scholarly journals Language deficits in schizophrenia and autism as related oscillatory connectomopathies: an evolutionary account

2016 ◽  
Author(s):  
Elliot Murphy ◽  
Antonio Benitez-Burraco
Keyword(s):  
Language Evolution ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Language Deficits ◽  
Linguistic Feature ◽  
Evolutionary Account ◽  
Risk Alleles ◽  
Gene Sets ◽  
High Prevalence ◽  
The Brain

Schizophrenia (SZ) and autism spectrum disorders (ASD) are characterised by marked language deficits, but it is not clear how these arise from gene mutations associated with the disorders. Our goal is to narrow the gap between SZ and ASD and, ultimately, give support to the view that they represent abnormal (but related) ontogenetic itineraries for the human faculty of language. We will focus on the distinctive oscillatory profiles of the SZ and ASD brains, in turn using these insights to refine our understanding of how the brain computes language by exploring a novel model of linguistic feature-set composition. We will argue that brain rhythms constitute the best route to interpreting language deficits in both conditions and mapping them to neural dysfunction and risk alleles of the genes. Importantly, candidate genes for SZ and ASD are overrepresented among the gene sets believed to be important for language evolution. This translational effort may help develop an understanding of the aetiology of SZ and ASD and their high prevalence among modern populations.

scholarly journals Bridging the gap between genes and language deficits in schizophrenia: an oscillopathic approach

2016 ◽  
Author(s):  
Elliot Murphy ◽  
Antonio Benitez-Burraco
Keyword(s):  
Candidate Genes ◽  
Language Processing ◽  
Language Evolution ◽  
Gene Mutations ◽  
Human Language ◽  
Language Deficits ◽  
Modern Language ◽  
Risk Alleles ◽  
High Prevalence ◽  
Neural Dysfunction

Schizophrenia is characterised by marked language deficits, but it is not clear how these deficits arise from gene mutations linked to or associated with the disease. The goal of this paper is to aid the bridging of the gap between genes and schizophrenia and, ultimately, give support to the view that it represents an abnormal ontogenetic itinerary for the human faculty of language, heavily rooted in the evolutionary processes that brought about modern language. To that end we will focus on how the schizophrenia brain processes language and, particularly, on its distinctive oscillatory profile during language processing: We will argue that brain rhythms constitute the best route to interpret language deficits in this condition and map them to neural dysfunction and risk alleles of the genes. Additionally, we will show that candidate genes for schizophrenia are overrepresented among the set of genes that are believed are important for the evolution of human language. These genes crucially include (and are related to) genes involved in brain rhythmicity. We will claim that this translational effort and the links we uncover may help develop an understanding of language evolution, along with the aetiology of schizophrenia, its clinical/linguistic profile, and its high prevalence among modern populations.

scholarly journals Language impairments in ASD resulting from a failed domestication of the human brain

2016 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Wanda Lattanzi ◽  
Elliot Murphy
Keyword(s):  
Human Brain ◽  
Neural Crest ◽  
Language Processing ◽  
Expression Profiles ◽  
Autism Spectrum ◽  
Human Populations ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
High Prevalence ◽  
The Brain

AbstractAutism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesised to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioural levels. We also discuss many ASD candidates represented among the genes known to be involved in the domestication syndrome (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behaviour of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the domestication syndrome and, ultimately, from the normal functioning of the neural crest.

scholarly journals Participation in a Science Festival Promotes Inclusive Science Communication around Autism Spectrum Disorder

2021 ◽  
Author(s):  
Chris Gunter ◽  
Cynthia B Sinha ◽  
David Jaquess
Keyword(s):  
Autism Spectrum Disorder ◽  
Science Communication ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Limited Information ◽  
High Quality ◽  
Negative Stereotypes ◽  
High Prevalence ◽  
The Brain ◽  
Qualitative Analyses

AbstractAs a high prevalence disorder with limited information about etiology, autism spectrum disorder (ASD) has been marked by confusion and miscommunication around its causes and treatments. To promote high-quality science communication, we participated in a local science festival, both providing information about the brain and ASD and asking passersby questions about their knowledge of ASD. We then asked the booth staffers to evaluate the program and conducted qualitative analyses of public and staffer responses. Public responses to the question “what would you like to know about autism?” most often concerned how the disorder was diagnosed or defined. In contrast, public responses to the question “what would you like others to know about autism?” centered around educating those unaffected by ASD on how to improve interactions and awareness, mentioning inclusivity and intersectionality, and dispelling negative stereotypes. The staffers overwhelmingly reported that in future years, they would include even more science and allow for more in-depth conversations with interested parties, as well as bringing materials in other languages. These responses are in keeping with a trend for more inclusive science communication, particularly in the field of behavioral health and ASD, and a desire to challenge myths around the condition. We conclude that our science festival interactions brought multiple benefits to public and staff.

