Pre-natal exposure to acute maternal trauma or chronic maternal distress can confer increased risk for psychiatric disorders in later life. Acute maternal trauma is the result of unforeseen environmental or personal catastrophes, while chronic maternal distress is associated with anxiety or depression. Animal studies investigating the effects of pre-natal stress have largely used brief stress exposures during pregnancy to identify critical periods of fetal vulnerability, a paradigm which holds face validity to acute maternal trauma in humans. While understanding these effects (...) is undoubtably important, the literature suggests maternal stress in humans is typically chronic and persistent from pre-conception through gestation. In this review, we provide evidence to this effect and suggest a realignment of current animal models to recapitulate this chronicity. We also consider candidate mediators, moderators and mechanisms of maternal distress, and suggest a wider breadth of research is needed, along with the incorporation of advanced -omics technologies, in order to understand the neurodevelopmental etiology of psychiatric risk. (shrink)

Disruptions in chromatin regulator genes are frequently the cause of neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are widely expressed in the brain, yet symptoms suggest that specific circuits can be preferentially altered when they are mutated. Using Drosophila allows targeted manipulation of chromatin regulators in defined neuronal classes, lineages, or circuits, revealing their roles in neuronal precursor self‐renewal, dendrite and axon targeting, neuron diversification, and the tuning of developmental signaling pathways. Phenotypes arising from chromatin regulator disruption are context dependent – (...) defined by interaction networks between the regulators, transcription factors, and chromatin remodeling complex partners. Future challenges are to determine the complexity of partner interactions, and to ascertain the degree to which cognitive deficits are due to loss of chromatin regulator activity in building a circuit or in maintaining homeostasis and activity within it. (shrink)

The World Health Organisation recently listed air pollution as the most significant threat to human health. Air pollution comprises particulate matter (PM), metals, black carbon and gases such as ozone (O3), nitrogen dioxide (NO2) and carbon monoxide (CO). In addition to respiratory and cardiovascular disease, PM exposure is linked with increased risk of neurodegeneration as well as neurodevelopmental impairments. Critically, studies suggest that PM crosses the placenta, making direct in utero exposure a reality. Rodent models reveal that neuroinflammation, neurotransmitter imbalance (...) and oxidative stress are triggered following gestational/early life exposure to PM, and may be exacerbated by concomitant mitochondrial dysfunction. Gestational PM exposure (potentiated by mitochondrial impairment in the metabolically active neonatal brain) not only impacts neurodevelopment but may sensitise the brain to subsequent cognitive impairment. Having reviewed this field, we conclude that strategies are urgently required to reduce exposure to PM during this sensitive developmental period. (shrink)

Hooks et al. posit that gastrointestinal microbes alter the end state of development indirectly. Here, we present the immune system as the link that facilitates communication between the gut and the brain. Illustrating the case of autism spectrum disorder, we explicate the role of the immune system in responding to microbial dysbiosis by inducing an inflammatory state that affects neurodevelopment. We propose two models: directly, within the infant, and indirectly, via maternal and infant systems.

Several recent research findings have implicated brain-derived neurotrophic factor (BDNF) as a mediator of neuronal plasticity. The BDNF gene is under extensive epigenetic regulation, which modulates how much or how little environmental experiences become encoded within neurons and neural circuits. Future scientific progress within the postgenomic paradigm requires elucidation of the functional trajectory in neogenetic and environment interactions.

Autism has been defined as a disorder of social cognition, interaction and communication where ritualistic, repetitive behaviors are commonly observed. But how should we understand the behavioral and cognitive differences that have been the main focus of so much autism research? Can high-level cognitive processes and behaviors be identified as the core issues people with autism face, or do these characteristics perhaps often rather reflect individual attempts to cope with underlying physiological issues? Much research presented in this volume will point (...) to the latter possibility, i.e. that people on the autism spectrum cope with issues at much lower physiological levels pertaining not only to Central Nervous Systems (CNS) function, but also to peripheral and autonomic systems (PNS, ANS) (Torres, Brincker, et al. 2013). The question that we pursue in this chapter is what might be fruitful ways of gaining objective measures of the large-scale systemic and heterogeneous effects of early atypical neurodevelopment; how to track their evolution over time and how to identify critical changes along the continuum of human development and aging. We suggest that the study of movement variability—very broadly conceived as including all minute fluctuations in bodily rhythms and their rates of change over time (coined micro-movements (Figure 1A-B) (Torres, Brincker, et al. 2013))—offers a uniquely valuable and entirely objectively quantifiable lens to better assess, understand and track not only autism but cognitive development and degeneration in general. This chapter presents the rationale firstly behind this focus on micro-movements and secondly behind the choice of specific kinds of data collection and statistical metrics as tools of analysis (Figure 1C). In brief the proposal is that the micro-movements (defined in Part I – Chapter 1), obtained using various time scales applied to different physiological data-types (Figure 1), contain information about layered influences and temporal adaptations, transformations and integrations across anatomically semi-independent subsystems that crosstalk and interact. Further, the notion of sensorimotor re-afference is used to highlight the fact that these layered micro-motions are sensed and that this sensory feedback plays a crucial role in the generation and control of movements in the first place. In other words, the measurements of various motoric and rhythmic variations provide an access point not only to the “motor systems”, but also access to much broader central and peripheral sensorimotor and regulatory systems. Lastly, we posit that this new lens can also be used to capture influences from systems of multiple entry points or collaborative control and regulation, such as those that emerge during dyadic social interactions. (shrink)

