Genetic factors and mental disorders



Genetic Factors And Mental Disorders 1061
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Introduction and overview

In recent years, mental health professionals have become increasingly aware of the importance of genetic factors in the etiology (causes) of mental disorders. Since the Human Genome Project began its mapping of the entire sequence of human DNA in 1990, the implications of its findings for psychiatric diagnosis and treatment have accumulated rapidly. A new subspecialty known as biological psychiatry (also called physiological psychology or psychiatric genetics) has emerged from the discoveries of the last two decades. Biological psychiatry got its start in the late 1980s, when several research groups identified genes associated with manic depression and schizophrenia respectively. These studies ran into difficulties fairly quickly, however, because of the complexity of the relationship between genetic factors and mental illness.

The ongoing search for genes related to psychiatric symptoms and disorders is complicated by several factors:

  • Psychiatric diagnosis relies on a doctor's human judgment and evaluation of a patient's behavior or appearance to a greater degree than diagnosis in other fields of medicine. For example, there is no blood or urine test for schizophrenia or a personality disorder. Diagnostic questionnaires for mental disorders are helpful in trimming the list of possible diagnoses but do not have the same degree of precision or objectivity as laboratory findings.
  • Mental disorders almost always involve more than one gene. Studies have shown that one mental disorder can be caused by different genes on different chromosomes in different populations. For example, one study in the late 1980s found two genes on two different chromosomes among two populations that caused manic depression. Studies of schizophrenia done in the late 1980s and early 1990s revealed the same finding— different genes on different chromosomes produced schizophrenia in different populations. It now appears that specific mental disorders are related to different sets of genes that vary across family and ethnic groups.
  • Genes associated with mental disorders do not always show the same degree of penetrance , which is defined as the frequency with which a gene produces its effects in a specific group of people. Penetrance is expressed as a percentage. For example, a gene for manic depression may have 20% penetrance, which means that 20% of the members of the family being studied are at risk of developing the disorder.
  • Genetic factors in mental disorders interact with a person's family and cultural environment. A person who has a gene associated with susceptibility to alcohol abuse, for example, may not develop the disorder if he or she grows up in a family that teaches effective ways to cope with stress and responsible attitudes toward drinking.

There are several terms in biological psychiatry that are important to understand:

  • Genotype: A person's genotype is the sum total of the genetic material transmitted from his or her parents.
  • Phenotype: A person's phenotype is the observable signs, symptoms, and other aspects of his or her appearance. The term is also used sometimes to refer to a person's outward appearance and behavior as these result from the interaction between the person's genotype and his or her environment.
  • Behavioral phenotype: The concept of a behavioral phenotype is used most often with reference to patterns of behavior found in certain developmental disorders of childhood, such as Down syndrome or Prader-Willi syndrome. Behavioral phenotype refers to the greater likelihood that people with a specific genetic syndrome will have certain behavioral or developmental characteristics compared to people who do not have the syndrome; it does not mean that every person diagnosed with a given genetic syndrome will invariably develop these characteristics.

Genetic causality in mental disorders

As of 2002, genes appear to influence the development of mental disorders in three major ways: they may govern the organic causes of such disorders as Alzheimer's disease and schizophrenia; they may be responsible for abnormalities in a person's development before or after birth; and they may influence a person's susceptibility to anxiety, depression, personality disorders , and substance abuse disorders.

One technological development that has contributed to the major advances in biological psychiatry in the last twenty years is high-speed computing. Faster computers have enabled researchers to go beyond rough estimates of the heritability of various disorders to accurate quantification of genetic effects. In some cases the data have led to significant reappraisals of the causes of specific disorders. As recently as the 1960s and 1970s, for example, schizophrenia was generally attributed to "refrigerator mothers" and a chilly emotional climate in the patients' extended families. As of 2002, however, the application of computer models to schizophrenia indicates that the heritability of the disorder may be as high as 80%. Another instance is autism , which was also blamed at one time on faulty parenting but is now known to be 90+% heritable.

