Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Inflamed brain: Targeting immune changes and inflammation for treatment of depression.

Although there are a number of clinically effective treatments for depression, many patients exhibit treatment resistance. Recent clinical and preclinical studies reveal that peripheral and brain immune changes and inflammation are involved in the pathophysiology of depression. This 'Inflamed Brain' research provides critical clues for understanding of disease pathophysiology and many candidate molecules that are potentially useful for identifying novel drug targets for the treatment of depression. In this review, we will present clinical evidence on the role of inflammation in the pathophysiology of depression. We will also summarize current clinical trials which test drugs targeting inflammation for the treatment of patients with depression. Furthermore, we will briefly provide preclinical evidence demonstrating altered immune system function and inflammation in stress-induced animal models and will discuss the future potential of inflammation-related drug targets. Collectively, inflammatory signatures identified in clinical and preclinical studies may allow us to stratify depressive patients based on biotypes, contributing to the development of novel mechanism-based interventions that target specific patient populations.

Microglial cannabinoid receptor type 1 mediates social memory deficits produced by adolescent THC exposure and 16p11.2 duplication.

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. Nonetheless, until now, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, has been unexplored. Here, we report that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in the mouse model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings highlight the importance of microglial Cnr1 to produce the adverse effect of cannabis exposure in genetically vulnerable individuals.

Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. However, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is not fully understood. Here, we report that in mice, adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in a model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings suggest the microglial Cnr1 may contribute to adverse effect of cannabis exposure in genetically vulnerable individuals.

Novice vs expert inter-rater reliability of the balance error scoring system in children between the ages of 5 and 14.

BACKGROUND: The Balance Error Scoring System (BESS) is a tool to measure balance, however, no studies have shown its reliability between novice and expert raters. RESEARCH QUESTION: What is the inter-rater reliability of BESS measurements when performed by novice raters compared to experts, and does completion of a focused, online training module increase the inter-rater reliability among novice raters? METHODS: In this reliability study, 5 novice volunteers were asked to independently rate BESS tests from 50 random prerecorded BESS videos of normal healthy subjects aged 5-14. Novice raters regraded the same 50 videos after receiving a formal training. The novices' scores before and after the formal training were compared to one another and then the scores were compared to 4 expert scores. Intraclass correlation (ICC) with 95 % confidence intervals or percent agreements were calculated and compared across groups. RESULTS: For the total BESS score, novice raters showed good reliability (ICC 0.845) which did not change with a formal training (ICC 0.846). Expert raters showed excellent reliability (ICC 0.929). Poor to moderate reliability was noted in the foam stance-single leg in the untrained novice and trained novice group (ICCs 0.452 and 0.64 L respectively). SIGNIFICANCE: BESS testing by novice raters with only written instruction and no formal training yields good inter-rater reliability. In contrast, BESS testing by expert raters yields excellent reliability. A focused training for novice raters conferred a small improvement in the reliability of the scoring of the single leg stance on foam condition but not a significant difference to the overall BESS score. While novices demonstrated promising reliability for overall BESS scores, optimizing clinical research using the BESS with expert raters show the highest reliability.