A Closer Look at Depression: Modern Science on Its Mechanisms, Diagnosis, and New Treatment Options

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This review summarizes key findings and modern perspectives on depression, based entirely on the publication "Major depressive disorder: hypothesis, mechanism, prevention and treatment" in the journal Signal Transduction and Targeted Therapy (2024), authored by Lulu Cui, Shu Li, Siman Wang, Xiafang Wu, Yingyu Liu, Weiyang Yu, Yijun Wang, Yong Tang, Maosheng Xia, and Baoman Li. The team includes researchers and clinicians from China Medical University, Chengdu University of Traditional Chinese Medicine, and leading laboratories in the fields of forensic medicine, biological sciences, and neuroscience.

In their article, the authors explore the pathogenesis, mechanisms, diagnosis, prevention, and treatment of major depressive disorder (MDD), presenting the latest scientific data, theories, and treatment opportunities that are reshaping how we understand and manage the condition. The following questions and answers are selected based on their analysis and conclusions, aiming to offer patients and their loved ones the most up-to-date, reliable, and evidence-based information available.

What the Experts Say 

Depression isn’t just a passing bad mood or a weakness of character. It’s a complex, multifactorial illness that involves biology, psychology, social environment, and even physical health. The scientific article "Major depressive disorder: hypothesis, mechanism, prevention and treatment" analyzes the latest theories on the origin and development of depression, as well as methods for its diagnosis and treatment. Below, we’ve selected five expert insights and scientific summaries, supported by direct quotes, to guide patients and their families toward a state-of-the-art understanding of this disorder.

1. Why can’t depression be explained by just one cause?

"The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis hypothesis, cytokine hypothesis, neuroplasticity hypothesis and systemic influence hypothesis, but these hypotheses cannot completely explain the pathological mechanism of MDD. Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD, thus in recent years, great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies, further revealing the disease features of MDD."

Explanation: Depression isn’t caused by one single factor. Today’s science considers a wide range of interacting elements—from brain chemistry and stress hormones to inflammation and genetics. As a result, treatment is becoming increasingly personalized and multidisciplinary.

2. What role do genetics and stress play? Can depression be inherited?

"As a genetically diverse illness, MDD has a heritability of 30–50%... genetic variants are expected to have only minor effects on the overall risk of disease, and various hereditary factors combined with environmental factors such as stress are likely more essential for the development of MDD."

Explanation: Yes, depression often runs in families, but it’s not inherited like eye color. It’s more the result of an interaction between genetic predisposition and life stressors. For example, major life disruptions like job loss or divorce can trigger a depressive episode, especially in those with a genetic vulnerability.

3. Can depression appear as part of other diseases? What are the risks?

"The presence of MDD is a risk factor for a variety of complications, including neurodegenerative diseases (such as dementia, Alzheimer’s disease, and Parkinson’s disease), cardiovascular diseases (such as ischemic coronary artery disease and myocardial infarction), metabolic and endocrine diseases (such as obesity in females and diabetes in males), and some autoimmune diseases... patients with MDD have been demonstrated to have a shorter life expectancy. Additionally, the worsening of comorbidities could be a factor in the premature mortality of MDD patients."

Explanation: Depression affects more than just the mind. It increases the risk of several serious physical illnesses—and chronic conditions can also trigger depression. Treating depression can improve not only mental but also physical health.

4. How do antidepressants work, and why don’t they help everyone the same way?

"Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that have been proven to successfully treat clinical depression, were developed in response to this hypothesis [monoamine hypothesis]... Monoamine oxidase (MAO) activates the metabolism of adrenaline and triggers calcium signaling in astrocytes, which suggests that antidepressants may directly affect astrocytes by preventing them from reabsorbing monoamines."

Explanation: Antidepressants work through complex mechanisms—they affect not only neurons but also other brain cells like astrocytes. This may explain why a medication helps one person but not another. It often takes different trials, combinations, and patience to find an effective treatment.

