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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 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.
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).
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).
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 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).
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).
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.
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.
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 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).
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).
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 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).
Primary youth mental health services in Australia have increased access to care for young people, yet the longer-term outcomes and utilisation of other health services among these populations is unclear.
To describe the emergency department presentation patterns of a help-seeking youth mental health cohort.
Data linkage was performed to extract Emergency Department Data Collection registry data (i.e. emergency department presentations, pattern of re-presentations) for a transdiagnostic cohort of 7024 youths (aged 12–30 years) who presented to mental health services. Outcome measures were pattern of presentations and reason for presentations (i.e. mental illness; suicidal behaviours and self-harm; alcohol and substance use; accident and injury; physical illness; and other).
During the follow-up period, 5372 (76.5%) had at least one emergency department presentation. The presentation rate was lower for males (IRR = 0.87, 95% CI 0.86–0.89) and highest among those aged 18 to 24 (IRR = 1.117, 95% CI 1.086–1.148). Almost one-third (31.12%) had an emergency department presentation that was directly associated with mental illness or substance use, and the most common reasons for presentation were for physical illness and accident or injury. Index visits for mental illness or substance use were associated with a higher rate of re-presentation.
Most young people presenting to primary mental health services also utilised emergency services. The preventable and repeated nature of many presentations suggests that reducing the ongoing secondary risks of mental disorders (i.e. substance misuse, suicidality, physical illness) could substantially improve the mental and physical health outcomes of young people.
The needs of young people attending mental healthcare can be complex and often span multiple domains (e.g., social, emotional and physical health factors). These factors often complicate treatment approaches and contribute to poorer outcomes in youth mental health. We aimed to identify how these factors interact over time by modelling the temporal dependencies between these transdiagnostic social, emotional and physical health factors among young people presenting for youth mental healthcare.
Dynamic Bayesian networks were used to examine the relationship between mental health factors across multiple domains (social and occupational function, self-harm and suicidality, alcohol and substance use, physical health and psychiatric syndromes) in a longitudinal cohort of 2663 young people accessing youth mental health services. Two networks were developed: (1) ‘initial network’, that shows the conditional dependencies between factors at first presentation, and a (2) ‘transition network’, how factors are dependent longitudinally.
The ‘initial network’ identified that childhood disorders tend to precede adolescent depression which itself was associated with three distinct pathways or illness trajectories; (1) anxiety disorder; (2) bipolar disorder, manic-like experiences, circadian disturbances and psychosis-like experiences; (3) self-harm and suicidality to alcohol and substance use or functioning. The ‘transition network’ identified that over time social and occupational function had the largest effect on self-harm and suicidality, with direct effects on ideation (relative risk [RR], 1.79; CI, 1.59–1.99) and self-harm (RR, 1.32; CI, 1.22–1.41), and an indirect effect on attempts (RR, 2.10; CI, 1.69–2.50). Suicide ideation had a direct effect on future suicide attempts (RR, 4.37; CI, 3.28–5.43) and self-harm (RR, 2.78; CI, 2.55–3.01). Alcohol and substance use, physical health and psychiatric syndromes (e.g., depression and anxiety, at-risk mental states) were independent domains whereby all direct effects remained within each domain over time.
This study identified probable temporal dependencies between domains, which has causal interpretations, and therefore can provide insight into their differential role over the course of illness. This work identified social, emotional and physical health factors that may be important early intervention and prevention targets. Improving social and occupational function may be a critical target due to its impacts longitudinally on self-harm and suicidality. The conditional independence of alcohol and substance use supports the need for specific interventions to target these comorbidities.
Understanding premature mortality risk from suicide and other causes in youth mental health cohorts is essential for delivering effective clinical interventions and secondary prevention strategies.
To establish premature mortality risk in young people accessing early intervention mental health services and identify predictors of mortality.
State-wide data registers of emergency departments, hospital admissions and mortality were linked to the Brain and Mind Research Register, a longitudinal cohort of 7081 young people accessing early intervention care, between 2008 and 2020. Outcomes were mortality rates and age-standardised mortality ratios (SMR). Cox regression was used to identify predictors of all-cause mortality and deaths due to suicide or accident.
There were 60 deaths (male 63.3%) during the study period, 25 (42%) due to suicide, 19 (32%) from accident or injury and eight (13.3%) where cause was under investigation. All-cause SMR was 2.0 (95% CI 1.6–2.6) but higher for males (5.3, 95% CI 3.8–7.0). The mortality rate from suicide and accidental deaths was 101.56 per 100 000 person-years. Poisoning, whether intentional or accidental, was the single greatest primary cause of death (26.7%). Prior emergency department presentation for poisoning (hazard ratio (HR) 4.40, 95% CI 2.13–9.09) and psychiatric admission (HR 4.01, 95% CI 1.81–8.88) were the strongest predictors of mortality.
Premature mortality in young people accessing early intervention mental health services is greatly increased relative to population. Prior health service use and method of self-harm are useful predictors of future mortality. Enhanced care pathways following emergency department presentations should not be limited to those reporting suicidal ideation or intent.
Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.
To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.
Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.
The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.
We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.