The current rise of neurodevelopmental disorders poses a critical need to detect risk early in order to rapidly intervene. One of the tools pediatricians use to track development is the standard growth chart. The growth charts are somewhat limited in predicting possible neurodevelopmental issues. They rely on linear models and assumptions of normality for physical growth data – obscuring key statistical information about possible neurodevelopmental risk in growth data that actually has accelerated, non-linear rates-of-change and variability encompassing skewed distributions. Here, (...) we use new analytics to profile growth data from 36 newborn babies that were tracked longitudinally for 5 months. By switching to incremental (velocity-based) growth charts and combining these dynamic changes with underlying fluctuations in motor performance – as the transition from spontaneous random noise to a systematic signal – we demonstrate a method to detect very early stunting in the development of voluntary neuromotor control and to flag risk of neurodevelopmental derail. (shrink)

This article views face perception as the ideal case study example for understanding the deeper principles underlying human neurodevelopment. It illustrates how face perception has been one of oldest battlegrounds for resolving key issues in human development. It argues that taking a developmental approach to face perception can resolve some of the major current debates in the adult face perception and cognitive neuroscience literature. Thus, face perception and development continue to be mutually informative domains of study. The work on (...) newborns designed to test the “innate knowledge” of faces, studying the development of face perception skills during infancy and childhood, has proved to be fertile ground for domain-general theories of perceptual and cognitive development. The study reviews recent literature on the factors that contribute to the specialization of certain cortical areas for face processing. It suggests an intriguing alternative middle-ground view in this polarized debate. (shrink)

The unpredictability of maternal sensory signals in caregiving behavior has been recently found to be linked with infant neurodevelopment. The research area is new, and very little is yet known, how maternal anxiety and depressive symptoms and specific parental characteristics relate to the unpredictable maternal care. The aims of the current study were to explore how pre- and postnatal maternal anxiety and depressive symptoms and self-regulation capacity associate with the unpredictability of maternal sensory signals. The study population consisted of (...) 177 mother-infant dyads. The unpredictability of the maternal sensory signals was explored from the video-recorded mother-infant free play situation when the infant was 8 months of age. Pre- and postnatal anxiety and depressive symptoms were measured by questionnaires prenatally at gwks 14, 24, 34, and 3 and 6 months postpartum. Maternal self-regulation capacity, a trait considered to be stable in adulthood, was assessed using adult temperament questionnaire when the infant was 12 months of age. We found that elevated prenatal maternal anxiety symptoms associated with higher unpredictability in the maternal care while depressive symptoms were unrelated to the unpredictability of maternal care. Moreover, the association was moderated by maternal self-regulation capacity, as higher anxiety symptoms during pre-and postnatal period were associated more unpredictability among the mothers with low self-regulation capacity. The combination of higher amount of maternal anxiety symptoms and lower self-regulation capacity seems to constitute specific risk for the unpredictable maternal care. (shrink)

Recent neuropaleontological research suggests that the parietal lobe has increased in size as much as the frontal lobes in Homo Sapiens over the past 150,000 years, but has not provided a neuropsychological explanation for the evolution of human socialization or the development of religion. Drawing from several areas of research, (i.e., neurodevelopment, neuropsychology, paleoneurology, cognitive science, archeology, and anthropology), we argue that parietal evolution in Homo sapiens integrated sensations and mental processes into a more integrated subjective “sense of self”. (...) This enhanced self advanced prosocial traits (e.g., increased empathy, greater social bonding, enhanced theory of mind capacities), promoting more effective socialization skills (e.g., parenting, group cooperation). Conversely, when this enhanced sense of self became inhibited, powerful experiences of self-transcendence occurred. We believe these potent selfless experiences became increasingly sought after though ritual means (e.g., music, dance, vision quests, spirit travel), providing the foundations for the development of shamanism and religion. (shrink)

