Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as \"neuroprotective\", \"anti-inflammatory\", and \"antioxidant\" given their main function of halting disease onset and promoting health. Research has shown that some polyphenols and their metabolites can penetrate the blood-brain barrier and hence increase neuroprotective signaling and neurohormonal effects to provide anti-inflammatory and antioxidant effects. Therefore, multi-targeted modulation of polyphenols may prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for difficult-to-treat neuropsychiatric disorders. Therefore, multi-target modulation of polyphenols has the potential to prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for such nervous system diseases. Herein, we review the therapeutic benefits of polyphenols on autism-spectrum disorders, anxiety disorders, depression, and sleep disorders, along with in vitro and ex vivo experimental and clinical trials. Although their methods of action are still under investigation, polyphenols are still seldom employed directly as therapeutic agents for nervous system disorders. Comprehensive mechanistic investigations and large-scale multicenter randomized controlled trials are required to properly evaluate the safety, effectiveness, and side effects of polyphenols.

While noise is generally believed to impair performance, the detection of weak stimuli can sometimes be enhanced by introducing optimum noise levels. This phenomenon is termed \'Stochastic Resonance\' (SR). Past evidence suggests that autistic individuals exhibit higher neural noise than neurotypical individuals. It has been proposed that the enhanced performance in Autism Spectrum Disorder (ASD) on some tasks could be due to SR. Here we present a computational model, lab-based, and online visual identification experiments to find corroborating evidence for this hypothesis in individuals without a formal ASD diagnosis. Our modeling predicts that artificially increasing noise results in SR for individuals with low internal noise (e.g., neurotypical), however not for those with higher internal noise (e.g., autistic, or neurotypical individuals with higher autistic traits). It also predicts that at low stimulus noise, individuals with higher internal noise outperform those with lower internal noise. We tested these predictions using visual identification tasks among participants from the general population with autistic traits measured by the Autism-Spectrum Quotient (AQ). While all participants showed SR in the lab-based experiment, this did not support our model strongly. In the online experiment, significant SR was not found, however participants with higher AQ scores outperformed those with lower AQ scores at low stimulus noise levels, which is consistent with our modeling. In conclusion, our study is the first to investigate the link between SR and superior performance by those with ASD-related traits, and reports limited evidence to support the high neural noise/SR hypothesis.

Autism spectrum disorder (ASD) is a neurological disorder that manifests during early development, impacting individuals through their ways of communicating, social behaviors, and their ability to perform day-to-day activities. There have been different proposed mechanisms on how ASD precipitates within a patient, one of which being the impact cytokines have on fetal development once a mother\'s immune system has been activated (referred to as maternal immune activation, MIA). The occurrence of ASD has long been associated with elevated levels of several cytokines, including interleukin-6 (IL-6) and interferon gamma (IFN-γ). These proinflammatory cytokines can achieve high systemic levels in response to immune activating pathogens from various extrinsic sources. Transfer of cytokines such as IL-6 across the placental barrier allows accumulation in the fetus, potentially inducing neuroinflammation and consequently altering neurodevelopmental processes. Individuals who have been later diagnosed with ASD have been observed to have elevated levels of IL-6 and other proinflammatory cytokines during gestation. Moreover, the outcome of MIA has been associated with neurological effects such as impaired social interaction and an increase in repetitive behavior in animal models, supporting a mechanistic link between gestational inflammation and development of ASD-like characteristics. The present review attempts to provide a concise overview of the available preclinical and clinical data that suggest cross-talk between IL-6 and IFN-γ through both extrinsic and intrinsic factors as a central mechanism of MIA that may promote the development of ASD.

