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Human Practices
After 2 times of brainstorms, we decided to do research on depressive disorder in 2022 iGEM competition season.
1. Survey work in our school
We know that some of students, our peers, in schools are suffering from depressive disorder since one our schoolmate dropped out of school because of this disease. In order to deeply understand this situation to help them, we did survey work in our school. To protect their privacy, we sent the questionnaires online, students may answer all questions with cellphone anonymously.
Fig.1 The questionnaire we set online for our school students.
We choose 2 questions’ responses to show here in the followings: The first question is that “Do you think you often feel depression?” From the result we can see that 20.54% of the respondents thought they often feel depression, indicating that depression accompanies some students’ daily life, and it happens often.
Fig.2 Responses to the question “Do you think you often feel depression?”
Note: About one fifth answered “yes” in our school students.
If the respondent answered “yes” to the above question, they would be asked the next question “when you feel depression, would you hurt yourself?" From the results we can see that more than half of the respondents thought they would hurt themselves, indicating that depressive disorder does great harm to the students. And the situation is very serious.
Fig.3 Responses to the question “when you feel depression, would you hurt yourself?”
(a): I've thought about it occasionally, but I haven't done it. (b): Occasionally thought about it and did it. (c): I hurt myself often, but not seriously. (d): Frequently engages in acts of serious self-harm. (e): attempted suicide.
2. Interview with the doctor of Shandong provincial mental health center
To understand the clinical situation, we interviewed Dr. Chen Xu, a doctor who ever studied in the United States, at Shandong provincial mental health center. Doctor Chen has devoted to the field of psychological consulting and treatment for more than 20 years. He knows the situation of depressive disorder, and is proficient in the diagnosis and treatment of this disease.
Fig.4 The doctor interview for depressive disorder
Here we summarized some contents of the interview with Dr. Chen as follows:
(1) Situations: The occurrence rate of depressive disorder is increasing with the fast pacing of society recent years, especially for the adolescent. People who come to his clinic ranges from teenager to the age of more than 50. As far as he knows, there are still some people suffering from this disease are not willing to see doctor because they are afraid that other people would treat them in a different way, and maybe keep away from them.
(2) progresses: Doctor Chen said that the onset of the depressive disorder is a long-term and gradual process. The early symptoms may be abnormal emotions, headache, prone to fatigue, weight loss, and quarrel with people, even muscle pain, itching and other symptoms. Most of the early depressive disorder will develop to the major depressive disorder (MDD) if they are not correctly diagnosed and intervened.
(3) Diagnosis and treatment: At present, the diagnosis of depressive disorder is mainly based on clinical symptoms, and the self-assessment scale, which is very subjective. Due to the lack of objective diagnosis method and concealed symptoms, as well as the privacy problems, missed diagnosis or misdiagnosis happens commonly in patients of MDD. It is reported that the misdiagnosis rate of MDD is more than 65%; the medical treatment rate of depressive disorder is very low; and 50% of patients are recurrent within 2 years after recovery. According to Dr. Chen’s introduction, that the mental health service resources are unevenly distributed in regions is another reason for low-rate recovery in China.
(4) Difficulty and challenge: From the interview with Dr. Chen, we know that the missed diagnosis, misdiagnosis, and lack of objective diagnosis method, as well as the misunderstanding for depressive disorder, are the main reasons that resulted in MDD, even some of them commit suicide. If the early depressive disorder patients could be diagnosed rapidly and intervened properly, or the MDD patients could be diagnosed objectively, they may receive appropriate medical treatment, preventing the development of MDD. So, it is particularly urgent to find a high sensitive and specific diagnostic method to increase the accuracy and objectivity of MDD diagnosis, helping clinicians make early screening and early intervention for MDD.
It is a challenge to everyone, making our team to develop a diagnosis method of MDD in our project.
3. Interview and Survey work in community
In order to understand people's cognition to depressive disorder and facilitate our project design, we set a questionnaire and interview some people to do a survey work in community. Our survey questions include people's attitude, communication, behavior, diagnosis, and treatment of depressive disorder, with the aim of which item would be focused on in our project.