Schizophrenia is a worldwide, prevalent disorder with a multifactorial but highly genetic aetiology. A constant prevalence rate in the face of reduced fecundity has caused some to argue that an evolutionary advantage exists in unaffected relatives. Here, I critique this adaptationist approach, and review – and find wanting – Crow's “speciation” hypothesis. In keeping with available biological and psychological evidence, I propose an alternative theory of the origins of this disorder. Schizophrenia is a disorder of the social brain, and it (...) exists as a costly trade-off in the evolution of complex social cognition. Paleoanthropological and comparative primate research suggests that hominids evolved complex cortical interconnectivity (in particular, frontotemporal and frontoparietal circuits) to regulate social cognition and the intellectual demands of group living. I suggest that the ontogenetic mechanism underlying this cerebral adaptation was sequential hypermorphosis and that it rendered the hominid brain vulnerable to genetic and environmental insults. I argue that changes in genes regulating the timing of neurodevelopment occurred prior to the migration of Homo sapiens out of Africa 100,000–150,000 years ago, giving rise to the schizotypal spectrum. While some individuals within this spectrum may have exhibited unusual creativity and iconoclasm, this phenotype was not necessarily adaptive in reproductive terms. However, because the disorder shared a common genetic basis with the evolving circuitry of the social brain, it persisted. Thus schizophrenia emerged as a costly trade-off in the evolution of complex social cognition. Key Words: cortical connectivity; evolution; heterochrony; metarepresentation; primates; psychiatry; schizophrenia; social brain; social cognition. (shrink)

We investigated the influence of maternal depression (MD) on the communication and motor dimensions of child neurodevelopment, by a longitudinal and descriptive study. We assessed 1,555 mother-baby dyads from two Brazilian cities with discrepant sociodemographic characteristics: Ribeirão Preto (RP) (N=663) and São Luís (SL) (N=892). MD during pregnancy and at the second year of child´s life was assessed, respectively, through the Center for Epidemiologic Studies Depression Scale-CES-D (≥24) and the Edinburg Postnatal Depression Scale-EPDS (≥12). Child development was assessed through (...) the screening test from the Bayley Scale (BSID-III), when children were 12-24 months old. There was association between MD at the second year of child´s life and impairment on the Receptive Communication dimension of language development, especially when analysis included depression during pregnancy and sociodemographic variables. Such association was found only in the city with worse sociodemographic indicators. Our findings supported the influence of MD in the second year of child´s life on child neurodevelopment, specifically on the Receptive Communication dimension of language development in SL. Moreover, findings suggested a possible role of environmental and socioeconomic variables in such association, drawing attention to prenatal care monitoring and intervention programs for mothers living in unfavorable socioeconomic contexts. (shrink)

Imprinted genes are monoallelically expressed in a parent‐of‐origin‐dependent manner and can affect brain and behavioural phenotypes. The X chromosome is enriched for genes affecting neurodevelopment and is donated asymmetrically to male and female progeny. Hence, X‐linked imprinted genes could potentially influence sexually dimorphic neurobiology. Consequently, investigations into such loci may provide new insights into the biological basis of behavioural differences between the sexes and into why men and women show different vulnerabilities to certain mental disorders. In this review, we (...) summarise recent advances in our knowledge of X‐linked imprinted genes and the brain substrates that they may act upon. In addition, we suggest strategies for identifying novel X‐linked imprinted genes and their downstream effects and discuss evolutionary theories regarding the origin and maintenance of X‐linked imprinting. BioEssays 28:35–44, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

D‐amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D‐cysteine in mammalian brain. D‐cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D‐cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D‐cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D‐cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D‐cysteine inhibits AKT phosphorylation at Thr 308 and Ser (...) 473 in NPCs. D‐cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D‐cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D‐cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD). (shrink)

Lack of guidance and regulation for authorizing medical cannabis for conditions involving the health and neurodevelopment of children is ethically problematic as it promulgates access inequities, risk-benefit inconsistencies, and inadequate consent mechanisms. In two virtual sessions using participatory action research and consensus-building methods, we obtained perspectives of stakeholders on ethics and medical cannabis for children and youth. The sessions focused on the scientific and regulatory landscape of medical cannabis, surrogate decision-making and assent, and the social and political culture of (...) medical cannabis. We found that evidence-gathering and data dissemination, pressures on clinical relationships, and the lack of integration of culturally diverse perspectives and Indigenous knowledges were key areas of concern. Participants emphasized the importance of utilizing adaptive study designs, highlighted the importance of trust-building between clinicians, patients and caregivers, and discussed barriers including historical and ongoing stigmatization of medical cannabis. We conclude that continued public consultation and strength-based research that integrate diverse perspectives are critical steps forward. (shrink)

