Browsing by Author "Stein Dan"

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    Executive function and contingency management for methamphetamine use disorder in South Africa: a comparison pre- and post-treatment
    (2021) van Nunen, Lara Jane; Ipser, Jonathan; Stein Dan
    Background: Methamphetamine dependence is associated with impairment in executive function, as well as brain functional and structural alterations, findings on the relationship between executive function impairment and brain alterations seem inconsistent. Methamphetamine dependence may respond to contingency management, yet it is unclear if the treatment response is predicted by these neuropsychological, and brain functional and structural changes, and whether treatment alters neuropsychological impairment. I first conducted a systematic review to rigorously assess available findings on the relationship between executive function impairment and brain functional changes. I then explored data from a study of contingency management in methamphetamine dependence with the aims of determining 1) whether treatment response was predicted by executive function impairment and brain functional and structural alterations, and 2) whether treatment led to changes in executive function and brain functional and structural impairment in treatment responders and non-responders. Methods: The systematic review involved a rigorous search and assessment of articles on the association of stimulant use and resting state functional connectivity. In the empirical study, 33 subjects underwent executive function testing, resting state-fMRI, and structural neuroimaging prior to contingency management treatment. Executive function was assessed with the trail making task, the Stroop-word task, and the Connors continuous performance task. Seed-based analysis was used for functional MRI, with a focus on brain regions associated with executive function, and brain structural alterations were assessed using measures of cortical thickness and surface area. In the statistical analysis, first associations of baseline executive function, rs-fMRI, and brain structural alterations with treatment outcome were assessed using linear regression, and second, comparison of executive function, rsfMRI, and brain structural parameters at baseline versus at treatment end in treatment responders and non-responders was undertaken using linear regression, Cohen's d and a change score. Results: The systematic review noted specific associations between executive function impairment and resting state-fMRI. While in the study, treatment responders had improved executive function at baseline as assessed by two measures (faster completion times on the trail making, and greater accuracy on the Connors continuous performance task), but worse executive function on a third measure (lower accuracy on the Stroop word task) when compared with non-responders. No statistically significant differences between groups was found with regards to rsFC, however greater cortical thickness was found in responders brain regions associated with executive function, in comparison to non-responders. Analysis of pre vs post treatment findings showed that in treatment responders there was better executive function after treatment, in comparison to non-responders (as assessed by greater accuracy on the Connors continuous performance task). Furthermore, in treatment responders there was greater increase in cortical volume in regions associated with executive function, than in non-responders. Conclusion: These findings support the hypothesis that better executive function at baseline (task switching and selective attention) is associated with better outcomes in a contingency management trial of 8-weeks. There is also evidence of improved executive function post trial (in selective attention and cortical thickness findings support improved executive function) implying that abstinence as a consequence of a contingency management trial of 8-weeks may improve executive function, a larger sample size would be needed to determine if improvements extend to other regions of executive function
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    Persistent (>6 months) Neuropsychiatric symptoms in a cohort of SARS- CoV-2 PCR positive patients in Cape Town, South Africa
    (2024) Van Niekerk, Inette; Peter, Jonathan; Stein Dan
    Background : SARS-CoV-2 is a neurotrophic and pro-inflammatory virus, with several acute and more persistent neuropsychiatric sequelae reported. There are limited data from younger African cohorts and few acute illness biomarkers of persistent neuropsychiatric symptoms. Objectives : To determine the prevalence of neuropsychiatric symptoms in a cohort of South African SARS-CoV-2 PCR positive patients at least six months following infection/hospitalization. Second, to examine the association of neuropsychiatric outcomes with clinical illness severity, systemic inflammation, cardiovascular and renin-angiotensin system (RAS) biomarkers. Methodology: SARS-CoV-2 PCR positive patients were recruited prospectively from Cape Town, South Africa, including hospitalized patients from ancestral, beta and delta-dominant COVID-19 waves (pre-vaccine rollout); and asymptomatic/mild SARS-CoV-2 positive patients. Telephonic interviews were conducted at least six months post infection/hospitalization. Validated measures employed were: WHO Self-Report Questionnaire (SRQ-20), Generalized Anxiety Disorder Scale (GAD-7), Chalder Fatigue Scale (CFS-11) and Telephonic Montreal Cognitive Assessment (T-MoCA). The 96-protein O-link inflammation and cardiovascular panels, RAS fingerprinting, and antibody responses were measured in plasma/serum samples collected at peak severity and recovery (>3 months post infection). Results: Ninety-seven participants completed telephonic interviews. The median (IQR) age was 48 (37-59) years, and 54% were female. More than half of this South African COVID19 cohort had one or more persistent neuropsychiatric symptoms >6 months post vaccine-naïve infection. On the T-MoCA, 44% of participants showed evidence of cognitive and/or memory impairments. There were no significant associations between neuropsychiatric outcomes and illness severity, systemic inflammation, cardiovascular and renin-angiotensin-system (RAS) biomarkers. Conclusion : The high prevalence of persistent neuropsychiatric symptoms in this young African cohort supports ongoing attention to long COVID. Persistent neuropsychiatric outcomes post-COVID are not associated with systemic inflammation or altered renin angiotensin physiology. Psychosocial variables affecting individual responses to the virus may explain the lack of association found on the biological front.