Neutrophil to-lymphocyte and platelet-to-lymphocyte ratios as biomarkers for suicidal behavior in children and adolescents with depression or anxiety treated with selective serotonin reuptake inhibitors.

BACKGROUND: Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) have been proposed as biomarkers of suicidal risk in adults with depression. We examined whether these ratios may be considered biomarkers for suicidal behavior in young patients with major depressive or anxiety disorders before treatment with selective serotonin reuptake inhibitors (SSRIs), or as biomarkers for the adverse event of SSRI-associated suicidality. METHODS: Children and adolescents meeting criteria for major depressive or anxiety disorder were recruited. Serum levels of three pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) were assessed; and NLR and PLR calculated, from blood samples collected at baseline and after 8 weeks treatment with SSRI. A Mann-Whitney test was performed to evaluate differences in NLR and PLR between children with and without a history of a suicide attempt prior to treatment. We compared hematological parameters before and after treatment, and between children who developed SSRI-associated suicidality versus children without treatment emergent suicidality. RESULTS: Among 91 children and adolescents (aged 13.9 ± 2.4 years), baseline NLR and PLR were significantly higher among those with a history of a suicide attempt versus those without such history. Statistically significant correlations were found for the suicide ideation subscale in the Columbia suicide severity rating scale with both baseline NLR and PLR. Baseline NLR and PLR were similar in children who did and did not develop SSRI-associated suicidality after 8 weeks. In the final logistic regression model (χ2 = 18.504, df = 4, p value = 0.001), after controlling for sex, depression severity and IL-6 levels, NLR was significantly associated with a past suicide attempt (ß = 1.247, p = 0.019; OR [95% CI] = 3.478 [1.230-9.841]), with a NLR cut-off value of = 1.76 (area under the curve = 0.75 (95% CI = 0.63-0.88, sensitivity = 73%, and specificity = 71%, p value = 0.003). CONCLUSIONS: High NLR and PLR values may be associated with suicidal behavior in depressed and anxious children and adolescents. NLR appears as a better predictor of suicide attempt than PLR, and thus may be a useful biomarker of suicidality in young patients with depression or anxiety.

Systematic analysis of long intergenic non-coding RNAs in C. elegans germline uncovers roles in somatic growth.

Long intergenic non-coding RNAs (lincRNAs) are transcripts longer than 200 nucleotides that are transcribed from non-coding loci yet undergo biosynthesis similar to coding mRNAs. The disproportional number of lincRNAs expressed in testes suggests that lincRNAs are important during gametogenesis, but experimental evidence has implicated very few lincRNAs in this process. We took advantage of the relatively limited number of lincRNAs in the genome of the nematode Caenorhabditis elegans to systematically analyse the functions of lincRNAs during meiosis. We deleted six lincRNA genes that are highly and dynamically expressed in the C. elegans gonad and tested the effects on central meiotic processes. Surprisingly, whereas the lincRNA deletions did not strongly impact fertility, germline apoptosis, crossovers, or synapsis, linc-4 was required for somatic growth. Slower growth was observed in linc-4-deletion mutants and in worms depleted of linc-4 using RNAi, indicating that linc-4 transcripts are required for this post-embryonic process. Unexpectedly, analysis of worms depleted of linc-4 in soma versus germline showed that the somatic role stems from linc-4 expression in germline cells. This unique feature suggests that some lincRNAs, like some small non-coding RNAs, are required for germ-soma interactions.

Progression of Meiosis Is Coordinated by the Level and Location of MAPK Activation Via OGR-2 in Caenorhabditis elegans.

During meiosis, a series of evolutionarily conserved events allow for reductional chromosome division, which is required for sexual reproduction. Although individual meiotic processes have been extensively studied, we currently know far less about how meiosis is regulated and coordinated. In the Caenorhabditis elegans gonad, mitogen-activated protein kinase (MAPK) signaling drives oogenesis while undergoing spatial activation and deactivation waves. However, it is currently unclear how MAPK activation is governed and how it facilitates the progression of oogenesis. Here, we show that the oocyte and germline-related 2 (ogr-2) gene affects proper progression of oogenesis. Complete deletion of ogr-2 results in delayed meiotic entry and late spatial onset of double-strand break repair. Elevated levels of apoptosis are observed in this mutant, independent of the meiotic canonical checkpoints; however, they are dependent on the MAPK terminal member MPK-1/ERK. MPK-1 activation is elevated in diplotene in ogr-2 mutants and its aberrant spatial activation correlates with stages where meiotic progression defects are evident. Deletion of ogr-2 significantly reduces the expression of lip-1, a phosphatase reported to repress MPK-1, which is consistent with OGR-2 localization at chromatin in germ cells. We suggest that OGR-2 modulates the expression of lip-1 to promote the timely progression of meiosis through MPK-1 spatial deactivation.