炎症是导致抑郁症的缺失环节吗？

了解抑郁症的神经炎症模型。

关键点

大脑的神经炎症会导致抑郁症。

神经炎症会损害大脑细胞。

慢性压力会导致神经炎症。

当我们想到抑郁症时，我们经常会听到大脑中涉及血清素、去甲肾上腺素和多巴胺等分子的化学失衡。但越来越多的研究表明，炎症（人体对压力、感染或伤害的自然免疫反应）可能在抑郁症的发展中起着关键作用。这种新颖的想法被称为抑郁症的神经炎症模型，它或许可以解释为什么抑郁症会让人感到如此身体疲惫和精神衰弱。

什么是神经炎症？

炎症是人体的天然防御机制。当你受伤、遭受创伤或感染时，你的免疫系统会释放一种叫做细胞因子的化学物质来抵抗问题。然而，炎症并不总是停留在它应该停留的地方。在神经炎症中，这些炎症化学物质会进入大脑并引起问题，导致情绪低落、疲劳和脑雾等症状，这些都是重度抑郁症 (MDD) 的典型症状。

传统上，抑郁症与大脑化学物质（即神经递质）的缺乏有关，但科学家们现在发现，慢性炎症可能同样重要，甚至更重要。所以，让我们仔细看看神经炎症如何成为理解抑郁症的缺失拼图。

炎症如何导致抑郁？

炎症会影响细胞因子水平和小胶质细胞的功能，从而导致抑郁症。细胞因子是免疫系统释放的小蛋白质，用于抵抗感染或修复损伤。但问题是：抑郁症患者的细胞因子水平通常异常高。两种关键的炎症细胞因子，白细胞介素 6 (IL-6) 和肿瘤坏死因子-α (TNF-α)，已被证明会导致抑郁症状，如疲劳、缺乏动力，以及认知障碍，如思考或集中注意力困难。

例如，一项大型研究分析发现，IL-6 水平较高的人更容易出现严重的抑郁症状。这些细胞因子可以穿过血脑屏障（大脑的保护屏障），并引发与情绪和认知有关的大脑区域的炎症。

一旦炎症细胞因子进入大脑，它们就会激活小胶质细胞，即大脑的免疫细胞。小胶质细胞就像大脑的清洁工，但当它们超负荷运转时，弊大于利。激活的小胶质细胞会释放活性氧(ROS) 和喹啉酸等有毒物质，这些物质会损害脑细胞并破坏正常的大脑功能。

喹啉酸会过度刺激一种称为 NMDA 受体的大脑受体，导致神经元受损或死亡。炎症还会减缓新脑细胞的产生，这一过程称为神经发生。这一过程发生在海马体中，海马体是大脑中在情绪调节和记忆方面发挥重要作用的区域。

研究发现，抑郁症患者的小胶质细胞活性增加，尤其是在海马体和前额叶皮质中。这可以解释为什么抑郁症常常伴有认知困难和情绪失调。

压力和免疫系统如何相互作用

炎症的最大诱因之一是慢性压力。当我们处于压力之下时，我们的身体会激活下丘脑-垂体-肾上腺 (HPA) 轴，从而刺激激素 皮质醇的释放。小剂量的皮质醇有助于对抗炎症，但当压力变成慢性时，就会发生一些奇怪的事情。身体对皮质醇产生抵抗力，因此不再有效抑制炎症。相反，IL-6 和 TNF-α 等炎症细胞因子会增加，形成压力和炎症的恶性循环。这就是为什么压力会在情感和身体上让人感到疲惫的原因。身体的免疫反应本质上会变得过度活跃，导致抑郁症状。

炎症与其他健康问题之间的联系

神经炎症模型的另一个有趣方面是它如何将抑郁症与其他健康状况联系起来。例如，患有自身免疫性疾病、肥胖症和心脏病等慢性炎症的人患抑郁症的风险要高得多。但为什么这些疾病会增加抑郁症的发病率呢？

其中一个原因可能是慢性疾病会引发持续性炎症。炎症细胞因子与大脑沟通，导致情绪和行为发生变化。结果就是身体疾病加剧抑郁症，而抑郁症又恶化身体健康。这凸显了在治疗抑郁症时，身心两方面治疗的重要性。

可以通过治疗炎症来缓解抑郁症吗？

好消息是，了解炎症在抑郁症中的作用为治疗开辟了新的机会。虽然传统抗抑郁药针对的是血清素、去甲肾上腺素和多巴胺等神经递质，但新研究表明，减少炎症也可能有助于改善抑郁症状。

抗炎药物，如非甾体抗炎药（例如布洛芬）和细胞因子抑制剂，在减轻抑郁症状方面已显示出良好的效果，尤其是对炎症水平较高的患者。例如，一项使用 TNF-α 抑制剂英夫利昔单抗的研究发现，它能改善炎症水平较高的患者的情绪。然而，这些药物也存在很大的风险。

