Hypothetical novel simulations to explain the evolutionary survival of the hypo-reproductive extreme tail in the complex human diversity.

Hierarchical structures which lie hidden between human complex conditions and reproductivity cannot be simple, and trends of each population component does not necessarily pertain to evolutionary theories. As an illustration, the fitness of individuals with heritable extreme conditions can be low across continuing generations in observational data. Autism and schizophrenia are characterized by such evolutionary paradox of survival and hypo-reproductivity in the complex human diversity. Theoretical mechanisms for the observational fact were evaluated using a simple formula which was established to simulate stochastic epistasis-mediated phenotypic diversity. The survival of the hypo-reproductive extreme tail could be imitated just by the predominant presence of stochastic epistasis mechanism, suggesting that stochastic epistasis might be a genetic prerequisite for the evolutionary paradox. As supplemental cofactors of stochastic epistasis, a random link of the extreme tail to both un- and hyper-reproductivity and group assortative mating were shown to be effective for the paradox. Especially, the mixed localization of un- and hyper-reproductivity in the tail of a generational population evidently induced the continuous survival of outliers and extremes. These hypothetical considerations and mathematical simulations may suggest the significance of stochastic epistasis as the essential genetic background of complex human diversity.

Working Memory-Related Prefrontal Hemodynamic Responses in University Students: A Correlation Study of Subjective Well-Being and Lifestyle Habits.

Identification of social risk factors and the promotion of stress coping mechanisms and mental resilience are topics of interest in the field of mental health. The relationships between risk- or tolerability-associated factors and task-related hemodynamic responses in the prefrontal cortex (PFC) in adolescents may have important implications for mental health challenges. The purpose of this study was to investigate the relationship between task-related PFC hemodynamic activities and subjective well-being or lifestyle habits using wearable near-infrared spectroscopy (NIRS). In this study, after sample refinement to reduce heterogeneity, 20 university students were included in verbal working memory (VWM) task analyses and 21 were included in spatial working memory (SWM) task analyses. The task-related hemodynamic responses were detected using wearable NIRS. To assess the risk- or tolerability-associated factors, the levels of positive and negative affect were assessed using the Subjective Well-Being Inventory (SUBI) and lifestyle habits (such as gaming) were evaluated using a nine-item questionnaire. There was a positive correlation between SUBI positive affect and VWM task-related oxy-hemoglobin signal changes in the right dorsolateral PFC (DLPFC), underlining the significance of subjective well-being as an important independent emotional domain and suggesting the possibility of the differential objective evaluations of subjective well-being in the right PFC. Negative correlations between PFC activities during both VWM and SWM tasks at the left DLPFC and the number of game playing days in 1 week were also statistically significant, suggesting the presence of modality-non-specific hemodynamic regulation by habitual game playing. Each correlation was still robust after the elimination of major confounding impacts. Although further replication studies are warranted to confirm these preliminary results, this investigation of the relationship between task-related PFC hemodynamic activities and emotional domains or lifestyle habits might have clinical significance with regard to primary prevention of mental health issues in university students. To our knowledge, this is the first demonstration of these relationships with the use of wearable NIRS, which enables measurement under near natural conditions and is easy to use in schools or workplaces.

The origin of complex human diversity: Stochastic epistatic modules and the intrinsic compatibility between distributional robustness and phenotypic changeability

The continuing prevalence of a highly heritable and hypo-reproductive extreme tail of a human neurobehavioral quantitative diversity suggests the reproductive majority retains the genetic mechanisms for extremes. From the perspective of stochastic epistasis, the effect of an epistatic modifier variant can randomly vary in both phenotypic value and effect direction among carriers depending on the genetic identity and the modifier carriers are ubiquitous in the population. The neutrality of the mean genetic effect in carriers ensures the survival of the variant under selection pressures. Functionally or metabolically related modifier variants make an epistatic network module and dozens of modules may be involved in the phenotype. To assess the significance of stochastic epistasis, a simplified module-based model was simulated. The individual repertoire of the modifier variants in a module also contributes in genetic identity, which determines the genetic contribution of each carrier modifier. Because the entire contribution of a module to phenotypic outcome is unpredictable in the model, the module effect represents the total contribution of related modifiers as a stochastic unit in simulations. As a result, the intrinsic compatibility between distributional robustness and quantitative changeability could mathematically be simulated using the model. The artificial normal distribution shape in large-sized simulations was preserved in each generation even if the lowest fitness tail was non-reproductive. The robustness of normality across generations is analogous to the real situation of complex human diversity, including neurodevelopmental conditions. The repeated regeneration of a non-reproductive extreme tail may be essential for survival and change of the reproductive majority, implying extremes for others. Further simulation to illustrate how the fitness of extreme individuals can be low across generations may be necessary to increase the plausibility of this stochastic epistasis model.

Quantitative Nature of Social Vulnerability and Autism: An Important Paradigm Shift in the DSM-5 for Autism Spectrum Disorder.

In the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), autistic characteristics in social interaction and communication are described as qualitative impairments. However, the difference between autistics and nonautistics in the draft of the 5th edition (DSM-5 draft) is quantitative rather than qualitative. The word "qualitative" is deleted in the draft text, and it is specified that the relation between social demands and individual limited capacities is critical for symptom manifestation (criterion C). Because the proposed levels of support requirement in the draft are mere observable outcomes of social vulnerability, the boundary between level 1 and nonautistic condition is determined by the relation between social demands and individual capacities. In addition to the introduction of the single category (autism spectrum disorder (ASD)) to cover the entire case spectrum, the DSM-5 draft is clearly based on a conviction that ASD is indistinguishable from the normal behavioral range. This concise review provides an explanation for this implicit paradigm shift from qualitative to quantitative. Importantly, the conditional role of social demands for symptom manifestation in the draft can be plausibly interpreted using a unique liability-probability model.