USE OF STRIATAL CONNECTIVITY PATTERNS FOR EVALUATING ANTIPSYCHOTIC AGENTS
A method of predicting the response of a subject to an antipsychotic agent is described. The method includes obtaining functional MRI (fMRI) scan data of the brain of the subject, modifying the scan data using a standardizing algorithm to provide modified scan data, calculating the value of a plurality of striatal connectivity dyads from the modified scan data using an extraction algorithm, calculating a combined score from the values of the striatal connectivity dyads using a combining algorithm; and comparing the combined score to a classifier value to determine if the subject is a responder or a non-responder. Systems for carrying out the method of predicting the response of a subject to an antipsychotic agent are also described.
1 . A method of predicting the response of a subject to an antipsychotic agent, comprising the steps of:
a) Obtaining functional MRI (fMRI) scan data of the brain of the subject;
b) Modifying the scan data using a standardizing algorithm to provide modified scan data;
c) Calculating the value of a plurality of striatal connectivity dyads from the modified scan data using an extraction algorithm;
d) Calculating a combined score from the values of the striatal connectivity dyads using a combining algorithm; and
e) Comparing the combined score to a classifier value to determine if the subject is predicted to be a responder or a non-responder.
2 . The method of claim 1 , further comprising the step of obtaining the fMRI scan data by conducting an fMRI scan of the subject using an fMRI imaging apparatus.
3 . The method of claim 1 , wherein the subject has been diagnosed as having a psychotic disorder selected from the group consisting of schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, shared psychotic disorder, brief psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, bipolar I disorder (with psychotic features) and major depressive disorder (with psychotic features).
4 . The method of claim 1 , wherein the subject has been diagnosed as having schizophrenia.
5 . The method of claim 1 , wherein the subject has been diagnosed as having a non-psychotic disorder selected from the group consisting of bipolar I disorder (acute treatment of manic, mixed, or depressive episodes; maintenance treatment), major depressive disorder, Irritability associated with autistic disorders, agitation associated with schizophrenia or bipolar mania, and irritability associated with autistic disorders.
6 . The method of claim 1 , wherein the value of at least 20 striatal connectivity dyads are calculated and combined.
7 . The method of claim 1 , wherein the value of at least 40 striatal connectivity dyads are calculated and combined.
8 . The method of claim 1 , wherein the value of at least 60 striatal connectivity dyads are calculated and combined.
9 . The method of claim 1 , wherein the value of at least 80 striatal connectivity dyads are calculated and combined.
10 . The method of claim 1 , wherein the plurality of striatal connectivity dyads are selected from the striatal connectivity dyads of Tables 3 and 4.
11 . The method of claim 1 , wherein the seed voxel of one or more of the striatal connectivity dyads is found in a brain region selected from the group consisting of the insula cortex, the opercular cortex, the anterior cingulate, the thalamus, the orbitofrontal cortex, and the precuneus regions.
12 . The method of claim 1 , further comprising administering a therapeutically effective amount of a non-clozapine atypical antipsychotic to the subject if the subject is predicted as a responder.
13 . The method of claim 1 , further comprising administering a therapeutically effective amount of clozapine to the subject if the subject is predicted as a non-responder.
14 . A system for predicting a response of a patient to a given antipsychotic drug comprising:
a medical diagnostic scanner configured to provide a spatial representation of neural activity within the brain;
a feature extractor configured to extract a set of striatal connectivity dyads representing the functional connectivity of specified nodes in the basal ganglia to other specified areas of the brain;
a classifier configured to classify the patient into one of a plurality of classes representing the likelihood that the patient will respond to the antipsychotic drug from the extracted set of striatal connectivity dyads; and
an output device configured to provide the resulting classification to a user in human comprehensible form.
15 . The system of claim 14 , further comprising a preprocessing component configured to condition the spatial representation of neural activity within the brain for analysis.
16 . The system of claim 15 , wherein the preprocessing component maps the data into the Montreal Neurological Institute standard brain.
17 . The system of claim 14 , wherein the medical diagnostic scanner is configured to perform a functional magnetic resonance imaging scan.
18 . The system of claim 14 , wherein the classifier performs a binary classification, such that the patients classified into a “responder” or “non-responder” class.