译语翻译分享-为什么精神类药物会使人变胖？

 

首先要搞明白药物是怎么起作用的。

The first step is to understand how the drug works.

针对精神病性症状（Psychosis）的病理机制有几个假说，其中一个假说就是多巴胺通路假说。

There are several hypotheses regarding the pathological mechanism of Psychosis, one of which is the dopamine pathway hypothesis.

 

这就要提到多巴胺的四条通路（指多巴胺在体内传播的路径）：

This will mention the four pathways of dopamine (referring to the way dopamine spreads in the body):

一、中脑边缘多巴胺通路：

1. Limbic dopamine pathway:

这条通路主要有两个作用。①产生欣快感（奖赏机制）。②对于当前情境作出快速评估，决策。

This pathway has two main functions. ① Produce euphoria (reward mechanism). ② Make a quick assessment and decision-making for the current situation.

欣快感很好理解，多巴胺是一种大脑分泌的神经递质，多巴胺水平高的时候，人会很开心，很兴奋，有很多吸毒、物质滥用的就是因为这个而上瘾，因为这条通路会不断让人获得精神上的|奖赏|。（所以会有那种物质滥用诱发的精神病性症状（Drug-induced psychosis)）

Euphoria is well understood. Dopamine is a neurotransmitter secreted by the brain. When the level of dopamine is high, people will be very happy and excited. Many drug users and substance abusers are addicted because of this, because this pathway will continue. Let people get a spiritual |reward|. (So ​​there will be that kind of substance abuse induced psychosis (Drug-induced psychosis))

但是，影响欣快感的同时，也会影响到我们的快速决策系统。当多巴胺分泌过多时，我们的决策系统会变得异常活跃，简单来说就是会变得过度敏感、过度反应。这就是常见的精神病性症状 - 妄想、幻觉产生的基础。

However, while affecting euphoria, it also affects our rapid decision-making system. When dopamine is secreted too much, our decision-making system will become abnormally active. Simply put, it will become over-sensitive and over-reacting. This is the basis for common psychotic symptoms-delusions and hallucinations.

比如，本来简单的和他人的目光接触，演变为“他为什么要盯着我看？他是不是想害我？“”刚才那个路人碰了我一下，他是不是借此在我饭菜里下毒？”由此产生的妄想、幻觉，也就是精神病性症状中常提到的阳性症状（Positive Symptoms）。

For example, the original simple eye contact with others has evolved into "Why is he staring at me? Is he trying to harm me?" The passerby just touched me, did he use it to poison my food? ?" The resulting delusions and hallucinations are the positive symptoms (Positive Symptoms) often mentioned in psychotic symptoms.

目前抗精神病药物的主要逻辑，就是阻滞多巴胺受体，受体接受不到多巴胺了，那么就相当于多巴胺的活跃度下降，给原本过于活跃的中脑边缘多巴胺通路[降降温]。

At present, the main logic of antipsychotic drugs is to block dopamine receptors, and the receptors cannot accept dopamine, then it is equivalent to a decrease in dopamine activity, and to the originally overactive midbrain limbic dopamine pathway [cooling down].

二、中脑皮质多巴胺通路：

2. Midbrain cortex dopamine pathway:

这一条通路主要和大脑的前额叶相关。前额叶在大脑结构中承担着相对高级的功能，包括认知、思考、动力、社交。和大脑的其他区域不同，前额叶显得相对“高级”。与之相反，比如，脑干主要是影响呼吸、影响心跳，这都是一个生物为了活着，发展出的相对基本、低级的功能，而高度发展的前额叶是[人之所以为人，区别于其他生物]的一个很大原因，因此其重要性可想而知。

This pathway is mainly related to the prefrontal lobe of the brain. The prefrontal lobe bears relatively high-level functions in the brain structure, including cognition, thinking, motivation, and social interaction. Unlike other areas of the brain, the prefrontal lobe appears relatively "advanced." On the contrary, for example, the brain stem mainly affects breathing and heartbeat. This is a relatively basic and low-level function developed by a creature in order to live, and the highly developed prefrontal lobe is [the reason why people are humans is different from other Biology] is a big reason, so its importance can be imagined.

在精神病性症状中，这一条与前额叶相关的多巴胺通路，恰恰不那么活跃，体现出机能的衰弱。因此造成的表现是，认知功能受损，社交功能退化。也就是常说的，阴性症状（Negative Symptoms）。

In psychotic symptoms, this dopamine pathway related to the prefrontal lobe is just not so active, reflecting the weakness of the function. The resulting performance is impaired cognitive function and degraded social function. That is to say, negative symptoms (Negative Symptoms).

