Metabolic Markers of Attention Deficit Hyperactivity Disorder

Abstract

Disclosed herein are methods for treating subjects having ADHD identifiable by levels of 3-IS in blood.

1 - 34 . (canceled) 
     
     
         35 . A method of treating a subject for attention deficit hyperactivity disorder, the method comprising administering to the subject a composition comprising methylphenidate, dextroamphetamine, dextroamphetamine-amphetamine, lisdexamfetamine, atomoxetine, bupropion, desipramine, clonidine, or guanfacine, wherein a blood sample from the subject has previously been identified as having an elevated level of 3-Indoxyl Sulfate (3-IS) compared to a reference. 
     
     
         36 . The method of  claim 35 , wherein the elevated level of 3-IS is greater than 14 μM. 
     
     
         37 . The method of  claim 35 , wherein the elevated level of 3-IS is greater than 457 μg/L. 
     
     
         38 . The method of  claim 35 , wherein the level of 3-IS is measured by mass spectrometry. 
     
     
         39 . The method of  claim 35 , wherein the subject is 5 years old or less. 
     
     
         40 . The method of  claim 35 , wherein the subject is 3 years old or less. 
     
     
         41 . The method of  claim 35 , wherein the subject is 2 years old or less. 
     
     
         42 . A method of identifying a subject for treatment with a therapy for attention deficit hyperactivity disorder, the method comprising:
 obtaining a blood sample from the subject;   measuring 3-Indoxyl sulfate (3-IS) level in the sample by mass spectrometry; and   identifying the sample as having a 3-IS level that is higher than a reference level.   
     
     
         43 . The method of  claim 42 , wherein the treatment is a behavioral therapy. 
     
     
         44 . The method of  claim 42 , wherein the treatment is selected from the group consisting of methylphenidate, dextroamphetamine, dextroamphetamine-amphetamine, lisdexamfetamine, atomoxetine, bupropion, desipramine, clonidine, guanfacine, and combinations thereof. 
     
     
         45 . The method of  claim 42 , wherein the reference level of 3-IS is 14 μM. 
     
     
         46 . The method of  claim 42 , wherein the reference level of 3-IS is 457 μg/L. 
     
     
         47 . The method of  claim 42 , wherein the 3-IS level in the sample is at least 1 fold higher than the reference level. 
     
     
         48 . The method of  claim 42 , wherein the 3-IS level in the sample is at least 1.5 higher than the reference level. 
     
     
         49 . The method of  claim 42 , wherein the 3-IS level in the sample is at least 2 fold higher than the reference level. 
     
     
         50 . The method of  claim 42 , wherein the 3-IS level in the sample is at least 2.5 fold higher than the reference level. 
     
     
         51 . The method of  claim 42 , wherein the 3-IS level in the subject is at least 3 fold higher than the reference level. 
     
     
         52 . The method of  claim 42 , wherein the 3-IS level in the sample is at least 4 fold higher than the reference level. 
     
     
         53 . A system for distinguishing between or among at least two conditions for diagnosis and/or risk assessment of an individual suspected of having or observed as having atypical development, wherein the at least two conditions comprise attention deficit hyperactivity disorder (ADHD) and non-attention deficit hyperactivity disorder (non-ADHD), the system comprising:
 a diagnostics kit comprising testing instruments for measuring a level of 3-Indoxyl Sulfate (3-IS) in a biological sample obtained from the individual; and a non-transitory computer-readable medium having instructions stored thereon, wherein the instructions, when executed by a processor, cause the processor to:
 optionally, identify a difference (e.g., an absolute difference or a relative difference) between (or ratio of) the measured 3-IS level and a predetermined control level; and 
 determine at least one of: (i) the existence (or non-existence) of ADHD in the individual as opposed to at least one other condition exclusive of ADHD, wherein the at least one other condition comprises non-ADHD, based at least in part on the measured 3-IS level and/or the difference between the measured 3-IS level and the predetermined control level (e.g., distinguishing between ADHD and non-ADHD in the individual based at least in part on the measured 3-IS level and/or the difference between the measured 3-IS level and the predetermined control level); and (ii) a likelihood the individual has (or does not have) ADHD as opposed to at least one other condition exclusive of ADHD, wherein the at least one other condition comprises non-ADHD, based at least in part on the measured 3-IS level and/or the difference between the measured 3-IS level and the predetermined control level.