Baseline gut microbiota profiles affect treatment response in patients with depression.

The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota.

Core antibiotic resistance genes mediate gut microbiota to intervene in the treatment of major depressive disorder.

INTRODUCTION: The relationship between depression and gut microbiota remains unclear, but an important role of gut microbiota has been verified. The relationship between gut microbiota and antibiotic resistance genes (ARGs) may be a potential new explanatory pathway. METHODS: We collected samples from 63 depressed patients and 30 healthy controls for metagenomic sequencing. The two groups' microbiota characteristics, functional characteristics, and ARG differences were analyzed. RESULTS: We obtained 30 differential KEGG orthologs (KOs) and their producers in 5 genera and 7 species by HUMAnN3. We found 6 KOs from Weissella_cibaria and Lactobacillus_plantaru are potentially coring functional mechanism of gut microbiota. Different metabolites including sphingolipids, pyrans, prenol lipids, and isoflavonoids also showed significance between MDD and HC. We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs, which indicated different mechanisms in affecting MDD. LIMITATIONS: The present study needs to be replicated in different ethnic groups. At the same time, a larger Chinese cohort study and detailed experimental verification are also the key to further discussion. CONCLUSION: Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota.

Relationship between human oral microbiome dysbiosis and neuropsychiatric diseases: An updated overview.

The role of the gut-brain axis in mental health disorders has been extensively studied. As the oral cavity is the starting point of the digestive tract, the role that the oral microbiota plays in mental health disorders has gained recent attention. Oral microbiota can enter the bloodstream and trigger inflammatory responses or translocate to the brain through the trigeminal nerve or olfactory system. Hence, the concept of the oral microbiota-brain axis has emerged. Several hypotheses have been suggested that the oral microbiota can enter the gastrointestinal tract and affect the gut-brain axis; however, literature describing oral-brain communication remains limited. This review summarizes the characteristics of oral microbiota and its mechanisms associated with mental health disorders. Through a comprehensive examination of the relationship between oral microbiota and various neuropsychiatric diseases, such as anxiety, depression, schizophrenia, autism spectrum disorder, epilepsy, Parkinson's disease, and dementia, this review seeks to identify promising avenues of future research.

Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders.

The field of neuropsychiatry is considered a middle ground between neurological and psychiatric disorders, thereby bridging the conventional boundaries between matter and mind, consciousness, and function. Neuropsychiatry aims to evaluate and treat cognitive, behavioral, and emotional disorders in individuals with neurological conditions. However, the pathophysiology of these disorders is not yet fully understood, and objective biological indicators for these conditions are currently lacking. Treatment options are also limited due to the blood-brain barrier, which results in poor treatment effects. Additionally, many drugs, particularly antipsychotic drugs, have adverse reactions, which make them difficult to tolerate for patients. As a result, patients often abandon treatment owing to these adverse reactions. Since the discovery of exosomes in 1983, they have been extensively studied in various diseases owing to their potential as nanocellulators for information exchange between cells. Because exosomes can freely travel between the center and periphery, brain-derived exosomes can reflect the state of the brain, which has considerable advantages in diagnosis and treatment. In addition, administration of engineered exosomes can improve therapeutic efficacy, allow lesion targeting, ensure drug stability, and prevent systemic adverse effects. Therefore, this article reviews the source and biological function of exosomes, relationship between exosomes and the blood-brain barrier, relationship between exosomes and the pathological mechanism of neuropsychiatric disorders, exosomes in the diagnosis and treatment of neuropsychiatric disorders, and application of engineered exosomes in neuropsychiatric disorders.

Strain-level structure of gut microbiome showed potential association with cognitive function in major depressive disorder: A pilot study.

BACKGROUND: Although the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether gut microbiota affects cognitive function in patients with MDD. In this study, we explored the association between gut microbiota and cognitive function in MDD and its possible mechanisms. METHODS: We enrolled 57 patients with MDD and 30 healthy controls (HCs) and used 16S rRNA gene sequencing analysis and shotgun metagenomic sequencing analysis to determine gut microbial composition. RESULTS: The richness and diversity of gut microbiota in patients with MDD were the same as those in HCs, but there were differences in the abundance of Bifidobacterium and Blautia. Compared with HCs, two strains (bin_32 and bin_55) were significantly increased, and one strain (bin_31) was significantly decreased in patients with MDD based on the strain-level meta-analysis. Time to complete the Stroop-C had significant negative correlations with bin_31 and bin_32. Bin_55 had significant negative correlations with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 s but significant positive correlations with correct answers in 120 s on the Stroop-CW. LIMITATIONS: This study only tested the cognitive function of MDD in a small sample, which may have caused some bias. CONCLUSIONS: Based on our strain-level analysis, we found that gut microbiota may be associated with the pathogenesis of MDD and may have potential effects on cognitive function.