5. What’s the link between inflammation, immunity, and depression? Can inflammation cause depression?

"MDD is accompanied by changes in the levels of proinflammatory cytokines and trophic factors, including BDNF, interleukins (IL-1β, IL-6), and tumor necrosis factor alpha (TNF-α). Increasing data suggest that the production of certain cytokines by brain astrocytes plays a significant role in the pathogenesis of MDD... using the right antioxidants to combat ROS may be a useful method for treating MDD."

Explanation: We now know that depression is often associated with chronic inflammation and immune system changes. For some people, depression may actually have an “inflammatory” origin. This discovery opens new treatment possibilities—including antioxidants and anti-inflammatory drugs.

Q&A

1. Why do depression symptoms vary so much from person to person? 

Answer: Depression manifests with a wide range of symptoms—not just low mood, but also physical changes like fatigue, weight loss or gain, lack of motivation, cognitive issues, sleep disturbances, guilt, and even suicidal thoughts. This variety exists because depression affects different brain and body regions and involves numerous biological, genetic, social, and psychological factors. That’s why diagnosis can be difficult—there’s no single biomarker or universal depression profile.

2. Is it possible to prevent depression, and what are today’s strategies for prevention? 

Answer: Preventing depression is challenging due to its complexity, but several approaches to early intervention are being explored. These include stress reduction, maintaining social connections, early identification of risk factors (e.g., family history, chronic illness), healthy lifestyle habits, and psychoeducation. Current research shows that improving psychosocial environments and managing chronic illnesses effectively can lower the risk of developing depression.

3. What are the latest therapeutic methods, and what alternatives exist beyond standard medications? 

Answer: Beyond traditional antidepressants, new medications and non-drug therapies are emerging. For example, some drugs now target specific receptors or immune mechanisms. The article highlights that phototherapy (light treatment) and acupuncture have shown positive effects in certain patients. Researchers are also exploring antioxidants and treatments aimed at inflammation. More and more therapies are being tailored to meet individual patient needs.

4. What is the connection between depression and brain cell function, especially astrocytes and glial cells? 

Answer: It’s now clear that not just neurons but also glial cells—especially astrocytes—play a key role in depression. Studies show that in depression, the number and function of astrocytes in areas like the prefrontal cortex and hippocampus are reduced. This impacts neurotransmitter metabolism, oxidative stress defense, and inflammation. New drugs are even being developed to improve astrocyte function and ease depression symptoms.

5. Could depression be caused by changes in the immune system and inflammation? What does that mean for treatment? 

Answer: The article confirms that depression is often linked to chronic inflammation and immune system imbalances, shown by elevated levels of proinflammatory cytokines (like IL-1β, IL-6, TNF-α). This link opens the door to using anti-inflammatory agents, antioxidants, and therapies that reduce oxidative stress. Scientific evidence suggests that for certain forms of depression—especially in patients with inflammation or autoimmune conditions—these treatments can be especially effective.

Conclusion 

Major depressive disorder remains one of the most complex and challenging conditions in modern medicine, affecting millions of people worldwide and impacting both mental and physical health. Recent research, as synthesized by Cui, Li, and co-authors (2024), shows that depression is a multidimensional illness that cannot be explained by a single mechanism or treated with a one-size-fits-all approach. Pathological changes in brain cells, the role of inflammation, genetic influences, comorbid conditions, and the social environment all create a complex picture that demands an individualized and holistic approach to each patient.

The hope these studies bring lies in the expanding possibilities for diagnosis and treatment—from traditional medications to innovative therapies targeting specific mechanisms. For patients, this means a greater chance of receiving effective care, staying informed, and enjoying a better quality of life when they seek support and treatment based on modern science.

Source: Cui, L., Li, S., Wang, S., et al. "Major depressive disorder: hypothesis, mechanism, prevention and treatment", Signal Transduction and Targeted Therapy (2024), 9:30. DOI: 10.1038/s41392-024-01738-y