Mental disorders with organic causes

The two most important examples of mental disorders caused by organic changes or abnormalities in the brain are late-onset Alzheimer's disease and schizophrenia. Both disorders are polygenic , which means that their expression is determined by more than one gene. Another disorder that is much less common, Huntington's disease, is significant because it is one of the few mental disorders that is monogenic , or determined by a single gene.

SCHIZOPHRENIA. Researchers have known for many years that first-degree biological relatives of patients with schizophrenia have a 10% risk of developing the disorder, as compared with 1% in the general population. The identical twin of a person with schizophrenia has a 40%–50% risk. The first instance of a specific genetic linkage for schizophrenia, however, was discovered in 1987 by a group of Canadian researchers at the University of British Columbia. A case study that involved a Chinese immigrant and his 20-year-old nephew, both diagnosed with schizophrenia, led the researchers to a locus on the short arm of chromosome 5. In 1988, a study of schizophrenia in several Icelandic and British families also pointed to chromosome 5. Over the course of the next decade, other studies of families with a history of schizophrenia indicated the existence of genes related to the disorder on other chromosomes. In late 2001, a multidisciplinary team of researchers reported positive associations for schizophrenia on chromosomes 15 and 13. Chromosome 15 is linked to schizophrenia in European American families as well as some Taiwanese and Portuguese families. A recent study of the biological pedigrees found among the inhabitants of Palau (an isolated territory in Micronesia) points to chromosomes 2 and 13. Still another team of researchers has suggested that a disorder known as 22q deletion syndrome may actually represent a subtype of schizophrenia, insofar as people with this syndrome have a 25% risk of developing schizophrenia.

ALZHEIMER'S DISEASE. Late-onset Alzheimer's disease (AD) is unquestionably a polygenic disorder. It has been known since 1993 that a specific form of a gene for apolipoprotein E (apoE4) on human chromosome 19 is a genetic risk factor for late-onset Alzheimer's. People who have the apoE4 gene from one parent have a 50% chance of developing AD; a 90% chance if they inherited the gene from both parents. They are also likely to develop AD earlier in life. One of the remaining puzzles about this particular gene, however, is that it is not a consistent marker for AD. In other words, some people who have the apoE4 gene do not develop Alzheimer's, and some who do not have the gene do develop the disorder. In 1998, another gene on chromosome 12 that controls the production of bleomycin hydrolase (BH) was identified as a second genetic risk factor that acts independently of the apoE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of amyloid-beta protein is also involved in the development of late-onset AD.

There are two other forms of AD, early-onset AD and familial Alzheimer's disease (FAD), which have different patterns of genetic transmission. Early-onset AD is caused by a defect in one of three genes known as APP, presenilin-1, and presenilin-2, found on human chromosomes 21, 14, and 1, respectively. Early-onset AD is also associated with Down syndrome, in that persons with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop this form of Alzheimer's. The brains of people with Down syndrome age prematurely, so that those who develop early-onset AD are often only in their late 40s or early 50s when the symptoms of the disease first appear. Familial Alzheimer's disease appears to be related to abnormal genes on human chromosomes 21 and 14.

HUNTINGTON'S DISEASE. Huntington's disease, or Huntington's chorea, is a neurological disorder that kills the cells in the caudate nucleus, the part of the brain that coordinates movement. It also destroys the brain cells that control cognitive functions. In 1983, the gene that causes Huntington's disease was discovered on the short arm of human chromosome 4. Ten years later, the gene was identified as an instance of a triplet or trinucleotide repeat. Nucleotides are the molecular "building blocks" of DNA and RNA. Three consecutive nucleotides form a codon, or triplet, in messenger RNA that codes for a specific amino acid. In 1991, researchers discovered not only that nucleotide triplets repeat themselves, but that these repetitions sometimes expand in number during the process of genetic transmission. This newly discovered type of mutation is known as a dynamic or expansion mutation. Since 1991, more than a dozen diseases have been traced to expansion mutations. Eight of them are caused by repeats of the triplet cytosine-adenine-guanine (CAG), which codes for an amino acid called glutamine. In 1993, Huntington's disease was identified as a CAG expansion mutation disorder. Where the genetic material from a normal chromosome 4 has about 20 repeats of the CAG triplet, the Huntington's gene has a minimum of 45 repeats, sometimes as many as 86. The higher the number of CAG triplet repeats in a Huntington's gene, the earlier the age at which the symptoms will appear. The expansion mutation in Huntington's disease results in the production of a toxic protein that destroys the cells in the patient's brain that control movement and cognition.

