Pamela Sklar | |
---|---|
Born | Baltimore, Maryland, U.S. | July 20, 1959
Died | November 20, 2017 58) | (aged
Alma mater | St. John's College Johns Hopkins University School of Medicine |
Scientific career | |
Fields | Neuroscience Genomics Psychiatry |
Institutions | Icahn School of Medicine at Mount Sinai |
Pamela Sklar (born July 20, 1959, in Baltimore, Maryland - died November 20, 2017, in New York City) was an American psychiatrist and neuroscientist. She was Chair of the Department of Genetics and Genomic Sciences and professor of psychiatry, neuroscience, and genetic and genomic sciences at the Icahn School of Medicine at Mount Sinai. [1] She was also chief of the Division of Psychiatric Genomics at the Icahn School of Medicine at Mount Sinai. Sklar is known for her large-scale gene discovery studies in bipolar disorder and schizophrenia and for making some of the first statistically meaningful gene identifications in both mental illnesses. [2] [3]
Sklar completed her bachelor's degree in classics and philosophy at St. John's College in 1981. She went on to complete her MD and then her PhD in neuroscience at Johns Hopkins School of Medicine. She carried out her residency in psychiatry at Columbia University Medical School, where she also carried out postdoctoral work in the laboratory of Richard Axel.
Sklar's research and clinical work focused on characterizing the biology underlying mental illnesses, in particular schizophrenia and bipolar disorder. Her studies of DNA variation have identified both common and rare genetic changes associated with these disorders. [4] [5] While working at the Broad Institute, Sklar co-founded the Stanley Center for Psychiatric Research and served as its genetics director. By studying thousands of affected individuals and comparing them with thousands of healthy people, she was the first to associate recurrent large deletions of DNA with the onset of schizophrenia and also found the first broadly reproducible genetic variants in schizophrenia as well as bipolar disorder using genome-wide association studies. [6] [7] [8] [9] Sklar and her colleagues discovered a molecular basis for polygenicity in schizophrenia among both rare and common DNA alterations [10] [11] and that schizophrenia and bipolar disorder are genetically linked through DNA variants that contribute to both illnesses. [12] [13] In 2011, Sklar joined the Icahn School of Medicine at Mount Sinai and became founding chief of the Division of Psychiatric Genomics there. [14] The division's scope includes stem cell biology, neurocognition, statistical genetics, and imaging approaches to elucidate the biological variation causing mental illness. While at Mount Sinai, Sklar published papers demonstrating that schizophrenia is linked to many ultra-rare genetic variants. [15] [16] Sklar served as a principal investigator for the Psychiatric Genomics Consortium, the largest international collaboration in the psychiatric community. [17] She helped lead the consortium's working group on bipolar disorder. She also co-founded the International Schizophrenia Consortium. After she died, Icahn School of Medicine renamed their Division of Psychiatric Genomics in her honor. [18]
Sklar edited the textbook Neurobiology of Mental Illness, [19] and published more than 140 peer-reviewed scientific papers.
She was elected to the National Academy of Medicine in 2013. [20]
Schizoaffective disorder is a mental disorder characterized by abnormal thought processes and an unstable mood. This diagnosis requires symptoms of both schizophrenia and a mood disorder: either bipolar disorder or depression. The main criterion is the presence of psychotic symptoms for at least two weeks without any mood symptoms. Schizoaffective disorder can often be misdiagnosed when the correct diagnosis may be psychotic depression, bipolar I disorder, schizophreniform disorder, or schizophrenia. This is a problem as treatment and prognosis differ greatly for most of these diagnoses.
Links between creativity and mental health have been extensively discussed and studied by psychologists and other researchers for centuries. Parallels can be drawn to connect creativity to major mental disorders including bipolar disorder, autism, schizophrenia, major depressive disorder, anxiety disorder, OCD and ADHD. For example, studies have demonstrated correlations between creative occupations and people living with mental illness. There are cases that support the idea that mental illness can aid in creativity, but it is also generally agreed that mental illness does not have to be present for creativity to exist.
Psychiatric genetics is a subfield of behavioral neurogenetics and behavioral genetics which studies the role of genetics in the development of mental disorders. The basic principle behind psychiatric genetics is that genetic polymorphisms are part of the causation of psychiatric disorders.
Calcium channel, voltage-dependent, L type, alpha 1C subunit is a protein that in humans is encoded by the CACNA1C gene. Cav1.2 is a subunit of L-type voltage-dependent calcium channel.
Peter McGuffin was a Northern Irish psychiatrist and geneticist from Belfast.
Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research. Although, recent genetic studies of large schizophrenia cohorts have failed to implicate DISC1 as a risk gene at the gene level, the DISC1 interactome gene set was associated with schizophrenia, showing evidence from genome-wide association studies of the role of DISC1 and interacting partners in schizophrenia susceptibility.
