One of the greatest global threats to mental health and wellbeing is the already discernible impact of climate change on local communities, particularly those living in the most vulnerable places on the planet, as well as the predicted impacts globally over the next 25–50 years (Romanello et al., 2021). Impacts have already been reported in those communities which have been devastated, often repeatedly, by extreme weather events (floods, cyclones, drought, bushfires, etc.) (Obradovich et al., 2018). These include massive social dislocation, loss of social connections and breakdowns in education, employment, economic and housing security – all factors known to increase the risk of common mental health conditions including anxiety, depression and other mood disorders.

Given the global prevalence of depression and other major mood disorders, the evidence of increasing rates among younger cohorts, the limited capacity of most treatment systems to respond to increasing demands for care, and the reality that services do not connect with a large proportion of those living with depressive disorders, a greater emphasis is being placed on our capacity to prevent the onset, recurrence, or persistence of these disabling conditions (Herrman et al., 2022).

Much attention in recent years has focused on the extent to which the risk of metabolic disturbances, and most fundamentally of glucose and insulin, are prevalent among those treated for depressive and other mood disorders (Osimo et al., 2021; Scott et al., 2019; Tickell et al., 2022). Public concern has also focused on the increased rates of premature mortality in those with chronic depression and other major mental disorders, with a significant proportion of that risk being due to early-onset cardiovascular disease (particularly among women). A common assumption is that much of this risk is a consequence of medical treatments for depression, and their possible adverse effects such as increased risk of diabetes, presumably mediated by long-term weight gain.

An area of great interest in Depression and Mood Disorder research has been highlighted by the Mental Health Priority Area of the Wellcome Trust (UK), namely sleep and circadian rhythm disturbances (SCRD). Wellcome has set out the background logic for this focus and clear research priorities (Wellcome Trust, 2022), leading to the funding of a series of international projects. This focus is a particularly good fit with the international agenda for development of more effective and scalable strategies for prevention, early intervention and secondary prevention of illness relapse, progression and downstream physical illnesses for adolescent-onset anxiety, depressive and psychotic disorders (Hickie et al., 2019).

In both population-based and clinical cohorts, cross-sectional and longitudinal studies have reported associations between a range of non-specific markers of immune activation (e.g., pro-inflammatory cytokines) or chronic inflammation (e.g., C-reactive protein [CRP]) and depressive and other mood disorders (Dowlati et al. 2010; Hickie et al. 2018; Khandaker et al. 2017; Orsolini et al. 2022; Valkanova et al. 2013). The clinico-pathological significance, and directional relationships, of these associations tended to be downplayed as the systemic levels of these inflammatory markers were not in the ranges typical of active infective, inflammatory or significant autoimmune diseases.