Reduced thalamic volume in first-episode non-affective psychosis: Correlations with clinical variables, symptomatology and cognitive functioning Benedicto Crespo-Facorro, a, ⁎ Roberto Roiz-Santiáñez, a José María Pelayo-Terán, a José Manuel Rodríguez-Sánchez, a Rocío Pérez-Iglesias, a César González-Blanch, a Diana Tordesillas-Gutiérrez, a Andrés González-Mandly, b Consuelo Díez, b Vincent A. Magnotta, c Nancy C. Andreasen, c and José Luis Vázquez-Barquero a a University Hospital Marqués de Valdecilla, Department of Psychiatry, Planta 2 a , Edificio 2 de Noviembre. Avda, Valdecilla s/n, 39008, Santander, Spain b University Hospital Marqués de Valdecilla, Department of Neuroradiology, Santander, Spain c Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA Received 2 November 2006; revised 5 January 2007; accepted 12 January 2007 Available online 13 February 2007 Structural studies have inconsistently shown the presence of thalamic volume differences in patients with schizophrenia. However, only a few studies have examined the relation between thalamic structure and clinical and cognitive variables in early phases of the illness. Thalamic volumes in right-handed minimally treated first episode patients with non-affective psychosis (N = 61) relative to those of right-handed healthy comparison subjects (N = 40) were measured. Thalamic volumes in the right and left hemispheres and total thalamic volume were automatically segmented and analyzed using BRAINS2. Analysis of covariance was used to control for intracranial volume. Clinical symptoms were assessed by total scores of BPRS, SAPS and SANS. The relationship between three cognitive dimensions (verbal learning and memory, speed processing/executive functioning and sustained attention/vigilance), and thalamic volume was evaluated. The impact of the duration of untreated illness, untreated psychosis and prodrome period in thalamic morphometry was also explored. Right, left, and total thalamic volumes of the patients with non-affective psychosis were significantly smaller than those of the healthy subjects. Larger thalamic volumes were associated with an earlier age of onset, a poorer cognitive functioning and a more severe negative symptomatology. Thalamic volumetric differences between patients with non-affective psychosis and healthy controls are already present at early phases of the illness. However, further investigations are warranted to fully clarify the relationship between those structural anomalies and clinical and cognitive outcomes. © 2007 Elsevier Inc. All rights reserved. Introduction The thalamus serves as a central relay station of the brain by filtering and gating sensory inputs to the cerebral cortex (Jones, 1985). Thalamic abnormalities have been implicated in neural models of schizophrenia (Andreasen, 1997). Postmortem (Baumer, 1954) functional (Crespo-Facorro et al., 1999), chemical (Talvik et al., 2003) and structural imaging studies (Andreasen et al., 1994) have revealed abnormalities in the thalamus, suggesting a disruption of distributed thalamocortical network in schizophrenia (Sim et al., 2006). However, structural MRI studies of the thalamus have drawn to inconsistent results. In chronic patients, a thalamic volume reduction was found in some (Flaum et al., 1995; Staal et al., 1998) but not in all investigations (Andreasen et al., 1994; Buchsbaum et al., 1996; Portas et al., 1998a). Studies of the early stages of schizophrenia have demonstrated that a thalamic volume reduction might be already present early in the course of the illness (Gilbert et al., 2001; Ettinger et al., 2001; Lawrie et al., 2001; Salgado-Pineda et al., 2003; Jayakumar et al., 2005; Lang et al., 2006). Recently, Preuss et al. (2005) have failed to find significant differences in thalamic gray matter volume in male first-episode schizophrenic subjects when compared to chronic patients and healthy volunteers. Factors such as age of onset and medications have been reported to have an effect on thalamic volume in schizophrenia (Corey-Bloom et al., 1995; Gur et al., 1998). Thus, the presence of confounding factors such as medications, age of onset, duration of untreated psychosis (DUP), and the small number of subjects included in the studies may account for these inconsistencies among investigations. It is of note that Konick and Friedman (2001), in a meta-analysis study, have described a small-to-moderate significant effect size for thalamic size reduction in schizophrenia, therefore large samples might be necessary to uncover them. www.elsevier.com/locate/ynimg NeuroImage 35 (2007) 1613 – 1623 ⁎ Corresponding author. Fax: +34 942 203447. E-mail address: bcfacorro@humv.es (B. Crespo-Facorro). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.01.048