减少炎症的生活方式改变也有助于控制抑郁症。例如，定期进行体育锻炼可以降低炎症标志物并改善情绪。此外，抗炎饮食也可能有帮助。富含omega-3脂肪酸的食物（如鱼）、水果和蔬菜可以减少炎症并改善心理健康。此外，正念、冥想和良好的睡眠卫生等减压技巧有助于舒缓 HPA 轴并减轻炎症。最后，具有抗炎特性的补充剂可以帮助缓解抑郁症状，进一步支持炎症与抑郁之间的联系。

抑郁症的神经炎症模型正在改变科学家对心理健康的理解。它表明抑郁症不仅仅是一种大脑疾病，也是一种免疫系统疾病。虽然需要更多的研究来充分了解这种联系，但这种模型强调了综合治疗方法的重要性，这种方法既能解决炎症问题，又能调节情绪。对于与抑郁症作斗争的人来说，这项研究充满希望。这意味着针对炎症的疗法，无论是通过药物、饮食还是生活方式的改变，都可以提供新的康复途径。

总结

如果你曾经觉得抑郁症不仅仅是一种“坏心情”，那么你并不孤单。神经炎症模型表明，炎症会影响大脑，导致疲劳、精力不足和思维困难。这一新认识为创新治疗打开了大门，并强调了照顾整个身体而不仅仅是大脑的重要性。通过针对炎症，我们可能能够比以往更有效地应对抑郁症。

因此，下次你听到有人说抑郁症完全是你的错觉时，你就会知道它实际上可能存在于你的免疫系统中。这种理解为与抑郁症作斗争的人们带来了希望，因为它提出了可能很快能提供更大缓解的新治疗方法。

参考

Su, Kuan-Pin 等人。“Omega-3 脂肪酸在预防干扰素-α 诱发的抑郁症中的作用：一项随机对照试验的结果。” 《生物精神病学》 76.7（2014 年）：559–566。

Raison, Charles L. 等人。“肿瘤坏死因子拮抗剂英夫利昔单抗治疗难治性抑郁症的随机对照试验：基线炎症生物标志物的作用。” JAMA Psychiatry 70.1（2013 年）：31–41。

Miller, Andrew H. 和 Charles L. Raison。“炎症在抑郁症中的作用：从进化必然性到现代治疗目标。” 《自然免疫学评论》 16.1（2016）：22–34。

Setiawan, Elaine 等人。“转运蛋白密度（神经炎症标志物）在重度抑郁发作期间在大脑中的作用。” JAMA Psychiatry 72.3（2015 年）：268–275。

Goldsmith, David R. 等人。“炎症相关的功能和结构失联是导致精神病理学的途径。” 《生物精神病学》 93.5（2023 年）：405–418。

Is Inflammation the Missing Link to Depression?

Understanding the neuroinflammation model of depression.

KEY POINTS

Neuroinflammation in the brain can cause depression.

Neuroinflammation can damage cells in the brain.

Chronic stress can lead to neuroinflammation.

Neuroinflammation

Source: peterschreiber/iStock

When we think of depression, we often hear about chemical imbalances in the brain involving molecules like serotonin, norepinephrine, and dopamine. But there’s a growing body of research suggesting that inflammation, which is the body’s natural immune response to stress, infection, or injury, could play a key role in the development of depression. This novel idea is called the neuroinflammation model of depression, and it may explain why depression can feel so physically exhausting and mentally debilitating.

What Is Neuroinflammation?

Inflammation is your body’s natural defense mechanism. When you have an injury, suffer a trauma, or develop an infection, your immune system releases chemicals called cytokines to fight off the problem. However, inflammation doesn’t always stay where it belongs. In neuroinflammation, these inflammatory chemicals cross into the brain and cause trouble, leading to symptoms like low mood, fatigue, and brain fog, which are classic symptoms of major depressive disorder (MDD).

Traditionally, depression has been linked to deficiencies in brain chemicals known as neurotransmitters, but scientists are now finding that chronic inflammation might be equally, if not more, important. So, let’s take a closer look at how neuroinflammation could be the missing puzzle piece in understanding depression.

How Does Inflammation Cause Depression?

Inflammation can cause depression by influencing the levels of cytokines and the functioning of microglia. Cytokines are small proteins released by the immune system to fight off infections or repair damage. But here’s the problem: In people with depression, cytokine levels are often abnormally high. Two key inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), have been shown to contribute to depressive symptoms like fatigue, lack of motivation, and cognitive impairments such as difficulty thinking or concentrating.

For example, a large analysis of studies found that people with higher levels of IL-6 were more likely to experience severe depressive symptoms. These cytokines can cross the blood-brain barrier, a protective shield for the brain, and trigger inflammation in brain regions involved in mood and cognition.