Gut microbes influence the development of central nervous system disorders through epigenetic inheritance.

Central nervous system (CNS) disorders, such as depression, anxiety, and Alzheimer's disease (AD), affect quality of life of patients and pose significant economic and social burdens worldwide. Due to their obscure and complex pathogeneses, current therapies for these diseases have limited efficacy. Over the past decade, the gut microbiome has been shown to exhibit direct and indirect influences on the structure and function of the CNS, affecting multiple pathological pathways. In addition to the direct interactions between the gut microbiota and CNS, the gut microbiota and their metabolites can regulate epigenetic processes, including DNA methylation, histone modification, and regulation of non-coding RNAs. In this review, we discuss the tripartite relationship among gut microbiota, epigenetic inheritance, and CNS disorders. We suggest that gut microbes and their metabolites influence the pathogenesis of CNS disorders at the epigenetic level, which may inform the development of effective therapeutic strategies for CNS disorders.

Different roles of microbiota and genetics in the prediction of treatment response in major depressive disorder.

The roles of gut microbiota and susceptibility genes in patients with major depression disorder (MDD) are not well understood. Examining the microbiome and host genetics might be helpful for clinical decision-making. Patients with MDD were recruited in this study and subsequently treated for eight weeks. We identified the differences between the population with a response after two weeks and those with a response after eight weeks. The factors that were significantly correlated with efficacy were used to predict the treatment response. The differences in the importance of microbiota and genetics in prediction were analyzed. Our study identified rs58010457 as a potentially key locus affecting the treatment effect. Different microbiota and enriched pathways might play different roles in the response after two and eight weeks. We found that the area under the curve (AUC) value was greater than 0.8 for both random forest models. The contribution of different components to the AUC was evaluated by removing genetic information, microbiota abundance, and pathway data. The gut microbiome was an important predictor of the response after eight weeks, while genetics was an important predictor of the response after two weeks. These results suggested a dynamic effect of interaction among genetics and gut microbes on treatment. Furthermore, these results provide new guidance for clinical decisions: in cases of inadequate treatment effects after two weeks, the composition of the intestinal flora can be improved by diet therapy, which could ultimately affect the efficacy.

Interactions Between Antidepressants and Intestinal Microbiota.

The microbiota-gut-brain axis has been shown to influence human health and diseases, including depression. The interactions between drugs and intestinal microbiota are complex and highly relevant to treat diseases. Studies have shown an interaction between antidepressants and intestinal microbiota. Antidepressants may alter the abundance and composition of intestinal microbiota, which are closely related to the treatment outcomes of depression. Intestinal microbiota can influence the metabolism of antidepressants to change their availability (e.g., tryptophan can be metabolized to kynurenine by intestinal microbiota) and regulate their absorption by affecting intestinal permeability. In addition, the permeability of the blood-brain barrier can be altered by intestinal microbiota, influencing antidepressants to reach the central nervous system. Bioaccumulation is also a type of drug-microbiota interaction, which means bacteria accumulate drugs without biotransformation. These findings imply that it is important to consider intestinal microbiota when evaluating antidepressant therapy regimens and that intestinal microbiota can be a potential target for depression treatment.

Plasma levels of interleukin-8 and response to paroxetine in patients with major depressive disorder.

OBJECTIVES: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD. METHODS: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment. RESULTS: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine. CONCLUSIONS: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD.

Neferine alleviates chronic stress-induced depression by regulating monoamine neurotransmitter secretion and gut microbiota structure.

Neferine (Nef) might possess anti-depressive properties; however, its therapeutic effects are yet to be elucidated. Therefore, in this study, we aimed to explore the anti-depressant property of Nef using a mouse model of chronic stress-induced depression. Fifteen depression-prone mice were randomly selected and divided into three groups, namely, the model, Nef, and fluoxetine (Flu) groups. We observed that in tail suspension and forced swimming tests, the Nef and Flu treatments significantly decreased the immobility time of the depressed mice, and increased their sucrose preference indices. Moreover, both Nef and Flu treatments induced significant increases in the levels of anti-depressant neurotransmitters, including dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and also reduced pathological damage to the hippocampus of the depressed mice. Incidentally, Illumina MiSeq sequencing analysis demonstrated that the relative abundance of Lactobacillus in the intestinal microbiota of depressed mice was restored after Nef/Flu treatment. Moreover, colonic Lactobacillus abundance was positively correlated with the levels of DA, 5-HT, and NE in the hippocampus of the mice. In conclusion, Nef improved monoamine neurotransmitter secretion and modulated the intestinal flora structure, particularly the abundance of Lactobacillus. Hence, it showed considerable anti-depressant potential, and might be a prospective anti-depressant therapeutic agent.