Volume II in the Evolution of Gestalt series, _Relational Child, Relational Brain_ continues the development of the paradigm shift that places human development in a field that is deeply complex and fundamentally one of interconnection, taking us away from the limiting view of us as separate individuals. It builds on the foundation of contemporary views of relational neurodevelopment and the profound influence of relationship on brain growth. It shows how, particularly in the first two years of life, but continuing (...) across the whole of childhood and adolescence into early adulthood, the relational field is the context of child development. The focus then broadens out to examine the intersubjective influence of community, culture, and social and physical support. Backed by neurobiological and related research, it offers many examples of relational Gestalt practice with children, adolescents, and their families, with stories of loss, trauma, isolation, and other adversities. Not just an invaluable resource for child and adolescent therapists, _Relational Child, Relational Brain_ goes beyond the Esalen Study Conference from which it emerged and is a further invitation and challenge to apply relational Gestalt practice as a coherent and effective way forward in the troubled world of today. (shrink)

The emergent Coronavirus Disease 2019 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 could produce a maternal immune activation via the inflammatory response during gestation that may impair fetal neurodevelopment and lead to postnatal and adulthood mental illness and behavioral dysfunctions. However, so far, limited evidence exists regarding long-term physiological, immunological, and neurodevelopmental modifications produced by the SARS-CoV-2 in the human maternal-fetal binomial and, particularly, in the offspring. Relevant findings derived from epidemiological and preclinical models show that a (...) MIA is indeed linked to an increased risk of neurodevelopmental disorders in the offspring. We hypothesize that a gestational infection triggered by SARS-CoV-2 increases the risks leading to neurodevelopmental disorders of the newborn, which can affect childhood and the long-term quality of life. In particular, disruption of either the maternal or the fetal cholinergic anti-inflammatory pathway could cause or exacerbate the severity of COVID-19 in the maternal-fetal binomial. From a translational perspective, in this paper, we discuss the possible manifestation of a MIA by SARS-CoV-2 and the subsequent neurodevelopmental disorders considering the role of the fetal-maternal cytokine cross-talk and the CAP. Specifically, we highlight the urgent need of preclinical studies as well as multicenter and international databanks of maternal-fetal psychophysiological data obtained pre-, during, and post-infection by SARS-CoV-2 from pregnant women and their offspring. (shrink)

The negative impact of adverse experiences in childhood on neurodevelopment is well documented. Less attention however has been given to the impact of variations in “normative” parenting behaviors. The influence of these parenting behaviors is likely to be marked during periods of rapid brain reorganization, such as late childhood. The aim of the current study was to investigate associations between normative parenting behaviors and the development of structural brain networks across late childhood. Data were collected from a longitudinal sample (...) of 114 mother-child dyads (54% female children,Mage 8.41 years, SD = 0.32 years), recruited from low socioeconomic areas of Melbourne, Australia. At the first assessment parenting behaviors were coded from two lab-based interaction tasks and structural magnetic resonance imaging (MRI) scans of the children were performed. At the second assessment, approximately 18 months later (Mage 9.97 years, SD = 0.37 years) MRI scans were repeated. Cortical thickness (CT) was extracted from T1-weighted images using FreeSurfer. Structural covariance (SC) networks were constructed from partial correlations of CT estimates between brain regions and estimates of network efficiency and modularity were obtained for each time point. The change in these network measures, from Time 1 to Time 2, was also calculated. At Time 2, less positive maternal affective behavior was associated with higher modularity (more segregated networks), while negative maternal affective behavior was not related. No support was found for an association between local or global efficacy and maternal affective behaviors at Time 2. Similarly, no support was demonstrated for associations between maternal affective behaviors and change in network efficiency and modularity, from Time 1 to Time 2. These results indicate that normative variations in parenting may influence the development of structural brain networks in late childhood and extend current knowledge about environmental influences on structural connectivity in a developmental context. (shrink)

Psychiatric disorders share an excess of seasonal birth in winter and spring, suggesting an increase of neurodevelopmental risks. Evidence suggests season of birth can serve as a proxy of harmful environmental factors. Given that prenatal exposure of these factors may trigger pathologic processes in the neurodevelopment, they may consequently lead to brain volume alterations. Here we tested the effects of season of birth on gray matter volume in a transdiagnostic sample of patients with schizophrenia and depression compared to healthy (...) controls. We found a significant effect of season of birth on gray matter volume with reduced right hippocampal volume in summer-born compared to winter-born patients with depression. In addition, the volume of the right hippocampus was reduced independent from season of birth in schizophrenia. Our results support the potential impact of season of birth on hippocampal volume in depression. (shrink)

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged (...) between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy. (shrink)

Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short- and long-term medical and neurodevelopment advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice.In a letter sent out to 2600 hospitals across the country they [Public Citizen] demand that healthcare facilities “immediately discontinue the distribution of commercial infant formula manufacturer discharge bags,” claiming it undermines women’s success at breastfeeding. What they failed to explain (...) is why a woman’s decision regarding her own tits is anyone’s fucking business but her own.Clearly, policies to promote breast-feeding.. (shrink)

