Dual hit mouse model to examine the long-term effects of maternal immune activation and post-weaning social isolation on schizophrenia endophenotypes.

Evidence suggests that early life adversity, such as maternal immune activation (MIA), can alter brain development in the offspring and confer increased risk for psychopathology and psychiatric illness in later life. In this study, the long-term effects of MIA, post-weaning social isolation, and the combination were assessed on behavioural and immunological profiles in adult male and female offspring. On gestation day 12.5, pregnant mice were weighed and injected with either polyinosinic:polycytidylic acid (5 mg/kg) or saline and cytokines levels were assayed 3 hrs later to confirm immune activation. The behaviour and immunological profiles of male and female offspring were examined in adolescence (P34-36), and adulthood (P55-80). MIA induced an increase in the pro-inflammatory cytokine IL-6 in pregnant dams three hours after administration (p < 0.001) that correlated with a decrease in body temperature (p < 0.05). The effect of MIA on the immunological phenotype of the offspring was evident in adolescence, but not in adulthood. MIA selectively induced hypoactivity in adolescent males, a phenotype that persisted until adulthood, but had no effect on cognition in males or females. In contrast, social isolation stress from adolescence resulted in impaired sociability (p < 0.05) and increased anxiety (p < 0.05) particularly in adult females. There was no synergistic effect of the dual-hit on immune parameters, sociability, anxiety or cognitive behaviours. Given the negative impact and sex-dependent effects of SI stress on locomotor and anxiety-like behaviour, future investigations should examine whether the health risks of social isolation, such as that experience during the COVID-19 pandemic, are mediated through increased anxiety.

A longitudinal evaluation of the impact of the COVID-19 pandemic on a cohort of patients treated with clozapine.

OBJECTIVES: We previously demonstrated that three months into the COVID-19 pandemic, the impact on individuals with treatment-resistant psychotic disorders was modest. Here, we examined and compared the psychological and social impact of the COVID-19 pandemic on the same patient cohort 12 months after their initial study engagement. METHODS: Semi-structured interviews were conducted with 54 individuals (85.7% response rate) between June 12 and July 29, 2021, 12 months after their initial interviews. Participants' subjective experience of the impact of the COVID-19 pandemic on anxiety symptoms, social and vocational functioning was measured utilising the same Likert scales at both time points. Anxiety symptoms were additionally measured using subjective (Beck Anxiety Inventory) and objective (Hamilton Anxiety Rating Scale (HARS)) psychometric instruments. Paired t-tests or Wilcoxon ranked tests compared parametric or non-parametric data over time. Free-text responses pertaining to participants' perspectives on the impact of COVID-19 were grouped into themes. RESULTS: A minor increase in anxiety symptoms was demonstrated utilising the HARS (1.9 points, z = 3.017, p = 0.003), with a minimal increase in depressive symptoms noted using Likert ratings (0.8 points, z = 2.119, p = 0.034). Five themes were identified with the most prevalent being (i) positivity regarding vaccination, (ii) social isolation from family members and (iii) looking forward to post-COVID-19 'normality'. However, negative views pertaining to the psychosocial impact of COVID-19 and vaccination were additionally reported. CONCLUSIONS: No significant overall clinical change in symptomatology or functioning over time was noted.The study demonstrated that positive views regarding vaccination and optimism for the future were evident for some participants.