HKU Bulletin November 2006 (Vol. 8 No. 1)

10 11 RESEARCH Faking It Is he or isn’t he? A team of psychologists hopes to expose the malingerers from the genuinely sick. T he ability to accurately detect whether a person is lying or not is a challenge that has occupied scientists for decades. And not just scientists either. Law enforcement agencies, Central Intelligence Agencies and suspicious spouses are just some of the parties concerned with lie detection. A simple Google search throws up more than eight million hits for lie detection and perhaps reveals how preoccupied we are with seeking the truth. But the fact remains that most of us make very poor lie detectors. Which is where the scientists come in. The development of functional Magnetic Resonance Imaging (MRI) has provided new insight into the way the brain processes information and has thrown some light on the neural pathways involved in attempts to deceive. Now a team in the Department of Psychology has conducted groundbreaking work in this area. Professor Tatia Lee, a neuroscientist and a clinical neuropsychologist, has been collaborating with researchers in the Mainland, US, and Taiwan to detect malingering among medical patients. She said: “Attempts to feign memory problems are especially common in clinical settings, where successfully faking a sickness can lead to attractive rewards like large financial settlements. “So we conducted a very simple test, using functional MRI, back in 2000, to see if there was a difference in the brain activity pattern associated with people simulating a memory problem and those making a genuine recall. “In this lab setting we were able to see a specific pattern of brain activation when a person is simulating a memory problem compared to someone who is making an accurate recall. In particular, relative to making an accurate recall, simulation of memory difficulty involves stronger activity in the prefrontal- cingulate-parietal neural network, which suggests that the subjects might use additional cognitive strategies for making calculated and goal-directed responses.” Two other teams, one in England and another in America, were carrying out similar projects at the same time, and although they were focusing more on forensic work all teams achieved similar findings. “That motivated us to do the second study, published in 2005, which looked at the generalizability of our findings,” said Lee. “In the first study we took a small group of subjects, all male and Chinese speaking. Then in the second we looked at male and female and people speaking Chinese and English and explored a different test format to see if there saw consistency with the original findings. Again we saw a very similar pattern. “It’s very fascinating and very encouraging and, of course, we acknowledge that this is still at a very experimental stage. There is no way we are advocating that this is the way to detect liars. At this point it is still a scientific research question, there are more things we need to bridge the laboratory setting with the real world. Although Lee is still treating the results as preliminary findings she considers it a very good start and wants to continue with the same line of research by exposing subjects to more difficult tasks. She believes this will become an important part of her team’s research. “We have been very encouraged by the results so far and we are looking forward to moving on to the next stage,” she said. Genes On and Off Buttons Scientists discover a new mechanism in the cause of hereditary colon cancer. T he groundbreaking discovery that malfunctioning genes could be at the root of hereditary cancers, like colon cancer, could have major implications for future drug design, according to scientists in the Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology. The team, led by Professor Leung Suet Yi, made its discovery by studying a single family in which multiple members had developed hereditary colon or uterine cancers. The rate of colon cancer in Hong Kong has risen dramatically over the last 20 years, with 3,200 new cases being diagnosed every year. This makes it the second most common cancer in the territory. It mostly affects the over-50s and is largely attributed to diet and environmental factors. However, around ten to 15 per cent of all cases have a hereditary basis, the most common being hereditary non-polyposis colorectal cancer (HNPCC) which accounts for four per cent of colon cancer cases. Patients with HNPCC show no symptoms until the cancer develops. The most important clue is the occurrence of colon or other specific types of cancers in multiple family members, or the onset of cancer at an early age. Most HNPCC cases are caused by inheriting a mutation that switches off one of the DNA repair genes. This can be detected by a simple blood test. However, in some HNPCC families, the DNA codes of their repair genes are completely normal, making the defect hard to detect. What the research team found was a new mechanism for HNPCC, which involves a heritable methylation of the repair gene’s promoter. A promoter is like a switch that controls the gene’s ‘on’ and ‘off’ button. Methylation ‘locks’ it into a permanently ‘off’ position, leading to a loss of the gene’s function and eventual cancer. Although scientists were of the view that methylation could not be passed from one generation to the next, the team found it in multiple members of the family across three generations it tracked, including three members who have developed cancer. Moreover, the methylation was prominent in colon cells, but difficult to detect in blood cells. Professor Leung said the findings, published in Nature Genetics , had revolutionised their understanding of hereditary disease. “The case shows that methylation patterns can be inherited and cause heritable diseases including cancer. “Since we need special techniques to test for methylation, and the test needs to be performed on colon instead of blood cells, our findings may change the way that genetic diagnoses and research is performed.” “Increasing our understanding of the way that methylation is regulated wi l l have huge impl ications in the development of anti-cancer drugs,” she added. Leung said the importance of genetic diagnosis is in prevention. “If a cancer patient’s family members know they have inherited the same mal funct ioning genes and have regular screening checks, there is a high likelihood that cancer can be prevented by treatment at the early benign phase”. Interestingly, Hong Kong’s young population has a uniquely high incidence of colon cancer and through DNA testing Leung and her team has been able to trace the source of the faulty gene. One-fifth of the local HNPCC families have inherited the same form of mutation from a common ancestor, estimated to have lived around 550 to 2,575 years ago in Guangdong Province. So the findings could also have serious implications for the genetic diagnosis of hereditary colon cancer in Southern Chinese populations worldwide. The research project is supported by the Hong Kong Cancer Fund and the Michael and Betty Kadoorie Cancer Genetics Research Programme.