Person:

Kamitaki, Nolan

Background: Depressive disorders are the second-leading cause of global disability, and an area of increasing focus in international health efforts. We describe a community health worker (CHW) program rolled out in a stepped-wedge design during the course of routine patient care to 74 patients with depression in 4 communities in rural Mexico. Methods: We used random effects models to calculate the change in Patient Health Questionnaire-9 (PHQ-9) scores, an internationally validated measure of depression, before and after the CHW program was introduced. As a secondary outcome, we also examined the change pre- and post-intervention in the proportion of patients who had a mean of at least one visit per month for depression follow-up, in accordance with clinic visit guidelines. Results: In multivariate mixed-effects regression, the introduction of the CHW program was associated with a 2.1-point decrease in PHQ-9 score (95% CI: -3.7 to -0.50) followed by a decrease in PHQ-9 score of 0.19 points per month (95% CI: -0.41 to 0.02), beyond standard care. There was strong evidence that patients were far more likely to attend a mean of at least one visit per month (adjusted OR = 8.5, 95% CI: 7.2 to 9.7) after the intervention was introduced in a community. Conclusions: Our results suggest an association between the introduction of a CHW program and improved depression outcomes and appointment adherence. Our findings are limited by missing data. Future research is necessary to develop evidence-based mental health interventions implementable in low-resource settings.

Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing—two conditions that involve declines in cognitive flexibility and plasticity —cells divested from SNAP: astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology.