Contents lists available at ScienceDirect Psychiatry Research: Neuroimaging journal homepage: www.elsevier.com/locate/psychresns Subcortical surface shape in youth at familial high risk for schizophrenia Kathryn Hill a,1 , Nicolas Bolo a,b,1, ⁎ , Suraj Sarvode Mothi a,c , Paulo Lizano a,b , Synthia Guimond a,b , Neeraj Tandon a,d , Elena Molokotos a , Matcheri Keshavan a,b a Department of Psychiatry, Beth Israel Deaconess Medical Center, 75 Fenwood Rd, Boston, MA 02115, USA b Department of Psychiatry, Harvard Medical School, 75 Fenwood Rd, Boston, MA 02115, USA c Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA d Baylor College of Medicine, Houston, TX, USA ABSTRACT Abnormalities in the subcortical brain regions that support cognitive functions have been reported in schizo- phrenia. Relatives of those with schizophrenia often present with psychosis-like traits (schizotypy) and similar cognition as those with schizophrenia. To evaluate the relationships between subcortical structure, schizotypy, and cognitive function, we assessed shape and volume of the hippocampus, amygdala and thalamus in untreated youth at familial high risk for schizophrenia (HRSZ). The sample consisted of 66 HRSZ and 69 age-matched healthy controls (HC). Subjects’ cognitive functions and schizotypy were assessed, and T1-weighted brain MRI were analyzed using the FSL software FIRST. The right hippocampus and right amygdala showed significantly increased concavity (inward displacement) in HRSZ compared to HC. While regional subcortical shape dis- placements were significantly correlated with sustained attention and executive function scores in HC, fewer correlations were seen in HRSZ. This suggests a possible alteration of the local structure-function relationship in subcortical brain regions of HRSZ for these cognitive domains, which could be related to anomalous plasticity. 1. Introduction Schizophrenia is an incapacitating disorder: the effects of cognitive deficits (e.g. impaired attention, memory), positive symptoms (e.g. delusions, hallucinations), and negative symptoms (e.g. social with- drawal) (Keshavan et al., 2011) may lead to severe functional disability. First-degree relatives of individuals with schizophrenia, including off- spring, dizygotic twins and full siblings, are at familial high risk for developing schizophrenia (HRSZ) and have about a 10% chance of developing the disorder (Gottesman, 1991). Schizotypy refers to traits, such as magical ideation and perceptual aberration, which may reflect psychosis proneness and may be present in HRSZ. We (Tandon et al., 2012a) and others (Kwapil et al., 2008) have shown that schizotypal features may be a good predictor of transition to psychosis. High schizotypy potentially identifies clinical high risk within the HRSZ group, as suggested by an association between schizotypy and working memory deficits and higher perseverative errors (Diwadkar et al., 2006). Additionally, it has been shown that HRSZ are impaired in cognitive functions such as sustained attention, executive functioning and verbal memory (Diwadkar et al., 2011; Keshavan et al., 2010; Seidman et al., 2006; Sitskoorn et al., 2004; Snitz et al., 2006). It is of importance to investigate the neurobiology of HRSZ, because detailed knowledge of neural abnormalities can help guide more effi- cient preventative care (Correll et al., 2010; Tandon et al., 2012b). Studying HRSZ during youth is opportune for analyzing aspects of premorbidity given that the peak age of schizophrenia conversion is in late adolescence and early adulthood. In the brain of youth, regional synaptic underdevelopment or excessive pruning due to genetic, epi- genetic or environmental factors, or pathophysiological factors such as inflammation, may result in regional structural deficits. Brain structures are not uniform, and specific structural alterations in individual sub- regions within the hippocampus, amygdala and thalamus may lead to deficits in brain networks that support specific cognitive function. Several groups have investigated structural anomalies in subcortical regions known to support cognition (Buchmann et al., 2014; Mathew et al., 2014; Rahm et al., 2015). http://dx.doi.org/10.1016/j.pscychresns.2017.07.002 Received 21 February 2017; Received in revised form 29 May 2017; Accepted 14 July 2017 ⁎ Correspondence to: Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, 75 Fenwood Rd, Boston, MA 02115, USA. 1 KH and NB are co-first authors. E-mail address: nbolo@bidmc.harvard.edu (N. Bolo). Abbreviations: HRSZ, familial high risk for schizophrenia; HC, healthy controls; FIRST, FMRIB's Integrated Registration and Segmentation Tool; CHR, clinical high risk for schizophrenia; SCID, Structured Clinical Interview for DSM-IV Disorders; SD, standard deviation; CPT, Continuous Performance Test; CPT-IP, Continuous Performance Test – identical pairs version; WCST, Wisconsin Card Sort Task; CVLT, California Verbal Learning Test; SPGR, spoiled gradient recall acquisition; MNI, Montreal Neurological Institute; ICV, intracranial volume; CA, Cornu Ammonis; DS-CPT, Degraded Stimulus CPT Psychiatry Research: Neuroimaging 267 (2017) 36–44 Available online 14 July 2017 0925-4927/ © 2017 Elsevier B.V. All rights reserved. MARK