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chapter five

HOW DO MENTAL DISORDERS EMERGE FROMTHE MIX OF GENES AND ENVIRONMENTS? 55

■ ■ ■ Lamar, a man with bad newsLamar is sitting in a coffee shop, stunned. His fiancée Marta has just broken

up with him. She gave him some odd reasons. “It’s important for me to have

children and I don’t think you should have them,” she said. She also said,

“I don’t think I’ll be able to take care of you.” Before Lamar could respond,

Marta fled from the restaurant.

At first Lamar couldn’t make sense of her remarks. Then it occurred to him

that this unhappy scene might be connected to the drama already taking

place in his family.

About a month ago, Lamar and Marta had plans to meet his mother Adele

for dinner at a new restaurant outside of town. Adele never showed up. Lamar

spent several hours calling and driving around, trying to locate her. Finally,

near midnight, his mother called him from a pay phone. She had no idea

where she was or how she had gotten there.

This was not the first time Adele had gotten lost, but before she had always blamed it on being distracted

and terrible with directions. This time Lamar did not buy the excuses. He insisted she go to her doctor.

After a thorough exam and several diagnostic tests, Adele was given a dreadful diagnosis. She has

Alzheimer’s disease. With this illness, plaques and tangles (two types of protein residue) build up in the brain,

destroying cells. Over the course of years, people with Alzheimer’s lose memory, reasoning and language abil-

ities, and their independence. Eventually the brain is unable to carry out basic tasks, causing death.

Alzheimer’s usually strikes people over age sixty-five, but some forms, known as early-onset Alzheimer’s, strike

people even younger. Adele is forty-eight.

Last week when Lamar learned about his mother’s diagnosis, he immediately shared the sad news with his

fiancée. So perhaps Marta has panicked about marrying a man she assumes will be afflicted by Alzheimer’s

at an early age.

Lamar wonders if Marta is right to worry. Perhaps he is at extra risk for early Alzheimer’s. Perhaps he should

not have a family and perhaps he could become a terrible burden to any spouse. Is Marta right to reject him?

Genotype/phenotype complexity Many genes interact with many physicaland social environments to shape normaltraits, but one gene misfiring is sometimessufficient to produce disorder. This is thecase with Alzheimer’s disease – which we will get back to in a moment — butalso with other medical conditions. An example is the rare dementing illnesscalled Huntington’s disease, whichdestroys the fatty lining of nerve cellsleading to loss of coordinated movement,emotional instability, psychosis, andmental decline. Huntington’s is a domi-

nant disorder, meaning that only one dis-ease-related allele at a single locus needbe present for the disease to manifestitself.

A gene on Chromosome 4 is implicatedin Huntington’s. (The chromosomes arenumbered in order of their relativelength; 4 is a relatively big chromosome.)However, this disease does not resultfrom a single mutation to this gene.Rather, many different alleles for the genelead to the same problematic result.These alleles differ from each other in oneimportant way: they have a differentnumber of tandem repeats — multiplecopies of the same base sequence (some-times called “stutters”).

Cystic fibrosis is another single-locusdisease that results from a great many(some 650) allelic variations of a singlegene. Unlike Huntington’s, cystic fibrosisis a recessive disorder; it takes two disease-related alleles at that locus for the disease

6 0 BEHAVIORAL GENETICS

One gene misfiring is sufficient toproduce some medical disorders.Such genes are relatively easy tofind, compared to the genes thatcontribute to complex disorders.

Cystic fibrosis

Chromosome 7Huntington’s

Chromosome 4

PKUphenylalanine

hydroxylase

Chromosome 12

CHAPTER 5: HOW DO MENTAL DISORDERS EMERGE FROM THE MIX OF GENES AND ENVIRONMENTS? 6 1

to emerge. Cystic fibrosis affects themucus lining of the lungs, leading tobreathing problems and other difficulties.

Some single-locus disorders follow aslightly different script: the allele or allelicpair contributing to disorder may occurin any of several different genes. As notedin Chapter 2, this is called genetic het-erogeneity, and it is a characteristic ofcertain rare forms of breast and coloncancer as well as the early-onset form ofAlzheimer’s.

The important point is that single-genedisorders may result from one of manydifferent alleles at one or more loci.Furthermore, any particular allele associ-ated with a disorder may sometimes, butnot always, lead to that disorder and maysometimes, but not always, lead to eithera mild or severe form of the disorder.