Fig. 5 We communicated with people and did survey work in community
We choose the responses of some questions in the survey as follows:
The first question is that "Do you hear about major depression disorder (MDD)?" The statistical result showed that 85.34% of respondents once hear about it; 13.51% of them are familiar with it; and 1.15% of them hear nothing of it. From the answers of this question, we know that most people know about MDD, indicating that MDD is a common disease at present society, which should be paid more attention to this disease.
Fig.6 Responses to the question “Do you hear about major depression disorder (MDD)”
The second question is that "Do you think that people have misunderstanding of depressive disorder?" The result showed that more than 90% of respondents thought people have different extent misunderstandings about depressive disorder, indicating that people lack cognition of it, and propaganda the knowledge of this disease is needed.
Fig.7 Responses to the question “Do you think that people have misunderstanding of depressive disorder?”
(a): People have many misunderstandings of depressive disorder. (b): People have a little misunderstanding of depressive disorder. (c): People have little misunderstanding of depressive disorder. (d): They don’t know.
The third question is that "Do you talk to the depressive disorder patient carefully and try not to approach them?" From the result we can see that 82.51% of respondents said YES, indicating that people have concerns about talking to them.
Fig.8 Reponses to the question “Do you talk to the depressive disorder patient carefully and try not to approach them?”
The next question is that "What do you think are the drawbacks of the current diagnosis for depressive disorder?" From the result we can see that most people thought time-consuming, subjective, and inconvenient, even thought that it is inaccurate for MDD diagnosis, indicating that people have doubts about the diagnosis method of depressive disorder at present.
Fig.9 Reponses to the question “What do you think are the drawbacks of the current diagnosis for depressive disorder?”
(a): time-consuming. (b): subjective. (c): inconvenient. (d): inaccurate. (e): no drawbacks.
The last question is that "Do you think a good diagnosis method of depressive disorder can lead to better treatment?" The result showed that 90.91% of respondents said YES. It is widely believed that good diagnosis is crucial to the treatment of depressive disorder, especially for MDD.
Fig.10 Reponses to the question “Do you think a good diagnosis method of depressive disorder can lead to better treatment?”
Conclusion:
Through the interview with the doctor and survey work in school and in community, we know that:
(1) depressive disorder or MDD is a common disease which situation is very serious;
(2) most people have some misunderstanding for this disease;
(3) the diagnosis of depressive disorder or MDD is not good or objective at present.
All these findings confirmed us to develop a good objective diagnostic method for depressive disorder or MDD in our project.
Integrated human practices
4. Interview with Dr. Liu, a Professor of Shandong University
After we decided to focus on developing an objective diagnosis method for depressive disorder or MDD, we wanted to know the new progress of diagnosis, including what molecule could be used for MDD diagnosis? And how to use these molecules objectively? To broaden our knowledge, we interviewed Dr. Liu Zhifang who is a professor of Shandong University. Due to the epidemic covid-19, we held a virtual meeting with Dr. Liu (Fig.11 ).
Fig.11 Interview with Dr. Liu Zhifang in virtual meeting.
Dr. Liu introduced that biomarkers could be served as the diagnostic target molecules, including proteins and nucleic acids. In recent years, non-coding microRNAs (miRNAs), one kind of the nucleic acids, has attracted more and more attention in molecule diagnosis. miRNAs are a class of endogenous single stranded non coding RNAs that widely exist in eukaryotic cells. miRNAs can block or inhibit the translation of target mRNAs by completely or partially complementary base pairing with the 3' non coding region, so as to regulate the expression of target genes, affecting a wide range of physiological and pathological processes.
In the genesis and development of brain nerves, miRNAs play an important regulatory role. Its dysregulation is related to neuro developmental disorders, neurodegenerative diseases, affective mental disorders and other human nervous system diseases. Because it can be detected in blood, which is easy to obtain with little trauma and simple operation, more and more researchers have joined in the exploration of miRNA biomarkers.
Dr. Liu also told us some specific miRNAs are differentially expressed in depressive disorder which is higher than that in normal people. These miRNAs are also present in peripheral blood which could be used as biomarker for diagnosis. but we should consider the consistency between the changes of microRNAs in blood and in cerebrospinal fluid.
Through interview with Dr. Liu, we knew that miRNA can be used as biomarker for depressive disorder diagnosis, giving us a great enlightenment and less detours. Then we search for some literature, and found the target miRNAs to develop a new objective diagnostic method for depressive disorder.
