title: Evidence for a SULT4A1 haplotype correlating with baseline psychopathology and atypical antipsychotic response.
abstract: OBJECTIVE
  This study evaluated the impact of SULT4A1 gene variation on psychopathology and antipsychotic drug response in Caucasian subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and a replication sample.
  
  
  METHODS
  SULT4A1 haplotypes were determined using SNP data. The relationship to baseline psychopathology was evaluated using linear regression of Positive and Negative Syndrome Scale (PANSS) total score. Drug response was evaluated using Mixed Model Repeat Measures (MMRM) for change in PANSS.
  
  
  RESULTS
  For the CATIE sample, patients carrying a haplotype designated SULT4A1-1(+) displayed higher baseline PANSS (p = 0.03) and, when treated with olanzapine, demonstrated a significant interaction with time (p = 0.009) in the MMRM. SULT4A1-1(+) patients treated with olanzapine displayed improved response compared with SULT4A1-1(-) patients treated with olanzapine (p = 0.008) or to SULT4A1-1(+) patients treated with risperidone (p = 0.006). In the replication sample, SULT4A1-1(+) patients treated with olanzapine demonstrated greater improvement than SULT4A1-1(-) patients treated with olanzapine (p = 0.05) or than SULT4A1-1(+) patients treated with risperidone (p = 0.05).
  
  
  CONCLUSIONS
  If validated, determination of SULT4A1-1 haplotype status might be useful for identifying patients who show an enhanced response to long-term olanzapine treatment. Original submitted 6 October 2010; Revision submitted 9 December 2010.
authors.affiliation: SureGene, LLC, 600 Envoy Circle, Louisville, KY 40299, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ramsey
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Guy N
authors.initials: GN
authors.lastname: Brock
authors.forename: Bharat
authors.initials: B
authors.lastname: Mehrotra
authors.forename: Karu
authors.initials: K
authors.lastname: Jayathilake
authors.forename: William V
authors.initials: WV
authors.lastname: Bobo
authors.forename: Mark D
authors.initials: MD
authors.lastname: Brennan
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D017321:Clinical Trials, Phase I as Topic; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D001569:Benzodiazepines; C479953:SULT4A1 protein, human; D015238:Sulfotransferases; D018967:Risperidone; D000077152:Olanzapine