title: Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.
abstract: Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida , Tampa, FL, USA.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Molina
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Hospital Neuropsiquiátrico Dr Néstor Sequeiros, San Salvador de Jujuy, Argentina.
authors.forename: María
authors.initials: M
authors.lastname: Calvó
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Hospital Neuropsiquiátrico Dr Néstor Sequeiros, San Salvador de Jujuy, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Padilla
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida , Tampa, FL, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Balda
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA , Buenos Aires, Argentina.
authors.forename: Gabriela González
authors.initials: GG
authors.lastname: Alemán
authors.affiliation: Unidad de Neurociencias, Dr J.J. Naón, Facultad de Medicina, Universidad de Buenos Aires , Buenos Aires, Argentina.
authors.forename: Néstor V
authors.initials: NV
authors.lastname: Florenzano
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Hospital Neuropsiquiátrico Dr Néstor Sequeiros, San Salvador de Jujuy, Argentina.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Guerrero
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida , Tampa, FL, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kamis
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Hospital Neuropsiquiátrico Dr Néstor Sequeiros, San Salvador de Jujuy, Argentina.
authors.forename: Beatriz Molina
authors.initials: BM
authors.lastname: Rangeon
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Hospital Neuropsiquiátrico Dr Néstor Sequeiros, San Salvador de Jujuy, Argentina.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Bourdieu
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA , Buenos Aires, Argentina.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Strejilevich
authors.affiliation: Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías, FULTRA, Buenos Aires, Argentina; Unidad de Neurociencias, Dr J.J. Naón, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Horacio A
authors.initials: HA
authors.lastname: Conesa
authors.affiliation: Rutgers University-Robert Wood Johnson Medical School , New Brunswick, NJ, USA.
authors.forename: Javier I
authors.initials: JI
authors.lastname: Escobar
authors.affiliation: Departments of Psychiatry and Genetics, Washington University School of Medicine , St Louis, MO, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Zwir
authors.affiliation: Departments of Psychiatry and Genetics, Washington University School of Medicine , St Louis, MO, USA.
authors.forename: C Robert
authors.initials: CR
authors.lastname: Cloninger
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Division of Neurosciences and Department of Psychiatry and Neurology, UTRGV School of Medicine, Harlingen, TX, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: de Erausquin