Childhood developmental disorders

Developmental disorders of childhood are another large category of mental disorders caused by mutations, deletions, translocations (rearrangements of the arms of chromosomes) and other alterations in genes or chromosomes.

TRIPLET REPEAT DISORDERS. Since 1991, expansion mutations have been identified as the cause of thirteen different diseases. Some, like Huntington's disease, are characterized by long expansion mutations of the trinucleotide sequence CAG, which in effect adds so much glutamine to the protein being synthesized that it becomes toxic to the nervous system. A second category of triplet repeat disorders contains extra triplets that add an amino acid called alanine to the protein. The sequence of nucleotides is cytosine-guanine-N, where N stands for any of the four basic nucleotides. Although the proteins produced by this type of expansion mutation are not toxic, their normal function in the body is disrupted. The developmental disorders related to these CGN triplets are characterized by abnormalities of the skeleton. One of these disorders is synpolydactyly, in which the patient has more than the normal number of fingers or toes. Another is cleidocranial dysplasia, a disorder marked by abnormal development of the skull.

Other developmental disorders are caused by expansion mutations outside the regions of the gene that code for proteins. The segments of DNA that specify the sequence of a portion of a protein are known as exons , while the stretches of DNA that lie between the exons and do not code for proteins are called introns . The CAG and CGN groups of triplet disorders described in the preceding paragraph are expansion mutations that occur within exons. A third group of triplet disorders results from expansion mutations in introns. Expansions in this third group are usually much longer than those in the first two categories; some repeat several hundred or even several thousand times. The best-known expansion mutation in this group causes the disorder known as fragile X syndrome. Fragile X syndrome is the most common inherited form of mental retardation and should be considered in the differential diagnosis of any child with developmental delays, mental retardation, or learning difficulties. The syndrome is caused by a large expansion of a cytosine-guanine-guanine (CGG) repeat which interferes with normal protein transcription from a gene called the FMR1 gene on the X chromosome. Males with the mutation lack a second normal copy of the gene and are more severely affected than females who have a normal FMR1 gene on their second X chromosome. In both sexes there is a correlation between the length of the expansion mutation and the severity of the syndrome.

The discovery of expansion mutations was the solution to a long-standing genetic riddle. Clinicians had noticed as early as 1910 that some disorders produce a more severe phenotype or occur at earlier and earlier ages in each successive generation of an affected family. This phenomenon is known as anticipation , but its biological basis was not understood until recently. It is now known that triplet repeats that are long enough to cause disorders are unstable and tend to grow longer from generation to generation. For example, an expansion mutation of the cytosine-thymine-guanine (CTG) triplet causes a potentially life-threatening developmental disorder known as myotonic dystrophy. Repeats of the CTG triplet that are just above the threshold for myotonic dystrophy itself may produce a relatively mild disorder, namely eye cataracts in later life. Within two to three generations, however, the CTG repeats become longer, producing a fatal congenital illness. In addition to developmental disorders of childhood, expansion mutations may also be involved in other psychiatric disorders. Anticipation has been found in some families affected by bipolar disorder and schizophrenia, and some researchers think that it may also be present in some forms of autism.

GENOMIC IMPRINTING. Another recent discovery in the field of biological psychiatry is the phenomenon of genomic imprinting, which distinguishes between chromosomes derived from a person's father and those derived from the mother. Genomic imprinting was discovered in the late 1980s as an exception to Gregor Mendel's laws of biological inheritance. A small subset of human genes are expressed differently depending on the parent who contributes them to a child's genetic makeup. This phenomenon has helped researchers understand the causation of three well-known genetic disorders— Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes.