Cannabis use in some individuals can meaningfully introduce de novo risk for the initiation of opioid use and development of opioid use disorder. These risks may be particularly high during adolescence when cannabis use may disrupt critical periods of neurodevelopment. Current research studying the combination of genetic and environmental factors involved in substance use disorders is poorly understood. More research is needed, particularly to identify which adolescents are most at risk and to develop effective interventions addressing contributing factors such (...) as trauma and psychiatric comorbidity. (shrink)

Many studies have shown that marijuana can negatively affect the cognitive development of adolescents. For some individuals, marijuana use may also initiate opioid use, dose escalation, and opioid use disorder. States that legalize marijuana should help adolescents through regulation of advertising and availability of marijuana-infused edibles. Such policies may assist in protecting neurodevelopment of the adolescent and young adult brain. The federal government should also remove its prohibition of marijuana sales and use, leaving their regulation to state law-makers.

Studies of childhood abuse and neglect haveimportant lessons for considerations of natureand nurture. While each child has uniquegenetic potentials, both human and animalstudies point to important needs that everychild has, and severe long-term consequencesfor brain function if those needs are not met. The effects of the childhood environment,favorable or unfavorable, interact with all theprocesses of neurodevelopment (neurogenesis,migration, differentiation, apoptosis,arborization, synaptogenesis, synapticsculpting, and myelination). The time coursesof all these neural processes are reviewed herealong with statements of core principles forboth genetic (...) and environmental influences onall of these processes. Evidence is presentedthat development of synaptic pathways tends tobe a ``use it or lose it'' proposition.Abuse studies from the author's laboratory,studies of children in orphanages who lackedemotional contact, and a large number of animaldeprivation and enrichment studies point to theneed for children and young nonhuman mammals tohave both stable emotional attachments with andtouch from primary adult caregivers, andspontaneous interactions with peers. If theseconnections are lacking, brain development bothof caring behavior and cognitive capacities isdamaged in a lasting fashion.These effects of experience on the brainimply that effects of modern technology can bepositive but need to be monitored. Whiletechnology has raised opportunities forchildren to become economically secure andliterate, more recent inadvertent impacts oftechnology have spawned declines in extendedfamilies, family meals, and spontaneous peerinteractions. The latter changes have deprivedmany children of experiences that promotepositive growth of the cognitive and caringpotentials of their developing brains. (shrink)

Animal and human studies suggest that parenting style is transmitted from one generation to the next. The hypotheses of this study were that a mother’s rearing experiences would predict her own parenting resources and current maternal mood, motivation to care for her offspring, and relationship with her parents would underlie this association. In a subsample of 201 first-time mothers participating in the longitudinal Maternal Adversity, Vulnerability and Neurodevelopment project, we assessed a mother’s own childhood maltreatment and rearing experiences using (...) the Childhood Trauma Questionnaire and the Parental Bonding Instrument. At 6 months postpartum, mothers completed questionnaires on parenting stress, symptoms of depression, maternal motivation, and current relationship with their own parents. The sample consisted of mostly high socioeconomic status mothers recruited from Montréal or Hamilton, Canada, with an age range from 18 to 43 years. More severe maltreatment and less supportive rearing by the mother’s parents predicted increased parenting stress at 6 months. These associations were mediated through distinct psychosocial pathways: maltreatment on parenting stress through symptoms of depression ; maternal rearing on parenting stress through maternal motivation and symptoms of depression ; and paternal rearing on parenting stress through current relationship with the father. Maternal rearing experiences predict a mother’s own parenting resources though distinct psychosocial pathways, including depressed mood, maternal motivation, and social support. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Vice and Naturalistic OntologyChristopher R. Williams (bio)Keywordscausality, criminality, determinism, medical model, positivismThese questions have been posed: Is vice (encompassing criminal and other wrongful conduct) best regarded as “sick” behavior, “immoral” behavior, or some other type altogether? Are we to understand vice in natural-medical terms, or are we better served by utilizing a moral framework? Is criminality reducible to and best categorized as a metaphysical type the essential features of (...) which are neurological or otherwise biological in nature? Or, perhaps, is criminality closer to a (non-natural) sociological type, the essential features of which can be understood only through reference to social norms and cultural conventions? These are torturously involved philosophical and theoretical questions that have given rise to an equally torturous volume of literature. Without pretending to do justice to these questions or their corresponding literature, several key considerations that must be inserted into and accounted for within the discursive pursuit of these inquiries are worth noting.Where a naturalistic ontology is employed within the study of vice, we reduce the intricacies of deviant behavioral phenomena to what we presume to be their underlying medical/biological properties. It is worth remembering that behavior itself cannot rightfully be said to be “sick”; rather, what we mean to say is that the behavior in question—in our case, various forms of “vice”—is symptomatic of some underlying illness or medical/biological condition. The presumed underlying sickness and the behavior itself are distinct, ontologically linked only through their theorized relationship to one another. This, then, is a key assumption of the medical approach to vice and its ontological classification as a natural-medical kind: that there exists a relationship between the behavior (a symptom) and the underlying illness or medical condition, and that the relationship is of the causal kind. Vice, it is suggested, is a change in state that is caused by (or, at the very least, is a direct consequence of) sickness or illness. Second, to legitimate such attributions, the illness supplying the requisite causal force must be identifiable and its causal connection to the behavior must be or be capable of being sufficiently explicated. In other words, once we have identified the relevant medical/biological properties and the behavior to which they stand in causal relatedness, we must be prepared to characterize this dynamic—we must be able to show exactly how and why such and such a condition gives rise to such and such a behavior.Problematically, causation itself is and has always been a contentious metaphysical specimen. Hume (1955) reminded us of the troubling reality [End Page 39] that we cannot ever “see” one thing cause or necessitate another. We are left, rather, to merely presume the existence of causal relationships between things. How is it, exactly, that disorder in neurodevelopment can necessitate certain behavioral outcomes? Even if we can “see” (in the empirical sense) the disorder and equally “see” the behavior, we cannot of course witness the precise causal action of the former upon the latter. Even if we are content inferring causal action in such cases, we still need to demonstrate the basic conditions of causality. To show that Condition X is causally related Behavior Y, we need to show that they are regularly associated with one another, that Condition X temporally preceded Behavior Y and, most challengingly, that no other conditions or factors have an intervening (e.g., additive, synergistic) influence. Hypothetically, if we were to posit a causal relationship between schizotypal personality traits and violent behavior, we would need to establish: (1) that schizotypal traits and violent behavior regularly coexist; (2) that those traits presented before the manifestation of the violent behavior; and (3) that no other factors (biological, psychological, and/or sociological) contributed in any meaningful way to those manifestations. We would thus need to systematically rule out family dynamics, income, education, intelligence, substance use, and so forth, as contributing factors. If, in turn, we were to determine that the presence of schizotypal traits alone is not sufficient—even if a necessary condition—to produce violent behavior but, rather, that those traits act in concert with other variables to produce the behavior, then we would not truly be... (shrink)

