title: Annual Research Review: The promise of stem cell research for neuropsychiatric disorders.
abstract: The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may function in human brain development and how they interact with each other leading to psychiatric disorders is unknown. Because of an increasing understanding of neural stem cells and how the nervous system subsequently develops from these cells, we have now the ability to study disorders of the nervous system in a new way - by rewinding and reviewing the development of human neural cells. Induced pluripotent stem cells (iPSCs), developed from mature somatic cells, have allowed the development of specific cells in patients to be observed in real time. Moreover, they have allowed some neuronal-specific abnormalities to be corrected with pharmacological intervention in tissue culture. These exciting advances based on the use of iPSCs hold great promise for understanding, diagnosing and, possibly, treating psychiatric disorders. Specifically, examination of iPSCs from typically developing individuals will reveal how basic cellular processes and genetic differences contribute to individually unique nervous systems. Moreover, by comparing iPSCs from typically developing individuals and patients, differences at stem cell stages, through neural differentiation, and into the development of functional neurons may be identified that will reveal opportunities for intervention. The application of such techniques to early onset neuropsychiatric disorders is still on the horizon but has become a reality of current research efforts as a consequence of the revelations of many years of basic developmental neurobiological science.
authors.affiliation: Child Study Center, Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA. flora.vaccarino@yale.edu
authors.forename: Flora M
authors.initials: FM
authors.lastname: Vaccarino
authors.forename: Alexander Eckehart
authors.initials: AE
authors.lastname: Urban
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Stevens
authors.forename: Anna
authors.initials: A
authors.lastname: Szekely
authors.forename: Alexej
authors.initials: A
authors.lastname: Abyzov
authors.forename: Elena L
authors.initials: EL
authors.lastname: Grigorenko
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Sherman
authors.initials: S
authors.lastname: Weissman
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000503:physiopathology; D001927:Brain Diseases / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D056914:Genomic Structural Variation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D008957:Models, Genetic; D009474:Neurons / Q000502:physiology; D058027:Neuropsychiatry / Q000639:trends*; D039904:Pluripotent Stem Cells / Q000502:physiology; D011247:Pregnancy; D057905:Stem Cell Research