The World Health Organization (WHO) estimates that 3.8% of the world’s population, or approximately 280 million people, suffer from depression. The incidence of this disease is increasing[1].
January 13 was established as World Depression Day to raise awareness of the importance of recognizing and treating depression as a major mental health problem.
Among the factors identified as contributing to the onset of depression are stress, family history, conflictual relationships in the family environment, consumption of psychoactive substances, migraine, cerebrovascular diseases, imbalances in neurotransmitters such as serotonin and norepinephrine, and genetic factors (MDD1 susceptibility, MDD2, gene SLC6A3 et variants TPH2).
Depression is a multifactorial disease involving neuroendocrine, genetic and environmental alterations.
It is therefore important to remember that depression is a multifactorial disease involving neuroendocrine, genetic and environmental alterations. To understand depression, we must explore its origins.
THE functional alterations between receptors and neurotransmitters in specific areas of the brain, such as the limbic system, prefrontal cortex, hippocampus, and amygdala, may be causes of depression. Serotonin and norepinephrine are considered the main neurotransmitters involved in this process, although studies suggest that dopamine may also play a role. A decrease in norepinephrine is associated with apathy and lethargy, while a decrease in serotonin is associated with irritability, hostility, and suicidal ideation.
On the other hand, the genetic factors play an important role in depression; Studies show 40-50% concordance in twins and a three times higher risk in first-degree relatives, although depression can also occur without a family history. Genes and their polymorphisms are particularly important because of their clinical relevance, as in the following cases: 1) SLC6A4whose promoter region polymorphism is associated with increased vulnerability to stress and depressive symptoms; 2) genes HTR3A et HTR3Bwhich encode serotonin receptors and are associated with depression in various populations, and 3) the T allele of the gene FKBP5which improves response to antidepressants but increases the recurrence of depressive episodes. Two susceptibility loci were also identified, one associated mainly with men (MDD1) and the other linked to early or recurrent episodes (MDD2).
Cognitive models of vulnerability and of stress suggest that people who attribute negative responsibility for life events are more likely to develop depression, which could also explain gender differences in depression after puberty. Behaviorally, a lack of positive reinforcement and inadequate social skills, as well as avoidant behaviors in the face of negative emotions, can exacerbate depression. Thus, factors such as early loss of parents, low paternal commitment, maternal overprotection and conflicting relationships contribute to the development of the disease.
The late-life depressionwhich occurs after the age of 60, has been shown to be a distinct syndrome in etiological and clinical terms, with less influence of genetic factors compared to early-onset depression. Family history of depression is less common in these cases. However, certain genetic markers, such as polymorphisms in the apolipoprotein E, BDNF, and serotonin transporter genes, have been associated with this disease, although the results are conflicting. These markers are also linked to cognitive impairment, hippocampal volume and response to antidepressants.
Some hypotheses also suggest that cerebrovascular diseases could cause or contribute to depression in older adults. Available data report a higher incidence of depression after left-sided stroke, a higher prevalence of ischemic white matter changes in older adults with depression, and bidirectional associations between depression and diseases such as coronary heart disease and diabetes. Additionally, rates of depression are higher in patients with vascular dementia than in those with Alzheimer’s disease.
There appears to be a close relationship between depression and migraine with aura, due at least in part to genetic factors. There is also a bidirectional relationship between obesity and depression.
Research is underway to deeply understand the causes of depression. A recent study identified that the expansion of the fronto-striatal salience network, involved in the reward and attention system, is significantly greater in people suffering from depression, remaining stable over time and detectable even before the onset of depression. onset of symptoms. This discovery, based on advanced brain mapping techniques, could serve as a biomarker to predict the risk of developing depression, particularly in predisposed children. Experts highlight the clinical potential of this discovery to personalize treatments by neuromodulation or digital therapies, and to identify new drug targets. The consistency of the data over time reinforces the idea that the expansion of this network does not depend on the depressive state, but that it is a stable marker. This paves the way for preventative interventions and more precise treatments in the field of mental health.
