Daniel H. Geschwind | |
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Alma mater | Dartmouth College, Yale School of Medicine |
Awards |
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Scientific career | |
Fields | Human genetics, neurogenetics |
Institutions | University of California, Los Angeles |
Doctoral advisor | Susan Hockfield |
Daniel H. Geschwind is an American physician-scientist whose laboratory has made pioneering discoveries in the biology of brain disorders and the genetic and genomic analyses of the nervous system. His laboratory showed that gene co-expression has a reproducible network structure that can be used to understand neurobiological mechanisms in health, evolution, and disease. [2] [3] [4] He led the first studies to define the molecular pathology of autism spectrum disorder (ASD) and several other psychiatric disorders, [5] [6] [7] and has made major contributions to defining the genetic basis of autism. [8] [9] [10]
Currently, he is the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). He also directs the UCLA Neurogenetics Program and the UCLA Center for Autism Research and Treatment (CART). [11] [12] Since March 1, 2016, he has served as the Senior Associate Dean and Associate Vice Chancellor for Precision Medicine at UCLA. [13]
Geschwind received his A.B. degree in psychology and chemistry at Dartmouth College, and his MD/PhD at Yale School of Medicine under the supervision of Susan Hockfield , graduating Alpha Omega Alpha [14] . [12] He then completed an internship at UCLA, [11] and has been a member of the UCLA faculty since 1997. [12]
Currently, he is the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). He has served as the Senior Associate Dean and Associate Vice Chancellor for Precision Health at UCLA since March, 2016. He also founded and directs the UCLA Neurogenetics Program and the UCLA Center for Autism Research and Treatment (CART). [15] He has trained over 70 graduate students and post-doctoral research fellows, [16] and is among the highest cited scientists in neurology, neuroscience, systems biology, and precision health (H index > 195). [17] He has been named in Clarivate Analytics’ Highly Cited Researchers list each year since 2017. [18]
Geschwind has served on several scientific advisory boards and review committees, including the Faculty of 1000 Medicine, the Executive Committee of the American Neurological Association, the Scientific Advisory Board for the Allen Institute for Brain Science, the NIMH Advisory Council and the NIH Council of Councils, and served as the first chair of Cure Autism Now's scientific review committee. [19] [20] Geschwind has been elected as member of the National Academy of Medicine and the Association of American Physicians. [20]
He has also been the Kavli Distinguished Visiting Professor at UCSD (2007), Visiting Professor at the Institute of Psychiatry, Kings College, London (2009-2010), the Wiersma Visiting Professor at Caltech (2012), and a Visiting Scientist at Wellcome Trust Sanger Institute, Cambridge UK (2009-2010) and an Affiliate Professor, Faculty of Health and Medical Sciences, University of Copenhagen. [21]
The Geschwind Lab at the UCLA David Geffen School of Medicine conducts research into three areas: autism and language, human cognitive specializations, and neurodegenerative syndromes. [12] [22] The overarching goal of Dr. Geschwind’s work is to develop a more mechanistic understanding of neurodevelopmental and neurodegenerative diseases by integrative analyses that connect human genetic variation to genes and neurobiological pathways. Through functional genomics and large-scale data analyses that permit a more unbiased understanding of disease mechanisms, his laboratory’s research has improved our understanding of human brain evolution and language, ASD and schizophrenia, repair of the damaged nervous system and neurodegenerative dementias including Frontotemporal Dementia, Progressive Supranuclear Palsy and Alzheimer’s disease. Together these studies have not only improved understanding of human brain disorders, but they also highlight the power of highly-parallel, high-throughput biology. [23]
Dr. Geschwind has published research on numerous genes involved in language, such as FOXP2, and how they differ between humans and chimpanzees. [24] [25] In 2011, he was the senior author of a study that identified chemical differences between the brains of people with autism and those without it. [26] Specifically, the study found common patterns in gene expression in the frontal and temporal lobes of autistic individuals. [27] Additionally, Dr. Geschwind is known for his research into factors affecting handedness and the differences in brain structure between left-handed and right-handed people. [28] [29]
Dr. Geschwind established the modern era of autism genetics research by developing and leading the Autism Genetic Resource Exchange (AGRE) [30] with the Cure Autism Now Foundation in 1997. AGRE was the first major community resource for genetic research on autism spectrum disorder (ASD), making biomaterials and phenotype data accessible to researchers worldwide. This initiative opened the field to many more researchers and led to significant discoveries, including the role of rare mutations and inherited variations in ASD. [10] He is an advocate for data sharing and is currently chair of the PsychENCODE consortium, a public genomic data resource.
