Return to routine household and community functions following uncomplicated caesarean delivery: ultra-short versus traditional hospital-stay; a randomized controlled trial.

Depression is among the most common psychiatric disorders [], with an average annual prevalence of 4.4% worldwide [], and a leading cause of disability []. Strikingly, women are twice as likely as men to develop depression [–]. Antidepressant medications are widely and increasingly prescribed, with women receiving about 68% of antidepressant prescriptions [, ]. Despite their wide use, antidepressants can have significant side effects and are not effective for all patients []. Thus, novel interventions for depression are desperately needed. Elevated inflammation may be an important new treatment target for depression and has even been proposed as a signifier for depression in the Diagnostic and Statistical Manual for Mental Disorders -VI []. Substantial preclinical and clinical evidence implicates elevated inflammation in the development of depressive symptoms [–], and in medical comorbidity associated with depression [–]. However, despite known sex differences in both inflammatory activity and depression, there has been no large-scale systematic meta-analysis focusing on sex differences in relationships between depression and inflammatory markers. Multiple factors related to sex (e.g., biological attributes) and gender (e.g., identity-based roles and behaviors) may contribute to differences in relationships between depression and inflammatory markers. First, sex differences in immune function are evident across species, with females exhibiting heightened immune responses compared to males []. While this pattern can reduce vulnerability to infection, it also places females at higher risk for some types of immunopathology, including autoimmune disorders []. Second, the underlying neurobiology of depression may differ by sex, with experimental studies indicating that acute inflammation may yield greater increases in depressive symptoms in females [, ]. Third, risk factors for depression differ by gender, with gender roles, stress exposure, and social desirability potentially contributing to differences in risk for depression [, ]. Thus, immunological, neurobiological, and sociocultural factors may drive sex differences in neural and psychological responses to inflammation. These differences have important implications for both theory and clinical research. First, if there are sex differences in associations between depression and inflammation, research progress will be hampered if we fail to include sex in our conceptual models. Second, sex differences in associations between inflammation and depression have important implications for clinical research. For example, strong sex differences could support sex stratification in clinical trials of anti-inflammatory interventions for depression, the development of different targeted interventions for females and males, and consideration of sex differences in studies examining mechanisms accounting for increased medical morbidity in depressed individuals. Thus, a better understanding of sex differences in associations between depression and inflammation can enhance theory and clinical research. Large-scale meta-analyses have reported elevated levels of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in depressed individuals versus controls [–]. Several of these meta-analyses reported no evidence of moderation by sex [–, ], but these meta-analyses were not specifically designed to address sex differences. One prior meta-analysis specifically addressing sex differences among samples with clinical depression reported that IL-6 and CRP were significantly higher in women but not men with depression, in a small selection of 23 studies with sex-stratified samples (5459 males, 7364 females in the CRP analysis) []. Thus, sex differences in the depression-inflammation relationship may exist. Extending this prior work, we conducted a dedicated large-scale systematic review and meta-analysis of sex differences in depression-inflammation associations encompassing clinical and non-clinical samples using cross-sectional and longitudinal designs.