Metabolic disturbances, hemoglobin A1c, and social cognition impairment in Schizophrenia spectrum disorders

Abstract

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HbA1c) > 6.5%. Tasks assessed emotion processing, theory of mind, and social perception. Functional connectivity within and between social cognitive networks was measured during a naturalistic social task. Among SSD, a significant inverse relationship was found between social cognition and cumulative metabolic burden (β = −0.38, p < 0.001) and HbA1c (β = −0.37, p < 0.001). The relationship between social cognition and HbA1c was robust across domains and measures of social cognition and after accounting for age, sex, race, non-social neurocognition, hospitalization, and treatment with different antipsychotic medications. Negative connectivity between affect sharing and motor resonance networks was a partial mediator of this relationship across SSD and HC groups (β = −0.05, p = 0.008). There was a group x HbA1c effect indicating that SSD participants were more adversely affected by increasing HbA1c. Thus, we provide the first report of a robust relationship in SSD between social cognition and abnormal glucose metabolism. If replicated and found to be causal, insulin sensitivity and blood glucose may present as promising targets for improving social cognition, functional outcomes, and quality of life in SSD.

Relationship between theory of mind and metabolic parameters and functioning in patients with bipolar I disorder

“…Recently, Tang et al investigated the link between social cognition impairment and metabolic disturbances in patients with schizophrenia spectrum disorders and they reported a robust relationship between abnormal glucose metabolism and social cognition. Moreover, the correlation with social cognition and glucose abnormality was stronger than for non-social cognition 42 . Similarly, our results are important to support the idea of there is a relationship between metabolic dysregulation and impaired social cognition in patients with BD.…”

“…First, BD is linked with increased inflammation and may cause metabolic abnormalities and decreased social cognition performance. Second, metabolic dysfunction causes large vessel and microvascular changes that damage cerebral circulation and brain structure 42 . However, social cognition requires more complex integration of multiple cognitive systems than nonsocial cognition, making it more susceptible to disruptions in connectivity 43 .…”

Neuronal alterations in AKT isotype expression in schizophrenia

“…It is widely accepted that metabolic dysfunction plays a key role in the etiopathogenesis of schizophrenia [13,21,55,59]. Alterations in glucose utilization, secondary to perturbed insulin signaling pathways, likely contributes to the cognitive deficits seen in schizophrenia [12,60,61]. AKT activity is dependent on activation of upstream growth factor (such as insulin) receptor occupancy and activation [21,62,63].…”

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders

“…There was no association between HbA1c and cognitive impairment. Previous studies have suggested a correlation between HbA1c level and poor cognition in recent onset psychosis patients [ 58 , 59 ]. Most of the previous results were found in patients with diabetes or in elderly population [ 60 , 61 ], and with differences in race among the included subjects.…”