炎癥是導致抑郁癥的缺失環(huán)節(jié)嗎？

了解抑郁癥的神經(jīng)炎癥模型。

關(guān)鍵點

大腦的神經(jīng)炎癥會導致抑郁癥。

神經(jīng)炎癥會損害大腦細胞。

慢性壓力會導致神經(jīng)炎癥。

當我們想到抑郁癥時，我們經(jīng)常會聽到大腦中涉及血清素、去甲腎上腺素和多巴胺等分子的化學失衡。但越來越多的研究表明，炎癥（人體對壓力、感染或傷害的自然免疫反應）可能在抑郁癥的發(fā)展中起著關(guān)鍵作用。這種新穎的想法被稱為抑郁癥的神經(jīng)炎癥模型，它或許可以解釋為什么抑郁癥會讓人感到如此身體疲憊和精神衰弱。

什么是神經(jīng)炎癥？

炎癥是人體的天然防御機制。當你受傷、遭受創(chuàng)傷或感染時，你的免疫系統(tǒng)會釋放一種叫做細胞因子的化學物質(zhì)來抵抗問題。然而，炎癥并不總是停留在它應該停留的地方。在神經(jīng)炎癥中，這些炎癥化學物質(zhì)會進入大腦并引起問題，導致情緒低落、疲勞和腦霧等癥狀，這些都是重度抑郁癥 (MDD) 的典型癥狀。

傳統(tǒng)上，抑郁癥與大腦化學物質(zhì)（即神經(jīng)遞質(zhì)）的缺乏有關(guān)，但科學家們現(xiàn)在發(fā)現(xiàn)，慢性炎癥可能同樣重要，甚至更重要。所以，讓我們仔細看看神經(jīng)炎癥如何成為理解抑郁癥的缺失拼圖。

炎癥如何導致抑郁？

炎癥會影響細胞因子水平和小膠質(zhì)細胞的功能，從而導致抑郁癥。細胞因子是免疫系統(tǒng)釋放的小蛋白質(zhì)，用于抵抗感染或修復損傷。但問題是：抑郁癥患者的細胞因子水平通常異常高。兩種關(guān)鍵的炎癥細胞因子，白細胞介素 6 (IL-6) 和腫瘤壞死因子-α (TNF-α)，已被證明會導致抑郁癥狀，如疲勞、缺乏動力，以及認知障礙，如思考或集中注意力困難。

例如，一項大型研究分析發(fā)現(xiàn)，IL-6 水平較高的人更容易出現(xiàn)嚴重的抑郁癥狀。這些細胞因子可以穿過血腦屏障（大腦的保護屏障），并引發(fā)與情緒和認知有關(guān)的大腦區(qū)域的炎癥。

一旦炎癥細胞因子進入大腦，它們就會激活小膠質(zhì)細胞，即大腦的免疫細胞。小膠質(zhì)細胞就像大腦的清潔工，但當它們超負荷運轉(zhuǎn)時，弊大于利。激活的小膠質(zhì)細胞會釋放活性氧(ROS) 和喹啉酸等有毒物質(zhì)，這些物質(zhì)會損害腦細胞并破壞正常的大腦功能。

喹啉酸會過度刺激一種稱為 NMDA 受體的大腦受體，導致神經(jīng)元受損或死亡。炎癥還會減緩新腦細胞的產(chǎn)生，這一過程稱為神經(jīng)發(fā)生。這一過程發(fā)生在海馬體中，海馬體是大腦中在情緒調(diào)節(jié)和記憶方面發(fā)揮重要作用的區(qū)域。

研究發(fā)現(xiàn)，抑郁癥患者的小膠質(zhì)細胞活性增加，尤其是在海馬體和前額葉皮質(zhì)中。這可以解釋為什么抑郁癥常常伴有認知困難和情緒失調(diào)。

壓力和免疫系統(tǒng)如何相互作用

炎癥的最大誘因之一是慢性壓力。當我們處于壓力之下時，我們的身體會激活下丘腦-垂體-腎上腺 (HPA) 軸，從而刺激激素 皮質(zhì)醇的釋放。小劑量的皮質(zhì)醇有助于對抗炎癥，但當壓力變成慢性時，就會發(fā)生一些奇怪的事情。身體對皮質(zhì)醇產(chǎn)生抵抗力，因此不再有效抑制炎癥。相反，IL-6 和 TNF-α 等炎癥細胞因子會增加，形成壓力和炎癥的惡性循環(huán)。這就是為什么壓力會在情感和身體上讓人感到疲憊的原因。身體的免疫反應本質(zhì)上會變得過度活躍，導致抑郁癥狀。

