System 1, system 2

October 27, 2013

I am spending my vacation with my mother at home recently. She is 83 years old without any illness. She still keeps a good memory, calculating ability and attention to surrounding changes. However, I found some subtle changes in her behavior. She usually watch TV dramas at home besides doing routine house cleaning, cooking, food shopping, and exercises with her friends, which she still does. However, she seems not interested in watching TV drama anymore; instead, she can stare at the screen for a long time watching TV advertisements. Moreover, she reads advertisements magazines rather than other entertainment magazines page by page. Is it a early sign of brain power decline? 

From what I am reading now from “Thanking Fast and Slow” by Daniel Kahneman, I found a possible explanation. He proposes there are two systems in our thinking: one is fast, intuitive, unconscious, pleasant, and effortless; the other is slow, reasoning, deliberative, and effortful. We need both system to live in this world, with system 1 responsible for familiar things and system 2 for new challenges. With bright colors, vivd acting and unstoppable repeating, the advertisements are the most easy thing to be remembered and familiar with, so that we can always reiterate some plots. This natural acceptance of advertisement by elder people may just reflect the easy, pleasant system 1 preference to lazy, effortful system 2, which is truly the reflection of neurological  functional decline in elders. 


A real hope for Down syndrome patients

September 11, 2013

This July, a research paper published in Nature shed some light on the treatment of Down syndrome, a genetic disorder due to an extra copy of chromosome 21 in human cells (1). A group in University of Massachusetts developed a strategy to silence the extra copy of chromosome 21 and restore the genes in Down syndrome cells to normal in the culture dish.

Down syndrome is a genetic disorder that affects one in 691 live births in US; it causes mental retardation, seizure, early onset of Alzheimer’s disease, heart disease, diabetes, cancer, and many others.  The British physician John Langdon Down first described the syndrome in 1866, and the French physician Jerome Lejeune first identified the cause of Down syndrome as the presence of an extra copy of chromosome 21 in cells of patients. In the past 147 years, generations of scientists have extensively studied this disorder, and gained much knowledge on the genetics, pathology, diagnosis, and management of Down syndrome. However, due to the complexity of multiple genes overexpressed from the extra copy of chromosome 21 (more than 500 genes have been identified on chromosome 21), there is no cure for this syndrome yet.

Nature is always our best teacher: we learned to use sonar navigation from bats and lighten up cells with green fluorescence protein from jelly fish. Women have two copies of X chromosomes in their cells, but only one copy is activated, with the other copy shutting down during early fetal development. This is caused by a gene on X chromosome, named X-inactive specific transcript (XIST). In 1990’s, scientists have discovered that XIST gene translocated to the other chromosomes can silence all the gene expression from that chromosome. But it is not until this year that scientists in University of Massachusetts use this strategy to shut down the genes on chromosome 21 in cells from Down syndrome.

The XIST gene was inserted into one selected location on chromosome 21 in induced pluripotent stem cells from Down syndrome patients by using a Zinc Finger protein targeting technique. The induced pluripotent stem cells were made from skin cells of a Down syndrome patient; with the characteristics of embryonic stem cells, they have the potential to develop into all types of tissues and organs. Because XIST functions in early embryonic development, they used induced pluripotent stem cells for XIST silencing. After the gene insertion by homologous recombination (a natural DNA replication and repair during cell division), they initiated the XIST gene expression by turning on a drug controlled switch. They then analyzed the gene profiles including mRNA expression and DNA methylation level and found the cellular activities restored to the normal two-copy chromosome level.

The limits of this technique include very low efficiency of inserting XIST gene into chromosome 21, and use of stem cells for the gene integration. However, with the first working proof, the improvement and alternative approaches will grow, and this strategy may provide a real cure for Down syndrome in the future.


Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB.  Translating dosage compensation to trisomy 21. Nature. 2013 Aug 15;500(7462):296-300. doi: 10.1038/nature12394. Epub 2013 Jul 17  (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12394.html)



Thanks for the reviewers’ comments in the Science writing course of Stanford, I corrected some according to reviewers’ advice, though there are still a lot to be improved. I used it in the course to get comments, not recycling, because this website is little visited, and I can not get feedback anyway. But I declare this is my original writing, not plagiarism. Thanks again for your criticize.


Open science for open mind

September 11, 2013

I have been working on neurobiological research for more than 15 years since I graduated from medical school. The first field in neuroscience attracted me is neural stem cells, then the neurodevelopment, and I saw the many breakthroughs happening in the past 15 years in understanding the pathogenesis of neurological diseases and normal cortical development. What Raymond Kurzweil described in his book ‘Singularity is Near”, that an exponential increase in technologies like computers and genetics is somehow true. During my study of Alzheimer’s disease and Down syndrome in the past 15 years, I saw the finish of human genome project, broad applications of high throughput sequencing technology, new frontiers of bioinformatics, epigenetics and induced pluripotent stem (iPS) cells, genome-wide association study (GWAS) to identify susceptible locus for depression and schizophrenia. I used these new technologies myself, including high throughput DNA methylation profiling and iPS cells to discover new pathways in Alzheimer’s disease and Down syndrome, which is unthinkable when PCR is still a new technique when I studied in medical school. I believe all these advances are unachievable without open science approaches.

When I prepared my master thesis 15 years ago, I had to go to libraries to get literature prints using copy machines, and prepared thesis defense slides using developed films. That is the start of my science career though watching copy machine working and staying in darkrooms for film development had not much fun. Nowadays, with one computer connected to internet, I can find almost all the resources and solutions to my questions and technique problems, from the open access to papers, protocols, methods, software, discussions, webinars, and Google becomes the most often used tool instead libraries. With the exponential increase of publications, you can imagine how much time it saves for you to keep you in the frontier of your research field.

The open science approaches not only include the free access to scientific publication like what NIH is doing in PubMed central, but also all other scientific resources that are shared by all the research community. In a recent project on Down syndrome study, we want to study a gene on chromosome 21, which has an extra copy in Down syndrome patients. To examine the gene expression in the Down syndrome brain, we got invaluable frozen brain tissue of specific ages from Brain Bank at National Institute of Child Health and Human Development (NICHD) in Maryland, who had collected thousands of brain samples from different neurological disorders. To manipulate this gene, we got this gene bacterial clone from BACPACResourceCenter” (BPRC) located at the Children’s Hospital Oakland, California. To target this gene in iPS cells, we got transcription activator-like (TAL) effectors nuclease (TALEN) constructs from Addgene contributed by Jung lab in Massachusetts general hospital (MGH), and Down syndrome iPS cells from Harvard Stem cell Institute in Boston. At last, to study the gene in animal models, we got the DS transgenic mice from Jackson Lab in Bar Harbor. With these tools, we can test our hypothesis in 1-2 years; without these resources, it could take years or decades to achieve our goal to find out the gene function in this disorder.

Above is a simple example from my research experience. In addition to this convenience brought by open science approaches, with more people involved, it may facilitate the improvement of quality, education and application of science to benefit the society. Moreover, current challenges are mainly from the increasing data in high throughput screens of genome or epigenome and imaging or electrological recording in normal and diseased people. One single person or organization cannot fulfill these data mining and interpretation work; it has to be a well-coordinated maneuver of many teams and groups. Many institutions and companies have begun to develop integration platforms from these data, such as ExPASy, NEXTBIO, SAGE and the Human Connectome Project, and the open accessibility of the data is essential to achieve the final goal. This open platform for the open mind ensures everyone with curiosity can think about it and contribute their ideas; they can download the data freely to analyze them with their own mathematical models; they can discuss the projects freely with professional or nonprofessional scientists. I believe these efforts will accelerate our understanding of the physiological and pathological mechanisms of human development and diseases, and find more pharmaceutical interferences for curing these diseases.