His work in autism genetics and functional genomics has been highly influential, focusing on translating genetic findings into biological understanding. He developed the concept of ASD as a developmental disconnection syndrome, recognizing its extreme heterogeneity and framing it as “the autisms.” Dr. Geschwind pioneered the study of language and social endophenotypes in genetic studies and demonstrated how transcriptomic and epigenetic profiling could define the molecular pathology of ASD and other neuropsychiatric disorders. Over the last decade, he has led efforts to increase diversity and inclusion in autism research, spearheading the only genetics study of African Americans, now in its seventh year. [10] Over the last 10 years, he and his collaborators, including John Constantino and Ami Klin, have been working as an Autism Center of Excellence Network [31] to increase the representation of groups that have been historically underrepresented in autism research. [32]
His brother, Michael Geschwind, is also a professor of neurology. Norman Geschwind, a pioneer in behavioral neurology, is his father’s first cousin. From 1965 to 1982, his father, Stanley Geschwind, served as the head of the Quantum and Solid-State Physics Department at Bell Labs. [33] [34] [8]
Asperger syndrome (AS), also known as Asperger's syndrome or Asperger's, is a term formerly used to describe a neurodevelopmental condition characterized by significant difficulties in social interaction and nonverbal communication, along with restricted, repetitive patterns of behavior and interests. Asperger syndrome has been merged with other conditions into autism spectrum disorder (ASD) and is no longer considered a stand-alone diagnosis. It was considered milder than other diagnoses which were merged into ASD due to relatively unimpaired spoken language and intelligence.
Diagnoses of autism have become more frequent since the 1980s, which has led to various controversies about both the cause of autism and the nature of the diagnoses themselves. Whether autism has mainly a genetic or developmental cause, and the degree of coincidence between autism and intellectual disability, are all matters of current scientific controversy as well as inquiry. There is also more sociopolitical debate as to whether autism should be considered a disability on its own.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that begins in early childhood, persists throughout adulthood, and affects two crucial areas of development: social communication and restricted, repetitive patterns of behavior. There are many conditions comorbid to autism spectrum disorder such as attention-deficit hyperactivity disorder and epilepsy.
The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. Autism has a strong genetic basis. Although the genetics of autism are complex, autism spectrum disorder (ASD) is explained more by multigene effects than by rare mutations with large effects.
Many causes of autism, including environmental and genetic factors, have been recognized or proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction, as well as restricted and repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals.
The epidemiology of autism is the study of the incidence and distribution of autism spectrum disorders (ASD). A 2022 systematic review of global prevalence of autism spectrum disorders found a median prevalence of 1% in children in studies published from 2012 to 2021, with a trend of increasing prevalence over time. However, the study's 1% figure may reflect an underestimate of prevalence in low- and middle-income countries.
Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene. In mice, it is a necessary part of the neural circuitry that controls breathing. The gene is also a homolog of the Drosophila melanogaster teashirt gene, which encodes a zinc finger transcription factor important for development of the trunk.
Classic autism, also known as childhood autism, autistic disorder, (early) infantile autism, infantile psychosis, Kanner's autism, Kanner's syndrome, or (formerly) just autism, is a neurodevelopmental condition first described by Leo Kanner in 1943. It is characterized by atypical and impaired development in social interaction and communication as well as restricted, repetitive behaviors, activities, and interests. These symptoms first appear in early childhood and persist throughout life.
