Cognitive clustering in schizophrenia patients, their first-degree relatives and healthy subjects is associated with anterior cingulate cortex volume

Abstract

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ.

Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

“…On the other hand, the ACC plays a role in mediating awareness and attention [ 43 , 44 ]. The ACC is thought to be a core region affected by schizophrenia [ 44 ] and dysfunction of the ACC may induce severity of symptoms or global impairment of cognitive function [ 45 , 46 , 47 ]. For example, a smaller volume of the ACC is significantly correlated with more severe positive symptoms of schizophrenia [ 45 ] and related to global cognitive impairment measured by the Brief Assessment of Cognition in Schizophrenia [ 47 ].…”

“…The ACC is thought to be a core region affected by schizophrenia [ 44 ] and dysfunction of the ACC may induce severity of symptoms or global impairment of cognitive function [ 45 , 46 , 47 ]. For example, a smaller volume of the ACC is significantly correlated with more severe positive symptoms of schizophrenia [ 45 ] and related to global cognitive impairment measured by the Brief Assessment of Cognition in Schizophrenia [ 47 ]. Notably, previous studies noted that patients with TRS had elevated levels of glutamatergic neurometabolites in the ACC [ 9 , 10 , 11 ].…”

Differential benefits of olanzapine on executive function in schizophrenia patients: Preliminary findings

“…Though previous work has divided schizophrenia patients into at least three cognitive subgroups (Hall et al, ; Lewandowski, Sperry, Cohen, & Ongur, ; Ohi et al, ), based on performance on the antisaccade task, we selected a median split of schizophrenia patients into High‐Deficit and Low‐Deficit subgroups due to the small sample size. It is possible that some other method of generating meaningful subgroups in a larger sample may be informative.…”

Implications of data-driven analyses for personalized therapy in psychosis: a systematic review of cluster- and trajectory-based modelling studies

“…Of these, 17 studies were longitudinal that involved 11,475 patients, 1,059 siblings and 2,194 controls/general population, whereas 33 studies were cross-sectional that involved 5,598 patients, 7,423 siblings, and 2,482 controls. Only one longitudinal study 64 and three cross-sectional studies [65][66][67] A minimum of two and maximum of five schizophrenia symptoms subtypes were discovered.…”

“…101,102 In addition, poor cognitive impairment cluster(s) were predicted by age, gender, non-Caucasian ethnicity, low socioeconomic and educational status, poor premorbid adjustment, low premorbid and current IQ, early age of illness onset, long duration of illness, severe positive and negative symptoms, poor social cognition, high antipsychotics dosage, use of second generation antipsychotics, and poor functioning and poor quality of life. 32,37,65,66,[79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] Siblings subgroups with impaired neurocognitive function were predicted by young age, low educational status, low IQ, poor premorbid adjustment, and severe positive schizotypy (Figure 4). 66 Figure 4: Schizophrenia spectrum circle illustrating predictors of symptomatic clusters.…”