1. METHODSMETHODSMETHODSMETHODS RESULTSRESULTS MMETETHHOODDSSRESULTSRESULTS MMETETHHOODDSS MHODS Neural and Behavioral Predictors of Drug-Induced Psychosis in Methamphetamine Abuse R Salo 1,TE Nordahl 1, MH Buonocore 3, MH Leamon 1, Y Natsuaki 1, GP Galloway 4, C Waters 5, C Moore 5 & CS Carter 1,2 Depts. of Psychiatry 1, Psychology 2, and Radiology 3 University of California, Davis, CA Pacific Medical Center 4, Kaiser Clinics 5  A subset of individuals who abuse methamphetamine [MA] develop recurrent psychotic symptoms commonly termed MA psychosis.  Little is known about the characteristics of those who develop MA psychosis vs those who do not.  We tested the hypothesis that a history of attention problems may represent a vulnerability for developing MA psychosis.  We also tested the hypothesis that impaired prefrontal cortical function may represent a vulnerability for developing MA psychosis.  Question 1: Will measures of attention function differ between those MA abusers who experience frequent psychotic symptoms compared to those who do not?  Question 2: Will frequency of episodes correlate with childhood measures of attention function?  Question 3: Will abnormal metabolite patterns be observed in those MA abusers who experience frequent psychotic symptoms compared to those who do not?I IINTNTRODUCTRODUCTIIONONIINTNTRODUCTRODUCTIIONONI  Significant correlations were observed in MA abusers between frequency of psychotic episodes and scores on the Wender-Utah Attention Scale.  MRS data yielded lower NAA/Cr levels in the Prefrontal cortex of the MA abusers who had frequent psychotic episodes compared to those who did not.  These data suggest the existence of possible neural and behavioral markers reflecting prefrontal cortical function that may be linked to the development of MA psychosis.DISCUSSION Participants: 22 male MA abusers (currently drug abstinent) and 36 female MA abusers (currently drug abstinent)..METHODS Slices36TR1500 ms Voxel20 x 20 x 10 mmTE30 ms Imaging ParametersRESULTS Imaging Results GroupAgeYrs UseMos Abst Educ MALES-Freq Psychosis 34.5 (9.5) 14.9 (10.3) 10.3 12.6 yrs FEMALES-Freq Psychosis 40.2 (7.2) 13.9 (5.6) 29 12.4 yrs MALES-Non-Freq Psychosis 37.5 (8.6) 17.1 (8.7) 7.6 12.7 yrs FEMALES-Non- Freq Psychosis 34.5 (8.9) 9.5 (4.7) 25.7 13.3 yrs The concentration of each metabolite represented in each spectrum is proportional to the area under the spectrum peak Areas of the Cr peaks served as reference values. Rostral ACC (BA 32,10) Mesial Occipital Cortex (BA 17) Right PFC (BA 9,46) Funded by NIDA UTAH Results RL RL Prefrontal Cortex Voxel Anterior Cingulate and Occipital Voxels Behavioral Results Introduction Subject Characteristics Results: The MA subjects who experienced frequent psychotic episodes did not differ in duration of drug use (p=.40), time drug abstinent (p=.64), nor age of first use (p=.37) from those who did not experience recurrent psychotic episodes. However, analyses revealed significant correlations between frequency of psychotic episodes and scores on the Wender Utah Attention Rating Scale [r=.418; p=.001]. The Wender Utah Rating Scale for ADD is a checklist developed to assess childhood history of Attention Deficit Disorder (Wender, Reimherr, & Wood, 1981). Sample UTAH Questions: As a child, I was (or had): 1. Concentration problems, easily distracted. 2. Acting without thinking, impulsive. 3. Trouble with following through, failing to finish things started. MA Experience Questionnaire (MEQ) is an interview based on the Cocaine Experience Questionnaire (Gelernter et al, 1994) designed to assess the tendency to experience paranoia while under the influence of MA. Sample MEQ Questions: 1. Have you ever had a paranoid experience when you were using methamphetamine? 2. The first time you got paranoid with methamphetamine, how long had you been awake when the paranoia started? 3. Did paranoia ever persist after you came down from methamphetamine? 0 10 20 30 40 50 60 70 80 Hi-freq PsychosisLow-freq Psychosis UTAH Score 0 2 4 6 8 10 12 14 16 Hi-freq PsychosisLow-freq Psychosis Years MA Use 0 5 10 15 20 25 30 35 Hi-freq PsychosisLow-freq Psychosis Use Characteristics Mos MA Abstinent 0.2.4.6.8 1 1.2 1.4 1.6 Hi-freq PsychosisLow-freq Psychosis 0.25.5.75 1 1.25 1.5 1.75 2 Hi-freq PsychosisLow-freq Psychosis 1.2 1.4 1.6 1.8 2 2.2 2.4 PFC NAA/Cr 2030405060708090100 UTAH score 0.25.5.75 1 1.25 1.5 1.75 2 2.25 Hi-freq PsychosisLow-freq Psychosis Imaging Subjects: MRS data were obtained from 14 chronic MA abusers. MRS metabolites of interest (NAA, Creatine and Choline) were obtained in the right Prefrontal Cortex, Rostral Anterior Cingulate Cortex [RACC] and Mesial Occipital Cortex. PFC NAA/Cr RACC NAA/Cr Occipital NAA/Cr R L Hypotheses 1.2 1.4 1.6 1.8 2 2.2 2.4 PFC NAA/Cr 0.511.522.533.544.555.5 Psychosis Frequency Behavioral Measures PFC Spectra (MA abuser) RACC Spectra (MA abuser) Psychosis Frequency