Background: There is similarity in schizophrenia and methamphetamine-induced psychosis neurobiology. Few studies have directly compared neurometabolites in thalamo-cortical circuitry across these disorders or assessed the relationship with peripheral cytokines. This study compared neurometabolites and neuronal integrity in thalamo-cortical circuitry, and investigated associations with peripheral cytokine levels in both disorders. Methods: Ninety-five participants were recruited – 36 with schizophrenia, 27 with methamphetamine-induced psychosis, and 32 healthy controls. All participants underwent a magnetic resonance imaging scan, which included magnetic resonance spectroscopy. Glutamatergic and neuroinflammatory neurometabolites were examined. Serum cytokine concentrations included Interleukin 1-beta, Interleukin-8, Interleukin-10, Tumor Necrosis Factor alpha and Interferon gamma. Parametric data were analyzed with one-way analysis of variance and non-parametric data were analyzed with Kruskal Wallis tests. Associations were determined using Spearman’s rank-order coefficient. Results: The methamphetamine-induced psychosis group had lower n-acetyl aspartate with n-acetyl-aspartyl glutamate in left dorsolateral prefrontal cortex and left frontal white matter, compared to controls. In schizophrenia, positive associations were found between glutamate and n-acetyl aspartate and n-acetyl aspartate with n-acetyl-aspartyl glutamate in the anterior cingulate cortex. In the methamphetamine-induced psychosis group, positive relationships were found between myo-inositol in the left thalamus and bilateral anterior cingulate cortex. Conclusion: In schizophrenia, there is suggestion of dysfunction in neuronal tissues in the glutamate-glutamine cycle within the thalamo-cortical circuit. In methamphetamine-induced psychosis, there is evidence of compromised neuronal integrity associated with chronic disease progression, and suggestion of aberrant neuroinflammatory regulation in the thalamus-ACC circuit. This study highlights similarities and differences in the psychobiology of the two disorders

Introduction This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach towards identifying risk factors for PTB may identify new directions for intervention. Methods Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with suspected TB. Characterization of the childhood ecosystem included proximal, medial and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors such as caregiver health that might impact interactions with the child. Distal determinants included macro-level determinants of disease such as socioeconomic status and food insecurity. Children started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children. Results Of 1,738 children enrolled in the study, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors such as male gender and hospitalization and low socio-economic status as a distal factor were associated with PTB. Conclusions Interventions may need to target subgroups of children and families at elevated risk for PTB. Screening for risk factors such caregiver health may guide targeting, and provision of social protection programs to bolster economic security may be important interventions for attenuating childhood exposure to risk factors.