The Roots of Science, Technology, Engineering, and Mathematics: What Are the Evolutionary and Neural Bases of Human Mathematics and Technology?

INTRODUCTION: Neural exaptations represent descent via transitions to novel neural functions. A primary transition in human cognitive and neural evolution was from a predominantly socially oriented primate brain to a brain that also instantiates and subserves science, technology, and engineering, all of which depend on mathematics. Upon what neural substrates and upon what evolved cognitive mechanisms did human capacities for science, technology, engineering, and mathematics (STEM), and especially its mathematical underpinnings, emerge? Previous theory focuses on roles for tools, language, and arithmetic in the cognitive origins of STEM, but none of these factors appears sufficient to support the transition. METHODS: In this article, I describe and evaluate a novel hypothesis for the neural origins and substrates of STEM-based cognition: that they are based in human kinship systems and human maximizing of inclusive fitness. RESULTS: The main evidence for this hypothesis is threefold. First, as demonstrated by anthropologists, human kinship systems exhibit complex mathematical and geometrical structures that function under sets of explicit rules, and such systems and rules pervade and organize all human cultures. Second, human kinship underlies the core algebraic mechanism of evolution, maximization of inclusive fitness, quantified as personal reproduction plus the sum of all effects on reproduction of others, each multiplied by their coefficient of relatedness to self. This is the only "natural" equation expected to be represented in the human brain. Third, functional imaging studies show that kinship-related cognition activates frontal-parietal regions that are also activated in STEM-related tasks. In turn, the decision-making that integrates kinship levels with costs and benefits from alternative behaviors has recently been shown to recruit the lateral septum, a hub region that combines internal (from the prefrontal cortex, amygdala, and other regions) and external information relevant to social behavior, using a dedicated subsystem of neurons specific to kinship. CONCLUSIONS: Taken together, these lines of evidence suggest that kinship systems and kin-associated behaviors may represent exaptations for the origin of human STEM.

Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. METHODS: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). CONCLUSIONS: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). FUNDING: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. TRIAL REGISTRATION: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

Experimental empathy induction promotes oxytocin increases and testosterone decreases.

Oxytocin and testosterone coordinate adaptive social behaviors with stimuli in the environment. Administration of oxytocin and testosterone is associated with increased and reduced indicators of empathy, respectively, but how levels of these hormones are jointly affected by naturalistic empathy-inducing stimuli remains unclear. In this study, salivary oxytocin and testosterone levels were measured in 173 healthy adults before and after watching a video involving a gravely ill child. Participants also completed questionnaires to assess psychological variables predicted to affect oxytocin reactivity (Autism-Spectrum Quotient, Interpersonal Reactivity Index, Empathy and Systemizing Quotients). On average, there was a 14% increase in oxytocin (p = 0.003) and 4% decrease in testosterone (p = 0.001) pre- to post-video. Opposite directional changes in hormone levels occurred together, as supported by a chi-square test (p < 0.001) and a circular statistics test (p < 0.05). Considered separately, psychological traits did not predict hormone levels or changes to any appreciable degree. However, oxytocin and testosterone changes were linked with empathy relative to systemizing such that: (1) 'Empathy Bias' was associated with a large oxytocin increase but little change in testosterone, while (2) 'Systemizing Bias' and 'Balance' between empathy and systemizing were associated with a decrease in testosterone but little change in oxytocin. These findings suggest that participants were divisible into 'high oxytocin responders' (relatively empathetic) and 'high testosterone responders' (balanced or systemizing-biased). These findings support a model of joint, opposite changes in oxytocin and testosterone under experimental empathy induction, with high, somewhat predictable, diversity in individual responses.

The blind men and the elephant: What is missing cognitively in the study of cumulative technological evolution.

I describe and explain (1) evidence regarding a key role for autism spectrum cognition in human technology; (2) tradeoffs of autistic cognition with social skills; and (3) a model of how cumulative technological culture evolves. This model involves positive feedback whereby increased technical complexity selects for enhanced social learning of mechanistic concepts and skills, leading to further advances in technology.

Socio-reproductive Conflicts and the Father's Curse Dilemma.