scholarly journals An evolutionary account of impairment of self in cognitive disorders

2021 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Ines Adornetti ◽  
Francesco Ferretti ◽  
Ljiljana Progovac
Keyword(s):  
Language Evolution ◽  
Cognitive Disorders ◽  
Autism Spectrum ◽  
Multiple Roles ◽  
The Self ◽  
Human Cognition ◽  
Narrative Self ◽  
Evolutionary Account ◽  
Evolutionary Changes ◽  
Spectrum Disorders

Recent research has proposed that certain aspects of psychosis, as experienced in e.g. schizophrenia (SCH), but also aspects of other cognitive conditions, such as autism spectrum disorders (ASD) and synesthesia, can be related to a shattered sense of the notion of self. In this paper, our goal is to show that altered processing of the self can be attributed to an abnormal functioning of cortico-striatal brain networks supporting, among other, one key human distinctive cognitive ability, namely, cross-modality, which plays multiple roles in human cognition and language. Specifically, our hypothesis is that this cognitive mechanism sheds light both on some basic aspects of the minimal self and on some aspects related to higher forms of the self, such as the narrative self. We further link the atypical functioning in these conditions to some recent evolutionary changes in our species, specifically, an atypical presentation of human self-domestication (HSD) features. In doing so, we also lean on previous work concerning the link between cognitive disorders and language evolution under the effects of HSD. We further show that this approach can unify both linguistic and non-linguistic symptoms of these conditions through deficits in the notion of self. Our considerations provide further support for the hypothesis that SCH and ASD are diametrically opposed cognitive conditions, as well for the hypothesis that their etiology is associated with recent human evolution, leading to a deeper understanding of the causes and symptoms of these disorders, and providing new cues, which can be used for an earlier and more accurate diagnostics.

scholarly journals Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders

2021 ◽  
Author(s):  
Giuseppe Fanelli ◽  
Barbara Franke ◽  
Ward De Witte ◽  
I Hyun Ruisch ◽  
Jan Haavik ◽  
...  
Keyword(s):  
Insulin Signalling ◽  
Genetic Correlations ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Genome Wide Association Studies ◽  
Compulsive Disorder ◽  
Gene Sets ◽  
Starting Point ◽  
Genetic Overlap ◽  
The Brain

The prevalence of Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) is higher among patients with somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie these observed comorbidities. We investigated genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise genetic correlations using the summary statistics of the largest available genome-wide association studies for these diseases. Stratified covariance analyses were performed to investigate the contribution of insulin-related gene-sets. Having tested these hypotheses, novel brain "insulinopathies" were explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Significant genetic correlations were found between OCD and MetS (rg=-0.315, p=3.9e-8), OCD and obesity (rg=-0.379, p=3.4e-5), and OCD and T2DM (rg=-0.172, p=3e-4). Stratified analyses showed negative genetic covariances between ASD and MetS/T2DM through gene-sets comprising insulin signalling and/or insulin processing genes, and between AD/OCD and MetS/T2DM through an insulin receptor recycling gene-set (p<6.17e-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa, attention-deficit/hyperactivity disorder, major depression, and schizophrenia (p<6.17e-4). Our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases and traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on "insulinopathies" of the brain, which may support the development of more effective/tolerated treatment strategies for neuropsychiatric disorders.

Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle

2020 ◽  
Vol 14 (2) ◽  
pp. 170-174
Author(s):  
Koichi Kawada ◽  
Nobuyuki Kuramoto ◽  
Seisuke Mimori
Keyword(s):  
Autism Spectrum Disorder ◽  
Endoplasmic Reticulum ◽  
Environmental Factors ◽  
Endoplasmic Reticulum Stress ◽  
Synapse Formation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neurodevelopmental Disease ◽  
Number Of Patients ◽  
The Brain

: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

Bilateral Striatal Necrosis with Polyneuropathy with a Novel SLC25A19 (Mitochondrial Thiamine Pyrophosphate Carrier OMIMI*606521) Mutation: Treatable Thiamine Metabolic Disorder—A Report of Two Indian Cases

2019 ◽  
Vol 50 (05) ◽  
pp. 313-317 ◽  
Author(s):  
Vykuntaraju K. Gowda ◽  
Varunvenkat M. Srinivasan ◽  
Kapil Jehta ◽  
Maya D. Bhat
Keyword(s):  
Gene Mutations ◽  
Febrile Illness ◽  
Flaccid Paralysis ◽  
Thiamine Pyrophosphate ◽  
Homozygous Mutation ◽  
Missense Variation ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Generation Sequencing ◽  
Striatal Necrosis