The less-than-straightforward associa-tion between an allele and a disorder hasto do with proteins. Recall that genescode for amino acids that combine intoproteins that make up the structure of cells and direct their activities. A so-called “disease gene” has somealleles whose code results in a necessaryprotein and other alleles whose codedoes not have the necessary result. Thegene “misfires” when the latter type ofallele is present. This could mean that asa result of that allele’s instructions, noneof, not enough of, or too much of aresulting protein is produced. Or it couldmean that the protein is not made prop-erly and quickly becomes degraded.

The same unhappy results can occurwhen an allele is affected by modifiergenes, that is, by alleles at other loci thatinteract with the allele in question.

Researchers theorize that the geno-type/phenotype relationship may bethreshold-dependent. Take, for example,a disorder that results when too little of aparticular protein is produced. If proteinquantities fall below a lower threshold,disorder will follow. When protein quan-tities rise above an upper threshold, nodisorder will follow.

But when protein quantities liebetween the two thresholds, disordermay or may not follow. There may be nosymptoms, unnoticeable symptoms, mildsymptoms, or serious symptoms. In otherwords, there is no predictable phenotypeassociated with that genotype. In suchcases, whether or how the disorder man-ifests itself depends on environmentalfactors.

PKU is a disease that results when thebody does not have enough of a partic-ular enzyme; this enzyme is a proteinthat acts upon the liver. As described inChapter 3, PKU can cause mental retar-dation. It also produces other effects,such as the lightening of hair and skincolor.

The gene associated with PKU is calledPAH (this stands for the enzymeinvolved, phenylalanine hydroxylase).More than 400 problematic alleles havebeen identified; according to one scien-tific report, the mutations include “dele-


tions, insertions, missense mutations,splicing defects, and nonsense muta-tions.” 1 Researchers had hoped that theycould match up genotype with phenotype— that is, that based on the problemallele that is present, they could predictthe symptoms and severity of the disease.If they could do this, then doctors couldadjust treatment plans to each individual.Babies having alleles known to producesevere effects could be put on the highlyrestricted diet that prevents symptomsfrom appearing. Babies with alleles associ-ated with milder effects could be put onless restrictive diets.

It has not turned out to be so simple.Many alleles are not consistently associ-ated with any one PKU phenotype, thatis, with any one set of symptoms. In theglum words of one research report,“Prognosis may not be predicted withprecision based on mutation analysis.” 2

More genotype/phenotypecomplexityPKU is a recessive disorder, like cysticfibrosis and unlike Huntington’s, a domi-nant disorder. The disease occurs only inpersons who inherit two problematicalleles of the same gene, one from eachparent. Recessive and dominant disordersof this type illustrate Mendelian inheri-tance patterns. “Mendelian” refers toGregor Mendel, a 19th century monkwho raised pea plants and carefullyrecorded various traits that appeared insuccessive generations (color, shape, tex-ture, size, etc.). Based on his experi-ments, Mendel proposed the theory thatdiscrete units of heredity (what we nowcall genes) are passed from generation togeneration in dominant and recessive pat-terns that can be calculated using simplemathematical formulas. All of moderngenetics builds upon his original ideas.

Geneticists today realize that inheri-tance is more complicated than a simpleMendelian passing down of immutablegenetic units. For example, withHuntington’s disease, the allele that ispassed down in dominant fashionthrough the generations alters slightlyalong the way. A sequence of DNA withinthe allele repeats itself (stutters) each timeit gets passed down. When the string ofrepeats exceeds a certain length, theallele begins to malfunction — fails toproperly instruct for the amino acids thatwill build a needed protein — and diseaseresults. The age at onset of disease and

Based on his careful study of pea plants in the mid-1800s,Gregor Mendel proposed the ideathat “discrete units of heredity” —what we now call the genes — are transmitted from one genera-tion to the next in recessive anddominant patterns. Researchersnow recognize that the inheri-tance patterns for many traits are more complicated.

the speed of decline correlate positivelywith the number of stutters. Huntington’sdisease appears when there are more than35 repeats but not when there are fewerthan 35 repeats. Importantly, there arerare, unexplained exceptions.

Fragile X syndrome, the most commonlyinherited form of mental retardation, isanother disorder that occurs when a stringof repeats in a gene lengthens. As withHuntington’s, Fragile X appears whenthere is a high number of base repeats(above 200) in the relevant gene. Thereappears to be only a modest relationshipbetween the number of repeats above 200and the severity of the disease.

There’s a second twist to the inheri-tance pattern of Fragile X. The disorder iswhat is known as an X-linked disorder or

trait. A gene with the disease-causingalleles appears on the X chromosomethat, along with its counterpart the Ychromosome, defines gender. Boys (XY)are more frequently and severely affectedby Fragile X because if they have a prob-lematic allele on their X chromosome,

they do not have a second X with anormal allele to compensate for the defi-ciency, the way that girls (XX) do.