In the 1980s, researchers studying Prader-Willi syndrome and Angelman syndrome noticed that both disorders were caused by a deletion on the long arm of chromosome 15 in the very same region, extending from 15q11 to 15q13. This finding was surprising, because the two syndromes have markedly different phenotypes. Children with Prader-Willi syndrome have severe mental retardation, poor muscle tone, small hands and feet, and a voracious appetite (hyperphagia) that begins in childhood. As a result, they are often obese by adolescence. Children with Angelman syndrome, on the other hand, do not speak, are often hyperactive, and suffer from seizures and sleep disturbances. In the late 1980s, advances in molecular genetics revealed that the different expressions of the same deletion on the same chromosome were determined by the sex of the parent who contributed that chromosome. Children with Prader-Willi syndrome had inherited their father's copy of chromosome 15 while the children with Angelman syndrome had inherited their mother's. Highly specific diagnostic tests for these two disorders have been developed within the past decade.

Beckwith-Wiedemann syndrome is an overgrowth condition in which patients develop abnormally large bodies. They often have low blood sugar at birth and are at high risk for developing Wilms tumor, a childhood form of kidney cancer. Beckwith-Wiedemann syndrome is caused by several different genetic mutations that affect imprinted genes on chromosome 11p15. One of these imprinted genes governs the production of a growth factor that is responsible for the children's large body size.

BEHAVIORAL PHENOTYPES. Although medical professionals are familiar with the physical phenotypes associated with genetic disorders, the notion of behavioral phenotypes is still controversial. A behavioral phenotype is the characteristic set of behaviors found in patients with a genetic disorder. Behavioral phenotypes include patterns of language usage, cognitive development, and social adjustment as well as behavioral problems in the narrow sense. It is important for psychiatrists who treat children and adolescents to understand behavioral phenotypes, because they are better able to identify problem behaviors as part of a genetic syndrome and refer children to a geneticist for an accurate genetic diagnosis.

Examples of behavioral phenotypes are those associated with Down, Prader-Willi, and Williams syndromes. Children with Down syndrome have an increased risk of developing early-onset Alzheimer's disease. They are usually quiet and good-tempered, but may also be hyperactive and impulsive. Their behavioral phenotype includes delayed language development and moderate to severe mental retardation.

Children with Prader-Willi syndrome are often quiet in childhood but develop stubborn, aggressive, or impulsive patterns of behavior as they grow older. The onset of their hyperphagia is often associated with temper tantrums and other behavioral problems. They are typically obsessed with food, frequently hoarding it, stealing it, or stealing money to buy food. About 50% of children diagnosed with Prader-Willi syndrome meet the criteria for obsessive-compulsive disorder (OCD).

Williams syndrome is a genetic disorder that results from a deletion of locus 23 on chromosome 7q11. Children with this syndrome often have an "elf-like" face with short upturned noses and small chins. Their behavioral phenotype includes talkativeness, friendliness, and a willingness to follow strangers. They are also hyperactive and easily distracted from tasks. The personality profile of children with Williams syndrome is so distinctive that many are diagnosed on the basis of the behavioral rather than the physical phenotype.

Psychological/behavioral vulnerability in adults

Although psychiatrists at one time regarded emotional wounds in early childhood as the root cause of anxiety and depressive disorders in later life, inherited vulnerability to these disturbances is the subject of intensive study at the present time. In the past two decades, genetic factors have been shown to influence the likelihood of a person's developing mood disorders or post-traumatic syndromes in adult life. A study done in 1990 showed that first-degree relatives of a person diagnosed with major depression were two to four times as likely to develop depression themselves as people in the general population. As of 2002, however, the genetic patterns involved in depression appear to be quite complex; there is some evidence that both genomic imprinting and the phenomenon of anticipation may be present in some families with multigenerational histories of depression. In addition, the evidence indicates that susceptibility to major depression is governed by several different genes on several different chromosomes. At present, genetic factors are thought to account for about 40% of a person's risk of depression, with environmental factors and personal temperament accounting for the remaining 60%.

With regard to manic depression, twin studies have shown that the twin of a patient diagnosed with manic depression has a 70%–80% chance of developing the disorder. As of January 2002, a team of German researchers studying 75 families with a total of 275 members diagnosed with manic depression (out of 445 persons) has narrowed its search for genes for manic depression to one locus on human chromosome 10 and another on the long arm of chromosome 8.

