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)

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)

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.

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)

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)

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 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 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)

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)

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)

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)

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)

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)

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.

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)

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)

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)

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)

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)

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 Disordered Mind: An Introduction to Philosophy of Mind and Mental Illness, second edition_ examines and explains, from a philosophical standpoint, what mental disorder is: its reality, causes, consequences, and more. It is also an outstanding introduction to philosophy of mind from the perspective of mental disorder. Revised and updated throughout, this _second edition_ includes new discussions of grief and psychopathy, the problems of the psychophysical basis of disorder, the nature of selfhood, and clarification of the relation (...) between rationality and mental disorder. Each chapter explores a central question or problem about mental disorder, including: what is mental disorder and can it be distinguished from neurological disorder? what roles should reference to psychological, cultural, and social factors play in the medical/scientific understanding of mental disorder? what makes mental disorders undesirable? Are they diseases? mental disorder and the mind–body problem is mental disorder a breakdown of rationality? What is a rational mind? addiction, responsibility and compulsion ethical dilemmas posed by mental disorder, including questions of dignity and self-respect. Each topic is clearly explained and placed in a clinical and philosophical context. Mental disorders discussed include clinical depression, dissociative identity disorder, anxiety, religious delusions, and paranoia. Several non-mental neurological disorders that possess psychological symptoms are also examined, including Alzheimer’s disease, Down’s syndrome, and Tourette’s syndrome. Containing chapter summaries and suggestions for further reading at the end of each chapter, _The Disordered Mind, second edition_ is a superb introduction to the philosophy of mental disorder for students of philosophy, psychology, psychiatry, and related mental health professions. (shrink)

Some would say that philosophy can contribute more to the occurrence of mental disorder than to the study of it. Thinking too much does have its risks, but so do willful ignorance and selective inattention. Well, what can philosophy contribute? It is not equipped to enumerate the symptoms and varieties of disorder or to identify their diverse causes, much less offer cures (maybe it can do that-personal philosophical therapy is now available in the Netherlands). On the other hand, (...) the scientific study of mental disorder has a long way to go. There is much disagreement and uncertainty about the nature, causes, and treatment of many specific disorders, as is evident from DSM's classification of them in predominantly symptomatic terms. And even if what is reflected in DSM were a consensus rather than a compromise, still this shifts periodically with each new edition. Moreover, it is a notorious fact that many patients who clearly have psychiatric abnormalities do not fit any of the recognized diagnostic categories.1. (shrink)

In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. The intense search for the biological basis of mental disorders, however, has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this target article, we show that this conceptualization can help explain why reductionist approaches in (...) psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition; in symptom networks, there is no such common cause. Second, symptom network relations depend on the content of mental states and, as such, feature intentionality. Third, the strength of network relations is highly likely to depend partially on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion ofreal patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders. (shrink)

With this manifesto, John Dupré systematically attacks the ideal of scientific unity by showing how its underlying assumptions are at odds with the central conclusions of science itself.

This paper examines two influential theoretical frameworks, set forth by Russell Barkley (1997) and Thomas Brown (2005), and argues that important headway in understanding attention deficit hyperactivity disorder can be made if we acknowledge the way in which human cognition and action are essentially embodied and enactive. The way in which we actively make sense of the world is structured by our bodily dynamics and our sensorimotor engagement with our surroundings. These bodily dynamics are linked to an individual's concerns (...) and felt needs, so that what she attends to in perception, decision-making, and action is partially constituted by her cares and concerns. What I call ?affective framing? engages the whole living body, and ordinarily contributes to attentional focusing, working memory, goal-formulation, and action-monitoring. However, due to affective framing deficits, subjects with ADHD find it difficult to focus their attention, kindle their motivation, and systematically simplify cognitive procedures according to considerations of relevance, salience, and context. Thus, what is impaired in ADHD is not simply a set of executive brain functions, but rather a range of bodily dynamics through which subjects engage with their world. For this reason, intensive behavioral intervention that engages the whole living body may be the most effective, lasting treatment for ADHD. (shrink)

