title: Grey matter volume patterns in thalamic nuclei are associated with familial risk for schizophrenia.
abstract: Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder. We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients. Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder.
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Pergola
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Silvestro
authors.initials: S
authors.lastname: Trizio
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Di Carlo
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Taurisano
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Mancini
authors.affiliation: National Institute of Nuclear of Physics-Branch of Bari, Via E. Orabona 4, 70125 Bari, Italy; Interuniversity Department of Physics 'M. Merlin', University of Bari 'Aldo Moro', Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Amoroso
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Nettis
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Andriola
authors.affiliation: Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Caforio
authors.affiliation: IRCCS "Casa Sollievo della Sofferenza", Viale Cappuccini, 1, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Popolizio
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy; Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampino
authors.affiliation: IRCCS "Casa Sollievo della Sofferenza", Viale Cappuccini, 1, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Giorgio
authors.affiliation: Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy; Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
authors.affiliation: Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124, Bari, Italy; IRCCS "Casa Sollievo della Sofferenza", Viale Cappuccini, 1, I-71013 San Giovanni Rotondo, Italy. Electronic address: blasi.seppe@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009929:Organ Size; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics*; D035781:Siblings; D000069553:Supervised Machine Learning; D013787:Thalamic Nuclei / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Familial risk for schizophrenia; Grey matter; Multivariate pattern analysis; Thalamus; VBM