| ObjectivePsychotic symptoms and cognitive impairments are core clinical features of schizophrenia.In addition to central nervous system abnormalities,schizophrenia patients often suffer from somatic diseases.Allostatic load(AL)is a chronic stress model which reflects the wear and tear of the brain and physiological systems caused by continuous stress stimulation or maladaptation of stress responses,and it has a certain scientific significance for understanding the pathophysiological mechanism of schizophrenia and susceptibility to somatic diseases.AL may help to predict adverse outcomes early and guide clinical intervention.We aimed to explore the pathogenesis of schizophrenia and the physiological abnormalities that are prone to comorbid somatic diseases from a multi-system perspective.The AL index was calculated to reflect the AL level of the subject,and the group difference of AL index between first-episode schizophrenic(FES)patients and healthy controls was explored.Combining brain structures as phenotypic characteristics,we explored relationships between AL index,subcortical structures,and psychopathological symptoms(Study 1).We further expanded the sample size to explore correlations of AL index,cognitive function,and cerebral cortical thickness in patients with schizophrenia(Study 2).MethodsThe cross-sectional observational study was conducted in this study.1.Seventy-nine FES patients who met the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems(ICD-10)diagnostic criteria for schizophrenia within 2-week antipsychotics initial stabilization and 41 age-and sexmatched healthy controls were enrolled in the study.Thirteen biological parameters reflecting the function status of the cardiovascular system,metabolic,immune and neuroendocrine systems were collected to calculate the AL index.Subcortical regional structures were measured by structural magnetic resonance imaging(sMRI).Group differences of the AL index and subcortical structure volumes as well as their relationships were explored.The Positive and Negative Symptom Scale(PANSS)was used to assess the psychopathological symptoms of FES patients,and its correlation with AL index was analyzed.2.One hundred and sixty-seven patients who met the ICD-10 diagnostic criteria for schizophrenia and 72 age-and sex-matched healthy controls were included.Biological parameters were collected to calculate the AL index and the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS)Consensus Cognitive Battery(MCCB)in Chinese version was used to assess cognitive function of all subjects.Cerebral cortical thickness was measured by sMRI.Group differences of the AL index,cognitive function,and cerebral cortical thickness as well as their correlation analyses were explored.The mediating effect models were used to explore relationships of AL index,cognitive function and cerebral cortical thickness in the schizophrenia group.Results1.FES patients had significantly higher AL index than healthy controls(F=11.87,P=0.001).Compared with controls,FES patients had larger lateral ventricle(P<0.001),lateral ventricular choroid plexus(P<0.001),and thalamus volumes(P<0.001),whereas amygdala volume(P=0.001)was significantly smaller.Multiple stepwise linear regression analyses showed AL index has a positive predictive effect on choroid plexus volume(?=0.29,t=3.60,P<0.001),while it has no significant effect on the volume of other brain regions(Ps>0.05).The AL index of the FES group was positively correlated with the volume of choroid plexus(r=0.34,P=0.010),but not in the control group(r=0.27,P=0.112).The AL index was also significantly correlated with PANSS positive symptom scale score(r=0.24,P=0.043),general psychopathology scale score(r=0.27,P=0.021)and negative symptom scale score(r=-0.28,P=0.018).2.Compared with healthy controls,the AL index of schizophrenia patients whose body-mass index(BMI),blood pressure and total cholesterol at normal or lower levels was still elevated(F=48.03,P<0.001),mainly due to their lower high-density lipoprotein cholesterol(P=0.001)while had higher heart rate(P<0.001),waist-hip ratio(P<0.001),hemoglobinAlc(P=0.002),hypersensitive C-reactive protein(P<0.001),and 12h overnight urine cortisol levels(P<0.001)than controls.Schizophrenia patients had lower MCCB total score as well as the 7 cognitive domain scores than controls(Ps<0.001).The average thickness of cerebral cortex in schizophrenia patients was thinner than controls(F=26.90,P<0.001).The AL index was inversely correlated with the average thickness of cerebral cortex(r=-0.31,P<0.001)and MCCB total score(r=-0.20,P=0.017)in schizophrenia patients,while none of these relationships existed in controls(Ps>0.05).Mediation analyses of schizophrenia group showed that cerebral cortical thickness played a significant mediating role in the impact of AL on cognitive function,and the most significant mediating cortical area was the left superior frontal gyrus.Conclusions1.These results suggest the AL of FES patients is higher than that of healthy controls,which indicate that schizophrenia patients have higher level of chronic stress than controls.The elevated AL in FES patients is associated with the increase of choroid plexus volume,suggesting that the abnormalities of the central nervous system and peripheral physiological system in schizophrenia may interact through the choroid plexus in the early stage of the disease,and the higher AL is related to the disease severity.2.The AL index of schizophrenia patients with lower blood pressure and cholesterol levels and normal BMI is still significantly higher than that of healthy controls.The elevated AL in patients with schizophrenia is associated with the decreased average cortical thickness as well as cognitive impairments.The cerebral cortical thickness plays a significant mediating role in the relationship between chronic stress and cognitive function in schizophrenia,and the brain area with the most significant mediating effect is the left superior frontal gyrus. |
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