biomarker diagnosis of chronic schizophrenia in the presence of cognitive impairment is confirmed when phosphocreatine ( pcr ) levels are increased , compared to normal levels , in both the left and right prefrontal cortices of the brain , with increased pcr specifically also in the left basal ganglia and also reduced na / cr t in the left superior temporal region of the brain . na / cr t is n - acetyl aspartate ( na ) divided by the total creatine signal ( cr t ). by contrast , in a cognitively impaired individual a differential diagnosis of chronic alcoholism may be made when the patient exhibits increased pcr levels in the right basal ganglia , reduced na / cr t in all three of : the left basal ganglia ; the right occipital cortex ; and the left centrum semiovale , together with reduced synaptic phosphodiester spde ( phosphodiesters with short correlation time such as the breakdown products of gpc and gpe produced from phosphatidylcholine and phosphatidylethanolomine respectively ) signal in the right inferior parietal and the right centrum semiovale . in cognitively intact individuals , both the chronic schizophrenia patient and the chronic alcoholism patient will demonstrate increased pcr in the right prefrontal cortex , but unlike the chronic schizophrenia patient the cognitively intact chronic alcoholism patient also will exhibit increased pcr in the right inferior parietal , the left superior temporal region , and the right basal ganglia , and will exhibit reduced spde in the left basal ganglia and in the left superior temporal region , whereas the chronic schizophrenia patient with intact cognition will comparatively present with increased pcr only in the right prefrontal cortex . the pcr , na / cr t , and spde biomarkers themselves , as well as techniques to assay their presence and quantity in the human brain , are already known from my previous published and patented work , such as u . s . pat . no . 7 , 700 , 074 . in u . s . pat . no . 7 , 700 , 074 ( incorporated herein by reference without limitation ) i have described how to quantify pcr , n - acetyl aspartate and ( s ) pde with medical imaging techniques , such as z - score plots using dichotomized data summarizing regional phosphorus - hydrogen magnetic resonance spectroscopic imaging ( 31 p — 1 h mrsi )— differences known in the art . the novel feature of the present invention is assessing the increase or decrease of particular biomarkers in very specific anatomic regions in the brain , where these various markers are reduced or increased and the differential diagnostic significance thereof . how to image the markers themselves , throughout the brain , is already known from my previous published and patented work . referring now to fig8 , it is easiest to envision the differential diagnosis possible with the instant invention when viewing the comparative loci of marker increase or decrease and the attribution to chronic schizophrenia or chronic alcoholism . as fig8 shows , increase in pcr level occurs in the right prefrontal cortex for both chronic schizophrenia and chronic alcoholism if the patient does not have cognitive impairment regardless of whether the patient has chronic schizophrenia or chronic alcoholism ( or both ). however , as to all the other markers shown in fig8 , the marker , its increase or decrease , and anatomic location in the brain , is specific to either chronic schizophrenia or chronic alcoholism , without overlap . therefore , at a minimum at least one of the biomarkers for either chronic schizophrenia or chronic alcoholism as shown in fig8 has diagnostic significance for chronic schizophrenia or chronic alcoholism , and ideally a patient will be assessed for all the applicable markers and anatomic locations described in fig8 in order to permit differential diagnosis of chronic schizophrenia or chronic alcoholism from the results of the biomarker tests . in its most complete iteration , therefore , the present invention allows differential diagnosis of chronic schizophrenia in the presence of cognitive impairment when not only the right prefrontal cortex shows increased pcr but also the left prefrontal cortex shows increased pcr also , the left basal ganglion shows increased pcr , and the left superior temporal exhibits reduced na / cr t . likewise , in a cognitively impaired individual a differential diagnosis of chronic alcoholism may be made when the patient exhibits increased pcr in the right basal ganglia , reduced na / cr t in all three of : the left basal ganglia ; the right occipital cortex ; and the left centrum semiovale , together with reduced spde signal in both the right inferior parietal and the right centrum semiovale . finally , as described above , in cognitively unimpaired individuals , both the chronic schizophrenia patient and the chronic alcoholism patient will demonstrate increased pcr in the right prefrontal cortex , but unlike the chronic schizophrenia patient the cognitively intact chronic alcohol patient also will exhibit increased pcr in the right inferior parietal , the left superior temporal region , and the right basal ganglia , and will exhibit reduced spde in the left basal ganglia and in the left superior temporal region , whereas the chronic schizophrenia patient with intact cognition will comparatively present with increased pcr only in the right prefrontal cortex . if a patient exhibits all the markers shown in fig8 , the presence of both chronic schizophrenia and chronic alcoholism may be confirmed . the remainder of this patent specification describes the research on which the above conclusions are based , and provides additional description of the figures included herewith . loess and sigmoidal curve fitting of brain molecular data obtained by 31 p — 1 h mrsi was used to examine age - related changes in brain regional metabolite levels in cohorts of chronic schizophrenia , chronic alcoholism and match control subjects as well as chronic smokers . the chronic smokers allowed examination of the possible confound of smoking since both chronic schizophrenia and chronic alcoholism subjects are usually heavy smokers . the chronic schizophrenia and chronic alcoholism cohorts were dichotomized into cognitive intact or impaired subgroups . the metabolites measured were phosphocreatine ( pcr ), phosphomonoesters with short correlation times ( spme ) which are precursors of membrane phospholipids and phosphodiesters with short correlation times ( spde ) which are membrane phospholipid breakdown products . in addition , we measured n - acetyl - containing molecules which in brain are predominantly n - acetyl aspartate , generally expressed as na divided by the total creatine signal cr t , or na / cr t . naa ( n - acetyl aspartate itself ) is thought to be a marker of neurons and neuronal processes . chronic alcoholism was chosen as a comparison group for chronic schizophrenia due to similar cognitive deficits , but some cognitive differences also are observed . because the cognitive abnormalities of the two disorders share similarities and differences , our research investigated whether there are also similarities and differences in brain molecular abnormalities , and ultimately led to the conclusions summarized in fig8 herewith . the increased level of pcr in the prefrontal cortex of chronic schizophrenia subjects reflects reduced synaptic terminals with reduced utilization of pcr . the prefrontal cortex undergoes synaptic elimination in humans during late - adolescence to young - adult life , which is the same time frame as the usual onset of clinical symptoms in chronic schizophrenia . in view of the data represented in fig1 - 7 and the application of those results as summarized in fig8 , we have investigated and validated the anatomic regions for particular biomarker and biomarker combinations to provide differential diagnosis of chronic schizophrenia and chronic alcoholism with or without cognitive impairment . although the invention has been described with particularity above , the invention is only to be considered to be limited insofar as is set forth in the accompanying claims .
the invention is a method for the differential diagnosis of chronic schizophrenia or chronic alcoholism , by imaging the brain of a subject to detect any or all of the markers phosphocreatine , n - acetyl aspartate divided by the total creatine signal , and synaptic phosphodiester , and determining any increase or decrease in the presence of such markers compared to normal levels in specified anatomic areas of the brain . the output of such a method , resulting from such imaging , is presented to be viewed by a diagnostician in order to support the differential diagnosis based on the data output .