Baseline global brain structural and functional alterations at the time of symptom onset can predict subsequent cognitive deterioration in drug-naïve first-episode schizophrenia patients: Evidence from a follow-up study

Abstract

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Keywords: cognition; correlation; schizophrenia; ΔgFCD; ΔgGMV.

FIGURE 1

The correlation between ΔGMV/ΔgFCD and the cognitive deterioration in the mild whole-brain alteration group. Correlation analysis was performed to determine the relationship between subsequent cognitive decline after two years of treatment and baseline ΔgGMV/ΔgFCD in the drug-naïve first-episode schizophrenia with 0.5 ≤ ΔgGMV < 1% at baseline in the mild whole-brain alteration group. (A) Relationship between ΔgGMV and ΔGDS; (B) Relationship between ΔgFCD and ΔGDS; (C) The mild whole-brain alteration group with 0.5 ≤ ΔgGMV < 1% at baseline; (D) ΔgFCD in the mild whole-brain alteration group.

FIGURE 2

The correlation between ΔGMV/ΔgFCD and cognitive deterioration in the moderate whole-brain alteration group. Correlation analysis was carried out to evaluate the relationship between subsequent cognitive decline after two years of antipsychotic treatment and baseline ΔgGMV/ΔgFCD in the drug-naïve first-episode schizophrenia with 1 ≥ ΔwGMV < 2% at baseline in the moderate whole-brain alteration group. (A) Relationship between ΔgGMV and ΔGDS; (B) Relationship between ΔgFCD and ΔGDS; (C) The moderate whole-brain alteration group with 1 ≥ ΔwGMV < 2% at baseline; (D) ΔgFCD in the moderate whole-brain alteration group.

FIGURE 3

The correlation between baseline ΔgGMV/ΔgFCD and cognitive deterioration in the severe whole-brain alteration group. Based on ΔgGMV at baseline, schizophrenia patients were divided into three different severity groups: mild, moderate, and severe brain alteration groups. Correlation analysis was conducted to examine the relationship between subsequent cognitive deterioration after two years of treatment and baselineΔgGMV/ΔgFCD in the drug-naïve first-episode schizophrenia with baseline ΔgGMV ≥ 2% in the severe whole-brain alteration group. (A) Relationship between ΔgGMV and ΔGDS; (B) Relationship between ΔgFCD and ΔGDS; (C) The severe whole-brain alteration group with ΔgGMV ≥ 2% at baseline; (D) ΔgFCD in the severe whole-brain alteration group.