POST-TRAUMATIC SYNDROMES. Researchers have found that some persons are more vulnerable than others to developing dissociative and anxiety-related symptoms following a traumatic experience. Vulnerability to trauma is affected by such inherited factors as temperament as well as by family or cultural influences; shy or introverted persons are at greater risk for developing post-traumatic stress disorder (PTSD) than their extroverted or outgoing peers. In addition, twin studies indicate that certain abnormalities in brain hormone levels and brain structure are inherited, and that these increase a person's susceptibility to developing acute stress disorder (ASD) or PTSD following exposure to trauma.

ANXIETY DISORDERS. It has been known for some time that anxiety disorders tend to run in families. Recent twin studies as well as the ongoing mapping of the human genome point to a genetic factor in the development of generalized anxiety disorder (GAD). One study determined the heritability of GAD to be 0.32.

Recent research has also confirmed earlier hypotheses that there is a genetic component to agoraphobia , and that it can be separated from susceptibility to panic disorder (PD). In 2001 a team of Yale geneticists reported the discovery of a genetic locus on human chromosome 3 that governs a person's risk of developing agoraphobia. Panic disorder was found to be associated with two loci, one on human chromosome 1 and the other on chromosome 11q. The researchers concluded that agoraphobia and PD are common, heritable anxiety disorders that share some but not all of their genetic loci for susceptibility.

BEHAVIORAL TRAITS. There has been considerable controversy in the past decade concerning the mapping of genetic loci associated with specific human behaviors, as distinct from behavioral phenotypes related to developmental disorders. In 1993 a group of Dutch researchers at a university-affiliated hospital in Nijmegen reported that a mutation in a gene that governs production of a specific enzyme (monoamine oxidase A or MAOA) appeared to be the cause of violent antisocial behavior in several generations of males in a large Dutch family. At least fourteen men from this family had been in trouble with the law for unprovoked outbursts of aggression, ranging from arson and attacks on employers to sexual assaults on female relatives. Tests of the men's urine indicated that neurotransmitters secreted when the body responds to stress were not being cleared from the bloodstream, which is the normal function of MAOA. In other words, the genetic mutation resulted in an overload of stress-related neurotransmitters in the men's bodies, which may have primed them to act out aggressively. As of 2002, however, the Dutch findings have not been replicated by other researchers.

Another controversial study in the early 1990s concerned the possible existence of "gay genes" as a factor in human homosexuality. A researcher at the Salk Institute found that cells in the hypothalamus, a structure in the brain associated with the regulation of temperature and sleep cycles, were over twice as large in heterosexual males as in homosexual men. Although the researcher acknowledged that the structural differences may have arisen in adult life and were not necessarily present at birth, he raised the possibility that sexual orientation may have a genetic component. Another study of affected sibling pairs reported a possible locus for a "gay gene" on the X chromosome, but as of 2002 the results have not been replicated elsewhere.

In general, however, research into the genetic component of human behavior is presently conducted with one eye, so to speak, on the social and political implications of its potential results. Given contemporary concerns about the misuse of findings related to biological race or sex, investigators are usually careful to acknowledge the importance of environmental as well as genetic factors.

Genetic epidemiology

Genetic epidemiology is the branch of medicine that investigates the incidence and prevalence of genetic disorders in specific populations. Researchers in this field make use of specific types of studies in order to assess the relative importance of genetic and environmental factors in families with a history of inherited disorders.

Twin studies

Twin studies are based on the assumption that twins reared in the same family share a common environment. Monozygotic (identical) twins have all their genes in common, whereas dizygotic (fraternal) twins share only half their genes. If a certain disorder appears more frequently in monozygotic twins of affected persons than in dizygotic twins, one may assume that the difference is due to genetic factors rather than the family environment. Some phenotypes show clear differences between identical and fraternal twins, including schizophrenia, childhood autism, attention-deficit/hyperactivity disorder , unipolar depression, manic depressive disorder, and cognitive abilities as measured by IQ tests.