A decade ago, leptin (from the greek lepto meaning ‘thin’) was identified as the product of the ob gene.1 This adipocyte‐derived hormone was found to suppress feeding and stimulate thermogenesis, and was thus proposed as a mediator in a negative feedback loop that controls body adiposity. This discovery led to a rapid revolution in the understanding of neurobiological mechanisms regulating obesity. However, while leptin's first life was as an adipostat, it is now known to have a wide range of additional (...) neuroendocrine, metabolic and behavioural functions in the CNS and periphery. Remarkably, the pleiotropic nature of the hormone continues to be extended with the recent publication of two papers that expand on leptin's neurobiological actions in the CNS.2,3 They indicate novel regulatory roles for the hormone in both synaptic plasticity and axon guidance. Crucially, in light of the rising incidence of obesity in modern society, both of the studies reveal leptin‐mediated links between nutrition and neurodevelopment, findings that have further implications for leptin's role in the regulation of energy homeostasis. BioEssays 26:1043–1045, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Autism spectrum disorder is a group of complex neurodevelopment disorders characterized by altered brain connectivity. However, the majority of neuroimaging studies for ASD focus on the static pattern of brain function and largely neglect brain activity dynamics, which might provide deeper insight into the underlying mechanism of brain functions for ASD. Therefore, we proposed a framework with Hidden Markov Model analysis for resting-state functional MRI from a large multicenter dataset of 507 male subjects. Specifically, the 507 subjects included 209 (...) subjects with ASD and 298 well-matched health controls across 14 sites from the Autism Brain Imaging Data Exchange. Based on the HMM, we can identify the recurring brain function networks over time across ASD and healthy controls. Then we assessed the dynamical configuration of the whole-brain networks and further analyzed the community structure of transitions across the brain states. Based on the 19 HMM states, we found that the global temporal statistics of the specific HMM states were significantly altered in ASD compared to HCs. These specific HMM states were characterized by the activation pattern of default mode network, sensory processing networks [including visual network, auditory network, and sensory and motor network ]. Meanwhile, we also find that the specific modules of transitions between states were closely related to ASD. Our findings indicate the temporal reconfiguration of the brain network in ASD and provide novel insights into the dynamics of the whole-brain networks for ASD. (shrink)

Macrocephaly is present in about 2–5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain (...) overgrowth on basic perceptual learning processes during the first year of life. We recorded high density electroencephalograms in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic and 81 normocephalic classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10–20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life. (shrink)