Authenticity has recently emerged as an important issue in discussions of mental disorder. We show, on the basis of personal accounts and empirical studies, that many people with psychological disorders are preoccupied with questions of authenticity. Most of the data considered in this paper are from studies of people with bipolar disorder and anorexia nervosa. We distinguish the various ways in which these people view the relationship between the disorder and their sense of their authentic self. We (...) discuss the principal modern ac-counts of authenticity within the analytic philosophical tradition. We argue that accounts based on autonomous, or wholehearted, endorsement of personal characteris-tics fail to provide an adequate analysis of authenticity in the context of mental disorder. Significant elements of true self accounts of authenticity are required. The concept of authenticity is a basic one that can be of particular value, in the context of self-development, to people with mental disorder and to others experiencing substantial inner conflict. (shrink)

I shall begin with the "anti-psychiatry" view that the lack of a physical basis excludes many familiar mental disorders from the category of "illness". My response to this argument will be that anti-psychiatrists are probably right to hold that most mental disorders do not involve any physical disorder, but that they are wrong to conclude from this that these mental disorders are not illnesses.

As it emerged from philosophical analyses and cognitive research, most concepts exhibit typicality effects, and resist to the efforts of defining them in terms of necessary and sufficient conditions. This holds also in the case of many medical concepts. This is a problem for the design of computer science ontologies, since knowledge representation formalisms commonly adopted in this field (such as, in the first place, the Web Ontology Language - OWL) do not allow for the representation of concepts in terms (...) of typical traits. The need of representing concepts in terms of typical traits concerns almost every domain of real world knowledge, including medical domains. In particular, in this article we take into account the domain of mental disorders, starting from the DSM-5 descriptions of some specific disorders. We favour a hybrid approach to concept representation, in which ontology oriented formalisms are combined to a geometric representation of knowledge based on conceptual space. As a preliminary step to apply our proposal to mental disorder concepts, we started to develop an OWL ontology of the schizophrenia spectrum, which is as close as possible to the DSM-5 descriptions. (shrink)

Josh is a typical 27-year-old in a career that he enjoys and a successful marriage. Josh begins to exhibit the symptoms of a manic episode. He is soon diagnosed with bipolar disorder. While non-manic, Josh’s preferences are typical. While manic, his preferences change dramatically. He quits his job, cheats on his partner, and squanders his savings. These are behaviors that Josh, when non-manic (euthymic), would never agree to. When Josh returns to a euthymic state, he regrets these decisions. Should (...) those close to Josh have prevented him from making these decisions, or does his competence to decide persist despite his acute mania? In this paper, I examine the connections be-tween bipolar disorder and consent. I defend the view that many (although far from all) individuals with bipolar disorder are competent to consent to a wide variety of things when they are in a manic state. This means that mania should not be presumed to undermine competence in clinical settings. -/- I have several goals in this paper. I want to bring philosophy to bear on the connection between consent and bipolar disorder. Additionally, I intend this paper to contribute to the general debate about the conditions of informed consent. Bipolar disorder presents novel challenges to existing conceptions of competence to consent which require stable core of values for an agent to be competent. For example, Buchanan and Brock endorse such a view. In showing that shifting values do not undermine the competence of a person experiencing acute mania, I show that the aforementioned views of competence are false. Overall, this paper makes substantive contributions to the debate about competence to consent and presents the first sustained philosophical treatment of consent among people with bipolar disorder. (shrink)

What is it to have a mental disorder? The paper proposes an ability-based view of mental disorder. It argues that such a view is preferable to biological dysfunction views such as Wakefield’s Harmful Dysfunction Analysis and Boorse’s Biostatistical Theory. According to the proposed view, having a mental disorder is basically a matter of having a certain type of inability (or: an ability that is not sufficiently high): the inability to respond adequately to some of one’s available reasons (...) in some of one’s reasons-sensitive attitudes or actions, where the threshold of inability is determined by one’s being harmed. The relevant concepts of inability, reasons, and harm are sketched. The paper argues that the proposed view evades some problems of biological dysfunction views by remaining neutral on questions of causation and the evolution of the mind. Furthermore, it can capture better what is distinctively “mental” about mental disorder. On the proposed view, it is the rational relations among an individual’s attitudes and actions that are “disordered” and the relevant norms in mental disorder are the norms of reasons. As further merits, the view can account for degrees of disorder, incorporate biological as well as social aspects, and elucidate the relations among disorders, symptoms, and their causes. (shrink)

'Cruel' simply ignores the supposed fact/value dichotomy and cheerfully allows itself to be used sometimes for a normative purpose and sometimes as a descriptive term.Personality disorders have always attracted considerable attention within the philosophy of psychiatry. It was not until two papers written by Louis Charland, however, that they simulated a wider and lively debate. The importance and, at least partly, the strength of Charland's analyses lie in the fact that they are relatively particular and focused in their...

