Abstract: The ACP1 *A allele provides a means for diagnosing susceptibility of a human subject to hyperlipidemia, especially hyperlipidemia associated with metabolic syndrome, a means for treating, or preventing the onset of, hyperlipidemia and metabolic syndrome, and a means for screening and identifying drugs suitable for use in treating or preventing hyperlipidemia, especially hyperlipidemia associated with metabolic syndrome. Diagnostic kits are also provided.

Abstract: The ACP1 *A allele provides a means for diagnosing susceptibility of a human subject to hyperlipidemia, especially hyperlipidemia associated with metabolic syndrome, a means for treating, or preventing the onset of, hyperlipidemia and metabolic syndrome, and a means for screening and identifying drugs suitable for use in treating or preventing hyperlipidemia, especially hyperlipidemia associated with metabolic syndrome. Diagnostic kits are also provided.

Abstract: A method for treating the psychiatric disorders known as oppositional defiant disorder and conduct disorder is disclosed. The method comprises the administration of a compound according to Formula I or II to a patient suffering from oppositional defiant disorder and/or conduct disorder. The compound may be either a racemic mixture or e.g. the levorotatory form. It may be short acting or in a sustained release, long acting form. Molindone or a pharmaceutically acceptable salt of molindone is a preferred embodiment.

Abstract: Alzheimer's disease is characterized by the presence of senile plaques formed from beta amyloid (A?), and neurofibrillary tangles (NTFs) formed from paired helical filaments consisting of hyperphosphorylated tau. A number of studies have shown that the NTFs correlate better with the duration and severity of Alzheimer's disease than senile plaques. However, a criticism of the primary etiological role of NTFs in Alzheimer's disease is the absence of variants of kinases or phosphatases associated with Alzheimer's disease. Acid phosphatase, a product of the ACP 1 gene, is a ubiquitous low molecular weight protein tyrosine phosphatase. A common allele, ACP 1*A, is associated with a lower activity of acid phosphatase. It is due to an Arg 105 Gln substitution of the ACP1 locus and detected as a Taq I polymorphism. We report a significant association of the low activity 2 allele with sporadic early onset Alzheimer's disease (EOAD).

Abstract: The present invention is directed to the identification of genostatic factors, methods of determining the association of a plurality of genes with polygenic disorders, and method of assessing the sensitivity and specificity of the risk of polygenic disorders. In particular, the present invention discovers that the association between a polygenic disorder phenotype and polygenes may be masked. Incorporating genostatic factor, such as maternal age, birth disorder, the androgen receptor gene, gender, and age, into the statistical analysis of the association between phenotypes and genotypes reveals statistically significant relationship between the two. Accordingly, the present invention provides novel methods in determining the association of a plurality of genes with a polygenic disease and the likelihood of having the polygenic disease.

Abstract: A method for treating the psychiatric disorders known as oppositional defiant disorder and conduct disorder is disclosed. The method comprises the administration of a compound according to Formula I or II to a patient suffering from oppositional defiant disorder and/or conduct disorder. The compound may be either a racemic mixture or e.g. the levorotatory form. It may be short acting or in a sustained release, long acting form. Molindone or a pharmaceutically acceptable salt of molindone is a preferred embodiment.

Abstract: The present invention relates to the observation that women having an A→T 1890 polymorphism in the 3′ UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene have an increased risk for developing major depression. The present invention provides diagnostic, screening and therapeutic methods based on that observation.

Abstract: The invention relates to methods for diagnosing a person's susceptibility for having an increased risk for the development of breast cancer. The invention relates further to methods for treating persons diagnosed for having increased risk for the development of said disease, in order to prevent the development of said disease.

Abstract: The present invention is directed to two single nucleotide polymorphisms, identified as G-182A and G-387A, in the promoter region of the human phenylethanolamine N-methyltransferase (PNMT) gene, the gene products thereof, and to methods for the determination (diagnosis) of susceptibility to (risk of) neurologic or neuropsychiatric diseases involving adrenergic neurons.

Abstract: Disclosed are methods for screening subjects to determine their risk for developing cardiovascular disease, screening methods to determine potential longevity, therapeutic methods and compositions for treating patients at risk for developing cardiovascular disease, and screening methods for identifying materials useful in the therapeutic methods.

Abstract: A method for treating the psychiatric disorders known as oppositional defiant disorder and conduct disorder is disclosed. The method comprises the administration of molindone or a pharmaceutically acceptable salt of molindone to a patient suffering from oppositional defiant disorder and/or conduct disorder. The molindone may be either a racemic mixture or the levorotatory form. It may be short acting or in a sustained release, long acting form.

