People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18 FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

Effective in treatment-resistant depression (TRD), repetitive transcranial magnetic stimulation (rTMS) presents a remission rate between 30% and 40%. Although genetics could be one potential source of inter-individual variability in rTMS responsiveness, few studies have sought to identify possible genetic basis of rTMS response [1,2]. Therefore, we used an extreme-phenotype design in which we compared genome-wide allelic variation between rigorously defined rTMS responders and non-responders.A total of 99 TRD patients provided informed consent and this study was approved by the Human Research and Ethics Committee of the Alfred Hospital. All were submitted to a rTMS protocol and completed at least 18 sessions of 10 Hz at left dorsolateral prefrontal cortex (DLPFC). Clinical outcomes (responder or non-responder) were determined based on scores on the Montgomery Asberg Depression Rating Scale (MADRS).We used the extreme-phenotype design. Patients were separated into two groups, responders -patients with at least 60% reduction on the MADRS scale (n ¼ 29) and non-responders -patients with 10% or less reduction on the MADRS scale (n ¼ 19). We used this criteria considering that extreme scoring patients (<10 >60) may present more representative genetic results, improving power to detect phenotype-genotype associations [3,4].Genotyping was performed using the Infinium PsychArray-24 BeadChip (Illumina, Inc., San Diego, CA, USA) and analyzed with PLINK 1.9. We performed quality control to remove individuals or markers with high error rates. Data quality control parameters were: call rate (GENO) > 90%, maximum individual missingness rate (MIND) < 10%, minor allele frequency (MAF) > 5% and Hardy-Weinberg equilibrium (HWE) p-value > 10e6. We performed standard association analysis to compare allele frequency in both groups with a 95% CI. After identifying the significant SNPs and genes a functional enrichment analysis using STRING and Cytoscape databases was performed.

Background: Major depressive disorder (MDD) is a debilitating illness characterized by the persistence of negative thoughts and emotions. Although antidepressant medications are effective, less than half of patients achieve complete remission despite multiple treatment trials. Repetitive transcranial magnetic stimulation (rTMS) has proven effective in the treatment of depression, especially for patients resistant to antidepressant medications. Remission rates when using rTMS for treatment-resistant depression (TRD) patients are between 30% and 40%. The responsiveness to pharmacotherapy and rTMS therapy may be influenced by genetic factors. Objective: Here we aim to characterize the genetic profile of refractory individuals with MDD and their rTMS responsiveness. Methods: We used an extreme-phenotype design (rTMS responders vs. non-responders) and conducted a genome wide association study on 48 participants and 593,260 SNPs. Results: We identified 53 significant SNP associations. Gene-set enrichment analysis showed that significantly associated genes loaded onto synaptic plasticity regulation pathways. Among the genes found differentially expressed in rTMS responders compared to non-responders were APP, GRID2 and SPPL2A genes. Conclusions: Based on these findings, we suggest that the identified genes may influence of rTMS responsiveness. Furthermore, the rTMS responsiveness may be associated with several pathways and not just to the influence of a single gene. To the best of our knowledge, this is the first report on the genetic profile of rTMS response using a GWAS approach. Nevertheless, further studies are necessary to enlight the molecular mechanism by which these genes affect response to rTMS treatment.