Major depressive disorder (MDD) is manifested by mood, behavioural, cognitive, and somatic symptoms. This is reflected in the diagnostic criteria of both DSM-5 and ICD-10. Differential diagnosis typically includes the consideration of other mood and psychiatric disorders, neurological, medical and genetic conditions, as well as bereavement. Diagnostic investigations are commonly combined with the evaluation of functioning since the vast majority of MDD patients experience functional impairment. Suicidality is a major challenge in the management of MDD. Rigorous risk assessment, minimisation of risk factors, and promotion of protective factors are essential in suicide prevention. Treatment strategies can be split into acute, continuation, and maintentance phases. Depending on depression severity and other specifiers (e.g., psychosis, risk) both pharmacotherapy and psychotherapy can be efficacious first-line treatment options. Switching or augmenting initial treatment can be considered for non-responders. For continuation and maintenance phases, the primary aim of treatement is prolonging remission, preventing episode recurrence, and restoring psychosocial functioning.

Mood disorders are the most common mental illnesses with a lifetime prevalence of up to 20% worldwide (1). Major depressive disorder (MDD) and bipolar disorder (BD) are significant health problems in the United States and worldwide (2). In the United States alone, the lifetime prevalence of MDD is up to 17%, and that of BD about 2.1% (2) that can go up to 4% of individuals with mood episodes not meeting episodic criteria included. Both are chronic illnesses characterized by recurrent episodes of depression and mania and depression in MDD and BD, respectively. Severe and disabling forms of BD and MDD are associated with increased risk of suicide, decline of physical health, and reduced productivity, and both conditions are associated with high rates of completed suicide of up to 8% (3).

To more effectively investigate, diagnose, and treat mood disorders, there is a need to move beyond standard clinical characterizations. While symptom-based nosology has provided a reliable and pragmatic framework for clinical practice, advances in neuroimaging research have permitted the possibility of identifying neurophysiologic biomarkers that index underlying pathophysiologic processes and provide an effective complement to clinical symptoms. Functional magnetic resonance imaging (fMRI) is one of the common state-of-the-art neuroimaging approaches for investigating brain disorders and has been very useful in providing a functional neuroanatomic account of neural disturbances in mood disorders.

The history of pharmacological treatments for depression began in the 1950s, with the serendipitous discovery of the antidepressant potential of drugs like the tricyclic antidepressant, imipramine. Since then, many new, safer, and better tolerated, antidepressant drugs have appeared on the market (1), and now depression can be treated widely in primary care. However, finding a treatment effective for an individual patient is not a trivial task, with only around 30% of patients responding to their first antidepressant (AD) medication, most requiring multiple changes, and about one-third not responding at all (2).