Abstract: The present invention relates to methods and compositions for enhancing neuronal connectivity. It is based, at least in part, on the discovery of a protein, termed “Mirta22,” that inhibits the formation of structures which create connections between neurons. It is further based, in part, on the discovery that inhibiting Mirta22 activity by short hairpin RNA was able to restore these structures. Mirta22 was discovered in experiments relating to 22q11 microdeletions, which have been linked to schizophrenia. Accordingly, the present invention provides for methods of treating schizophrenia comprising administering an agent that inhibits Mirta22 activity. It may also be used in the treatment of other disorders that would benefit from enhanced neural connectivity, including learning and memory disorders.

Abstract: The present invention relates to methods of treating various neurodevelopmental and neuropsychiatric diseases which employ inhibition of the mTOR pathway, particularly using mTOR kinase inhibitors. It is based, at least in part, on extensive phenotypic characterization of a knock-out mouse model of Caspr2, the murine ortholog of CNTNAP2, which indicate that the mechanism via which CNTNAP2 deficits lead to neuropsychiatric disorders is overactivation of the mTOR pathway. Accordingly, the present invention provides for methods of treating subjects suffering from neurodevelopmental and/or neuropsychiatric disorders comprising administering, to the subject, an agent that inhibits the mTOR pathway. In particular non-limiting embodiments, the inhibitor of the mTOR pathway is a mTOR kinase inhibitor such as, but not limited to, WYE125132 and analogous compounds.

Abstract: The present invention relates to compounds that inhibit VIPR2 in the CNS, pharmaceutical compositions comprising said compounds, and methods of using such compounds and compositions in the treatment of a CNS disorder such as a behavioral disorder, including but not limited to schizophrenia.

Abstract: The present invention relates to compounds that inhibit VIPR2 in the CNS, pharmaceutical compositions comprising said compounds, and methods of using such compounds and compositions in the treatment of a CNS disorder such as a behavioral disorder, including but not limited to schizophrenia.

Abstract: The present invention relates to methods and compositions for enhancing neuronal connectivity. It is based, at least in part, on the discovery of a protein, termed “Mirta22,” that inhibits the formation of structures which create connections between neurons. It is further based, in part, on the discovery that inhibiting Mirta22 activity by short hairpin RNA was able to restore these structures. Mirta22 was discovered in experiments relating to 22q11 microdeletions, which have been linked to schizophrenia. Accordingly, the present invention provides for methods of treating schizophrenia comprising administering an agent that inhibits Mirta22 activity. It may also be used in the treatment of other disorders that would benefit from enhanced neural connectivity, including learning and memory disorders.

Abstract: The present disclosure relates to compositions and methods for the diagnosis of schizophrenia. In particular, the instant disclosure is directed to identification of novel copy number variants of sequences associated with the VIPR2 gene, including certain micro-duplications and triplications, and correlation of these copy number variants with schizophrenia.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

Abstract: The present invention relates to the role of mutations that perturb expression of ZDHHC8 in increased susceptibility to schizophrenia. It is based, at least in part, on the discovery of a mechanism by which a high risk allele disrupts expression of functional ZDHHC 8, and on the discovery that two proteins involved in synaptic pathways associated with schizophrenia interact with ZDHHC8, at least one of which is a substrate for that enzyme.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in genes encoding an EGR molecule or an EGR interacting molecule, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by perfoming the screens.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by perfoming the screens.

Abstract: Variations in the DNA sequence of the human proline dehydrogenase gene (PRODH) which correlate to an increased susceptibility to, or presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder (OCD), bipolar disorder (BP), or major depressive disorder (MDD) are provided, along with assays to diagnosing schizophrenia or a disease or disorder related thereto, and evaluating potential drugs or agents for using in treating such diseases or disorders.

Abstract: Variations in the DNA sequence of the human proline dehydrogenase gene (PRODH) which correlate to an increased susceptibility to, or presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder (OCD), bipolar disorder (BP), or major depressive disorder (MDD) are provided, along with assays to diagnosing schizophrenia or a disease or disorder related thereto, and evaluating potential drugs or agents for using in treating such diseases or disorders.

Abstract: Methods of identifying patients having a susceptibility to obsessive-compulsive disorder resultant from a reduced level of Catechol-O-methyltransferase (COMT) are described. Therapies, utilizing COMT or COMT agonists, or dopamine antagonists in combination therewith, are also envisioned, as well as methods for determining the patients which will benefit the most from such therapies.