Neurogenomics is the study of how the genome of an organism influences the development and function of its nervous system. This field intends to unite functional genomics and neurobiology in order to understand the nervous system as a whole from a genomic perspective.
Autism, also called autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder characterized by symptoms of deficient reciprocal social communication and the presence of restricted, repetitive and inflexible patterns of behavior that are impairing in multiple contexts and excessive or atypical to be developmentally and socioculturally inappropriate. Other common signs include difficulty with social interaction, verbal and nonverbal communication, along with perseverative interests, stereotypic body movements, rigid routines, and hyper- or hyporeactivity to sensory input. Autism is clinically regarded as a spectrum disorder, meaning that it can manifest very differently in each person. For example, some are nonspeaking, while others have proficient spoken language. Because of this, there is wide variation in the support needs of people across the autism spectrum.
The imprinted brain hypothesis is an unsubstantiated hypothesis in evolutionary psychology regarding the causes of autism spectrum and schizophrenia spectrum disorders, first presented by Bernard Crespi and Christopher Badcock in 2008. It claims that certain autistic and schizotypal traits are opposites, and that this implies the etiology of the two conditions must be at odds.
Cognitive genomics is the sub-field of genomics pertaining to cognitive function in which the genes and non-coding sequences of an organism's genome related to the health and activity of the brain are studied. By applying comparative genomics, the genomes of multiple species are compared in order to identify genetic and phenotypical differences between species. Observed phenotypical characteristics related to the neurological function include behavior, personality, neuroanatomy, and neuropathology. The theory behind cognitive genomics is based on elements of genetics, evolutionary biology, molecular biology, cognitive psychology, behavioral psychology, and neurophysiology.
Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.
The development of an animal model of autism is one approach researchers use to study potential causes of autism. Given the complexity of autism and its etiology, researchers often focus only on single features of autism when using animal models.
Evolutionary psychiatry, also known as Darwinian psychiatry, is a theoretical approach to psychiatry that aims to explain psychiatric disorders in evolutionary terms. As a branch of the field of evolutionary medicine, it is distinct from the medical practice of psychiatry in its emphasis on providing scientific explanations rather than treatments for mental disorder. This often concerns questions of ultimate causation. For example, psychiatric genetics may discover genes associated with mental disorders, but evolutionary psychiatry asks why those genes persist in the population. Other core questions in evolutionary psychiatry are why heritable mental disorders are so common how to distinguish mental function and dysfunction, and whether certain forms of suffering conveyed an adaptive advantage. Disorders commonly considered are depression, anxiety, schizophrenia, autism, eating disorders, and others. Key explanatory concepts are of evolutionary mismatch and the fact that evolution is guided by reproductive success rather than health or wellbeing. Rather than providing an alternative account of the cause of mental disorder, evolutionary psychiatry seeks to integrate findings from traditional schools of psychology and psychiatry such as social psychology, behaviourism, biological psychiatry and psychoanalysis into a holistic account related to evolutionary biology. In this sense, it aims to meet the criteria of a Kuhnian paradigm shift.
Paul Thompson is a British-American neuroscientist, and a professor of neurology at the Imaging Genetics Center at the University of Southern California. Thompson obtained a bachelor's degree in Greek and Latin languages and mathematics from Oxford University. He also earned a master's degree in mathematics from Oxford and a PhD degree in neuroscience from University of California, Los Angeles.
Sex and gender differences in autism exist regarding prevalence, presentation, and diagnosis.
John N. Constantino is a child psychiatrist and expert on neurodevelopmental disorders, especially autism spectrum disorders (ASD). Constantino is the Blanche F. Ittleson Professor of Psychiatry and Pediatrics at Washington University School of Medicine.
Marian Diamond Sigman (1941–2012) was a developmental and child clinical psychologist known for her research on autism spectrum disorder (ASD). At the time of her death, she was Professor Emeritus of Psychiatry and Biobehavioral Sciences and Psychology at the University of California, Los Angeles (UCLA).
The pathophysiology of autism is the study of the physiological processes that cause or are otherwise associated with autism spectrum disorders.
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