‘Melancholy can be overwhelmed only by melancholy.’ Robert Burton, Anatomy of Melancholy

Whilst the above 17th Century view of what we would now term melancholic depression may be pessimistic, it does remind us of how the concept and treatments for depression have changed over time.

The Diagnostic and Statistical Manual, Third Edition (DSM-III), for better or worse, expanded the concept of depression, and now it is generally agreed that current classification systems encompass a heterogenous group of disorders, with varying aetiologies (Shorter, 2014). Where the field does appear to have stalled-till relatively recently, has been novel and effective treatments, with drugs affecting monoamines continuing as the mainstay of pharmacotherapy and cognitive behavioural therapy (CBT) the most evidence-based psychotherapy available. In this issue of International Review of Psychiatry we have contributions almost as varied as the various symptom domains of what is classified as Major Depressive Disorder (MDD) in DSM-5, relating to aetiology and treatments.

In terms of aetiology, Serna and McPherson provide a timely overview of the medical illness associated with MDD, ranging from cardiovascular disease to rheumatoid arthritis, providing evidence on predisposing factors, as well as suggesting possible bi-directional effects between these illnesses and MDD.

Oakley et al, in their comprehensive review of autism and mood disorders neatly summarise this often neglected co-morbidity, pointing out that MDD presents earlier than bipolar disorder, and -importantly- symptoms of depression may be overshadowed in population, and therefore missed. They go on to examine aetiological factors and treatments.

Arnone et al, in a rigorous study of childhood maltreatment in the United Arab Emirates (UAE), expand on current knowledge of prevalence and role of childhood maltreatment (emotional and physical abuse), gained from mainly Western countries, showing an association, with strong methodology for this type of research, and high survey response rate (>80%).

As with aetiology, there is a significant breadth of interventions for depression. Escobar-Viera et al. examine an important public health aspect of treatment- mental health interventions in Latin American countries, where significant gaps in mental health treatment are seen. Their systematic review identified 8 studies, which, allowing for heterogeneity, suggest such interventions are feasible, predominantly in primary care.

The relationship between diet and mood (‘mood and food’) has been a hot topic in affective disorders and Young et al. report promising results from a feasibility randomised controlled trial (RCT), of a smartphone intervention to improve diet quality in people with depression symptoms. In this 8-week trial they found the smartphone intervention improved diet quality, and an inverse association between improvement in diet and scores on the PHQ 8, suggesting an improvement in diet quality may result in an Improvement in depression symptoms-and though caveats apply, a larger trial appears warranted.

Whilst there is little doubt that electroconvulsive therapy (ECT) is effective in MDD (it is the most effective treatment), for various reasons it is not a usual first-line treatment for MDD (Kirov et al., 2021). Rimmer et al. examine the role of transcranial direct current stimulation (tDCS), a therapy that administers current through scalp electrodes, suggesting its potential as a first-line therapy. Citing their prior meta-analysis, where tDCS was associated with higher response rates (Odds Ratio of around 4), compared to placebo. Intriguingly they extrapolate from their prior analysis, where best rates of response were in people with non-resistant depression. They suggest tDCS for people with first episode illness and give various neurobiological hypotheses for the mode of action.

For those of a certain vintage, psychedelics have a chequered history in psychiatry, with their widespread- and unregulated-use in the 1960s leading to significant morbidity and their subsequent classification as illicit substances. However, cautious optimism now exists for their therapeutic use in mood disorders, and Bird and Rucker assiduously review their use in trauma, linking this to PTSD and MDD.

Probably the most significant therapeutic advance in the treatment of MDD in the last few years has been ketamine, and though there is controversy around its use and licencing, the RCT evidence in treatment-resistant depression certainly warrants a degree of optimism (Jauhar & Morrison, 2019). What is unclear about ketamine is how it exerts effects, and Jelen and Stone make a concerted effort in their authoritative review to examine this, pointing out some of the potential targets, and also some fallacies in recent literature examining this compound’s use in MDD.

Finally, acknowledging that MDD has significant effects on wider aspects of cognition, we borrow from the psychosis literature, where Riches et al examine the evidence for virtual-reality based interventions in psychosis, and find a paucity of well conducted RCTs, suggesting further work is required. Overall, we conclude there is much evidence in this edition of the Journal that melancholy will be overwhelmed by Science, not melancholy!