Nanoparticles-based delivery system and its potentials in treating central nervous system disorders.

Central nervous system (CNS) disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become severe health concern worldwide. The treatment of the CNS diseases is of great challenges due largely to the presence of the blood-brain barrier (BBB). On the one hand, BBB protects brain from the harmful exogenous molecules via inhibiting their entry into the brain. On the other hand, it also hampers the transport of therapeutic drugs into the brain, resulting in the difficulties in treating the CNS diseases. In the past decades, nanoparticles-based drug delivery systems have shown great potentials in overcoming the BBB owing to their unique physicochemical properties, such as small size and specific morphology. In addition, functionalization of nanomaterials confers these nanocarriers controlled drug release features and targeting capacities. These properties make nanocarriers the potent delivery systems for treating the CNS disorders. Herein, we summarize the recent progress in nanoparticles-based systems for the CNS delivery, including the conventional and innovative systems. The prerequisites, drawbacks and challenges of nanocarriers (such as protein corona formation) in the CNS delivery are also discussed.

Ginsenoside Rb1 Improves Metabolic Disorder in High-Fat Diet-Induced Obese Mice Associated With Modulation of Gut Microbiota.

Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller, and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes.

The host genetics affects gut microbiome diversity in Chinese depressed patients.

The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10-9), Actinobacteria and rs77379751 (p = 8.56 × 10-9), and PWY-5913 and rs1775633082 (p = 4.54 × 10-8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10-4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.

Preeclampsia Drives Molecular Networks to Shift Toward Greater Vulnerability to the Development of Autism Spectrum Disorder.

Preeclampsia (PE) confers a significant risk for subsequent diagnosis with autism spectrum disorder (ASD), with the mechanisms underlying this observation being largely unknown. To identify molecular networks affected by both PE and ASD, we conducted a large-scale literature data mining and a gene set enrichment analysis (GSEA), followed by an expression mega-analysis in 13 independently profiled ASD datasets. Sets of genes implicated in ASD and in PE significantly overlap (156 common genes; p = 3.14E-67), with many biological pathways shared (94 pathways; p < 1.00E-21). A set of PE-driven molecular triggers possibly contributing to worsening the risk of subsequent ASD was identified, possibly representing a regulatory shift toward greater vulnerability to the development of ASD. Mega-analysis of expression highlighted RPS4Y1, an inhibitor of STAT3 that is expressed in a sexually dimorphic manner, as a contributor to both PE and ASD, which should be evaluated as a possible contributor to male predominance in ASD. A set of PE-driven molecular triggers may shift the developing brain toward a greater risk of ASD. One of these triggers, chromosome Y encoded gene RPS4Y1, an inhibitor of STAT3 signaling, warrants evaluation as a possible contributor to male predominance in ASD.

Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice.

BACKGROUND: Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied. METHODS: An intravenous injection of Adv-IFN-α (10 mice, 10 × 109 vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 109 vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. RESULTS: In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. CONCLUSIONS: Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.

A core collection of pan-schizophrenia genes allows building cohort-specific signatures of affected brain.

To investigate whether pan-schizophrenia genes could be leveraged for building cohort-specific signatures reflecting the functioning of the affected brain, we first collected 1,518 schizophrenia-related genes upon analysis of 12,316 independent peer-reviewed literature sources. More than half of these genes have been reported in at least 3 independent studies, and a majority (81.4%) were enriched within 156 functional pathways (p-values < 1e-15). Gene expression profiles of brain tissues were extracted from 14 publicly available independent datasets, and classified into "schizophrenia" and "normal" bins using dataset-specific subsets of core schizophrenia collection genes built with either a sparse representation-based variable selection (SRVS) approach or with analysis of variance (ANOVA)-based gene selection approach. Results showed that cohort-specific classifiers by both SRVS and ANOVA methods are capable of providing significantly higher accuracy in the diagnosis of schizophrenia than using the whole core genes (p < 3.38e-6), with relatively low sensitivity to the ethnic backgrounds or areas of brain biopsies. Our results suggest that the formation of consensus collection of pan-schizophrenia genes and its dissection into the functional components could be a feasible alternative to the expansion of sample size, which is needed for further in-depth studies of the pathophysiology of the human brain.

Long-term effects of prenatal exposure to metformin on the health of children based on follow-up studies of randomized controlled trials: a systematic review and meta-analysis.

