4.6 Article

Allostatic Load Effects on Cortical and Cognitive Deficits in Essentially Normotensive, Normoweight Patients with Schizophrenia

期刊

SCHIZOPHRENIA BULLETIN
卷 47, 期 4, 页码 1048-1057

出版社

OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbaa196

关键词

Schizophrenia; chronic stress; allostatic load; cortical thickness; cognitive function

资金

  1. National Natural Science Foundation of China [81761128021, 81771452]
  2. National Institute of Health [R01MH112180, R01MH116948]
  3. Estonian Research Council-European Union Regional Developmental Fund Mobilitas Pluss Program [MOBTT77]
  4. Peking University Health Science Center Excellent Doctoral Innovation Fund [71006Y2464]

向作者/读者索取更多资源

Reduced cortical gray matter integrity and cognitive abilities are core deficits in schizophrenia. Higher allostatic load (AL), even in patients with normal weight, blood pressure, and cholesterol levels, is associated with structural and cognitive deficits in schizophrenia. Specific aspects of high AL should be targeted in early intervention strategies for reducing cortical thinning and cognitive dysfunction in schizophrenia.
Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinAlc, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels.

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