Evolutionary conflicts between males and females can manifest over sexually antagonistic interactions at loci or over sexually antagonistic interests within a locus. The latter form of conflict, intralocus sexual conflict, arises from sexually antagonistic selection and constrains the fitness of individuals through a phenotypic compromise. These conflicts, and socio-reproductive interactions in general, are commonly mediated by hormones, and thus predictive insights can be gained from studying their mediating effects. Here, we integrate several lines of evidence to describe a novel, hormonally mediated reproductive dilemma that we call the father's curse, which results from an intralocus conflict between mating and parental efforts. Essentially, a genetic locus exerts pleiotropic and antagonistic effects on the mating effort of one individual and the parental effort of a related individual who is the primary provider of parental care. We outline the criteria for operation of the father's curse dilemma, provide evidence of the phenomenon, and discuss the predictions and outcomes arising from its dynamics. By integrating the effects of hormones into socio-reproductive conflicts and socio-reproductive effort, clearer links between genotypes, phenotypes, and fitness can be established.

The SETDB2 locus: evidence for a genetic link between handedness and atopic disease.

The gene SETDB2, which mediates aspects of laterality in animal model systems, has recently been linked with human handedness as measured continuously on a scale from strong left to strong right. By contrast, it was marginally associated with a left-right dichotomous measure, and it showed no evidence of association with absolute handedness strength independent of direction. We genotyped the SETDB2 handedness-associated single nucleotide polymorphism, rs4942830, in a large healthy population likewise phenotyped for continuous, absolute, and dichotomous handedness variables. Our results demonstrated significant effects of rs4942830 genotype on continuous handedness, and weaker, marginal effects on dichotomous handedness, but no effects on absolute handedness. These results help to establish the locus marked by the SNP rs4942830 as a strong candidate for mediating human handedness. Intriguingly, rs4942830 is also in complete linkage disequilibrium with rs386770867, a polymorphism recently shown to affect human serum levels of IgE production and other atopic phenotypes. These findings implicate this locus in the longstanding links of handedness with asthma and other atopic diseases.

A genetic locus for paranoia.

The psychological effects of brain-expressed imprinted genes in humans are virtually unknown. Prader-Willi syndrome (PWS) is a neurogenetic condition mediated by genomic imprinting, which involves high rates of psychosis characterized by hallucinations and paranoia, as well as autism. Altered expression of two brain-expressed imprinted genes, MAGEL2 and NDN, mediates a suite of PWS-related phenotypes, including behaviour, in mice. We phenotyped a large population of typical individuals for schizophrenia-spectrum and autism-spectrum traits, and genotyped them for the single-nucleotide polymorphism rs850807, which is putatively functional and linked with MAGEL2 and NDN Genetic variation in rs850807 was strongly and exclusively associated with the ideas of reference subscale of the schizophrenia spectrum, which is best typified as paranoia. These findings provide a single-locus genetic model for analysing the neurological and psychological bases of paranoid thinking, and implicate imprinted genes, and genomic conflicts, in human mentalistic thought.

Meta-Analysis of BDNF Levels in Autism.

Brain-derived neurotrophic factor (BDNF) centrally mediates growth, differentiation and survival of neurons, and the synaptic plasticity that underlies learning and memory. Recent meta-analyses have reported significantly lower peripheral BDNF among individuals with schizophrenia, bipolar disorder, and depression, compared with controls. To evaluate the role of BDNF in autism, and to compare autism to psychotic-affective disorders with regard to BDNF, we conducted a meta-analysis of BDNF levels in autism. Inclusion criteria were met by 15 studies, which included 1242 participants. The meta-analysis estimated a significant summary effect size of 0.33 (95 % CI 0.21-0.45, P < 0.001), suggesting higher BDNF in autism than in controls. The studies showed notable heterogeneity, but no evidence of publication biases. Higher peripheral BDNF in autism is concordant with several neurological and psychological theories on the causes and symptoms of this condition, and it contrasts notably with the lower levels of BDNF found in schizophrenia, bipolar disorder, and depression.

Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder.

Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease.

The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population.

The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I (general transcription factor II-I), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations.

Inclusive fitness theory and eusociality.

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.

The convergent and divergent evolution of social-behavioral economics.

Human hunter-gatherers share a suite of traits with social insects, which demonstrates convergent social evolution of these taxa prior to agriculture. Humans differ from social insects in that their divisions of labor are more competitive than cooperative. Resulting higher within-group competition in humans has been alleviated by religion and culturally imposed monogamy, both of which also find parallels among social insects.

Female Stick Insects Mate Multiply to Find Compatible Mates.