Abstract Background SLC25A19 gene mutations cause Amish congenital lethal microcephaly and bilateral striatal necrosis with polyneuropathy. We are reporting two cases of bilateral striatal necrosis with polyneuropathy due to SLC25A19 gene mutations. Methods A 36-month-old boy and a 5-year-old girl, unrelated, presented with recurrent episodes of flaccid paralysis and encephalopathy following nonspecific febrile illness. Examination showed dystonia and absent deep tendon reflexes. Results Nerve conduction studies showed an axonal polyneuropathy. Magnetic resonance imaging (MRI) of the brain in both cases showed signal changes in the basal ganglia. Next-generation sequencing revealed a novel homozygous missense variation c.910G>A (p.Glu304Lys) in the SLC25A19 gene in the boy and a homozygous mutation c.869T > A (p. Leu290Gln) in the SLC25A19 gene in the girl. Mutations were validated by Sanger sequencing, and carrier statuses of parents of both children were confirmed. Both children improved with thiamine supplementation. Conclusion If any child presents with recurrent encephalopathy with flaccid paralysis, dystonia, and neuropathy, a diagnosis of bilateral striatal necrosis with polyneuropathy due to SLC25A19 mutations should be considered and thiamine should be initiated.

scholarly journals FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Reymundo Lozano ◽  
Catherine Gbekie ◽  
Paige M. Siper ◽  
Shubhika Srivastava ◽  
Jeffrey M. Saland ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Medical Assessment ◽  
Forkhead Box ◽  
Organ Systems ◽  
Practice Parameters ◽  
Assessment And Monitoring ◽  
Multidisciplinary Group ◽  
The Brain

AbstractFOXP1 syndrome is a neurodevelopmental disorder caused by mutations or deletions that disrupt the forkhead box protein 1 (FOXP1) gene, which encodes a transcription factor important for the early development of many organ systems, including the brain. Numerous clinical studies have elucidated the role of FOXP1 in neurodevelopment and have characterized a phenotype. FOXP1 syndrome is associated with intellectual disability, language deficits, autism spectrum disorder, hypotonia, and congenital anomalies, including mild dysmorphic features, and brain, cardiac, and urogenital abnormalities. Here, we present a review of human studies summarizing the clinical features of individuals with FOXP1 syndrome and enlist a multidisciplinary group of clinicians (pediatrics, genetics, psychiatry, neurology, cardiology, endocrinology, nephrology, and psychology) to provide recommendations for the assessment of FOXP1 syndrome.

025 Sleep Disruption on an Orbital Shaker alters Glutamate in Prairie Vole Prefrontal Cortex

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A12
Author(s):  
Carolyn Jones ◽  
Randall Olson ◽  
Alex Chau ◽  
Peyton Wickham ◽  
Ryan Leriche ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Early Life ◽  
Autism Spectrum ◽  
Prairie Vole ◽  
Sleep Disruption ◽  
Glutamatergic Synapses ◽  
The Brain ◽  
Orbital Shaker

Abstract Introduction Glutamate concentrations in the cortex fluctuate with the sleep wake cycle in both rodents and humans. Altered glutamatergic signaling, as well as the early life onset of sleep disturbances have been implicated in neurodevelopmental disorders such as autism spectrum disorder. In order to study how sleep modulates glutamate activity in brain regions relevant to social behavior and development, we disrupted sleep in the socially monogamous prairie vole (Microtus ochrogaster) rodent species and quantified markers of glutamate neurotransmission within the prefrontal cortex, an area of the brain responsible for advanced cognition and complex social behaviors. Methods Male and female prairie voles were sleep disrupted using an orbital shaker to deliver automated gentle cage agitation at continuous intervals. Sleep was measured using EEG/EMG signals and paired with real time glutamate concentrations in the prefrontal cortex using an amperometric glutamate biosensor. This same method of sleep disruption was applied early in development (postnatal days 14–21) and the long term effects on brain development were quantified by examining glutamatergic synapses in adulthood. Results Consistent with previous research in rats, glutamate concentration in the prefrontal cortex increased during periods of wake in the prairie vole. Sleep disruption using the orbital shaker method resulted in brief cortical arousals and reduced time in REM sleep. When applied during development, early life sleep disruption resulted in long-term changes in both pre- and post-synaptic components of glutamatergic synapses in the prairie vole prefrontal cortex including increased density of immature spines. Conclusion In the prairie vole rodent model, sleep disruption on an orbital shaker produces a sleep, behavioral, and neurological phenotype that mirrors aspects of autism spectrum disorder including altered features of excitatory neurotransmission within the prefrontal cortex. Studies using this method of sleep disruption combined with real time biosensors for excitatory neurotransmitters will enhance our understanding of modifiable risk factors, such as sleep, that contribute to the altered development of glutamatergic synapses in the brain and their relationship to social behavior. Support (if any) NSF #1926818, VA CDA #IK2 BX002712, Portland VA Research Foundation, NIH NHLBI 5T32HL083808-10, VA Merit Review #I01BX001643

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

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