Twin studies have proved to be particularly important in genetic research into autism. Until the early 1970s, autism was assumed to be caused primarily by parental coldness toward the child. In part, the lack of interest in genetic aspects of the disorder was due to the fact that cytogenetic research (research that studies the links between genetic inheritance and cell structure) was not sufficiently advanced in the late 1960s to have demonstrated any chromosomal abnormalities in people diagnosed with autism. The first small-scale twin study of children with autism was done in 1977; its findings showed, first, that there is a significant difference between monozygotic and dizygotic twin pairs with regard to the appearance of the disorder in siblings. More importantly, the study showed that the similarities within monozygotic pairs of twins included a range of social and cognitive disabilities, not just autism itself. This finding implied that the phenotype of autism is broader than the older diagnostic categories implied. In the 1970s and 1980s, advances in cytogenetic techniques led to the discovery that autism is associated with several different chromosomal abnormalities, including the defect that produces fragile X syndrome. A much larger British twin study done in 1995 confirmed earlier findings in the United States: a monozygotic twin of a child diagnosed with autism was 12 times more likely to have the disorder than a dizygotic twin (60% vs 5%). Secondly, the British study confirmed the hypothesis that the genetic risk of autism extends to a broader phenotype; over 90% of the monozygotic twin pairs in the British study shared social and intellectual disabilities similar to those found in patients with autism, but less severe.

Adoption studies

Adoption studies are used less frequently than twin studies, but are crucial in researching such conditions as schizophrenia and alcoholism. Studies of schizophrenia done in Denmark, for example, showed that the frequency of schizophrenia was 16% in the biological relatives of patients with schizophrenia who had been adopted as infants, compared with 1.8% in the adoptive relatives and the relatives of a group of adopted children who did not have schizophrenia.

Family studies

Family studies are important tools for evaluating environmental effects on children with genetic disorders— and also for evaluating the impact of the disorder on the family environment. Family studies have indicated that families may develop problems in response to a child's illness as well as affecting the child's prognosis for recovery.

Family factors fall into three categories: shared genetic material; shared environment; and nonshared environment. These three categories are complicated, however, by the fact that genetic as well as environmental factors affect interactions between parents and children. For example, a parent's behavior toward a child diagnosed with depression is partly shaped by the parent's genetic vulnerability to depression.

In general, much of the impact of a family's environment on a child with a mental disorder is due to nonshared rather than shared interactions. A clinical research measurement called expressed emotion, or EE, originally developed to study young adults with schizophrenia, is now used to study families with younger children with mental disorders. EE measures three primary aspects of family members' attitudes toward the child with the illness: criticism, hostility, and emotional overinvolvement. A growing number of research studies indicate that EE is a good predictor of the outcome of the child's illness; high EE is a marker of a more difficult course of the disorder and a poorer prognosis.

Clinical applications of biological psychiatry

As of 2002, recent advances in genetics have affected the practice of psychiatry in several ways:

  • Genetic counseling. Genetic counseling is recommended when a couple has already produced a child with mental retardation, dysmorphic (malformed) features, or developmental delays; when either parent is suspected or known to have a genetic disorder; when the mother is over 35; when there is a family history of a genetic disorder, especially if several members are affected; or if the mother has been exposed during pregnancy to drugs or environmental toxins known to cause birth defects. Genetic counselors do not try to control the couple's decision about a present or future pregnancy; rather, they offer information about the disorder, including treatment options as well as the risk of recurrence. They discuss possible reproductive choices available to the couple and help them adjust to caring for a child who is already affected.
  • Medication selection and dosage. Preliminary studies of patients with schizophrenia indicate that DNA testing of the gene for a specific serotonin receptor can predict the patient's response to antipsychotic drugs. A similar form of gene testing can predict which children with asthma will respond to an inhaled medication known as albuterol and which will not. In the near future, researchers hope to devise genetic tests that will measure patients'responsiveness to specific antidepressant and anti-anxiety medications. Such tests would greatly simplify the present process of trial-and-error prescribing of drugs for psychiatric disorders.
  • Psychiatric nosology. Nosology is the branch of psychiatry that deals with the classification of mental disorders. Some current diagnostic labels, including autism and attention-deficit/hyperactivity disorder, may represent groups of related syndromes rather than a single diagnostic entity. In other instances, genetic studies may lead to eventual reclassification of certain disorders. Some studies, for example, suggest that body dysmorphic disorder is more closely related to obsessive-compulsive disorder than to the somatoform disorders with which it is presently grouped.
  • Diagnosis of disorders with major psychological consequences. As of 2002, it is possible for people to find out whether they have the gene for Huntington's disease or the BRCA1 or BRCA2 genes for breast cancer. Although some people may choose not to know, others may prefer the possibility of bad news to years of chronic uncertainty and anxiety.

