High SARS-CoV-2 infection rates and viral loads in community-dwelling individuals from rural indigenous and mestizo communities from the Andes during the first wave of the COVID-19 pandemic in Ecuador.

Background: Neglected indigenous groups and underserved rural populations in Latin America are highly vulnerable to COVID-19 due to poor health infrastructure and limited access to SARS-CoV-2 diagnosis. The Andean region in Ecuador includes a large number of isolated rural mestizo and indigenous communities living under poverty conditions. Objective: We herein present a retrospective analysis of the surveillance SARS-CoV-2 testing in community-dwelling populations from four provinces in the Ecuadorian Andes, carried out during the first weeks after the national lockdown was lifted in June 2020. Results: A total number of 1,021 people were tested for SARS-CoV-2 by RT-qPCR, resulting in an overall high infection rate of 26.2% (268/1,021, 95% CI: 23.6-29%), which was over 50% in several communities. Interestingly, community-dwelling super spreaders with viral loads over 108 copies/mL represented 7.46% (20/268, 95% CI: 4.8-11.1%) of the SARS-CoV-2 infected population. Conclusion: These results support that COVID-19 community transmission in rural communities from the Andean region was happening at the early stages of the COVID-19 pandemic in Ecuador and point out the weakness of the COVID-19 control program. Community-dwelling individuals in neglected rural and indigenous communities should be considered for a successful control and surveillance program in future pandemics in low- and middle-income countries.

The association between antidepressant treatment and brain connectivity in two double-blind, placebo-controlled clinical trials: a treatment mechanism study.

BACKGROUND: Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects. Toward this goal, we aimed to identify the effects of antidepressant treatment on neural connectivity, the relationship with symptom improvement, and to test whether these effects were reproducible across two studies. METHODS: We completed two double-blind, placebo-controlled trials of SNRI antidepressant medications with MRI scans obtained before and after treatment. One was a 10-week trial of duloxetine (30-120 mg daily; mean 92·1 mg/day [SD 30·00]) and the other was a 12-week trial of desvenlafaxine (50-100 mg daily; 93·6 mg/day [16·47]). Participants consisted of adults with persistent depressive disorder. Adjusting for sex and age, we examined the effect of treatment on whole-brain functional connectivity. We also examined correlations between change in functional connectivity and improvement in symptoms of depression (24-item Hamilton Depression Rating Scale) and pain symptom severity (Symptom Checklist-90-Revised). FINDINGS: Participants were enrolled between Jan 26, 2006, and Nov 22, 2011, for the duloxetine RCT and Aug 5, 2012, and Jan 28, 2016, for the desvenlafaxine RCT. Before and after treatment MRI scans were collected in 32 participants for the duloxetine RCT and 34 participants for the desvenlafaxine RCT. In both studies, antidepressants decreased functional connectivity compared with placebo (duloxetine study: ß=-0·06; 95% CI -0·08 to -0·03; p<0·0001, ηp2=0·44; desvenlafaxine study: -0·06, -0·09 to -0·03; p<0·0001, ηp2=0·35) within a thalamo-cortico-periaqueductal network that has previously been associated with the experience of pain. Within the active drug groups, reductions in functional connectivity within this network correlated with improvements in depressive symptom severity in both studies (duloxetine study: r=0·38, 95% CI 0·01-0·65; p=0·0426; desvenlafaxine study: 0·44, 0·10-0·69; p=0·0138) and pain symptoms in the desvenlafaxine study (0·39, 0·04 to 0·65; p=0·0299). INTERPRETATION: The findings suggest the thalamo-cortico-periaqueductal network associated with the experience of pain is a new and potentially important target for novel antidepressant therapeutics. FUNDING: National Mental Health Institute, Eli Lilly and Company, Pfizer Pharmaceuticals, and the Edwin S Webster Foundation.

Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy.

Importance: Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Animal studies show that perinatal SSRI exposure alters limbic circuitry and produces anxiety and depressive-like behaviors after adolescence, but literature on prenatal SSRI exposure in humans is limited and mixed. Objective: To examine associations between prenatal SSRI exposure and brain development using structural and diffusion magnetic resonance imaging (MRI). Design, Setting, and Participants: A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Data were collected between January 6, 2011, and October 25, 2016. Exposures: Selective serotonin reuptake inhibitors and untreated maternal depression. Main Outcomes and Measures: Gray matter volume estimates using structural MRI with voxel-based morphometry and white matter structural connectivity (connectome) using diffusion MRI with probabilistic tractography. Results: The sample included 98 mother (31 [32%] white, 26 [27%] Hispanic/Latina, 26 [27%] black/African American, 15 [15%] other) and infant (46 [47%] boys, 52 [53%] girls) dyads. Mean (SD) age of the infants at the time of the scan was 3.43 (1.50) weeks. Voxel-based morphometry showed significant gray matter volume expansion in the right amygdala (Cohen d = 0.65; 95% CI, 0.06-1.23) and right insula (Cohen d = 0.86; 95% CI, 0.26-1.14) in SSRI-exposed infants compared with both healthy controls and infants exposed to untreated maternal depression (P < .05; whole-brain correction). In connectome-level analysis of white matter structural connectivity, the SSRI group showed a significant increase in connectivity between the right amygdala and the right insula with a large effect size (Cohen d = 0.99; 95% CI, 0.40-1.57) compared with healthy controls and untreated depression (P < .05; whole connectome correction). Conclusions and Relevance: Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing. The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.