title: Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia.
abstract: In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=-5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=-0.247; P=0.004) and Hopkins total (r=-0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Vendramini
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.|Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Yonamine
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Nering
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Berberian
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Suiama
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: M T
authors.initials: MT
authors.lastname: Lima-Landman
authors.affiliation: Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Breen
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.|Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Abílio
authors.affiliation: Integrated Laboratory of Clinical Neurosciences and Schizophrenia Program, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.|Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: M A F
authors.initials: MA
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D003072:Cognition Disorders / Q000097:blood* / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000150:complications*; D055815:Young Adult
chemical_list: D007703:Peptidyl-Dipeptidase A