补充说明：阴性症状：指人们似乎对周围的世界感到孤立，对日常的社会交往不感兴趣，而且经常表现得没有感情和平淡

Supplementary note: Negative symptoms: People seem to feel isolated from the world around them, are not interested in daily social interactions, and often show no emotion and flatness

药物的副作用（药物的作用机制是让多巴胺受体阻滞，接收不到多巴胺），可能会加重阴性症状。不过这种副作用已经在非典型抗精神病药物（新一代）中得以改善，非典型抗精神病药物可以在降温中脑边缘多巴胺通路的同时（即减轻阳性症状），增加中脑皮质多巴胺通路的活性（减轻阴性症状）。

The side effects of the drug (the mechanism of action of the drug is to block the dopamine receptors and not receive dopamine), which may aggravate the negative symptoms. However, this side effect has been improved in atypical antipsychotics (new generation). Atypical antipsychotics can reduce the temperature of the limbic dopamine pathway (that is, reduce the positive symptoms) and increase the activity of the dopamine pathway in the midbrain cortex ( Alleviate negative symptoms).

三、黑质纹状体多巴胺通路：

3. Dopamine pathway in substantia nigra striatum:

这条通路是锥体外系神经系统的一部分，控制着运动神经，如果有问题可能会产生帕金森病。这条通路的过度活跃，可能会产生运动机能亢进（比如舞蹈症、局部抽搐）。

This pathway is part of the extrapyramidal nervous system and controls the motor nerves. If there is a problem, Parkinson's disease may occur. Overactivity of this pathway may cause hyperkinesis (such as chorea, local convulsions).

精神分裂症患者的这条通路本身没有大问题。但是由于抗精神病药物是专注于多巴胺的，我们很难控制多巴胺在具体某个通路上的活动如何，所以当给药时，影响到通路一，就会影响到通路二、三、四。也就产生了，抗精神病药物的常见副作用：

There is no major problem with this pathway for schizophrenic patients. However, since antipsychotic drugs are focused on dopamine, it is difficult for us to control how dopamine is active in a specific pathway. Therefore, when the drug is administered, it affects pathway one, and will affect pathway two, three, and four. This also resulted in the common side effects of antipsychotic drugs:

①静坐不能（Akathisia):表现为烦躁不安，不能静坐或静卧，反复走动或原地踏步走，可伴有不自主运动。

①Akathisia: manifested as irritability, inability to sit or lie still, walk around repeatedly or walk in place, which may be accompanied by involuntary movement.

②急性肌张力不全：表现为眼、面、口、颈等局部性肌痉挛所致的怪异表现。

②Acute dystonia: manifested as strange manifestations caused by local muscle spasms of the eyes, face, mouth, and neck.

四、结节漏斗多巴胺通路：

4. Nodular funnel dopamine pathway:

从下丘脑发出投射到垂体前叶，影响催乳素的分泌。

Projections from the hypothalamus to the anterior pituitary gland affect the secretion of prolactin.

精神分裂症患者这一条通路本身没有大问题。只是药物的副作用对这条通路有所影响。多巴胺受体 D2 被阻滞后，会引起催乳素升高，引起泌乳现象（即使未怀孕），月经紊乱等。确实在病房里，经常会看到，刚进来比较瘦弱的女孩子，吃药吃了一个多月之后，体重明显上升,这种现象比较常见。

There is no major problem with this pathway in schizophrenia. It's just the side effects of the drug that affect this pathway. The delayed dopamine receptor D2 will cause the increase of prolactin, cause lactation (even if not pregnant), menstrual disorders, etc. Indeed, in the ward, one often sees that a relatively thin girl who has just come in has a significant increase in weight after taking medicine for more than a month. This phenomenon is more common.

to sum up:

本文介绍了一些常见的抗精神病药物（Antipsychotics)的副作用，包括：锥体外系症状（静坐不能、急性肌张力不全等）、引发泌乳，月经紊乱等。其余的副作用通常还包括体重增加

、口干、便秘等。

This article introduces the side effects of some common antipsychotics, including: extrapyramidal symptoms (akathisia, acute dystonia, etc.), lactation, menstrual disorders, etc. Other side effects usually include weight gain

, dry mouth, constipation, etc.

副作用这么多，我该怎么选择？

With so many side effects, how should I choose?

总的来说，医生会根据你的情况，帮你匹配合适的药物，这通常需要一些“试验”和耐心。不是副作用越小就越好，虽然副作用小，但这药可能对你也没有用。而且不是所有的副作用对每个人来说都同等重要。比如，一个肝功能代谢本来就不太好的人，可能不适合药物 A（药物 A 对肝脏的影响更大，但疗效更好），更适合药物 B；而另一个没有代谢问题的人，可能就适合药物 A 多一些（但是肝脏负担重一些）。副作用只是我们选择药物时考虑的其中一个维度。

In general, the doctor will help you match the right medicine according to your situation, which usually requires some "testing" and patience. It’s not that the smaller the side effects, the better. Although the side effects are small, the medicine may not be useful for you. And not all side effects are equally important to everyone. For example, a person with poor liver function metabolism may not be suitable for drug A (drug A has a greater impact on the liver, but the effect is better), and is more suitable for drug B; while another person without metabolic problems may It is more suitable for drug A (but heavier burden on the liver). Side effects are just one of the dimensions we consider when choosing drugs.