Method for the diagnosis and follow up of schizophrenia and other mental and neurodegenerative disorders

Abstract

A method for the diagnosis and follow up of a mental disorder or of a neurodegenerative disorder in an individual, comprises: (i) measuring mRNA of D 3 dopamine receptor and/or of α7 nicotinic acetylcholine receptor (α7 AChR) and of a control gene in peripheral blood lymphocytes (PBLs) of said individual and of at least one healthy control individual; (ii) calculating the ratio between the D 3 dopamine receptor mRNA and the control gene mRNA and/or the ratio between α7 AChR mRNA and the control gene mRNA for each individual; and (iii) evaluating the ratio between the ratios obtained in (ii) for the tested individual and for the at least one healthy control individual, wherein an increase in the D 3 dopamine receptor mRNA and/or a decrease in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having said mental disorder or neurodegenerative disorder, wherein said increase in the D 3 dopamine receptor mRNA and/or decrease in the α7 AChR mRNA in the tested individual is correlated to said mental disorder or neurodegenerative disorder. When the mental disorder is schizophrenia, an increase of above 1.6 fold in the D 3 dopamine receptor mRNA and/or a decrease of more than 20% in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having schizophrenia.

1 . A method for the diagnosis and follow up of a mental disorder or of a neurodegenerative disorder in an individual, comprising: 
 (i) measuring mRNA of D 3  dopamine receptor and/or of α7 nicotinic acetylcholine receptor (α7 AChR) and of a control gene in peripheral blood lymphocytes (PBLs) of said individual and of at least one healthy control individual;    (ii) calculating the ratio between the D 3  dopamine receptor mRNA and the control gene mRNA and/or the ratio between α7 AChR mRNA and the control gene mRNA for each individual; and    (iii) evaluating the ratio between the ratios obtained in (ii) for the tested individual and for the at least one healthy control individual, wherein an increase in the D 3  dopamine receptor mRNA and/or a decrease in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having said mental disorder or neurodegenerative disorder, wherein said increase in the D 3  dopamine receptor mRNA and/or decrease in the α7 AChR mRNA in the tested individual is correlated to said mental disorder or neurodegenerative disorder.    
     
     
         2 . A method according to  claim 1  wherein said mental disorder is schizophrenia, maniac depression, Tourette syndrom, or a similar disorder.  
     
     
         3 . A method according to  claim 1  wherein said generative disorder is Parkinson's disease, disease, or Huntington disease.  
     
     
         4 . A method according to  claim 1  for the diagnosis and follow up of schizophrenia in an individual, comprising: 
 (i) measuring mRNA of D 3  dopamine receptor and/or of α7 AChR and of a control gene in PBLs of said individual and one healthy control individual;    (ii) calculating the ratio between the D 3  dopamine receptor mRNA and the control gene mRNA and/or the ratio between the α7 AChR and the control gene mRNA for each and    (iii) evaluating the ratio between the ratios obtained in (ii) for the individual tested for schizophrenia and for the at least one healthy control individual, wherein an increase of above 1.6 fold in the D 3  dopamine receptor mRNA and/or a decrease of more than 20% in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having schizophrenia.    
     
     
         5 . A method according to  claim 4  for the diagnosis and follow up of schizophrenia in an individual, comprising: 
 (i) measuring mRNA of D 3  dopamine receptor and of a control gene in PBLs of said individual and of at least one healthy control individual;    (ii) calculating the ratio between the D 3  dopamine receptor mRNA and the control gene mRNA for each individual; and    (iii) evaluating the ratio between the ratios obtained in (ii) for the individual tested for schizophrenia and for the at least one healthy control individual, wherein an increase of above 1.6 fold in the D 3  dopamine receptor mRNA in the tested individual in comparison to healthy individuals, indicates that said tested individual has a high likelihood of having schizophrenia.    
     
     
         6 . A method according to  claim 4  for the diagnosis and follow up of schizophrenia in an individual, comprising: 
 (i) measuring mRNA of the α7 AChR and of a control gene in PBLs of said individual and of at least one healthy control individual;    (ii) calculating the ratio between the α7 AChR mRNA and the control gene mRNA for each individual; and    (iii) evaluating the ratio between the ratios obtained in (ii) for the individual tested for schizophrenia and for the at least one healthy control individual, wherein a decrease of more than 20% in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicates that said tested individual has a high likelihood of having schizophrenia.    
     
     
         7 . A method according to  claim 1 , wherein the mRNA of D 3  dopamine receptor, of α7 AChR and of the control gene in step (i) is measured by reverse transcription-polymerase chain reaction (RT-PCR).  
     
     
         8 . A method according to  claim 1 , wherein the control gene is β-actin.  
     
     
         9 . A method according to  claim 1 , which comprises calculating in step (ii) the ratio between the D 3  dopamine receptor mRNA and/or the ratio between the α7 AChR and the control gene mRNA of the individual tested for a mental or neurodegenerative disorder and the ratio between the D 3  dopamine receptor mRNA and/or the ratio between the α7 AChR and the control gene mRNA of a sole healthy individual.  
     
     
         10 . A method according to  claim 1 , wherein said mental disorder is schizophrenia and in the schizophrenic individual the increase of D 3  dopamine receptor mRNA evaluated in step (iii) is of 2-4 folds and/or the decrease of the α7 AChR mRNA evaluated in step (iii) is 20-98%, in comparison to healthy individuals,.  
     
     
         11 . A kit for use in a method according to  claim 1 .  
     
     
         12 . A kit according to  claim 11 , comprising: 
 (i) means for isolating mRNA from PBL;    (ii) means for reverse transcription and for PCR; and    (iii) means for detection of PCR products.    
     
     
         13 . A kit according to  claim 12 , further comprising means for separating PBL from whole blood.