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      Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates

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          Abstract

          Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.

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          Most cited references 31

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          Plasma oxytocin levels in autistic children.

          Social impairments are central to the syndrome of autism. The neuropeptide oxytocin (OT) has been implicated in the regulation of social behavior in animals but has not yet been examined in autistic subjects. To determine whether autistic children have abnormalities in OT, midday plasma samples from 29 autistic and 30 age-matched normal children, all prepubertal, were analyzed by radioimmunoassay for levels of OT. Despite individual variability and overlapping group distributions, the autistic group had significantly lower plasma OT levels than the normal group. OT increased with age in the normal but not the autistic children. Elevated OT was associated with higher scores on social and developmental measures for the normal children, but was associated with lower scores for the autistic children. These relationships were strongest in a subset of autistic children identified as aloof. Although making inferences to central OT functioning from peripheral measurement is difficult, the data suggest that OT abnormalities may exist in autism, and that more direct investigation of central nervous system OT function is warranted.
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            Sniffing neuropeptides: a transnasal approach to the human brain.

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              Use of the extreme groups approach: a critical reexamination and new recommendations.

              Analysis of continuous variables sometimes proceeds by selecting individuals on the basis of extreme scores of a sample distribution and submitting only those extreme scores to further analysis. This sampling method is known as the extreme groups approach (EGA). EGA is often used to achieve greater statistical power in subsequent hypothesis tests. However, there are several largely unrecognized costs associated with EGA that must be considered. The authors illustrate the effects EGA can have on power, standardized effect size, reliability, model specification, and the interpretability of results. Finally, the authors discuss alternative procedures, as well as possible legitimate uses of EGA. The authors urge researchers, editors, reviewers, and consumers to carefully assess the extent to which EGA is an appropriate tool in their own research and in that of others.
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                Author and article information

                Journal
                Science Translational Medicine
                Sci. Transl. Med.
                American Association for the Advancement of Science (AAAS)
                1946-6234
                1946-6242
                May 02 2018
                May 02 2018
                May 02 2018
                : 10
                : 439
                : eaam9100
                Article
                10.1126/scitranslmed.aam9100
                © 2018

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