In this article I examine some of the issues involved in taking psychiatric disorders as natural kinds. I begin by introducing a permissive model of natural kind-hood that at least prima facie seems to allow psychiatric disorders to be natural kinds. The model, however, hinges on there in principle being some grounding that is shared by all members of a kind, which explain all or most of the additional shared projectible properties. This leads us to the following question: what grounding (...) do psychiatric disorders qua natural kinds have? My principal method for examining the issue is a case study of a particular psychiatric disorder: the so-called “apathetic children.” I argue that there appear to be at least two competing models that both appeal to non-organic a grounding of the disorder. However, for other psychiatric disorders, such as Alzheimer’s disease, the evidence points toward an organic explanation of the disorder. I contend that what unites psychiatric disorders is not a distinctive type of grounding that all psychiatric disorders share, but the distinctive set of determinable properties that is shared by all psychiatric disorders. (shrink)

In this chapter, we investigate whether psychopathy is a mental disorder. We argue that addressing this question requires engaging, at least, with three principal issues that have conceptual, empirical, and normative dimensions. First, it must be established whether current measures of psychopathy individuate a unitary class of individuals. By this we mean that persons classifed as psychopaths should share some relevant similarities that support explanation, prediction, and treatment. Second, it must be proven that psychopathy harms the person who has (...) it. Third, it must be established that the harm associated with psychopathy is relevant for the ascription of disorder status. Regarding this latter issue, we argue that psychopathy should be considered a disorder if its harmfulness derives from certain incapacities or limited capacities. These incapacities should affect basic competences that are justifably required for conducting a preferable type of life. Within this framework, we tentatively advance the hypothesis that some normatively justifed conclusions and empirical evidence about psychopathy, that needs nonetheless to be further investigated, might support the claim that people with psychopathy have a mental disorder. (shrink)

Eating disorders are evolutionarily novel conditions that lead to some of the highest mortality rates of all psychiatric disorders. Several evolutionary hypotheses have been proposed for eating disorders, but only the intrasexual competition hypothesis is extensively supported by evidence. We present the mismatch hypothesis as a necessary extension to the current theoretical framework of eating disorders. This hypothesis explains the evolutionarily novel adaptive metaproblem that has arisen when mating motives and readily available food rewards conflict with one another. This situation (...) is exacerbated in contemporary environments characterized by sedentary lifestyles, caloric surplus and the ubiquity of social comparisons that take place via social media. Our psychoneuroimmunological model connects ultimate-level causation with proximate mechanisms by showing how the adaptive metaproblem between mating motives and food rewards leads to chronic stress and, further, to disordered eating. Chronic stress causes neuroinflammation, which increases susceptibility to OCD-like behaviors that typically co-occur with eating disorders. Chronic stress upregulates the serotonergic system and causes dysphoric mood in patients with restricting-type anorexia nervosa. Dieting, however, reduces serotonin levels and dysphoric mood, leading to a vicious serotonergic-homeostatic stress/starvation cycle whereby cortisol and neuroinflammation increase through stringent dieting. Between-individual and within-individual variation in eating disorders partially arises from (co)variation in gut microbiota and stress responsivity, which influence neuroinflammation and the serotonergic system. In binge-related eating disorders, even a short period of fasting drops serotonin levels, a state alleviated by binge eating. Eating disorder treatments should aim to reduce the chronic stress, neuroinflammation, stress responsivity and gut dysbiosis that fuel the disorders. We review the advances that have been made in recent years in understanding how to best treat eating disorders, outlining directions for future clinical research. Connecting ultimate causes with proximate mechanisms and treating biopsychosocial causes rather than manifest symptoms will enable more effective and sophisticated long-term interventions for the millions of people who suffer from eating disorders. (shrink)

This book offers a comprehensive study of the views of ancient philosophers on mental disorders. Relying on the original Greek and Latin textual sources, the author describes and analyses how the ancient philosophers explained mental illness and its symptoms, including hallucinations, delusions, strange fears and inappropriate moods and how they accounted for the respective roles of body and mind in such disorders. Also considered are ethical questions relating to mental illness, approaches to treatment and the position of mentally ill people (...) in societies of the times. The volume opens with a historical overview that examines ancient medical accounts of mental illness, from Hippocrates' famous Sacred Disease to late antiquity medical authors. Separate chapters interpret in detail the writings of Plato, Aristotle, Galen and the Stoics and a final chapter summarises the views of various strains of Scepticism, the Epicurean school and the Middle and Neo-Platonists. Offering an important and useful contribution to the study of ancient philosophy, psychology and medicine. This volume sheds new light on the history of mental illness and presents a new angle on ancient philosophical psychology. (shrink)