Once inflammatory cytokines enter the brain, they activate microglia, the brain’s immune cells. Microglia are like the brain’s cleanup crew, but when they’re in overdrive, they can do more harm than good. Activated microglia release toxic substances like reactive oxygen species (ROS) and quinolinic acid, which damage brain cells and disrupt normal brain function.

Quinolinic acid overstimulates a type of brain receptor known as NMDA receptors, causing neurons to become damaged or die. Inflammation also slows the creation of new brain cells, a process known as neurogenesis. This occurs in the hippocampus, a region of the brain that plays a major role in mood regulation and memory.

Studies have found evidence of increased microglial activation in people with depression, particularly in the hippocampus and prefrontal cortex. This could explain why depression often comes with cognitive difficulties and emotional dysregulation.

Depression and neuroinflammation

Source: Alena Darmel / Pexels

How Stress and the Immune System Interact

One of the biggest triggers of inflammation is chronic stress. When we’re under stress, our body activates the hypothalamic-pituitary-adrenal (HPA) axis, which stimulates the release of the hormone cortisol. In small doses, cortisol helps fight inflammation, but when stress becomes chronic, something strange happens. The body becomes resistant to cortisol, so it no longer suppresses inflammation effectively. Instead, inflammatory cytokines like IL-6 and TNF-α increase, creating a vicious cycle of stress and inflammation. This is why stress can feel both emotionally and physically draining. The body’s immune response essentially becomes overactive, leading to symptoms of depression.

The Link Between Inflammation and Other Health Problems

Another fascinating aspect of the neuroinflammation model is how it connects depression to other health conditions. For example, people with chronic inflammatory conditions like autoimmune disorders, obesity, and heart disease are at a much higher risk of developing depression. But why do these conditions increase depression?

One reason may be that chronic medical conditions trigger persistent inflammation. Inflammatory cytokines communicate with the brain, causing changes in mood and behavior. The result is a cycle where physical illness worsens depression, and depression worsens physical health. This highlights the importance of treating both the mind and the body when it comes to depression.

Can Inflammation Be Treated to Help Depression?

The good news is that understanding the role of inflammation in depression opens up new opportunities for treatment. While traditional antidepressants target neurotransmitters like serotonin, norepinephrine, and dopamine, new research suggests that reducing inflammation may also help improve depressive symptoms.

Anti-inflammatory medications like NSAIDs (e.g., ibuprofen) and cytokine inhibitors have shown promise in reducing depressive symptoms, especially in people with elevated inflammation. For example, a study using infliximab, a TNF-α inhibitor, found that it improved mood in patients with high levels of inflammation. However, these medicines are also associated with significant risks.

Lifestyle changes that reduce inflammation can also help manage depression. For example, regular physical activity lowers inflammatory markers and boosts mood. Also, an anti-inflammatory diet may help. Foods rich in omega-3 fatty acids (like fish), fruits, and vegetables can reduce inflammation and improve mental health. Additionally, stress reduction techniques such as mindfulness, meditation, and good sleep hygiene help calm the HPA axis and lower inflammation. Finally, supplements with anti-inflammatory properties can help alleviate depressive symptoms, further supporting the inflammation-depression link.

The neuroinflammation model of depression is changing the way scientists understand mental health. It shows that depression isn’t just a disorder of the brain; it’s also a disorder of the immune system. While more research is needed to fully understand the connection, this model highlights the importance of an integrative approach to treatment that addresses both inflammation and mood regulation. For people struggling with depression, this research is hopeful. It means that therapies targeting inflammation, whether through medications, diet, or lifestyle changes, could offer new pathways to recovery.

The Takeaway

If you’ve ever felt like depression is more than just a “bad mood,” you’re not alone. The neuroinflammation model reveals that inflammation can affect the brain, leading to fatigue, low energy, and difficulty thinking. This new understanding opens the door to innovative treatments and highlights the importance of caring for your whole body, not just your brain. By targeting inflammation, we might be able to tackle depression more effectively than ever before.

So, the next time you hear someone say depression is all in your head, you’ll know thaf it may actually be in your immune system. This understanding provides hope for people battling depression by suggesting new treatments that may soon provide greater relief.

References

Su, Kuan-Pin, et al. "Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial." Biological Psychiatry 76.7 (2014): 559–566.

Raison, Charles L., et al. "A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers." JAMA Psychiatry 70.1 (2013): 31–41.

Miller, Andrew H., and Charles L. Raison. "The role of inflammation in depression: from evolutionary imperative to modern treatment target." Nature Reviews Immunology 16.1 (2016): 22–34.

Setiawan, Elaine, et al. "Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes." JAMA Psychiatry 72.3 (2015): 268–275.

Goldsmith, David R., et al. "Inflammation-related functional and structural dysconnectivity as a pathway to psychopathology." Biological Psychiatry 93.5 (2023): 405–418.

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