not in males (Z = 0.69, p = 0.49). The findings provide further support for the need of subtype classification of this heterogeneous disorder. Future studies should clearly examine sex differences and OCD age-of-onset. In particular, emphasis should be placed on the effect of female reproductive milestones on OCD onset and symptom exacerbation.