Background: Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. Methods: A PubMed literature search combined the terms “depression,” “depressive disorder,” “stool,” “fecal,” “gut,” and “microbiome” to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Results: Six eligible studies were found in which 50 taxa exhibited differences (p < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla—Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria, and Protobacteria—were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum Firmicutes, in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family Lachnospiraceae differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (Anaerostipes, Blautia, Clostridium, Klebsiella, Lachnospiraceae incertae sedis, Parabacteroides, Parasutterella, Phascolarctobacterium, and Streptococcus), six were lower (Bifidobacterium, Dialister, Escherichia/Shigella, Faecalibacterium, and Ruminococcus), and six were divergent (Alistipes, Bacteroides, Megamonas, Oscillibacter, Prevotella, and Roseburia). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. Conclusions: No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.

Suicide and nonfatal suicidal behaviors are major causes of mortality and morbidity worldwide. Variability in rates of suicide and suicidal behaviors within and between countries has been attributed to population and individual risk factors, including economic status and cultural differences, both of which can have suicide risk effects mediated through a variety of factors, of which perhaps the least understood is the role of diet. We therefore review the scientific literature concerning two major dietary lipid classes, cholesterol and polyunsaturated fatty acids (PUFAs), that have been associated with higher risk of suicide attempts and suicide. We consider potential mechanistic intermediates including serotonin transporters and receptors, toll-like receptors (TLRs), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and peroxisome proliferator activated receptors (PPARs). Based on this review, we describe a theoretical model linking cholesterol and PUFA status to suicide risk, taking into account the effects of cholesterol-lowering interventions on PUFA balance, membrane lipid microdomains (rafts) as a nexus of interaction between cholesterol and omega-3 PUFAs, and downstream effects on serotonergic neurotransmission and specific inflammatory pathways.

Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules (p < 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p < 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability.