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Causes of schizophrenia (Click to select text)
Causes of schizophrenia, bipolar disorder and related illnesses Illnesses like schizophrenia bring untold misery to sufferers and their families. The suffering is magnified because of the unique stigma attached to these illnesses. Unlike other illnesses, it marks not only afflicted individuals, but also their relatives. For example the concept of the "schizophrenogenic mother" was rife till recently. Such suffering is unnecessary and probably arises from fear bred by ignorance. Our primary aim - search for the causes of psychotic illnesses like schizophrenia - may help dispel these notions. Our research is hampered by the relatively few clues available about the causes. This is not for lack of effort. Literally hundreds of causes have been proposed. They include viruses, accidental injury before and after birth, as well as illicit substances. However, only inherited factors are generally accepted as significant causes. Evidence for such factors comes from every day experience: it is common to find families with several affected members. While such clustering'could also be due to shared non-inherited (environmental') factors,more convincing evidence has come from twin studies, as well as studies of ill individuals who were adopted away before the onset of illness. It is fair to say that even such studies do not suggest inherited factors as the sole causes. A more reasonable explanation is that there are individuals who have an inherited proneness to illness. Such individuals may fall ill, if in addition, they are exposed to noxious factors in the environment such as drugs. This model' is similar to that already proven in the causation of diseases like diabetes and raised blood pressure. It is important to stress that statistical analysis does not support the presence of a single genetic factor in this scheme. Rather, the inheritance is probably due to several factors which may be inherited from either side of one's family. We have based our research on this model. We assume that a single genetic factor is unlikely to cause psychotic illnesses like schizophrenia. Therefore, we do not trace the inheritance of genetic factors in families, as is done in classical genetic studies. Instead, we attempt to identify genetic factors which are present at higher rates among ill individuals compared with ill individuals. If such factors are identified, they may give us clues about the location of genes which alter the susceptibility to illness. We initially compared ill individuals with unrelated unaffected individuals. Though we identified some differences in this manner, it was difficult to say if the differences reflected proneness to illness or some other unrelated characteristics which happened to be different in the two groups. To overcome these difficulties, we are now conducting such comparisons among ill individuals and a hypothetical' group. This group is made up of genetic factors not inherited by a given ill person from his or her parents. Families with one or more ill members can participate in such studies. The ill member and the parents are required. If one of the parents are unavailable, the other parent and the siblings can be of help to construct' the comparison group. It should be noted that the family members are required in order to obtain estimates for the hypothetical control group and not in order to apportion blame. If we identify differences between ill members and the comparison group in this way, we will test our findings more strictly. We will see if such genetic factors are also shared by pairs of brothers or sisters, both of whom are ill. For analytical reasons, it would also be helpful if parents participated. If one of the parents are unavailable, the other parent and the siblings can be of help. Such studies would help to identify predisposing inherited factors, but would not yield information about a given family. These concepts may appear obscure, but they have helped to identify inherited Factors predisposing to diabetes mellitus, another potentially disabling illness. They are being used actively in a host of other diseases, including increased blood pressure. All these investigations have been made possible by miraculous advances in genetic research. These include the discovery of thousands of genetic markers in DNA, the seat of inheritance. Such markers can be investigated rapidly and cheaply because of a process known as the polymerase chain reaction. This process enables scientists to obtain multiple copies of a given region of DNA from even small quantities of blood. Thus, the stage has been set for dramatic advances in our knowledge about numerous diseases. Such information will be useful in several ways. Besides helping to dispel ignorance and fear, discovery of causative factors may help us to find out why and how individuals become ill. This in turn may help us to devise better, more rational treatment. Once inherited susceptibility' factors are identified, we will be able to understand how such predisposition leads to illness in the presence of environmental' precipitants. This may ultimately lead to prevention, because we will be able to target and counsel individuals at increased risk of illness. We are aware that such research can be misused in the wrong hands. We ensure strict confidentiality in our research. We adhere strictly to guidelines set by the US Government and by our university. We vehemently oppose eugenic policies which brought disrepute to this field of research in Nazi Germany. Such research is not easy. In order to obtain results which are undisputed, we will need to screen hundreds of families. Therefore, we have established collaborations with other scientists t Cleveland, Ohio, Stockholm, Sweden, and New Delhi, India. Nearer home, we have spoken to dozens of clinicians in Western Pennsylvania, Ohio, and West Virginia. At present, we have a central clinical resource at Pittsburgh, with satellite centers in Pennsylvania, West Virginia and New Delhi, India. Our laboratories are located at the University of Pittsburgh.
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