Ethical concerns

As the number of tests available for determining genetic markers for mental disorders continues to increase, ethical issues are being debated. These concerns include:

  • Regulation of genetic testing. Some companies have started to market tests for the apoE4 Alzheimer's gene even though the present benefits of such testing are not clear. The Department of Health and Human Services has established an advisory committee to study the question of government regulation of genetic testing.
  • Confidentiality. The fear of losing health insurance is a major barrier to acceptance of genetic testing in the general population. Many people do not trust hospitals or research laboratories to keep test results confidential.
  • Discrimination. Others are concerned that genetic findings could be used to deny college or graduate school admission to persons at risk for certain disorders, or to restrict their access to employment opportunities.
  • Reproductive issues. A recent controversy in the British Medical Journal erupted over the question of using genetic testing for "social engineering" by forcing couples to abort fetuses with "undesirable" psychological characteristics or restricting people's right to have children. As more and more human traits are found to have a genetic component, questions inevitably arise regarding the possibility of government control over reproduction. But while few people would want to preserve the gene for Huntington's disease, for example, they are likely to disagree about the desirability of other human traits, such as a tendency toward short stature.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, text revised. Washington, DC: American Psychiatric Association, 2000.

Faraone, Stephen B., Ming T. Tsuang, and Debby W. Tsuang. Genetics of Mental Disorders: A Guide for Students, Clinicians and Researchers. New York: The Guilford Press, 1999.

Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York and London: W. W. Norton and Co., Inc., 1996.

PERIODICALS

Axelsson, J., J. G. Stefansson, A. Magnusson, and others. "Seasonal Affective Disorders: Relevance of Icelandic and Icelandic-Canadian Evidence to Etiologic Hypotheses." Canadian Journal of Psychiatry 47 (March 2002): 153-158.

Cardno, A. G., F. V. Rijsdijk, P. C. Sham, and others. "A Twin Study of Genetic Relationships Between Psychotic Symptoms." American Journal of Psychiatry 159 (April 2002): 539-545.

Collins, Francis S. "Genetics: An Explosion of Knowledge is Transforming Clinical Practice." Geriatrics 54 (January 1999): 41-47.

Dal Forno, G., K. A. Carson, R. Brookmeyer, and others. "APOE Genotype and Survival in Men and Women with Alzheimer's Disease." Neurology 58 (April 2002): 1045-1050.

Everman, David B., and S. B. Cassidy. "Genetics of Childhood Disorders: XII. Genomic Imprinting: Breaking the Rules." Journal of the American Academy of Child and Adolescent Psychiatry 39 (March 2000): 445-448.

Janssen, J. C., E. K. Warrington, H. R. Morris, and others. "Clinical Features of Frontotemporal Dementia Due to the Intronic Tau 10 (+16) Mutation." Neurology 58 (April 2002): 1161-1168.

Klump, K. L., S. Wonderlich, P. Lehoux, and others. "Does Environment Matter? A Review of Nonshared Environment and Eating Disorders." International Journal of Eating Disorders 31 (March 2002): 118-135.

Koenen, K. C., R. Harley, M. J. Lyons, and others. "A Twin Registry Study of Familial and Individual Risk Factors for Trauma Exposure and Posttraumatic Stress Disorder." Journal of Nervous and Mental Disorders 190 (April 2002): 209-218.

Lieb, R., B. Isensee, M. Hofler, and others. "Parental Major Depression and the Risk of Depression and Other Mental Disorders in Offspring: A Prospective-Longitudinal Community Study." Archives of General Psychiatry 59 (April 2002): 365-374.

McGuffin, Peter, and Neilson Martin. "Behaviour and Genes." British Medical Journal 319 (July 3, 1999): 1097-1101.

