Patterns of Impaired Neurocognitive Performance on the Global Neuropsychological Assessment, and Their Brain Structural Correlates in Recent-onset and Chronic Schizophrenia

Abstract

Objective: Schizophrenia is associated with impairment in multiple cognitive domains. There is a paucity of research on the effect of prolonged illness duration (≥ 15 years) on cognitive performance along multiple domains. In this pilot study, we used the Global Neuropsychological Assessment (GNA), a brief cognitive battery, to explore the patterns of cognitive impairment in recent-onset (≤ 2 years) compared to chronic schizophrenia (≥ 15 years), and correlate cognitive performance with brain morphometry in patients and healthy adults.

Methods: We assessed cognitive performance in patients with recent-onset (n = 17, illness duration ≤ 2 years) and chronic schizophrenia (n = 14, duration ≥ 15 years), and healthy adults (n = 16) using the GNA and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted magnetic resonance imaging images.

Results: We observed cognitive deficits affecting multiple domains in the schizophrenia samples. Selectively greater impairment of perceptual comparison speed was found in adults with chronic schizophrenia (p = 0.009, η²_partial = 0.25). In the full sample (n = 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes (TFCE, FWE p < 0.01).

Conclusion: Along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Anterior-medial temporal gray matter volumes especially of the left hemisphere might underlie the impairment noted in this domain in schizophrenia.

Keywords: Cognitive aging; Cognitive dysfunction; Magnetic resonance imaging; Neuropsychological tests; Schizophrenia; Temporal lobe.

Fig. 1

Violin plots depicting the do-main-wise cognitive z-score distri-bution in the three groups. As the violin plots are based on kernel density estimates, they extend be-yond the range of actual scores in the sample depicted by the jittered dots. The solid horizontal lines within the boxplots represent the median z-score. Group 1: Healthy control subjects (HCS); Group 2: Recent-onset schizophrenia (ROSZ); Group 3: Chronic schizophrenia (CHSZ).

Fig. 2

Mean z-scores with standard error bars across cognitive domains in HCS, ROSZ and CHSZ (upper panel), and their effect sizes (Hedge’s g) of difference from HCS in ROSZ and CHSZ (lower panel). The domains are arranged in the ascending order of the magnitudes of difference between ROSZ and CHSZ groups. The dashed line in the lower panel is the effect size plotted for both the patient groups combined. See Supplementary Tables 3 and 4 (available online) for all effect size estimates with their 95% confidence intervals.

Fig. 3

Voxel-wise correlational an-alysis results showing gray matter clusters with statistically significant positive correlation (TFCE, FWE p < 0.0083) with perceptual comparison (PC) speed scores, adjusted for total intracranial volume (TIV) and age (n = 47). Coronal (A) and sagittal (B) slices are displayed in neurological convention (left side corresponds to the left hemisphere) and show sig-nificant clusters in bilateral anterior and medial temporal lobe regions, predominantly in the left hemisphere. The slices were chosen based on the MNI coordinates of the peak voxel in each cluster. The gradient of the colormap is based on negative loga-rithm of pvalues with a minimum threshold at 2.0792 (p = 0.0083).

Fig. 4

Voxel-wise correlational analysis results showing gray matter clusters with statistically significant positive correlation (TFCE, FWE p < 0.01) with verbal working memory (VWM) scores, adjusted for total intracranial volume (TIV) and age (n = 47). The coronal (panel A) and sagittal (panel B) slices displayed in the neurological convention (left hand side corresponding to the left hemisphere) show significant clusters covering adjacent regions in the precentral gyrus on the right hemisphere (upper row in A and lower row in B), and the inferior frontal gyrus, the anterior lateral temporal lobe, and the precentral gyrus on the left hemisphere (lower row in A and upper row in B). The slices were chosen based on the MNI coordinates of the peak voxel in each cluster. The gradient of the colormap is based on negative logarithm of pvalues with a minimum threshold at 2.0792 (p = 0.0083).