So much has been written on this vexed issue, that one hesitates to reopen it. Yet one has no other choice when one finds scholars accepting as generally agreed a view which rests on altogether insufficient evidence. I propose, therefore, to examine the main grounds on which recent authorities interpret the disorderly motion of Tm 30a, 52d–53b, and 69b as a mythical symbol. They are four: I. That the Timaios is a myth; II. The testimony of the Academy; III. That (...) motion could not antecede the creation of time; IV. That motion could not antecede the creation of soul. (shrink)

Asian American women demonstrate higher rates of disordered eating than other women of color and comparable rates to European American women. Research suggests that leading sociocultural predictors, namely pressures for thinness and thin-ideal internalization, are predictive of disordered eating in Asian American women; however, no known studies have tested the intersection of sociocultural and culture-specific variables (e.g., ethnic identity, biculturalism, acculturative stress) to further elucidate disordered eating risk in this vulnerable, understudied group. Accordingly, this project used path analysis to simultaneously (...) examine the role of sociocultural and culture-specific effects on disordered eating in Asian American college women (N = 430). Self-report measures assessing disordered eating, sociocultural (pressures for thinness; thin-ideal internalization) and culture-specific (ethnic identity, biculturalism, acculturative stress) variables revealed that a number of sociocultural and culture-specific factors are predictive of disordered eating. Consistent with prior research, heightened perceived pressures for thinness and thin-ideal internalization were predictive of disordered eating, and thin-ideal internalization partially mediated the relationship between pressures for thinness and disordered eating. Acculturative stress predicted disordered eating and fully accounted for the inverse relationship between biculturalism and disordered eating. Overall, findings highlighted the salience of sociocultural predictors for disordered eating in Asian American women and identified biculturalism and acculturative stress as culture-specific contributors that may uniquely impact vulnerability to disordered eating in Asian American women. Thus, the combined consideration of sociocultural and culture-specific factors may be important in disordered eating research and in the development of individualized treatment plans for Asian American women. (shrink)

This is a reply to Gipps' commentary on my 'The Concept of Mental Disorder'.

It is now generally agreed that we have to rely on value judgments to distinguish mental disorders from other conditions, but it is not quite clear how. To clarify this, we need to know more than to what extent attributions of disorder are dependent on values. We also have to know (1) what kind of evaluations we have to rely on to identify the class of mental disorder; (2) whether attributions of disorder contain any implicit reference to (...) some specific evaluative standard; and (3) whether the concept of mental disorder is value laden in the definitional or in the epistemic sense. I will argue that the evaluations we have to rely on are mainly considerations of harm, but that we also need to rely on other evaluations; that there should be no references to specific evaluative standards; and that even though mental disorders are necessarily undesirable, "mental disorder" may well be a descriptive phrase. (shrink)

A recent qualitative study published in Neuroethics by Schembs and colleagues explores how functional neurodiagnostics of consciousness inform surrogate decision making in cases of disorders of consciousness. In this commentary, we argue that the chosen methodology significantly limits the scope of the potential conclusions and suggest an embedded ethnographic approach of co-presence as an alternative.

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and Germ-Line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive and negative eugenics, the concept of malady (...) is applied as a definitional criterion for identifying genetic disorders that could qualify for Germ-Line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we dissuss the issue of iatrogenic disorders associated with gene therapy and discuss several ‘real world considerations.’. (shrink)

A flood of new multidisciplinary work on the causes of depersonalization disorder provides a new way to think about the feeling that experiences “belong” to the self. In this paper I argue that this feeling, baptized “mineness” or “subjective presence” : 565–573, 2013) emerges from a multilevel interaction between emotional, affective and cognitive processing. The “self” to which experience is attributed is a predictive model made by the mind to explain the modulation of affect as the organism progresses through (...) the world. When the world no longer produces predicted affect the organism needs to explain this unpredicted absence of feeling. It is important to this account that cognition and perception are otherwise intact. Consequently the mind’s representation of the world and its emotionally salient properties are unchanged, leading the mind to predict a characteristic affective response. When that prediction is not fulfilled the organisms feels as if she is no longer present in experience. This is reported at the as feeling of depersonalization. (shrink)

