Association Between the Duration of Untreated Psychosis and Selective Cognitive Performance in Community-Dwelling Individuals With Chronic Untreated Schizophrenia in Rural China

Abstract

IMPORTANCE Cognitive deficits constitute core features of schizophrenia, but the trajectories of cognitive difficulties in chronic untreated schizophrenia remain unclear. OBJECTIVE To assess the association of neuropsychological deficits with duration of untreated psychosis in individuals with chronic untreated schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Community-dwelling individuals with chronic untreated schizophrenia (untreated patient group) and individuals without mental illness (control group) were recruited from predominantly rural communities in Ningxia, China between June 20, 2016, and August 6, 2019, and administered the Structured Clinical Interview for DSM-IV, the Mini-Mental State Examination, an 8-test version of the MATRICS Consensus Cognition Battery adapted for use in individuals with low levels of education, and a measure of social cognition. MAIN OUTCOMES AND MEASURES Comparison of cognitive test scores between the two groups and association of cognitive test scores with duration of untreated schizophrenia. RESULTS The patient group included 197 individuals with chronic untreated schizophrenia (101 men [51.3%]; mean [SD] age, 52.1 [11.8] years; median [interquartile range] years of schooling, 3 [0-6] years; median [interquartile range] years of untreated psychosis, 22.9 [14.9-32.8] years). The control group included 220 individuals (118 men [53.6%]; mean [SD] age, 52.1 [11.2] years; median [interquartile range] years of schooling, 4 [0-6] years). The untreated patient group performed significantly worse than the control group on all cognitive measures (adjusted partial Spearman correlation coefficient [Spearman ρ] ranged from −0.35 for the revised Chinese version of the Reading the Mind in the Eyes Test to −0.60 for the Brief Visuospatial Memory Test-Revised; P < .001 for all comparisons). Longer durations of untreated psychosis were associated with lower performance in 3 MATRICS Consensus Cognition Battery measures assessing different aspects of executive functioning (Brief Visuospatial Memory Test-Revised [ρ = −0.20; P = .04]; Brief Assessment of Cognition in Schizophrenia, Symbol Coding subtest [ρ = −0.35; P < .001]; and Neuropsychological Assessment Battery, Mazes subtest [ρ = −0.24; P = .01]). The median duration of untreated psychosis (22.9 years) was associated with estimated score reductions in the 3 measures of 34% (95% CI, 10%-52%), 43% (95% CI, 28%-55%), and 57% (95% CI, 31%-73%), respectively. CONCLUSIONS AND RELEVANCEThe findings of this study suggest that long-term untreated schizophrenia was associated with decreases in selective cognitive abilities; both neurodegenerative pathology and neurodevelopmental dysfunction may be factors in cognition in persistent psychosis. Expanding research to include cohorts of patients from underserved rural communities in low-and middle-income countries may provide new insights about the etiological factors, disease course, and management of schizophrenia.

Prevalence, profile and associations of cognitive impairment in Ugandan first-episode psychosis patients

“…Further, no statistically significant differences were evident between the mean scores of FEP patients and healthy controls in this domain. This finding is consistent with work from other LMICs suggesting poor psychometric properties of the MSCEIT in such settings ( Kurtz et al, 2018 ; Mehta et al, 2011 ; Emsley et al, 2005 ; Lim et al, 2020 ; Stone et al, 2020 ).…”

“…There is also an association between childhood trauma with impairment in the verbal learning and memory domain ( Ayesa-Arriola et al, 2020 ). Long durations of untreated psychosis have been associated with impairment in selected cognitive domains in patients from HIC but primarily among chronically medicated and not first episode psychosis patients ( Stone et al, 2020 ; Bora et al, 2018 ).…”

“…There are also differing clinical, environmental, and sociodemographic exposures in low resource settings, yet how they are associated with cognitive impairment is still limited. For example, previous work and education history may be the best source of a patient's previous level of cognitive functioning when determining if there is a current decline, yet their association with cognitive impairment has not been well described in low resource settings ( Stone et al, 2020 ; Stone et al, 2016 ). The association between cognitive impairment and clinical characteristics that are more prevalent in FEP patients from low resource settings like longer duration of untreated psychosis (DUP), higher rates of childhood trauma, and greater psychosis severity are unclear ( Aas et al, 2013 ; Kilian et al, 2018 ; Lezak et al, 2004 ; Fawzi et al, 2013 ; Hecker et al, 2015 ).…”

Grey matter connectome abnormalities and age-related effects in antipsychotic-naive schizophrenia

“…Our findings in the nodal properties of the thalamus in the brain connectome included its association with symptom severity. Decreased nodal properties of thalamus were observed in long-term untreated schizophrenia patients only, who had greater impairment of social function and cognitive ability as reported previously [2] , [3] , [4] , [5] . This pattern of altered brain activity may be an important contributing factor to the anatomical alterations observed early in the illness, and its reduction with age and the negative changes related to longer DUP may reflect a reduction of functional connectivity later in the illness course [25] .…”

“…To date, it remains unclear whether brain changes found in the early stage of illness deteriorate during the course of illness and in which way they may contribute to persistent disabilities. Although substantial evidence demonstrates that some patients manifest progressive deterioration of social functioning [2] , [3] , [4] , [5] as well as grey/white matter volume reduction [6] , [7] , [8] after illness onset, the nature of connectome level changes and the degree to which drug effects contribute to such changes are not clear [8] , [9] , [10] , [11] , [12] , [13] . Furthermore, the follow-up period of previous longitudinal studies is usually restricted to the first few years after illness onset, so longer-term effects are unclear.…”