炎癥與其他健康問題之間的聯(lián)系

神經(jīng)炎癥模型的另一個有趣方面是它如何將抑郁癥與其他健康狀況聯(lián)系起來。例如，患有自身免疫性疾病、肥胖癥和心臟病等慢性炎癥的人患抑郁癥的風險要高得多。但為什么這些疾病會增加抑郁癥的發(fā)病率呢？

其中一個原因可能是慢性疾病會引發(fā)持續(xù)性炎癥。炎癥細胞因子與大腦溝通，導致情緒和行為發(fā)生變化。結(jié)果就是身體疾病加劇抑郁癥，而抑郁癥又惡化身體健康。這凸顯了在治療抑郁癥時，身心兩方面治療的重要性。

可以通過治療炎癥來緩解抑郁癥嗎？

好消息是，了解炎癥在抑郁癥中的作用為治療開辟了新的機會。雖然傳統(tǒng)抗抑郁藥針對的是血清素、去甲腎上腺素和多巴胺等神經(jīng)遞質(zhì)，但新研究表明，減少炎癥也可能有助于改善抑郁癥狀。

抗炎藥物，如非甾體抗炎藥（例如布洛芬）和細胞因子抑制劑，在減輕抑郁癥狀方面已顯示出良好的效果，尤其是對炎癥水平較高的患者。例如，一項使用 TNF-α 抑制劑英夫利昔單抗的研究發(fā)現(xiàn)，它能改善炎癥水平較高的患者的情緒。然而，這些藥物也存在很大的風險。

減少炎癥的生活方式改變也有助于控制抑郁癥。例如，定期進行體育鍛煉可以降低炎癥標志物并改善情緒。此外，抗炎飲食也可能有幫助。富含omega-3脂肪酸的食物（如魚）、水果和蔬菜可以減少炎癥并改善心理健康。此外，正念、冥想和良好的睡眠衛(wèi)生等減壓技巧有助于舒緩 HPA 軸并減輕炎癥。最后，具有抗炎特性的補充劑可以幫助緩解抑郁癥狀，進一步支持炎癥與抑郁之間的聯(lián)系。

抑郁癥的神經(jīng)炎癥模型正在改變科學家對心理健康的理解。它表明抑郁癥不僅僅是一種大腦疾病，也是一種免疫系統(tǒng)疾病。雖然需要更多的研究來充分了解這種聯(lián)系，但這種模型強調(diào)了綜合治療方法的重要性，這種方法既能解決炎癥問題，又能調(diào)節(jié)情緒。對于與抑郁癥作斗爭的人來說，這項研究充滿希望。這意味著針對炎癥的療法，無論是通過藥物、飲食還是生活方式的改變，都可以提供新的康復途徑。

總結(jié)

如果你曾經(jīng)覺得抑郁癥不僅僅是一種“壞心情”，那么你并不孤單。神經(jīng)炎癥模型表明，炎癥會影響大腦，導致疲勞、精力不足和思維困難。這一新認識為創(chuàng)新治療打開了大門，并強調(diào)了照顧整個身體而不僅僅是大腦的重要性。通過針對炎癥，我們可能能夠比以往更有效地應對抑郁癥。

因此，下次你聽到有人說抑郁癥完全是你的錯覺時，你就會知道它實際上可能存在于你的免疫系統(tǒng)中。這種理解為與抑郁癥作斗爭的人們帶來了希望，因為它提出了可能很快能提供更大緩解的新治療方法。

參考

Su, Kuan-Pin 等人?！癘mega-3 脂肪酸在預防干擾素-α 誘發(fā)的抑郁癥中的作用：一項隨機對照試驗的結(jié)果?！?《生物精神病學》 76.7（2014 年）：559–566。

Raison, Charles L. 等人。“腫瘤壞死因子拮抗劑英夫利昔單抗治療難治性抑郁癥的隨機對照試驗：基線炎癥生物標志物的作用。” JAMA Psychiatry 70.1（2013 年）：31–41。

Miller, Andrew H. 和 Charles L. Raison?！把装Y在抑郁癥中的作用：從進化必然性到現(xiàn)代治療目標。” 《自然免疫學評論》 16.1（2016）：22–34。

Setiawan, Elaine 等人?！稗D(zhuǎn)運蛋白密度（神經(jīng)炎癥標志物）在重度抑郁發(fā)作期間在大腦中的作用?！?JAMA Psychiatry 72.3（2015 年）：268–275。

Goldsmith, David R. 等人?！把装Y相關(guān)的功能和結(jié)構(gòu)失聯(lián)是導致精神病理學的途徑?！?《生物精神病學》 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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