Abstract: Polygenic disorders are due to the additive effect of multiple genes interacting with the environment. Because of the small effect size of each gene and considerable genetic heterogeneity, when single genes are examined, the outcome of association and linkage analyses are variable from study to study. Techniques are needed that take these unique characteristics of polygenic disorders into consideration. The present invention discloses that the formation of a polygenic score, consisting of the additive effect of multiple candidate genes, and its assessment using receiver operating characteristic (ROC) plots, provides such a technique. Six genes previously shown to be associated with Alzheimer's disease were examined, APOE, ACE, ACP1, ESR1, PNMT and SLC6A4.

Abstract: Alzheimer's disease is characterized by the presence of senile plaques formed from beta amyloid (A&bgr;), and neurofibrillary tangles (NTFs) formed from paired helical filaments consisting of hyperphosphorylated tau. A number of studies have shown that the NTFs correlate better with the duration and severity of Alzheimer's disease than senile plaques. However, a criticism of the primary etiological role of NTFs in Alzheimer's disease is the absence of variants of kinases or phosphatases associated with Alzheimer's disease. Acid phosphatase, a product of the ACP1 gene, is a ubiquitous low molecular weight protein tyrosine phosphatase. A common allele, ACP1*A, is associated with a lower activity of acid phosphatase. It is due to an Arg 105 Gln substitution of the ACP1 locus and detected as a Taq I polymorphism. We report a significant association of the low activity 2 allele with sporadic early onset Alzheimer's disease (EOAD).

Abstract: The present invention relates to the observation that women having an A→T 1890 polymorphism in the 3′ UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene have an increased risk for developing major depression. The present invention provides diagnostic, screening and therapeutic methods based on that observation.

Abstract: The present invention is directed to polymorphisms in the MME gene (encoding metalo-membrane endopeptidase, neutral endopeptidase (NEP), enkephalinase) and the ANPEP gene (encoding amino peptidase N (APN), alanyl membrane aminopeptidase) or their gene products and to a process for the diagnosis of internalizing disorders. Internalizing disorders, such as depression, withdrawal, negative affect, anxiety, social problems, phobias, paranoid ideation, alcoholism and interpersonal sensitivity, are diagnosed in accordance with the present invention by analyzing the DNA sequences of the MME and/or ANPEP genes of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal MME and/or ANPEP gene. Alternatively, the MME and ANPEP genes of an individual to be tested can be screened for mutations which cause internalizing disorders. Prediction of internalizing disorders will enable practitioners to treat internalizing disorders using existing medical therapy.

Abstract: The present invention is directed to two single nucleotide polymorphisms, identified as G-182A and G-387A, in the promoter region of the human phenylethanolamine N-methyltransferase (PNMT) gene, the gene products thereof, and to methods for the determination (diagnosis) of susceptibility to (risk of) neurologic or neuropsychiatric diseases involving adrenergic neurons.

Abstract: A method for treating the psychiatric disorders known as oppositional defiant disorder and conduct disorder is disclosed. The method comprises the administration of molindone or a pharmaceutically acceptable salt of molindone to a patient suffering from oppositional defiant disorder and/or conduct disorder. The molindone may be either a racemic mixture or the levorotatory form. It may be short acting or in a sustained release, long acting form.

Abstract: The present invention is directed to the C-45T polymorphism in the Sp1 binding region of the CCK gene and the role of genetic variants in the CCK gene as a risk factor for smoking and/or unsuccessful smoking cessation in women. In particular, the invention is directed to a method for diagnosing a polymorphism which is a risk factor for smoking comprising hybridizing a nucleic acid probe, which hybridizes specifically to an isolated DNA comprising a nucleotide sequence coding for human CCK containing a polymorphism described herein or its complement, to a patient's sample of DNA or RNA under stringent conditions which allows hybridization of said probe to nucleic acid comprising said polymorphism but prevents hybridization of said probe to a wild-type nucleic acid, wherein the presence of a hybridization signal indicates the presence of said polymorphism.

Abstract: The present invention relates to methods of profiling candidate genes as risk factors for attention deficit hyperactivity disorder, oppositional defiant disorder and conduct disorder. In one embodiment, the invention relates to a method of determining a genetic predisposition of a subject to ADHD, comprising detecting at least one allele from the group comprising the TPH, PNMT, ADO42A, NOS3, and NAT1 genes. By focusing on the additive effect of multiple genes and on the cumulative effect of functionally related groups of genes, a powerful approach is provided for the dissection of the genetic basis of ADHD, ODD and CD.

Abstract: The human tryptophan oxygenase gene sequence and chromosomal location are described. Procedures for the diagnosis of genetic Tourette syndrome and many psychiatric and behavioral disorders by genetic tests to identify deletions or defective alleles in the human tryptophan oxygenase (TO) gene and cDNA probes for use in such tests are also described.