Marble, M., and G. Pridjian. "Scalp Defects, Polythelia, Microcephaly, and Developmental Delay: A New Syndrome with Apparent Autosomal Dominant Inheritance." American Journal of Medical Genetics 108 (April 2002): 327-332.

Margolis, Russell L., and C. A. Ross. "Genetics of Childhood Disorders: IX. Triplet Repeat Disorders." Journal of the American Academy of Child and Adolescent Psychiatry 38 (December 1999): 1241-1245.

Middleton, F. A., K. Mirnies, J. N. Pierri, and others. "Gene Expression Profiling Reveals Alterations of Specific Metabolic Pathways in Schizophrenia." Journal of Neuroscience 22 (April 2002): 2718-2729.

Mimmack, M. L., M. Ryan, H. Baba, and others. "Gene Expression Analysis in Schizophrenia: Reproducible Up-Regulation of Several Members of the Apolipoprotein L Family Located in a High-Susceptibility Locus for Schizophrenia on Chromosome 22." Proceedings of the National Academy of Sciences of the USA 99 (April 2002): 4680-4685.

Moldavsky, Maria, and others. "Behavioral Phenotypes of Genetic Syndromes: A Reference Guide for Psychiatrists." Journal of the American Academy of Child and Adolescent Psychiatry 40 (July 2001): 749-761.

Rose, Steven P. R. "Neurogenetic Determinism and the New Euphenics." British Medical Journal 317 (December 1998): 1707-1708.

Rutter, Michael. "Gene-Environment Interplay in Relation to Emotional and Behavioral Disturbance." Annual Review of Psychology (2002).

Scarmeas, N., J. Brandt, M. Albert, and others. "Association Between the APOE Genotype and Psychopathologic Symptoms in Alzheimer's Disease." Neurology 58 (April 2002): 1182-1188.

Scott, William K., Martha A. Nance, Ray L. Watts, and others. "Complete Genomic Screen in Parkinson Disease: Evidence for Multiple Genes." Journal of the American Medical Association 286 (November 14, 2001): 2239-2244.

State, Matthew W., and E. M. Dykens. "Genetics of Childhood Disorders: XV. Prader-Willi Syndrome: Genes, Brain, and Behavior." Journal of the American Academy of Child and Adolescent Psychiatry 39 (June 2000): 795-799.

Stein, M. B., K. L. Jang, W. J. Livesley. "Heritability of Social Anxiety-Related Concerns and Personality Characteristics: A Twin Study." Journal of Nervous and Mental Disorders 190 (April 2002): 219-224.

Wamboldt, Marianne S. "Role of the Family in the Onset and Outcome of Childhood Disorders: Selected Research Findings." Journal of the American Academy of Child and Adolescent Psychiatry 39 (October 2000): 1212-1219.

ORGANIZATIONS

National Coalition for Health Professional Education in Genetics. <www.nchpeg.org> .

National Human Genome Research Institute of the National Institutes of Health. <www.nhgri.nih.gov> .

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. <www.nimh.nih.gov> .

OTHER

Office of the Surgeon General. Mental Health: A Report of the Surgeon General. Washington, DC: Government Printing Office, 1999. A copy of the report may be ordered by faxing the Superintendent of Documents at (202) 512-2250.

Rheinische Friedrich-Wilhelms-Universität (Bonn). News Release, April 14, 2002. "Bonn Researchers Localise Manic Depression Gene.". <www.uni-bonn.de/en/News> .

Rutter, Michael. "Genetic Studies of Autism: From the 1970s into the Millennium." Presidential Address, Ninth Biennial International Society for Research in Child and Adolescent Psychopathology Conference, Barcelona, Spain, July 16-20, 1999.

Rebecca J. Frey, Ph.D.



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Oct 21, 2011 @ 3:03 am
Excellent article. I have been writing and presenting at professional conferences the past two years on the patterns of self-destructiveness. This article supports the core belief and offers much more research then I had access to prior to today. Thank you! After 30 plus years of performing psychotherapy I have started to formulate a number of issues and patterns that I have noted. This type of research is up there with Piaget and Erickson, Levinson, et. al., and Maslow.

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