Prenatal alcohol exposure interferes with neurodevelopment. The brain is particularly susceptible to the adverse consequences of prenatal alcohol exposure, and numerous studies have documented changes to brain anatomy and function, as well as consequences for cognition, behavior, and mental health. Studies in typically developing individuals have shown that the brain undergoes dynamic developmental processes over an individual’s lifespan. Furthermore, magnetic resonance imaging studies in other neurodevelopmental and psychiatric disorders have shown that their developmental trajectories differ from the typical pattern. (...) Therefore, to understand long-term clinical outcomes of fetal alcohol spectrum disorders, it is necessary to investigate changes in neurodevelopmental trajectories in this population. Here we review studies that have used MRI to evaluate changes in brain structure and function over time via cross-sectional or longitudinal methods in individuals with PAE. Research demonstrates that individuals with PAE have atypical cortical and white matter microstructural developmental trajectories through childhood and adolescence. More research is needed to understand how factors such as sex and postnatal experiences may further mediate these trajectories. Furthermore, nothing is known about the trajectories beyond young adulthood. (shrink)

_Background:_ Preterm infants are still at an increased risk for suboptimal neurodevelopmental outcomes when compared with term born infants. The development of a child born preterm can be jeopardized by suboptimal conditions during pregnancy, in addition to the suboptimal growth environment postnatally compared to the normal in utero environment. This review summarizes the literature on the role of chorioamnionitis, placental insufficiency, and maternal smoking on the developmental outcomes of preterm infants. _Methods:_ A systematic database search was performed to identify all (...) original articles published on or before September 12, 2018 that evaluated the impact of clinical or histological chorioamnionitis, abnormal prenatal fetal and placental blood flow, and prenatal smoking exposure on the neuropsychological and cognitive outcomes of preterm infants. We identified a total of 54 studies. Thirty five original articles evaluated the effects of clinical or histological chorioamnionitis; 15 studies evaluated the effects of abnormal blood flow patterns; and four studies evaluated the effects of maternal smoking during pregnancy. _Results:_ The studies on prenatal risk factors showed conflicting results about the impact on the neurodevelopment of preterm infants. The majority of the studies did not show that chorioamnionitis poses a direct risk to the development of preterm infants. The role of abnormal prenatal placental and fetal blood flow on the development of preterm infants remained inconclusive because the sample sizes were often small and methodological problems complicated the interpretation of the data. Maternal smoking during pregnancy was assessed only in one cohort which showed that maternal smoking is a risk for suboptimal cognitive and neuropsychological development in preterm infants. _Conclusions:_ This review summarizes the data on several prenatal risk factors which play a role in the developmental outcomes of preterm infants. To optimize the developmental outcomes, we need to first optimize the fetal wellbeing before birth. More research that extends from the fetal life to long-term developmental outcomes is needed. (shrink)

Early life adversity, such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe (...) integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA. (shrink)

Transposable elements (TEs) are mobile genomic elements constituting a big fraction of eukaryotic genomes. They ignite an evolutionary arms race with host genomes, which in turn evolve strategies to restrict their activity. Despite being tightly repressed, TEs display precisely regulated expression patterns during specific stages of mammalian development, suggesting potential benefits for the host. Among TEs, the long interspersed nuclear element (LINE‐1 or L1) has been found to be active in neurons. This activity prompted extensive research into its possible role (...) in cognition. So far, no specific cause‐effect relationship between L1 retrotransposition and brain functions has been conclusively identified. Nevertheless, accumulating evidence suggests that interactions between L1 RNAs and RNA/DNA binding proteins encode specific messages that cells utilize to activate or repress entire transcriptional programs. We summarize recent findings highlighting the activity of L1 RNAs at the non‐coding level during early embryonic and brain development. We propose a hypothesis suggesting a mutualistic relationship between L1 mRNAs and the host cell. In this scenario, cells tolerate a certain rate of retrotransposition to leverage the regulatory effects of L1s as non‐coding RNAs on potentiating their mitotic potential. In turn, L1s benefit from the cell's proliferative state to increase their chance to mobilize. (shrink)

Many sensory processing regions of the central brain undergo critical periods of experience‐dependent plasticity. During this time ethologically relevant information shapes circuit structure and function. The mechanisms that control critical period timing and duration are poorly understood, and this is of special importance for those later periods of development, which often give rise to complex cognitive functions such as social behavior. Here, we review recent findings in Drosophila, an organism that has some unique experimental advantages, and introduce novel views for (...) manipulating plasticity in the post‐embryonic brain. Critical periods in larval and young adult flies resemble classic vertebrate models with distinct onset and termination, display clear connections with complex behaviors, and provide opportunities to control the time course of plasticity. These findings may extend our knowledge about mechanisms underlying extension and reopening of critical periods, a concept that has great relevance to many human neurodevelopmental disorders. (shrink)