The open access to scientific resources has changed our view of traditional research. In a time of self-education with free access to information, knowledge and known techniques, it will stimulate more innovative thoughts without restrains. The most important thing is how to use this free information to produce new ideas and techniques. With this knowledge, we could avoid the known knowns and known unknowns to focus on the unknown unknowns, which are the real gold mine of scientific discovery.


Some books on psychiatry in China

October 24, 2012

Kleinman, Arthur: Deep China: The Moral Life of the Person, What Anthropology and Psychiatry Tell Us about China Today

Incayawar, Mario: Psychiatrists and Traditional Healers: Unwitting Partners in Global Mental Health

Ramsay, Guy: Shaping Minds: A Discourse Analysis of Chinese-Language Community Mental Health Literature

Martha Livingston: The Minds of the Chinese People: Mental Health in New China

Wen-Shing Tseng, David Y.H. Wu: Chinese Culture And Mental Health

Veronica Pearson: Mental Health Care in China: State Policies, Professional Services and Family Responsibilities

Peggy Simpson: Family-Based Mental Health Care in Rural China

Kam-shing Yip: Mental Health Service In The People’s Republic Of China: Current Status And Future Developments

Tsung-yi Lin: Mental Health Planning For One Billion People: A Chinese Perspective

John J. Kao: Three Millennia Of Chinese Psychiatry

Hugh L. Shapiro: The view from a Chinese asylum: defining madness in 1930s Peking

Wai-On Phoon and Ian Macindoe: Untangling the threads: perspectives on mental health in Chinese communities


Psychiatry in current China

October 24, 2012

John G. Kerr (China Presbyterian medical missionary)

Neurasthenia was coined by George Beard, meaning exhaustion of nervous system, the symptoms include weakness, fatigue, anxiety, headache, poor concentration and memory loss. It has been supplanted by depression in US, but still used in China, though the diagnosis of neurasthenia is reducing and depression is increasing in China. Arthur Kleinman did research in China in 1980’s, diagnosed 87% of neurasthenia patients as depression in American standard, and concluded that the physical symptoms of neurasthenia represented “somatic idioms of distress”.

There are less than 20000 psychiatrists in China with 1.3 billion people, which is 15 times less than that in USA.

5.6% people who developed depression in Beijing/Shanghai received treatment (2009), which is 6 times below that in USA.

___from Kleinman, Arthur: Deep China: The Moral Life of the Person, What Anthropology and Psychiatry Tell Us about China Today

Psychiatry in China:

  1. Mentally ill patients with obvious disorganized behavior will be sent to psychiatric hospitals. But there are still many patients who have never been diagnosed and treated due to lack of access to psychiatric facilities or due to poverty.
  2. Patients with neurosis and most patients with depression are often diagnosed with neurasthenia, autonomous nervous disorder or other somatic illness. Most of them seek treatment from internal medicine doctors or other non-psychiatric physicians.
  3. People who are facing life stress, crisis or suffering from emotional stress without somatic complains mainly need psychological counseling or psychotherapy.
  4. All patients are likely to seek help from TCM.

____from Zhao, Xudong: Mental Health in Contemporary China in Incayawar, Mario: Psychiatrists and Traditional Healers: Unwitting Partners in Global Mental Health




Quote of the day

October 24, 2012

 “If in life we are surrounded by death, so, too, in the health of our intellect we are surrounded by madness”.



Theory on Psychiatry and Psychology

October 24, 2012

Four humors of blood, phlegm, yellow bile, and black bile. //Darwinism, psychoanalysis, behaviorism, and phenomenology, social constructionist analyses, biological psychiatry// Monism, materialism, mechanism, realism, normalism//


1) beck’s cognitive behavioral therapy; 2) klerman and Weissman’s interpersonal therapy; 3) Sifneos’s and Davanloo’s brief psychoanalytically oriented psychotherapy; 4) Kernberg’s transference focused psychoanalytic psychotherapy.