According to a popular line of thought, being excluded from interpersonal life is to be exempted from accountability, and vice versa. In ordinary life, this is most often illustrated by the treatment of people with serious psychological disorders. When people are excluded from valuable domains on the basis of their arbitrary characteristics (such as race and sex), they are discriminated against, prevented from receiving the benefits of participation in those domains for morally irrelevant reasons. Exemption from accountability—via exclusion from the (...) interpersonal domain—seems to prevent exempted parties from receiving crucial human goods for morally irrelevant reasons. This chapter discusses two widely deployed ways of trying to ameliorate morally costly disabilities. Both fail to apply viably to various psychopathologies. The solution involves disentangling accountability and interpersonality in a way that also provides insights into our shared human nature. (shrink)

This article critically examines Louis Charland’s claim that personality disorders are moral rather than medical kinds by exploring the relationship between personality disorders and virtue ethics. We propose that the conceptual resources of virtue theory can inform psychiatry’s thinking about personality disorders, but also that virtue theory as understood by Aristotle cannot be reduced to the narrow domain of ‘the moral’ in the modern sense of the term. Some overlap between the moral domain’s notion of character-based ethics and the medical (...) domain’s notion of character-based disorders is unavoidable. We also apply a modified version of John Sadler’s “moral wrongfulness test” to borderline and narcissistic personality disorders. With respect to both diagnoses, we argue that they involve negative moral evaluations, but may also have indispensable nonmoral features and, therefore, classify legitimate psychiatric disorders. (shrink)

Worries about the potential medicalization of social and moral problems has propelled the debate on the nature of mental disorder, with normativists insisting that psychiatric classification is inherently value-laden and naturalists maintaining that a purely descriptive account of disease is possible. In recent work, some authors take a different path, accepting that the concepts of disease and mental disorder are value-laden but maintaining that this does not prevent objective truths regarding mental disorder attribution. This paper explores two (...) such accounts and the important steps they provide toward rethinking the nature and metaphysical status of mental disorder. The challenges raised in this paper are meant to contribute to the further development of this stimulating work. (shrink)

This paper offers a philosophical analysis of the connection between mental disorder and suicide risk. In contemporary psychiatry, it is commonly suggested that this connection is a causal connection that has been established through empirical discovery. Herein, I examine the extent to which this claim can be sustained. I argue that the connection between mental disorder and increased suicide risk is not wholly causal but is partly conceptual. This in part relates to the way suicidality is built into (...) the definitions of some psychiatric diagnoses. It also relates to the broader normative assumption that suicidal behavior is by definition mentally disordered behavior. The above has significant epistemological implications, which I explore. I propose that the claim that suicide is connected with mental disorder cannot be justified solely by appealing to empirical evidence but also warrants a justification on conceptual and normative grounds. (shrink)

The effects of mental disorder are apparent and pervasive, in suffering, loss of freedom and life opportunities, negative impacts on education, work satisfaction and productivity, complications in law, institutions of healthcare, and more. With a new edition of the 'bible' of psychiatric diagnosis - the DSM - under developmental, it is timely to take a step back and re-evalutate exactly how we diagnose and define mental disorder. This new book by Derek Bolton tackles the problems involved in the (...) definition and boundaries of mental disorder. It addresses two main questions regarding mental illness. Firstly, what is the basis of the standards or norms by which we judge that a person has a mental disorder - that the person's mind is not working as it should, that their mental functioning is abnormal? Controversies about these questions have been dominated by the contrast between norms that are medical, scientific or natural, on the one hand, and social norms on the other. The norms that define mental disorder seem to belong to psychiatry, to be medical and scientific, but are they really social norms, hijacked and disguised by the medical profession? Secondly, what is the validity of the distinction between mental disorder and order, between abnormal and normal mental functioning? To what extent, notwithstanding appearances, does mental disorder involve meaningful reactions and problem-solving? These responses may be to normal problems of living, or to not so normal problems - to severe psycho-social challenges. Is there after all order in mental disorder? With the closing of asylums and the appearance of care in the community, mental disorder is now in our midst. While attempts have been made to define clearly a concept of mental disorder that is truly medical as opposed to social, there is increasing evidence that such a distinction is unviable - there is no clear line between what is normal in the population and what is abnormal. 'What is Mental Disorder?' reviews these various crucial developments and their profound impact for the concept and its boundaries in a provocative and timely book. (shrink)