System and method for diagnosis and treatment of neuropsychiatric disorders

Abstract

An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen or diagnose subjects at risk for developing a psychiatric, neuropsychiatric, or neurological disorder. The genetic assay, with or without a biopterin or BH4 system assay, may also be used to determine treatment regimens. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.

What is claimed is: 
     
         1 . A kit for addressing schizophrenia or schizoaffective disorder, comprising:
 an assay for determining a GTP cyclohydrase I (GCH1) −959 nt G/A genotype of a patient; and   an assay for determining a level of a tetrahydrobiopterin (BH4) system pathway component.   
     
     
         2 . The kit of  claim 1 , wherein said assay for determining said G/A genotype of said patient comprises at least one primer for amplifying a genomic region spanning said G/A genotype. 
     
     
         3 . The kit of  claim 1 , wherein said primer comprises SEQ. ID. NO. 3. 
     
     
         4 . The kit of  claim 1 , wherein said primer comprises SEQ. ID. NO. 4. 
     
     
         5 . The kit of  claim 2 , wherein said assay further comprises a restriction enzyme that cleaves the A allele of the G/A genotype. 
     
     
         6 . The kit of  claim 3 , wherein said restriction enzyme comprises BsrD1. 
     
     
         7 . The kit of  claim 4 , wherein said cleaved allele comprises a 191/160 bp doublet. 
     
     
         8 . The kit of  claim 5 , further comprising means for visualizing said 191/160 bp doublet. 
     
     
         9 . The kit of  claim 1 , wherein said tetrahydrobiopterin (BH4) system pathway component comprises at least one of total biopterins, BH4, 7,8-dihydrobiopterin, and fully oxidized biopterin. 
     
     
         10 . The kit of  claim 1 , further comprising a therapeutic compound for treating a schizophrenia or schizoaffective disorder based on said assay for determining said G/A genotype and said assay for determining level of a BH4 system pathway component. 
     
     
         11 . The kit of  claim 10 , wherein said therapeutic compound comprises tetrahydrobiopterin (BH4). 
     
     
         12 . The kit of  claim 10 , wherein said therapeutic compound comprises a drug that modulates the level of at least one of total biopterins, BH4, 7,8-dihydrobiopterin, and fully oxidized biopterin. 
     
     
         13 . The kit of  claim 12 , wherein said therapeutic compound increases the level of at least one of total biopterins, BH4, 7,8-dihydrobiopterin, and fully oxidized biopterin. 
     
     
         14 . The kit of  claim 10 , wherein said therapeutic compound comprises at least one compound selected from the group consisting of pterin, biopterin, dihydrobiopterin, neopterin, 6-pyruvoyl-tetrahydrobiopterin, tetrahydrobiopterin, phenylalanine, aspartame, sepiapterin, and sapropterin dihydrochloride. 
     
     
         15 . The kit of  claim 10 , wherein said therapeutic compound comprises at least one compound selected from the group consisting of haloperidol, risperidone, Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine, Mesoridazine, Promazine, Triflupromazine, Levomepromazine, Chlorprothixene, Flupenthixol, Thiothixene, Zuclopenthixol, Droperidol, Pimozide, Melperone, Clozapine, Olanzapine, Risperidone, Quetiapine, Ziprasidone, Amisulpride, fluoxetine, Paliperidone, Aripiprazole, LY2140023, Lithium compounds, Lithium chloride, Lithium carbonate, Valproic acid, divalproate, divalproex sodium, sodium valproate, valproate, Lamotrigine, Carbamazepine, Gabapentin, Oxcarbazepine, and Topiramate.