Cortical thickness, schizophrenia


Schizophrenia is a chronic and potentially disabling disorder with widespread neuroanatomical abnormalities thought to be caused by progressive brain changes (Andreasen, 2010), and an equally wide variety of impairments in cognitive functioning (Palmer et al., 2009). In general, individuals with schizophrenia demonstrate significantly impaired performance on a full range of neuropsychological tasks, often reaching greater than one standard deviation below the norm (Dickinson et al., 2007). One particularly puzzling issue is that approximately 15–30% of schizophrenia patients have been found to perform in the normal range of neuropsychological functioning (Kremen et al., 2000; Palmer et al., 1997). Given hypothesized relationships between brain structure and cognitive function in both health and disease, the question arises whether schizophrenia subjects with neuropsychological performance in the normal range also demonstrate “normal” brain structure commensurate with their cognitive abilities. Brain abnormalities are a hallmark of schizophrenia, with widespread cortical thinning across various regions (Kuperberg et al., 2003; Schultz et al., 2010). Relatively few studies have examined the brain structure of cognitive subgroups, including neuropsychologically normal subjects, and to date, no detailed examination of cortical thinning patterns have been performed to compare these subgroups. In an early computerized tomography (CT) study, Allen and colleagues (2000) found no difference in ventricular size between schizophrenia subgroups clustered by cognitive performance, but greater global sulcal widening was evident in the severely impaired group. Recently, Wexler and coworkers (2009) assessed magnetic resonance imaging (MRI)-based measures in “neuropsychologically near-normal” (NPNN) and “neuropsychologically impaired” (NPI) schizophrenia subjects, and reported smaller cortical gray matter and larger third ventricular volumes for NPI and NPNN groups relative to healthy subjects. Furthermore, NPI subjects demonstrated additional reductions in white matter volumes and enlargements in lateral ventricle volumes as compared to the NPNN subgroup. Interestingly, NPNN subjects exhibited significantly smaller orbitofrontal volumes in relation to the other groups. In this study, we sought to identify neuropsychologically near-normal (i.e., NPNN) schizophrenia subjects from a large sample of participants through use of a series of unsupervised clustering techniques. It was hypothesized that a stable classification of subjects would emerge, with one or more clusters containing subjects with few neuropsychological deficits (NPNN), while subjects with typical schizophrenia profiles of broad neuropsychological impairment (i.e., NPI) being contained in other clusters. We then tested the hypothesis that NPI subjects would demonstrate widespread cortical thinning in regions similar to those found in previous studies, while NPNN subjects would exhibit a more limited pattern, with perhaps small regions of thinning corresponding to a milder form of the disease. Finally, we examined whether selfreported duration of illness was associated with group membership, the severity of cognitive deficits, or the degree of cortical thinning. We hypothesized that the absence of such associations would suggest that the presence or absence of widespread neuropsychological impairments in schizophrenia is a stable trait of the disorder, and therefore potentially valuable in defining and understanding disease heterogeneity

Original Publication Citation

Schizophr Res. 2011 December ; 133(1-3): 68–76. doi:10.1016/j.schres.2011.08.017.

Document Type

Peer-Reviewed Article

Publication Date



National Institutes of Health




Family, Home, and Social Sciences



University Standing at Time of Publication

Assistant Professor

Included in

Psychology Commons