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Biotechnology and Society---Part VII

Human Behavior Genes

Nothing that grieves us can be called little; by the eternal laws of proportion a child’s loss of a doll and king’s loss of a crown are events of the same size.
------Mark Twain (1835—1910)

Examine the following:

A lady walks into a psychiatrist’s office and tells him, “Doctor, I have a problem. My husband thinks he is a chicken.” The doctor asks, “How long has this been going on?” the lady says, “For three years.” The doctor was puzzled and queries, “Why did you wait this long to come to me?” The lady retorts, “But, doctor, we needed the eggs.” The doctor thinks, “Ha! Now I have two patients instead of one.”

It may be a jocular matter but such instances are real. There are probably millions of people who are afflicted with various cases of mental illness. In the past such folks were put away in mental institutions and subjected to punishing regimens of treatments. Now there is an awakening that some of the mental illnesses are not just due to “craziness” but a consequence of defective genes.

In the previous articles we established a one-to-one connection between a defective gene and the manifestation of a physiological disorder. However, it is currently recognized that mental diseases may also be gene-related phenomena. Research is unraveling new clues in the search for genetic causes of behavioral illnesses.

Two movies, one recent (“A Beautiful Mind”) and another vintage one (“Psycho”) were based on themes surrounding behavioral illnesses. In Psycho the heroine was a compulsive neurotic while the hero was a psychotic. The hero was dominated by his mother while she was alive. He killed his mother and her lover but preserved her body and kept it in his hillside house. The childhood repression he experienced began to haunt him in his adult life. His mother continued to “live” with him in his mind and was instrumental in killing the heroine. He was torn between himself and his mother. The movie’s theme was partly based on reality.

A Beautiful Mind was based on real life story of John F. Nash Jr., a brilliant mathematician at Princeton University who was a victim of schizophrenia, characterized by frightening delusions, for over 25 years. He heard “voices” and believed that the Russians were sending him coded messages via the New York Times newspaper. He found patterns where none existed. He was subjected to shock therapy off and on. Finally with help from his wife he overcame his afflictions, returned to Princeton, and went on to receive a Nobel Prize in Economics in 1994 for work done in 1950. At the bodily level, the transition from physical disability to physical good health is not that eventful as at the mental level of going from the rational to the delusional and then back to rational state of mind. Let us look at the behavioral illness from the genetic standpoint.

Schizophrenia: Schizophrenia is a complex psychiatric disorder and affects 1% of the population. A special case of schizophrenia called “catatonic schizophrenia”, an inherited disorder, is characterized by acute psychotic episodes with hallucinations, delusions, and disturbed body movements. Scientists in Julius Maximillians University in Wuerzburg, Germany found that a gene called WKL1 in chromosome 22, which produces a protein responsible for transmission of electric currents along the nerves, exhibits a mutation (change in the codon letters) in seven family members with the disease but not in six others who had no symptoms of schizophrenia. People with schizophrenia usually have a poor working memory and that causes their speech to be incoherent.

A group of researchers at MIT led by Susumu Tonegawa has created a genetically modified mouse which is schizophrenic and displayed a behavior of social withdrawal. The modified mice reacted in the same way as sick people do when a diagnostic test for schizophrenia was conducted. The mice had been modified in part of their forebrain so they did not make the particular chemical called calcineurin. Having a genetically modified mouse as a model for the disease is helpful in finding drugs designed to counter the genetic causes. Once the gene is identified and its function determined, either protein-based drugs or small molecules can be tailored which will mitigate the illness without much of an undesirable side effect.

Bipolar Disorder: Bipolar disorder, also known as manic depression, is characterized by extreme mood states alternating between euphoria and terrible depression. Current treatments help many but a significant percentage of the patient population receives little benefit from existing therapies. Researchers at the University of California, San Diego (UCSD) have recently identified a specific gene called GRK3, in chromosome 22, in which a mutation in a specific region causes bipolar disorder. The UCSD researchers determined that there were six mutations in the GRK3 gene and that one of these mutations occurred three times more frequently in manic-depressive patients. The researchers hypothesized that GRK3’s role may be to turn down the level of response to neurotransmitters such as dopamine. A defect in the GRK3 gene may make one super-sensitive to dopamine which leads to symptoms of alternating exhilaration and in-the-dumps feeling.

In the September 6, 2003 issue of the British medical journal, The Lancet, researchers from the Johns Hopkins University Children’s Center, University of Cambridge, and the Stanley Medical Research Institute proposed that schizophrenia and bipolar disorder may have similar genetic roots. They trace the disorders to “reduced expression of the genes, known as oligodendrocytes, responsible for myelin development in brain cells”. Composed of lipids and proteins, myelin is needed for insulating nerve cells thereby enabling the nerve cells to conduct electric signals between the brain and other parts of the body. The reason for the myelin dysfunction is not currently known but may be related, in some cases, to infections of the central nervous system. Because symptoms of schizophrenia and bipolar disorder typically are evident only in late adolescence and early adulthood, it may become possible to screen children whose family histories put them at risk for developing these disorders and treat them before they exhibit symptoms.

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Tourette Syndrome: Tourette Syndrome (TS) is a neurological disorder characterized by tics—involuntary, rapid, sudden movements or vocalizations that occur repeatedly in the same way. The TS patients exhibit a wide range of behaviors including attention deficit hyperactivity disorder (ADHD), Obsessive-compulsive disorder (OCD), panic attacks, and sleep disorders, among others. Research efforts are currently under way to locate the TS genes so that effective therapies can be devised. It is currently understood that TS is a polygenic (multiple genes are involved) disorder coming together from both parents of a number of genes affecting dopamine, serotonin, and other brain chemicals. Current treatment employs drugs such as haloperidol (haldol), Pimozide (blocks dopamine) and anti-depressants such as fluoxetine. Once the culprit genes are identified and their function defined, it may be possible to institute intervention therapies which are specific to the disease.