Social dysfunction is an intractable problem in a wide spectrum of psychiatric illnesses, undermining patients\' capacities for employment, independent living, and maintaining meaningful relationships. Identifying common markers of social impairment across disorders and understanding their mechanisms are prerequisites to developing targeted neurobiological treatments that can be applied productively across diagnoses and illness stages to improve functional outcome. This project focuses on eye gaze perception, the ability to accurately and efficiently discriminate others\' gaze direction, as a potential biomarker of social functioning that cuts across psychiatric diagnoses. This premise builds on both the monkey and human literatures showing gaze perception as a basic building block supporting higher-level social communication and social development, and reports of abnormal gaze perception in multiple psychiatric conditions accompanied by prominent social dysfunction (e.g., psychosis-spectrum disorders, autism-spectrum disorders, social phobia). A large sample (n = 225) of adolescent and young adult (age 14-30) psychiatric patients (regardless of diagnosis) with various degrees of impaired social functioning, and demographically-matched healthy controls (n = 75) will be recruited for this study. Participant\'s psychiatric phenotypes, cognition, social cognition, and community functioning will be dimensionally characterized. Eye gaze perception will be assessed using a psychophysical task, and two metrics (precision, self-referential bias) that respectively tap into gaze perception disturbances at the visual perceptual and interpretation levels, independent of general deficits, will be derived using hierarchical Bayesian modeling. A subset of the participants (150 psychiatric patients, 75 controls) will additionally undergo multimodal fMRI to determine the functional and structural brain network features of altered gaze perception. The specific aims of this project are three-fold: (1) Determine the generality of gaze perception disturbances in psychiatric patients with prominent social dysfunction; (2) Map behavioral indices of gaze perception disturbances to dimensions of psychiatric phenotypes and core functional domains; and (3) Identify the neural correlates of altered gaze perception in psychiatric patients with social dysfunction. Successfully completing these specific aims will identify the specific basic deficits, clinical profile, and underlying neural circuits associated with social dysfunction that can be used to guide targeted, personalized treatments, thus advancing NIMH\'s Strategic Objective 1 (describe neural circuits associated with mental illnesses and map the connectomes for mental illnesses) and Objective 3 (develop new treatments based on discoveries in neuroscience and behavioral science).

Young women posting their edited face photographs on social networking sites have become a popular phenomenon, but an excessively retouched face image sometimes gives a strange impression to its viewers. This study investigates what personal characteristics facilitate a bias toward an excessively edited face image. Thirty young Asian women evaluated the attractiveness and naturalness of their face images, which were edited in eight different levels-from mild to excessive-by expanding their eyes and thinning their chin. The mildly retouched face was evaluated as more attractive than the original face, but the excessively retouched face was evaluated as unattractive and unnatural in comparison with the original face. The preferred face edit level was higher for one\'s own face than for others. Moreover, participants with higher autism-spectrum quotient (AQ) scores were found to regard excessively edited face images as more attractive. The attention to detail subscale of the AQ showed a significant positive correlation with the preferred face edit level. The imagination subscale, on the contrary, showed a significant negative correlation with the preferred face edit level. The pupil response for self-face images was significantly larger than those for others\' face images, but this difference decreased with higher AQ scores. This study suggests that an increased attractiveness in their mildly retouched face promotes this behavior of retouching one\'s own face, but autistic traits, which are insensitive to the creepiness of the excessively retouched face, might pose a potential risk to inducing retouch dependence.

Newborn neurons in developing brains actively migrate from germinal zones to designated regions before being wired into functional circuits. The motility and trajectory of migrating neurons are regulated by both extracellular factors and intracellular signaling cascades. Defects in the molecular machinery of neuronal migration lead to mis-localization of affected neurons and are considered as an important etiology of multiple developmental disorders including epilepsy, dyslexia, schizophrenia (SCZ), and autism spectrum disorders (ASD). However, the mechanisms that link neuronal migration deficits to the development of these diseases remain elusive. This review focuses on neuronal migration deficits in ASD. From a translational perspective, we discuss (1) whether neuronal migration deficits are general neuropathological characteristics of ASD; (2) how the phenotypic heterogeneity of neuronal migration disorders is generated; (3) how neuronal migration deficits lead to functional defects of brain circuits; and (4) how therapeutic intervention of neuronal migration deficits can be a potential treatment for ASD.

Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a \'knockout\' rat model of fragile-X, we examined whether deletion of the Fmr1 gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X \'knockout\' rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.

The age neutrality of the Social Communication Questionnaire (SCQ) was examined as a common screener for ASD. Mixed findings have been reported regarding the recommended cutoff score\'s ability to accurately classify an individual as at-risk for autism spectrum disorder (ASD) (sensitivity) versus accurately classifying an individual as not at-risk for ASD (specificity). With a sample from the National Database for Autism Research, this study examined the SCQ\'s sensitivity versus specificity. Analyses indicated that the actual sensitivity and specificity scores were lower than initially reported by the creators of the SCQ. Autism Res 2016, 9: 838-845. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.