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

ABSTRACT: 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, hemoglobinA1c, 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.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC8266595 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Efforts to remediate the multiple cognitive function impairments in schizophrenia should consider white matter as one of the underlying neural mechanisms. Objective:To determine whether altered structural brain connectivity is responsible for 2 of the core cognitive deficits in schizophrenia- reduced information processing speed and impaired working memory. Design, Setting, and Participants:This cross-sectional study design took place in outpatient clinics from August 1, 2004, to August 31, 2015. Participants included 166 patients with schizophrenia and 213 healthy control individuals. These participants were from 3 independent cohorts, each of which had its own healthy control group. No participant had current or past neurological conditions or major medical conditions. Patients were diagnosed with either schizophrenia or schizoaffective disorder as defined by the DSM-IV. Controls had no Axis I psychiatric disorder. Main Outcomes and Measures:Mediation analyses and structural equation modeling were used to analyze the associations among processing speed, working memory, and white matter microstructures. Whole-brain and regional diffusion tensor imaging fractional anisotropy were used to measure white matter microstructures. Results:Of the study participants, the 166 patients with schizophrenia had a mean (SD) age of 38.2 (13.3) years and the 213 healthy controls had a mean (SD) age of 39.2 (14.0) years. There were significantly more male patients than controls in each of the 3 cohorts (117 [70%] vs 91 [43%]), but there were no significant differences in sex composition among the 3 cohorts. Patients had significantly reduced processing speed (Cohen d?=?1.24; P?=?6.91?×?10-30) and working memory deficits (Cohen d?=?0.83; P?=?1.10?×?10-14) as well as a significant whole-brain fractional anisotropy deficit (Cohen d?=?0.63; P?=?2.20?×?10-9). In schizophrenia, working memory deficit was mostly accounted for by processing speed deficit, but this deficit remained when accounting for working memory (Cohen d?=?0.89; P?=?2.21?×?10-17). Mediation analyses showed a significant association pathway from fractional anisotropy to processing speed to working memory (P?=?5.01?×?10-7). The strength of this brain-to-cognition pathway in different white matter tracts was strongly associated with the severity of schizophrenia-associated fractional anisotropy deficits in the corresponding white matter tracts as determined by a meta-analysis (r?=?0.85-0.94; all P?<?.001). The same pattern was observed in patients and controls either jointly or independently. Conclusions and Relevance:Study findings suggest that (1) processing speed contributes to the association between white matter microstructure and working memory in schizophrenia and (2) white matter impairment in schizophrenia is regional tract-specific, particularly in tracts normally supporting processing speed performance.

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

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