PURPOSE: Oral antidiabetic medication of metformin is increasingly used in pregnant women with gestational diabetes mellitus (GDM), polycystic ovary syndrome (PCOS) and obesity. The drug passes through the placenta and can potentially influence the fetus. The aim of the study is to investigate the possible long-term effects of prenatal exposure to metformin on growth and development of the offspring. METHODS: A systematic review and meta-analysis was conducted to examine the longer term outcomes by the follow-up studies of the already published RCTs focusing on the body composition, metabolic parameters and neurophysiological development of the children prenatally exposed to metformin. The primary sources of the reviewed studies through August 2018, with restriction on the language of English, were Pubmed and Embase. RESULTS: 11 follow-up studies were included, with a maximal age of children being 13 years, comprising 823 children of mothers with GDM or PCOS who were randomized to either metformin or insulin/placebo during pregnancy. From the pooled meta-analysis we found that children prenatal exposure to metformin were associated with a significantly heavier weight (MD = 0.48 kg, 95% CI 0.24 kg, 0.73 kg; P = 0.0001, I2 = 0). As for other parameters of body composition, metabolic parameters and neurophysiological development, the results were similar between metformin and placebo/insulin use. CONCLUSION: Increased offspring weight was more observed in children prenatal exposure to metformin. Heathcare providers and patients should be aware that metformin is increasingly prescribed in pregnancy based on the relatively limited evidences but nonetheless encouraging long-term offspring data are available.

Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective for treating PTSD, but whether different frequencies have different effects remains controversial. We conducted this systematic review and meta-analysis to address this question. We searched the literature for studies written in English or Chinese in 9 electronic databases from the databases' inception to August 1, 2016. Additional articles were identified from the reference lists of identified studies and from personal reference collections. Eighteen articles were included, and 11 were suitable for the meta-analysis (Combined sample size was 377 (217 in active rTMS groups, 160 in sham-controlled groups)). Low-frequency (LF) rTMS resulted in a significant reduction in the PTSD total score and the depression score (1. PTSD total score: pooled SMD, 0.92; CI, 0.11-1.72; 2. Depression: pooled SMD, 0.54; CI, 0.08-1.00). High-frequency (HF) rTMS showed the following results: 1. PTSD total score: pooled SMD, 3.24; CI, 2.24-4.25; 2. re-experiencing: pooled SMD, -1.77; CI, -2.49-(-1.04); 3. Avoidance: pooled SMD, -1.57; CI, -2.50-(-0.84); 4. hyperarousal: pooled SMD, -1.32; CI, -2.17-(-0.47); 5. depression: pooled SMD, 1.92; CI, 0.80-3.03; and 6. Anxiety: pooled SMD, 2.67; CI, 1.82-3.52. Therefore, both HF and LF rTMS can alleviate PTSD symptoms. Although the evidence is extremely limited, LF rTMS can reduce overall PTSD and depression symptoms. HF rTMS can improve the main and related symptoms of PTSD. However, additional research is needed to substantiate these findings.

Pattern of novel object exploration in cynomolgus monkey Macaca fascicularis.

BACKGROUND: Primates exhibit substantial capacity for behavioral innovation, expanding the diversity of their behavioral repertoires, and benefiting both individual survival and species development in evolution. Novel object exploration is an integral part of behavioral innovation. Thus, qualitative and quantitative analysis of novel object exploration helps to better understand behavioral innovation. METHODS: To study the pattern of novel object exploration, two different sized balls were sequentially introduced to singly caged cynomolgus monkeys. Two aspects of monkeys' behaviors were analyzed: the types of motor activities in toy playing and whether there is an orderly sequence of such motor activities during novelty exploration. RESULTS: Four types of behavioral activities (oral contact, gross and fine forelimb motor, and hind limb motor) followed a pattern: first forelimb gross motor and oral contact, followed by forelimb fine motor and hind limb activities. Oral contact appeared to be an important behavior in monkeys' repertoire of novelty exploratory behaviors, both as an early appearing activity, and showing a consistent pattern of high cumulative time for two different novel objects. CONCLUSIONS: These results provide a profile of novel object exploratory behaviors in cynomolgus monkeys, contributing to a better understanding of this aspect of behavioral innovation.

Differential behavior patterns in cynomolgus monkey Macaca fascicularis in home cage in response to human gaze.

BACKGROUND: Non-human primates, when encountering human beings, show wariness and alertness. These behaviors differ when there is direct human gaze vs. when human averts his gaze. METHODS: We observed cynomolgus monkey in their home cage and studied their behaviors in response to human gaze. Four behaviors were analyzed: opening mouth, staring at observer, agitated activity, and approaching observer. RESULTS: Three behaviors appeared to be sensitive to human gaze between when the human observer gazed at the monkey and when the human observer looked away. Individual animals also displayed subpatterns of responses to human gaze. CONCLUSIONS: These results indicate that, even in their home cage, monkeys display a heightened level of awareness when gazed upon by a human observer, suggesting that human gaze may elicit emotional reactions. Further, under the human gaze, distinct behavioral subpatterns were apparent within the monkey cohort in our study, indicative of subgroups within the cohort.