Gene Tests for Diagnostics of Psychiatric Disorders
The Invention We suggest two novel gene tests for psychiatric disorders:1.Diagnostics of susceptibility to schizophrenia, based on single nucleotide polymorphism (SNPs) of the golli myelin basic protein (golli-MBP) gene.
2.A methods for predicting the response to lithium therapy in bipolar patients, based on specific SNPs in the calcium channel γ-2 subunit (Cacng2) gene.
The Need Bipolar disorder (BPD; also called manic-depressive illness) and schizophrenia are severe, chronic and life threatening illnesses, both characterized by extremely high suicide rates. The etiology of these diseases demonstrates strong genetic factors characterized by a complex inheritance pattern. Like other common, complex disorders, schizophrenia and BPD are considered as multifactor disorders characterized, to a large extent, by the contribution of multiple susceptibility genes, which may interact stochastically with epigenetic processes and environmental factors. Presently, there are no biological tests to aid in the diagnosis of psychiatric disorders, or in prediction of patient response to existing treatments. Diagnosis is, therefore, largely based on behavior, requiring years for the course of symptoms to become clear. Thus, current behavior based diagnostics have a limited ability to predict the disease, its course or response to treatment. Genetic tests for disease prediction and for potential response to treatment of these psychiatric disorders will enable more rapid and accurate diagnosis, leading to better treatment and possibly prevention of these diseases.
Potential Applications Early diagnosis of schizophrenia Diagnosis of response to lithium and antidepressants
Advantages Novel diagnostic approach. Meets large unmet marked need. Allows prediction of response to lithium, enabling to avoid its severe side effects to non responders, and allowing better and more predictive treatment to patients.
Stage Gene testing for schizophrenia: A case-control association analysis of golli-MBP in two separate Jewish-Ashkenazi cohorts (cohort I: 120 patients, 236 controls; cohort II: 379 patients, 380 controls) was performed. In addition an expression analysis of golli-MBP mRNA in postmortem dorsolateral prefrontal cortex (DLPFC) samples of schizophrenia patients, and matched controls was performed. In the first cohort we observed association between 6 (out of 26 tested) single nucleotide polymorphisms (SNPs) and the disease. Haplotype analysis revealed significant risk- and protective-haplotypes for schizophrenia. The 3 SNPs were then genotyped in the second cohort. The combined results showed strong effects, both in the single marker and in the haplotype analyses. Expression analysis found no significant differences in golli-MBP mRNA levels. The association findings suggest that golli-MBP is a possible susceptibility gene for schizophrenia.
Predicting the response to lithium therapy: The expression levels of cacng2 in post-mortem brain samples of patients with schizophrenia, bipolar disorder (BPD) and healthy controls, was tested. Expression analysis was carried out by quantitative reverse transcription-PCR in RNA samples from dorsolateral prefrontal cortices of patients with schizophrenia, BPD and controls (n=35 each). Twelve single nucleotide polymorphisms encompassing cacng2 were genotyped in DNA samples from two cohorts (n= 410, 170). Patients were treated with lithium and divided into groups according to their response. A 1.6-fold overexpression of cacng2 was observed in patients with BPD. Three of the genotyped single nucleotide polymorphisms were associated with lithium response. Haplotype analysis revealed significant ‘response-protective’ and ‘responseinhibitive’ haplotypes in both cohorts. These findings suggest that cacng2 dysregulation may be involved with the pathophysiology of BPD, but not with that of schizophrenia, and those cacng2 polymorphisms may play a role in the response to lithium treatment.
Inventor(s): Ruth Navon
Type of Offer: Licensing
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