Vishwajit L. Nimgaonkar, M.D., Ph.D., Principal Investigator

 

 
 

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An Overview of Our Work

A Brief Overview of the Program for Genetics and Psychoses

 

MOTIVATION FOR OUR RESEARCH

Illnesses like schizophrenia, bipolar disorder and schizoaffective disorder bring untold misery to sufferers and their families. The suffering is magnified by the enormous stigma attached to these illnesses.  It marks afflicted individuals as well as their relatives. Thus, millions of individuals are forced to suffer in silence.  Such suffering is unnecessary and arises partly from fear, bred by ignorance.  We sincerely hope that apart from its scientific value, our work may help dispel these hardships.

 

OUR GOALS

The overarching goal of our research is to find safe and effective treatment for severe psychiatric disorders.  We believe that such treatment can be developed in a rational manner if we have a better understanding of the causes and how they lead to illness.  Hence much of our work focuses on finding causes. 

Apart from the research on causative factors, we are separately evaluating novel treatment methods that may prove to be helpful in addition to conventional treatment. 

We are dedicated to training the next generation of researchers, teachers and therapists.

 

OUR MODEL FOR CAUSATION

Our research is hampered because few clues are available about the causes of these illnesses.   This is not for lack of effort. Literally hundreds of causes have been proposed. They include viruses, accidental brain injury, as well as illicit substances.  There is much disagreement about the impact of these factors, because researchers have been unable to find them consistently in different studies. 

It is now well accepted that inherited factors explain a significant proportion of the causation (over two thirds or more).  We stress that several genetic factors, rather than one gene are likely to be involved in causation.  Therefore, it may be incorrect to assign ‘blame’ for one’s illness on a particular relative. The inheritance is probably due to several factors which may be inherited from either side of one's family.   We also know that inherited factors can not be the sole causes.  Indeed, most individuals, even those born into families with several ill members lead normal, healthy lives.  On the other hand there are probably 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 ‘gene-environment interaction’ model is similar to that already proven in the causation of diseases like diabetes and raised blood pressure.

 

STUDIES BASED ON OUR CAUSATIVE MODEL

Finding genetic factors

We have based our research on the gene-environment interaction model. We seek genetic factors which are present at higher rates among ill individuals compared with well  individuals.  If such factors are identified, they may give us clues about the location of genes which alter the susceptibility to illness.  We compare the ill persons with unrelated healthy persons, as well as unaffected relatives.  Families with one or more ill members can participate in our studies.  If we identify differences between ill members and the comparison groups, 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 can participate.  If one of the parents are unavailable, the other parent and the siblings caDiagram of a DNA strand about to replicaten be of help. Such studies would help to identify predisposing inherited factors, but would probably not yield information about a given family.

These concepts have helped to identify inherited factors predisposing to diabetes mellitus, another potentially disabling illness.  Such strategies being used actively in a host of other diseases, including increased blood pressure and cancer. 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 now be investigated rapidly and cheaply.

Our research scheme 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 in the USA, Europe, India and Egypt. 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 surrounding regions. Our laboratories are located at the University of Pittsburgh.

Finding genetic factors for ‘complementary traits’:  cognition and brain imaging features

It has been very difficult to find genetic factors predisposing to many severe complex disorders, including the psychotic disorders we are investigating.  Therefore we are also trying to find genes to features or traits that either predispose to these disorders or are tied intimately to them.  We are very interested in cognition, or thought processes because these processes can be severely impaired when persons fall ill.  We are also investigating daily rhythms, also called circadian rhythms as normal patterns are frequently disrupted when persons fall ill.  We are also focusing on different types of brain imaging techniques.  We are collaborating with groups at the University of Pennsylvania (Raquel Gur, MD PhD) and the San Antonio Foundation for Biomedical Research (Laura Almasy, PhD).

 

FINDING ENVIRONMENTAL FACTORS THAT MAY INCREASE RISK

For several decades, researchers have speculated whether infectious agents that target the brain, particularly certain types of viruses may increase the chances of illness.  We are pursuing this possibility in collaboration with at Johns Hopkins University (Robert H Yolken, MD PhD) and Sheppard Pratt Hospital (Faith Dickerson, MD).

 

LOOKING FOR GENE ENVIRONMENT INTERACTIONS

We are combining our gene mapping studies with our studies of brain infectious agents to see whether inherited factors in susceptible persons may provoke the illness if such persons are also exposed to infectious agents that target the brain.

 

EVALUATING NOVEL THERAPIES

We are targeting dysfunction in thought processes as part of our efforts to improve the lives of ill individuals.  We are partnering with our colleagues in India to evaluate Yoga, the ancient Indian form of meditation and relaxation.

 

TRAINING

We are deeply invested in training the next generation of researchers and therapists.  With help from the National Institute of Health, we are training new investigators not only in the USA, but also in India and Egypt.

 

FUTURE PROSPECTS

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.

 

ETHICAL ISSUES

We explain our studies in detail to prospective participants and request written consent before enlisting their help.  We are aware that such research can be misused in the wrong hands. We ensure strict confidentiality in our research. We also adhere strictly to guidelines set by the US Government and by our universities. We vehemently oppose eugenic policies which brought disrepute to this field of research in Nazi Germany.

 

AGENCIES THAT ARE HELPING US

We have been most fortunate in receiving enthusiastic support from over twenty groups affiliated with the National Alliance for the Mentally Ill (NAMI).  This help is most gratifying. It also boosts our commitment.

We have also received generous support for our research from the National Institutes of Health and from the Stanley Medical Research Institute.

 

CAN YOU HELP US?

We are extremely grateful to those of you who have participated in our research.  If you or some one you know could help us, we would be delighted to hear from you. We require only two tablespoonfuls of blood and 2-3 hours of your time!