Depression is the leading cause of disability worldwide and impacts both mental and physical health. It increases the risk of heart disease, diabetes, osteoporosis, and stroke, reducing life expectancy by up to 10 years. Changes in the brain, such as hippocampal atrophy and amygdala hyperactivity, along with inflammation and elevated cortisol levels, worsen symptoms and make it difficult to cope.
Depression is recognized globally as a serious health problem and is considered the leading cause of disability worldwide. However, its impact goes far beyond mental well-being, profoundly affecting the physical health of those who suffer from it.
Alarmingly, individuals with depression are at increased risk of developing problems such as early heart disease, diabetes, osteoporosis, and even a stroke. These physical health problems can reduce life expectancy by around 7 to 10 years.
Depression does not only impact the brain. It causes changes in several systems of the body. These biological changes, which are linked to emotional and psychological symptoms, also contribute to the development of physical illnesses.
For example, there is an imbalance in the neuroendocrine system, the set of interactions between the brain and the glands that control hormones in the body. This causes disruptions in important functions, such as those related to stress and mood regulation.
Melancholic depression is a particular form of depression. Contrary to what many people think, it does not necessarily manifest as sluggishness or apathy. Instead, people experience high levels of anxiety, heightened vigilance (a constant state of alertness), and intense feelings of worthlessness.
Other characteristic symptoms include anhedonia, which is the difficulty or inability to experience pleasure in activities previously considered enjoyable, difficulty falling asleep or staying asleep, and finally, morning despair, in which symptoms tend to be more intense in the morning.
At a biological level, melancholic depression is associated with an overactivity of stress response systems, such as the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system.
These systems increase the production of cortisol, known as the stress hormone, and other substances such as norepinephrine, intensifying symptoms of anxiety and despair.
Stress, anxiety, and depression overlap. However, in the etiology of anxiety and depression, psychological stress is an important risk factor. Source: Joodaki M, Radahmadi M.
Melancholic depression causes changes in several areas of the brain, some of which have vital functions in emotional regulation and behavior.
These changes include a reduction in the subgenual prefrontal cortex. This region of the brain helps control stress and process positive emotions. Its reduction can reduce the ability to cope with anxiety and negative emotions.
Atrophy of the hippocampus also occurs. The hippocampus, which is crucial for memory and learning, also regulates stress responses. When it shrinks, the ability to cope with challenging situations decreases.
The amygdala, responsible for processing fear and anxiety, increases in size and becomes more active, exacerbating feelings of panic and worry.
Finally, the dorsolateral prefrontal cortex and the orbitofrontal cortex shrink. This affects emotional control, decision-making, and the ability to experience pleasure, making it even harder to cope with depressive symptoms.
These structural and functional changes in the brain help explain why it is so difficult to overcome depression through willpower alone. They also show how depression affects not only mood, but also important cognitive functions.
Some areas of the brain are underactive, while other regions are overactive in depression. Red shows overactive areas and blue shows underactive areas. Source: Joodaki M, Radahmadi M.
Stress and inflammation play interconnected roles in depression. Stressful situations can trigger inflammation in the body, and this inflammation, in turn, worsens depressive symptoms.
In people with depression, levels of cytokines, an inflammatory protein, are elevated, which activate cells in the brain called microglia, generating even more inflammation. This inflammatory state can worsen the emotional and physical symptoms of depression.
Stress hormones, such as CRH (corticotropin-releasing hormone), play a central role in this cycle. They increase anxiety, reduce appetite, impair sleep, and affect the ability to experience pleasure. High levels of cortisol, for example, can even cause damage to the hippocampus, worsening memory loss and learning disabilities.
While depression has profound impacts, many of these changes in the brain are reversible with appropriate treatment. Antidepressants can help restore hippocampal volume, improve the integrity of regions such as the subgenual prefrontal cortex, and reduce inflammation.
Research is also exploring new treatments that go beyond traditional antidepressants. Medications that block the effects of CRH can reduce anxiety and stress. Glucocorticoid modulators can also help control the negative effects of cortisol on the brain.
Another group of therapies is hormone therapies, such as estrogenic compounds, which protect against inflammation and support brain plasticity. Another avenue of treatment is interventions to regulate insulin, which can improve brain health and cognitive resilience.
These advances offer hope for more effective treatments in the future, addressing not only the symptoms of depression but also the physical impacts associated with the disorder.
Understanding the neurobiological aspects of depression, such as the interplay between stress, inflammation, and brain changes, is crucial to improving treatments and patient well-being. This knowledge reinforces the importance of treating depression as a complex condition that affects the mind and body in an integrated manner.
READ MORE:
Is depression a neuroendocrine disease?
Philip W. Gold et al.
Brain Medicine, Published online: 14 November 2024.
Abstract:
Depression, according to the World Health Organization, stands as one of the most impactful disabilities worldwide. Its toll reaches beyond mood and thought, extending into physical health risks like coronary artery disease, diabetes, osteoporosis, and stroke, leading to a lifespan reduction of approximately 7 to 10 years in those affected. This paper explores the view of depression as a neuroendocrine disorder, especially focusing on the subtype of melancholic depression. Structural and functional disruptions in brain areas—such as the prefrontal cortex and hippocampus—reveal a misalignment in the stress response system that might drive depressive symptoms. Specifically, the roles of corticotropin-releasing hormone, norepinephrine hyperactivity, glucocorticoid levels, and inflammation-related mechanisms are investigated here. These insights point to promising new treatments targeting these neuroendocrine pathways that may enhance therapeutic responses.
IMAGENS:
Depression and Different Brain Areas: Neural Activity and Potential Mechanisms
Joodaki M, Radahmadi M.
Avicenna J Neuro Psycho Physiology 2022; 9 (4) : 150-162
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