| Detection of antidepressant induced mania -> Monitor Keywords |
|
|
 
Detection of antidepressant induced maniaRelated Patent Categories: Chemistry: Molecular Biology And Microbiology, Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip, Involving Nucleic AcidDetection of antidepressant induced mania description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060286594, Detection of antidepressant induced mania. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application is a continuation of U.S. patent application Ser. No. 10/075,249, filed Feb. 15, 2002, which claims the benefit under 35 USC .sctn.119(e) from U.S. provisional patent application No. 60/268,918, filed Feb. 16, 2001 and U.S. provisional patent application No. 60/287,128, filed Apr. 30, 2001. FIELD OF THE INVENTION [0002] The present invention relates to methods and kits for determining the susceptibility of a patient to antidepressant-induced mania. BACKGROUND OF THE INVENTION [0003] The induction of mania in patients treated with antidepressants is a complex and not rare phenomenon, which has been described to occur with different frequencies in Bipolar Disorder (BP), Unipolar Disorder (UP), and Obsessive-Compulsive Disorder (OCD) (1-8). In Mood Disorder (MD) patients, the frequency of induction of mania during antidepressant treatment has been estimated to be 9.5-33%, varying in the different studies including different diagnoses (i.e. UP and BP) and different antidepressant treatments (9-11). More recently, it has become clearer that the phenomenon of antidepressant-induced mania is strictly related to a diagnosis of BP. In BP patients the switch rate during antidepressant treatment is definitively higher than in UP patients (12) and represents a critical issue for the long-term management of the disorder. Whether the type of antidepressant treatment can affect the risk of developing manic switches remains controversial. According to the report of Solomon et al (2), an antidepressant-induced manic episode occurs in approximately 20% of the inpatient admissions with a diagnosis of BP, independently from the treatment status (tricyclic antidepressants -TCAs-, monoamine oxidase inhibitors -MAOIs- or electroconvulsive therapy -ECT-). On the other hand, some studies have shown that the rate of induction of mania is higher in BP patients treated with TCAs and MAOIs than in BP patients treated with selective serotonin reuptake inhibitors (SSRIs) (8, 13). [0004] As the impact on the natural course of BP and on the clinical management of the disease created by the occurrence of antidepressant-induced manic switches is quite high (1, 14), the detection of possible predictors of this phenomenon has become one of the primary goals of clinical studies. A higher number of previous manic or hypomanic episodes appeared to be the only clinical variable affecting the risk for developing induced mania during antidepressant treatment (8, 12). According to the report of Stoll et al. (15) antidepressant-induced manic/hypomanic episodes appear to be also clinically different from the spontaneous ones, usually having a shorter duration and less severe psychotic symptoms (15). [0005] Most of the antidepressants commonly used to treat the depressive episodes that occur in the course of BP, act on the serotonin transporter (5HTT) (16). The 5HTT is located on the terminals of serotonergic neurons and its function is to reuptake serotonin from the synaptic cleft into the cell (16). Family, twin, and molecular genetic studies, have shown that BP has a strong genetic component (17-20), and thus, the 5HTT protein gene has been considered an good candidate for the investigation of the genetic component of both BP and the response to antidepressant medication. [0006] The 5HTT gene is located on Chromosome 17, spans 31 kilobases (KB) and consists of 14 exons. This gene has two polymorphisms known. One is in the promoter region (5HTTLPR) consisting of 44 bp insertion/deletion (21). Studies employing lymphoblastoid cell lines containing different genotypes with respect to the 5-HTTLPR (21) showed that cells homozygous for the l allele produced steady-state concentrations of 5-HTT mRNA that were 1.4 to 1.7 times those in cells containing 1 or 2 copies of the s. At the protein level, membrane preparations from l/l lymphoblasts bound 30% to 40% more of a labeled marker than did membranes from l/s or s/s cells. Moreover, uptake of labeled serotonin in cells homozygous for the l allele of the promoter polymorphism was 1.9 to 2.2 times that in cells carrying 1 or 2 endogenous copies of the s variant. These data also suggested that the polymorphism has more of a dominant-recessive than a