Depression

Major depressive disorder (MDD) is one of the most prevalent and disabling mental health conditions worldwide. According to the DSM-5, diagnosis requires the presence of at least five symptoms over a minimum of two weeks, necessarily including depressed mood or loss of interest or pleasure (anhedonia). Other symptoms include significant changes in weight or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or excessive guilt, difficulty concentrating, and recurrent thoughts of death. Depression is not simply sadness but a profound alteration affecting cognition, emotions, the body, and relationships.

Aaron Beck revolutionized the understanding of depression with his cognitive model, proposing that depression is maintained by the negative cognitive triad: a negative view of oneself ("I am a failure"), of the world ("everything is unfair and hostile"), and of the future ("things will never get better"). These automatic negative thoughts arise from dysfunctional cognitive schemas formed by early experiences. Thinking errors — such as overgeneralization, mental filter, personalization, and dichotomous thinking — maintain and reinforce the depressive state. Beck's cognitive therapy seeks to identify, challenge, and modify these distorted thinking patterns.

From a neurochemical perspective, the monoamine hypothesis has been the dominant framework for decades, postulating that depression results from a deficit of neurotransmitters such as serotonin, norepinephrine, and dopamine. Although this hypothesis guided the development of effective antidepressants, it is clearly insufficient: antidepressants increase monoamine levels within hours, yet the therapeutic effect takes weeks. More recent models include alterations in neuroplasticity, chronic inflammation, HPA axis dysregulation, and dysfunctions in brain circuits connecting the prefrontal cortex, amygdala, and hippocampus.

Treatment for depression encompasses a broad range of evidence-based options. Cognitive-behavioral therapy and interpersonal therapy are the most validated psychological treatments. Pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) is the first-line treatment for moderate to severe depression. Cuijpers and colleagues demonstrated in extensive meta-analyses that psychotherapy and pharmacotherapy have similar efficacies for moderate-severity depression, and their combination is superior to either treatment alone. For treatment-resistant depression, options such as electroconvulsive therapy, ketamine, and transcranial magnetic stimulation offer alternatives with growing evidence.