Why females of many species mate multiply in the absence of direct benefits remains an open question in evolutionary ecology. Interacting and mating with multiple males can be costly to females in terms of time, resources, predation risk, and disease transmission. A number of indirect genetic benefits have been proposed to explain such behaviors, but the relative importance of these mechanisms in natural systems remains unclear. We tested for several direct and indirect benefits of polyandry in the walking stick Timema cristinae. We found no evidence of direct benefits with respect to longevity or fecundity. However, male × female genotypic interactions affected egg-hatching success and offspring production independent of relatedness, suggesting that mating with certain males benefits females and that the best male may differ for each female. Furthermore, multiply mated females biased paternity toward one or few males, and the extent of this bias was positively correlated to egg-hatching success. Our data, therefore, provide evidence for indirect benefits through compatibility effects in this species. By mating multiply, females may improve their chances of mating with a compatible male if compatibility cannot be assessed before mating. Such compatibility effects can explain the evolution and maintenance of polyandry in Timema and many other species.

Cognitive trade-offs and the costs of resilience.

Genetic, endocrinological, and psychological evidence demonstrates that resilience commonly trades off with sensitivity. The existence of such trade-offs indicates that resilience bears costs as well as benefits, and that some disorders can best be conceptualized in terms of extremes of trade-offs rather than expression of deficits. Testing for cognitive trade-offs should be a priority for psychiatry, psychology, neuroscience, and genetics.

Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population.

BACKGROUND: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated. RESULTS: We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies. CONCLUSIONS: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

The imprinted gene LRRTM1 mediates schizotypy and handedness in a nonclinical population.

Imprinted genes have been posited to have important roles in human brain development and cognition, but their effects in nonclinical populations have yet to be investigated. Single-nucleotide polymorphisms (SNPs) of the imprinted gene LRRTM1 have previously been associated with schizophrenia risk and with handedness in individuals with dyslexia. We tested the hypothesis that genetic variation (SNPs) and epigenetic variation (methylation) in this gene are associated with schizotypy and handedness in a nonclinical population. Risk alleles of the three schizophrenia-linked SNPs were associated with significantly and substantially higher levels of total schizotypy. Variation in SNP genotypes was not associated with handedness, but levels of methylation in a block of CpG sites in the putative LRRTM1 promoter region were associated with more-mixed handedness. These findings provide evidence of continuity between schizophrenia and schizotypy with regard to the psychological effects of allelic variation in this imprinted gene, and show that epigenetic variation in an imprinted gene mediates the development and expression of human handedness.

Pathology from evolutionary conflict, with a theory of X chromosome versus autosome conflict over sexually antagonistic traits.

Evolutionary conflicts cause opponents to push increasingly hard and in opposite directions on the regulation of traits. One can see only the intermediate outcome from the balance of the exaggerated and opposed forces. Intermediate expression hides the underlying conflict, potentially misleading one to conclude that trait regulation is designed to achieve efficient and robust expression, rather than arising by the precarious resolution of conflict. Perturbation often reveals the underlying nature of evolutionary conflict. Upon mutation or knockout of one side in the conflict, the other previously hidden and exaggerated push on the trait may cause extreme, pathological expression. In this regard, pathology reveals hidden evolutionary design. We first review several evolutionary conflicts between males and females, including conflicts over mating, fertilization, and the growth rate of offspring. Perturbations of these conflicts lead to infertility, misregulated growth, cancer, behavioral abnormalities, and psychiatric diseases. We then turn to antagonism between the sexes over traits present in both males and females. For many traits, the different sexes favor different phenotypic values, and constraints prevent completely distinct expression in the sexes. In this case of sexual antagonism, we present a theory of conflict between X-linked genes and autosomal genes. We suggest that dysregulation of the exaggerated conflicting forces between the X chromosome and the autosomes may be associated with various pathologies caused by extreme expression along the male-female axis. Rapid evolution of conflicting X-linked and autosomal genes may cause divergence between populations and speciation.

Nausea, vomiting and conflict in pregnancy: The adaptive significance of Growth-Differentiation Factor 15.

Nausea and vomiting in pregnancy (NVP) is heritable, common and aversive, and its extreme, hyperemesis gravidarum (HG), can be highly deleterious to the mother and fetus. Recent influential studies have demonstrated that HG is caused predominantly by high levels of Growth-Differentiation Factor 15 (GDF15), a hormone produced by the placenta in substantial amounts. This work has led to calls for therapeutic modulation of this hormone to reduce GDF15 levels and ameliorate HG risk. I describe three main lines of evidence relevant to the hypothesis that GDF15 production is typically adaptive for the fetus, in the context of enhanced placental invasion, reduced rates of miscarriage and preterm birth and higher birth weight. These considerations highlight the medical implications of maternal-fetal conflict, in the context of tradeoffs between aversive symptoms during gestation, rare disorders of pregnancy with major adverse effects and moderate fitness-enhancing benefits to fetuses.