codominant-additive effect. [0007] In rare circumstances, particularly in Asian and African-American populations, additional variants such as the vl (very long) allele and the xl (extra long) allele may occur (22). [0008] Investigation for the possible involvement of the 5HTTLPR in the pathogenesis of BP, applying different methods, has lead to conflicting results. Two linkage studies to date using multiplex families have provided negative results (23-24). Among the several case-control association studies performed, only two studies detected a positive association between the s variant of the gene and BP (25-26). Two studies applying strategies for the detection of association in presence of linkage disequilibrium, which are particularly useful for assessing gene susceptibility in psychiatric disorders where genes may be of small effect (27), gave negative results (28-29). [0009] The other polymorphism known for the 5HTT gene is a variable number of tandem repeats (VNTR) polymorphism in the second intron, with three alleles (Stin2.9, Stin2.10 and Stin2.12) (30). The Stin2.12 allele was found to be associated with BP in two studies (25, 31), while more recent studies appear to exclude any associations between this polymorphism and BP (32-35). [0010] At least three studies to date have considered the two known polymorphisms of the 5HTT gene in a haplotype analysis, with negative results (26, 35, 36). [0011] With respect to the role of the 5HTTLPR in the antidepressant response, patients with Major Depression and homozygous or heterozygous for the l variant appear to show a better response to fluvoxamine (37) and paroxetine (38) and patients with Bipolar Depression who are homozygous for the l variant of the 5HTTLPR have been found to have a better clinical response to total sleep deprivation (39). [0012] On the other hand, the meaning of these findings, as well as the relationships with the functional variations associated with the gene are controversial (40). SUMMARY OF THE INVENTION [0013] The present inventors have determined that there is correlation between the presence of a polymorphism in the serotonin transporter 5HTT gene and the occurrence of antidepressant-induced mania. In particular, the inventors have shown that a DNA sequence variant in the promoter region of 5HTT (5HTTLPR) consisting of a 44 bp deletion in the gene (which is called the s variant) appears to be involved in the pathogenesis of manic/hypomanic switches in a bipolar patients treated with pro-serotonergic antidepressant agents. [0014] Accordingly, the present invention provides a method of determining the susceptibility of a patient to antidepressant-induced mania comprising: [0015] (a) obtaining a sample from the patient; and [0016] (b) testing the sample for the presence of the s variant of the 5HTTLPR polymorphism in the 5HTT gene, wherein the presence of the s variant indicates that the patient is more susceptible to antidepressant-induced mania. [0017] The patient is preferably a patient with Bipolar Disorder who has been treated with a proserotonergic agent. [0018] The present invention also provides a kit for determining the susceptibility of a patient to antidepressant-induced mania comprising reagents necessary for determining the presence of the s variant of the 5HTTLPR polymorphism and directions for its use. [0019] Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating preferred embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTION OF THE DRAWINGS [0020] The invention will now be described in relation to the drawings in which: [0021] FIG. 1 shows the nucleic acid sequence of the s variant of the 5HTTLPR gene (SEQ ID NO:1). [0022] FIG. 2 is an electrophoresis gel showing the size of the s variant of the 5HTTLPR gene. Continue reading about Detection of antidepressant induced mania... Full patent description for Detection of antidepressant induced mania Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Detection of antidepressant induced mania patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Detection of antidepressant induced mania or other areas of interest. ### Previous Patent Application: Detection of 5t4 rna in plasma and serum Next Patent Application: Fluid container for electrohydrodynamic spray device and method of using same Industry Class: Chemistry: molecular biology and microbiology ### FreshPatents.com Support Thank you for viewing the Detection of antidepressant induced mania patent info. IP-related news and info Results in 0.4292 seconds Other interesting Feshpatents.com categories: Electronics: Semiconductor , Audio , Illumination , Connectors , Crypto , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