Myosin-Vb, a myosin V type protein, is encoded by the MYO5B gene in humans.
Cingulin-like protein 1, also known as paracingulin or junction-associated-coiled-coil protein (JACOP), is a protein which is encoded by the CGNL1 gene.
Sophia Frangou is a professor of psychiatry at the Icahn School of Medicine at Mount Sinai where she heads the Psychosis Research Program. She is a Fellow of the Royal College of Psychiatrists and vice-chair of the RCPsych Panamerican Division. She is a Fellow of the European Psychiatric Association (EPA) and of the American Psychiatric Association (APA). She served as vice-president for Research of the International Society for Bipolar Disorders from 2010 to 2014. She has also served on the Council of the British Association for Psychopharmacology. She is founding member of the EPA NeuroImaging section and founding chair of the Brain Imaging Network of the European College of Neuropsychopharmacology. She is one of the two Editors of European Psychiatry, the official Journal of the European Psychiatric Association.
In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.
The International Society of Psychiatric Genetics (ISPG) is a learned society that aims to "promote and facilitate research in the genetics of psychiatric disorders, substance use disorders and allied traits". To this end, among other things, it organizes an annual "World Congress of Psychiatric Genetics".
Schizophrenia is a primary psychotic disorder, whereas, bipolar disorder is a primary mood disorder which can also involve psychosis. Both schizophrenia and bipolar disorder are characterized as critical psychiatric disorders in the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). However, because of some similar symptoms, differentiating between the two can sometimes be difficult; indeed, there is an intermediate diagnosis termed schizoaffective disorder.
The Icahn Genomics Institute is a biomedical and genomics research institute within the Icahn School of Medicine at Mount Sinai in New York City. Its aim is to establish a new generation of medicines that can better treat diseases afflicting the world, including cancer, heart disease and infectious pathogens. To do this, the institute’s doctors and scientists are developing and employing new types of treatments that utilize DNA and RNA based therapies, such as CRISPR, siRNA, RNA vaccines, and CAR T cells, and searching for novel drug targets through the use of functional genomics and data science. The institute is led by Brian Brown, a leading expert in gene therapy, genetic engineering, and molecular immunology.
The Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard is a multi-disciplinary biomedical research program located in Cambridge, Massachusetts that studies the biological basis of psychiatric disease.
ABI family member 3 binding protein is a protein that in humans is encoded by the ABI3BP gene.
Bipolar disorder is an affective disorder characterized by periods of elevated and depressed mood. The cause and mechanism of bipolar disorder is not yet known, and the study of its biological origins is ongoing. Although no single gene causes the disorder, a number of genes are linked to increase risk of the disorder, and various gene environment interactions may play a role in predisposing individuals to developing bipolar disorder. Neuroimaging and postmortem studies have found abnormalities in a variety of brain regions, and most commonly implicated regions include the ventral prefrontal cortex and amygdala. Dysfunction in emotional circuits located in these regions have been hypothesized as a mechanism for bipolar disorder. A number of lines of evidence suggests abnormalities in neurotransmission, intracellular signalling, and cellular functioning as possibly playing a role in bipolar disorder.
Shaun M. Purcell is a British genetic epidemiologist and statistical geneticist.
Benjamin Michael Neale is a statistical geneticist with a specialty in psychiatric genetics. He is an institute member at the Broad Institute as well as an associate professor at both Harvard Medical School and the Analytic and Translational Genetics Unit at Massachusetts General Hospital. Neale specializes in genome-wide association studies (GWAS). He was responsible for the data analysis of the first GWAS on attention-deficit/hyperactivity-disorder, and he developed new analysis software such as PLINK, which allows for whole-genome data to be analyzed for specific gene markers. Related to his work on GWAS, Neale is the lead of the ADHD psychiatric genetics and also a member of the Psychiatric GWAS Consortium analysis committee.
Michael C. O'Donovan is a Scottish psychiatric geneticist who researches the genetics of schizophrenia. He is a clinical professor in the Division of Psychological Medicine and Clinical Neurosciences and the deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at the Cardiff University School of Medicine in Cardiff, Wales. He also leads the Schizophrenia Group of the Psychiatric Genomics Consortium. Educated at Glasgow University, he also serves as Academic Psychiatry Lead for the Royal College of Psychiatrists in Wales. He was lead author of a 2014 study in Nature which identified over 100 genetic loci associated with an increased risk of schizophrenia. The study, the largest of its kind undertaken at the time, was covered extensively in the media. It was also praised by Thomas Insel, the then-director of the National Institute of Mental Health, who described the study as "a big step forward".
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