5. Interview and survey work again in the community
After we designed our project that some miRNAs in blood are detected to diagnose the depressive disorder, we did the interview and survey work again, to understand the acceptability of this new objective diagnosis method by people in the community. Here we choose the responses to some questions, shown as follows:
The first question is that "Do you know that miRNA could be used as a biomarker to diagnose depressive disorder?" The result showed that more than 80% respondents answered NO, indicating that miRNA serving as a biomarker, is a new molecule, which needs to publicize (Fig.12 ).
Fig.12 Responses to the question “Do you know that miRNA could be used as a biomarker to diagnose depressive disorder?”
The next question is that "Do you accept the diagnosis method of depressive disorder by detecting miRNA in blood samples?" The result showed that most respondents can accept it, indicating that our project could be accepted by people (Fig.13 ).
Fig.13 Responses to the question “Do you accept the diagnosis method of depressive disorder by detecting miRNA in blood samples?”
We continued to ask the following question, “Do you go to hospital for diagnosis of depressive disorder by detecting miRNA in blood if you often feel depression?” The result showed that only 26.32% of respondents said YES, indicating that most people would not like to go to hospital for privacy protection, maybe they are prone to detect at home by himself (Fig.14 ).
Fig.14 Reponses to the question “Do you go to hospital for diagnosis of depressive disorder by detecting miRNA in blood if you often feel depression?”
From the responses above to the questions of the survey in community, we know that most people don’t know about miRNAs, but they can accept the diagnosis by detecting miRNAs in the blood. However, people still want to protect their privacy that they are not willing to go to hospital for diagnosis.
On the other hand, with the proceeding of our experiment, we found that the report proteins (amilCP, mRFP and amilGFP) we used to detect the miRNA are not very sensitive. With the two problems we encountered, we made appointment to interview Dr. Liu again.
6. Interview Dr. Liu again to solve problems
Dr. Liu suggested that it would be better if we use lacZ marker gene to replace the chromoprotein genes, because lacZ gene encodes β-galactosidase which catalyzes the enzymatic reaction to amplify the signals. Many different substrates are available for this enzyme. We can use the substrate X-Gal to test β-galactosidase activity, showing the levels of miRNA in the samples. This is really helpful!
To solve the problem that people are not willing to go to hospital, Dr. Liu also gave us a good suggestion. She suggested that we may develop a paper based biosensor using the cell free system, so that people can detect the changes of miRNA in blood by himself at home.
With the help of Dr. Liu, we constructed a toehold switch plasmid containing lacZ gene to replace the chromoprotein gene in vector; in addition, filter paper and cell free system were applied in the experiment, both of which modified the design of our project.
Since our product would be used at home, how to design it to be a convenient, portable device is important. Based on this idea, we interviewed a company to consult the design of our end product.
7. Communication with a technician of a company
With the question that how to translate our project into a product, we visited Shandong Bianjing Pharmaceutical Co., Ltd to understand the research and exploration process of the company's reagents and device (Fig.15 ). We listened to the introduction and explanation of technicians. Through communication, we got the inspiration to make a device for detecting paper strip, which is convenient, concise and portable. They are very interested in our project and look forward to further cooperation in the future.
Fig.15 We visited a company for inspiration to design a device for our project.
After visiting the company, we got the inspiration to make a 3D device model for detecting paper strip, which is convenient, concise, and portable (Fig.16 ).For detail contents, please refer to the hardware in contribution section.
Fig.16 3d-printed device, filter, and paper strip sensor
8. Education and communication
From the survey work in school, we know that some students are suffering from depressive disorder. In order to help them and introduce our project, we gave some lectures for students, please refer to Education and Communication section.
Conclusion:
(1) From the first interview with Dr. Liu, we found the miRNA serving as biomarker to diagnose depressive disorder, and we designed our project.
(2) The survey work in community let us know what type of product people need, which gave us idea to design the end product of our project.
(3) The second time of interview with Dr. Liu modified our project that chromoprotein gene was replaced by LacZ gene, and the filter paper biosensor and cell free system were introduced into project design.
(4) Visiting company inspirited us to design a 3D device model of the end product.
All these human practices helped us to design, develop and modify a detector based on the filter paper biosensor and cell free system to diagnose depressive disorder or MDD objectively.