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).

The advent of new non-invasive (largely EEG and MRI-based) methods for recording the activity of critical brain circuits (frontotemporal and subcortical) and networks (Default Mode, Salience, Central Executive), cross-sectionally and longitudinally, as well as concurrently (EEG and fMRI), has led to a focus on whether such techniques could be used to guide individual treatment selection. While this work has commenced with specific relevance to depression and other mood disorders (Goldstein-Piekarski et al., 2022; Hack et al., 2023; Scangos et al., 2023), there is still much to be learnt and a great need to replicate findings across different cohorts and different research centres.

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.

One of the most strongly held beliefs in developmental psychiatry is that various emotional, cognitive, behavioural and temperamental factors observed in childhood set the individual trajectory for the risk of onset, course and likely response to treatments in youth and adults with depressive and other mood disorders (Hickie et al., 2019).

There is much conjecture about which social factors underpin an apparent increase in the incidence of psychological distress, depression and other mood disorders, self-harm and suicidal behaviour and presentations for mental health care (in economically-developed countries). These concerns are particularly focused on younger birth cohorts, where the epidemiological evidence appears strongest for a genuine increase in incidence of mood disorders and self-harming behaviours (Twenge et al., 2019).

The most basic distinction between depressive (and other mood) disorders and other major mental disorders is the notion that they are primarily mood or affective disorders and not fundamentally perturbations of other cognitive, perceptual, motor, communication, impulse, sleep−wake, fear-response, arousal, developmental or personality functions. The primacy of mood or affective state is captured in the ‘core’ criteria for major depression (depressed mood or loss of pleasure) and the other major mood disorders (e.g., for dysthymia – prolonged depressed mood) (American Psychiatric Association, 2013). For bipolar disorder, while the presence of manic features (with increased motor activity) (Scott et al., 2017) is the core element, the depressive phase is described in similar terms, with the emphasis on the same shared features of major depression (i.e., depressed mood or loss of pleasure).

The potential relationships between traumatic experiences and the onset and course of major mood disorders have always been controversial. Some experiences, most notably physical or sexual abuse, as well as substantive bullying in childhood, are clearly recognised as major risk factors for a range of mental disorders, as well as a range of linked phenomena including self-harm and suicidal behaviours (McKay et al., 2021; Zatti et al., 2017). There is considerable interest and ongoing research into how these adverse experiences come to be ‘encoded’ via neurobiological or genetic mechanisms that then transmit those effects into later-onset major mental disorders, substance misuse or other self-harming behaviours (Maddox et al., 2019).

In recent years, there has been considerable enthusiasm among research groups focused on developing novel therapies for treatment-resistant depression, and a wider community that has had experiences using recreational drugs, in more systematic evaluation of the therapeutic value of these compounds (Goodwin et al., 2022; Young, 2023). This has also been associated with advocacy for decriminalization, legalization and possible public licensing for their ‘medicinal’ use (Siegel et al., 2023).

One of the areas of greatest public interest is whether altering your diet can reduce your risk of developing depression and whether there are any dietary manipulations that are effective treatments for depression? Many epidemiological studies have suggested associations between lower rates of depression and specific dietary types (e.g., Mediterranean, ‘anti-inflammatory’, Keto, low carbohydrate and Fish oil-rich) (Dietch et al., 2023). These epidemiological data are buttressed by post hoc analyses of several large-scale clinical trials with other primary outcomes – the PREDIMED study being an exemplar (Sánchez et al., 2013). In addition, the first generation of randomised controlled trials is now available suggesting that a healthier diet pattern especially the Mediterranean diet reduces the symptoms of depression in clinical populations (Jacka et al., 2017).

The field of therapeutic interventions available for depression and other mood disorders has been radically transformed over the last decade by the introduction of a range of new brain stimulation therapies. There is strong professional and public interest in the relative efficacy, and side effect profiles, of these approaches compared with conventional pharmacotherapy and older methods such as electro-convulsive therapy (Brunoni et al., 2022; Fitzgerald, 2021; Fitzgerald et al., 2022).

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.

The clinical field of depression and other mood disorders is characterised by the vast heterogeneity between those who present for care, and the highly variable degree of response to the range of psychological, pharmacological and physical treatments currently provided. These individual differences likely have a genetic component, and leveraging genetic risk is appealing because genetic risk factors point to causality. The possibility that individual genotyping at entry to health care may be a key way forward is worthy of discussion (Torkamani et al., 2018).

One of the long-standing challenges in the field of depressive and other mood disorders is to have a clear conceptualisation of the relationships between childhood temperaments, personality development and adult self and interpersonal function, and depressive and other mood disorders. Some biologically-based dispositional (or temperamental) traits are present from birth and are relatively stable from infancy through to adulthood. These characteristics (e.g., anxious attachment or social inhibition) are commonly seen as ‘at-risk’ traits for later formal diagnoses of anxiety disorders in pre-pubertal children and anxiety and depression in teenagers (Compas et al., 2004; Rothbart, 2007).

The increasing rates of anxiety, depression and self-harm reported by young people in developed countries over the last decade has led to speculation about the associations between this evidence of deteriorating mental health and wellbeing and the rapid spread and use of new digital technologies, social media and personal messaging platforms (Orben and Przybylski, 2019; Nesi, 2020). It has become commonplace to assert that these rapid technological changes, and their associated adverse impacts on social group function and interpersonal behaviour, are the cause of these fundamental epidemiological shifts.

A clinical concept that has been taken up with some enthusiasm in mental health services for young people experiencing major mental disorders is that of clinical staging, with the emphasis on identifying and intervening in youth with various ‘at-risk’, ‘sub-threshold’ or ‘attenuated’ syndromes, before the onset of first major episodes (Shah et al 2020). While these concepts were initially developed within the rather focused context of major psychotic disorders, they are now being deployed much more widely and applied to young people presenting with a variety of mental disorders (Hickie et al 2019; Shah 2019).

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).

The recognised heterogeneity of clinical cohorts of people with depression and other mood disorders has been held to be one of the central reasons why so many studies of causation, neurobiological or psychological correlates, or the effectiveness of treatments have failed to yield significant findings or be easily replicated by independent groups.

One of the most used, but poorly defined, terms in the management of clinical depression is that of treatment-resistant depression (TRD) (McIntyre et al., 2023). It implies that persons with major depression have received a range of appropriate psychological, medical or physical treatments (at appropriate doses and for appropriate durations) but have not experienced a significant clinical response. Intrinsically, it does not require consideration as to whether those treatments provided were relevant to their age or developmental stage, clinical phenotype, interpersonal or social context, or personal illness trajectory. These broader clinical considerations often influence initial and subsequent treatment choices.