The placenta arose during mammalian evolution, which is recent in evolutionary terms. Genetic changes underlying placental development remain identifiable by the new science of comparative genomics (approximately post‐2000). Randomly arising features of genomes including endogenous retroviruses and transposable elements have provided structural genes and gene‐regulatory motifs responsible for innovations in placental biology. Stochastic genetic events indeed contribute to new functionality. Theologically, random mutations are part of the strategy by which the divine purpose for humanity is attained. Placental function critically underlies (...) human brain development, and suboptimal function, associated with environmental conditions and maternal distress, contributes to mental health deficits in the offspring. Many enter life with handicaps arising from contingent events in utero, mandating understanding, compassion, and socioemotional support, imperatives native to moral including biblical values. The extended period of development afforded by placentation enables prenatal parenting, with implications for sensitive and devoted parental commitment. (shrink)

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 adolescents with ADHD and (...) 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD. (shrink)

The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome (...) has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors. (shrink)

Objectives: The objective of this post hoc exploratory analysis was to examine the relationship between age and measures of cortical excitability and inhibition. Methods: Forty-six participants (24 with major depressive disorder and 22 healthy controls) completed MT, SICI, ICF, and CSP testing in a cross-sectional protocol. Of these 46 participants, 33 completed LICI testing. Multiple linear robust regression and Spearman partial correlation coefficient were used to examine the relationship between age and the TMS measures. Results: In the overall sample of (...) 46 participants, age had a significant negative relationship with motor threshold in both the right (rs = -0.49, adjusted p =.007; β= -0.08, adjusted p=.001) and left (rs = -0.42, adjusted p =.029; β= -0.05, adjusted p=.004) hemispheres. This significant negative relationship of age with motor threshold was also observed in the sample of depressed youth in both the right (rs = -0.70, adjusted p =.002; β= -0.09, adjusted p=.001) and left (rs = -0.54, adjusted p =.034; β= -0.05, adjusted p=.017) hemispheres, but not in healthy controls. In the sample of the 33 participants who completed LICI testing, age had a significant negative relationship with LICI (200 millisecond interval) in both the right (rs = -0.48, adjusted p =.05; β= -0.24, adjusted p=.007) and left (rs = -0.64, adjusted p =.002; β= -0.23, adjusted p=.001) hemispheres. This negative relationship between age and LICI (200 millisecond interval) was also observed in depressed youth in both the right (rs = -0.76, adjusted p =.034; β= -0.35, adjusted p=.004) and left (rs = -0.92, adjusted p =.002; β= -0.25, adjusted p=.001) hemispheres. Conclusion: These findings suggest that younger children have higher motor thresholds. This is more pronounced in depressed youth than healthy controls. LICI inhibition may also increase with age in youth. (shrink)

A ubiquitous feature of active sleep in mammals and birds is its relative abundance in early development. In rat pups across the first two postnatal weeks, active sleep promotes the expression of synchronized oscillatory activity within and between cortical and subcortical sensorimotor structures. Sensory feedback from self-generated myoclonic twitches – which are produced exclusively during active sleep – also triggers neural oscillations in those structures. We have proposed that one of the functions of active sleep in early infancy is to (...) provide a context for synchronizing developing structures. Specifically, neural oscillations contribute to a variety of neurodevelopmental processes, including synapse formation, neuronal differentiation and migration, apoptosis, and the refinement of topographic maps. In addition, synchronized oscillations promote functional connectivity between distant brain areas. Consequently, any condition or manipulation that restricts active sleep can, in turn, deprive the infant animal of substantial sensory experience, resulting in atypical developmental trajectories. The synchronization of rhythmic neural activity across brain structures provides evidence of communication. In developing sensorimotor networks, such oscillations are triggered most clearly and prominently during REM sleep. We propose that REM sleep provides a context for the emergence and expression of functional connectivity in the developing sensorimotor system. (shrink)

Neurodevelopmental disorders such as autism affect one-eighth of all U.S. newborns. Yet scientists, accessing the same data and using Bradford-Hill guidelines, draw different conclusions about the causes of these disorders. They disagree about the pesticide-harm hypothesis, that typical United States prenatal pesticide exposure can cause neurodevelopmental damage. This article aims to discover whether apparent scientific disagreement about this hypothesis might be partly attributable to questionable interpretations of the Bradford-Hill causal guidelines. Key scientists, who claim to employ Bradford-Hill causal guidelines, yet (...) fail to accept the pesticide-harm hypothesis, fall into errors of trimming the guidelines, requiring statistically-significant data, and ignoring semi-experimental evidence. However, the main scientists who accept the hypothesis appear to commit none of these errors. Although settling disagreement over the pesticide-harm hypothesis requires extensive analysis, this article suggests that at least some conflicts may arise because of questionable interpretations of the guidelines. (shrink)