Background Prospective studies are needed to assess the influence of pre-pandemic risk factors on mental health outcomes following the COVID-19 pandemic. From direct interviews prior to (T1), and then in the same individuals after the pandemic onset (T2), we assessed the influence of personal psychiatric history on changes in symptoms and wellbeing. Methods Two hundred and four (19–69 years/117 female) individuals from a multigenerational family study were followed clinically up to T1. Psychiatric symptom changes (T1-to-T2), their association with lifetime psychiatric history (no, only-past, and recent psychiatric history), and pandemic-specific worries were investigated. Results At T2 relative to T1, participants with recent psychopathology (in the last 2 years) had significantly fewer depressive (mean, M = 41.7 v. 47.6) and traumatic symptoms (M = 6.6 v. 8.1, p < 0.001), while those with no and only-past psychiatric history had decreased wellbeing (M = 22.6 v. 25.0, p < 0.01). Three pandemic-related worry factors were identified: Illness/death, Financial, and Social isolation. Individuals with recent psychiatric history had greater Illness/death and Financial worries than the no/only-past groups, but these worries were unrelated to depression at T2. Among individuals with no/only-past history, Illness/death worries predicted increased T2 depression [B = 0.6(0.3), p < 0.05]. Conclusions As recent psychiatric history was not associated with increased depression or anxiety during the pandemic, new groups of previously unaffected persons might contribute to the increased pandemic-related depression and anxiety rates reported. These individuals likely represent incident cases that are first detected in primary care and other non-specialty clinical settings. Such settings may be useful for monitoring future illness among newly at-risk individuals.

Phencyclidine (PCP) causes psychosis, is abused with increasing frequency, and was extensively used in antipsychotic drug discovery, but how this uncompetitive NMDA-receptor antagonist impairs cognition remains unknown. Using rats and mice, we report that, consistent with ionotropic actions, PCP discoordinated hippocampus CA1 action potential discharge and impaired a well-learned hippocampus-dependent active place avoidance that requires cognitive control. However, consistent with metabotropic actions, PCP exaggerated protein-synthesis dependent DHPG-induced mGluR-LTD. Pretreatment with anisomycin or the group I mGluR antagonist MPEP, both of which repress translation, prevented the discoordination and PCP-induced cognitive and sensorimotor impairments. Both PCP and the NR2A-containing NMDA-receptor antagonist NVP-AAM077 unbalanced translation that engages the AKT, mTOR and 4EBP1 translation machinery and increased protein synthesis, whereas the NR2B-containing antagonist Ro25-6981 did not. We conclude that PCP dysregulates translation acting through NR2A receptor subtypes recruiting group 1 mGluR signaling pathways, leading to the neural discoordination that is central to the cognitive and sensorimotor impairments.

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Serotonin shapes brain structure and function during early development across phylogenetically diverse species. In mice and humans, perinatal SSRI exposure produces brain alterations and increases anxiety/depression-related behaviors in the offspring. It remains unclear whether shared brain circuit changes underlie the behavioral impact of perinatal SSRIs across species. We examine how developmental SSRI-exposure in mice and humans changes fear-related brain activation and behavior. SSRI-administered mice showed increased defense responses to a predator odor that were associated with stronger fMRI-based fear circuit activation when compared to saline controls. Similarly, human adolescents exposed to SSRIsin uteroshowed greater activation of fear brain structures and exhibited higher anxiety and depressive symptoms than unexposed adolescents. Perinatal SSRI enhances innate fear-related responses and fear brain circuit activation that are conserved across species.One Sentence SummarySince SSRI use in pregnancy is common, we determined the effects of altered serotonin signaling during development in mice and humans.

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