Chronic adolescent marijuana use has been linked to the later development of psychiatric diseases such as schizophrenia. GABAergic hypofunction in the prefrontal cortex (PFC) is a cardinal pathological feature of schizophrenia and may be a mechanism by which the PFC loses its ability to regulate sub-cortical dopamine (DA) resulting in schizophrenia-like neuropsychopathology. In the present study, we exposed adolescent rats to Δ-9-tetra-hydrocannabinol (THC), the psychoactive component in marijuana. At adulthood, we characterized the functionality of PFC GABAergic neurotransmission and its regulation of sub-cortical DA function using molecular, behavioral and in-vivo electrophysiological analyses. Our findings revealed a persistent attenuation of PFC GABAergic function combined with a hyperactive neuronal state in PFC neurons and associated disruptions in cortical gamma oscillatory activity. These PFC abnormalities were accompanied by hyperactive DAergic neuronal activity in the ventral tegmental area (VTA) and behavioral and cognitive abnormalities similar to those observed in psychiatric disorders. Remarkably, these neuronal and behavioral effects were reversed by pharmacological activation of GABAA receptors in the PFC. Together, these results identify a mechanistic link between dysregulated frontal cortical GABAergic inhibition and sub-cortical DAergic dysregulation, characteristic of well-established neuropsychiatric endophenotypes.

Intensive care unit healthcare workers (ICU HCW) are at risk of mental health issues during emerging disease outbreaks. A study of ICU HCW from France revealed symptoms of anxiety and depression in 50.4% and 30.4% of workers at the peak of the first wave of the pandemic. The level of COVID-19 exposure of these ICU HCW was very high. In Canada, ICU HCW experienced variable exposure to COVID-19 during the first wave of the pandemic, with some hospitals seeing large numbers of patients while others saw few or none. In this study we examined the relationship between COVID-19 exposure and mental health in Canadian ICU HCW. We conducted a cross-sectional cohort study of Canadian ICU HCW in April 2020, during the acceleration phase of the first wave of the pandemic. Psychosocial distress was assessed using the 12-item General Health Questionnaire (GHQ-12). Participants were asked about sources of stress as well as about exposure to COVID-19 patients and availability of personal protective equipment (PPE). Factors associated with clinically-relevant psychosocial distress were identified. Responses were received from 310 Canadian ICU HCW affiliated with more than 30 institutions. Of these, 64.5% scored ≥ 3 points on the GHQ-12 questionnaire, indicating clinically-relevant psychosocial distress. The frequency of psychosocial distress was highest amongst registered nurses (75.7%) and lowest amongst physicians (49.4%). It was also higher amongst females (64.9%) than males (47.6%). Although PPE availability was good (> 80% of participants reported adequate availability), there was significant anxiety with respect to PPE availability, with respect to the risk of being infected with COVID-19, and with respect to the risk of transmitting COVID-19 to others. In multivariable regression analysis, Anxiety with respect to being infected with COVID-19 (OR 1.53, CI 1.31–1.81) was the strongest positive predictor of clinically-relevant psychosocial distress while the Number of shifts with COVID-19 exposure (OR 0.86, CI 0.75–0.95) was the strongest negative predictor. In summary, clinically-relevant psychosocial distress was identified amongst a majority of ICU HCW during the acceleration phase of the first wave of the COVID-19 pandemic, including those with minimal or no exposure to COVID-19. Strategies to support mental health amongst ICU HCW are required across the entire healthcare system.

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