The bottom line is that even for asingle-locus disorder, inheriting a disease-related allele does not by itself foretell thepresence of disease and the severity ofsymptoms. Once again, genotype may notalways predict phenotype.

Polygenic disorders: complexity multiplied Some mental disorders have no conspic-uous genetic component; the loss ofmemory that we call amnesia is typicallycaused by a hit to the head, not a geneticproblem. And as we emphasized earlier,most genetic disorders do not result fromalleles at a single locus. PKU, Hunting-ton’s, and Fragile X are exceptions to therule.

The vast majority of mental disordersare believed to be polygenic: health prob-lems occur when disease-related allelesare inherited for many different genes.Most mental disorders also are multifacto-

rial, which means that multiple environ-mental and genetic factors are operatingin an intricate, epigenetic fashion to upsetthe stable development and functioningof cells. (The adjective “complex” is oftenused in the same sense as “multifacto-rial.”)

Earlier in this chapter, we pointed outthat with most single-gene disorders, adisease-related allele sometimes, but not

6 3CHAPTER 5: HOW DO MENTAL DISORDERS EMERGE FROM THE MIX OF GENES AND ENVIRONMENTS?

Fragile X syndrome can result in mild learning disabilities ormore severe mental retardation.Resulting from a mutation in asingle gene on the X chromosome,it occurs in 1 in 3,600 males andless often in females.

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always, leads to the disorder and some-times, but not always, leads to either amild or severe form of the disorder. This qualifying statement applies to allelesinvolved in polygenic disorders, too. Each of the many potentially problematicalleles sometimes, but not always, contributes to triggering a disorder andsometimes, but not always, contributes toa mild or severe form of the disorder.

A polygenic disorder results only whenall of the pertinent genetic and environ-mental factors are in place, and the extentof disorder depends on when those factorsoccur and how they affect each other. Thedifficulty of predicting phenotype fromgenotype is compounded exponentially.

Schizophrenia, a polygenic disorderSchizophrenia is an example of a poly-genic mental disorder with an ambiguousgenotype-phenotype relationship. It is acommon form of mental illness comparedto PKU and Huntington’s, affecting about1 percent of the general population.About half of all cases manifest them-selves in adolescence or early adulthood.

Schizophrenia stems from incoordina-tion of brain function. It is as though circuits inside the brain get crossed. Thebrain loses its ability to process thoughts,words, and emotions as it normallywould. Affected persons become con-fused, paranoid, and/or delusional. Theymay believe spies are following them or

that aliens are beaming them messages.They can become apathetic and emotion-ally stunted, which causes them to isolatethemselves from other people and toabandon cleanliness or other socialnorms. People affected by an episode ofschizophrenia often make no sense toothers and can be impossible to reasonwith. They often become social outcasts.Many of the homeless suffer from this disorder.

With some people the symptoms ofschizophrenia appear gradually. Withothers the symptoms show up in asudden, dramatic change of behavior.Some people experience schizophrenicsymptoms only occasionally, while othersare chronically affected. Like manychronic diseases, schizophrenia is not cur-able, though medicine and behaviortherapy can often control some symp-toms. In some cases — not predictably —improvement and virtually full recoveryoccur. Symptoms often decline with age.

For a long time schizophrenia wasbelieved to be the result of faulty par-enting, the victim’s weak personality, orGod’s punishment. But beginning in the1960s, researchers conducting family,twin, and adoption studies recognizedthat relatives of affected persons are muchmore likely to themselves become schizo-phrenic, compared to people in the gen-eral population. Indeed, there is a ten-foldincrease in risk for persons who have sib-lings with the disease. This implies thatschizophrenia has a familial, perhaps


hereditary, component. That research didnot lead to a cure for schizophrenia, but itdid provide great relief to parents andpatients who had previously shoulderedthe blame for the disease.

Molecular scientists have put a greatdeal of effort into finding the susceptibility

genes for schizophrenia. A susceptibilitygene is one for which certain alleles makeyou susceptible to — at higher risk for —a disorder, while other alleles make youless liable to have the disorder. A disorderwill appear in those instances where aparticular allele appears in conjunctionwith problematic alleles at other loci plusenvironmental triggers. (“Susceptibility”as an adjective also is used to describegenes that affect traits not associated withdisorder, such as a “susceptibility gene”for musicality.)

Studies on schizophrenia have “impli-cated” various genes and chromosomalregions, but they have produced only ten-tative results that remain unconfirmeddespite replication studies that have beenattempted.3 The failure to pin down schiz-ophrenia susceptibility genes is frustrating,but it does not mean that such genes donot exist. Rather, it underscores the com-plexity of the disease. It serves as evidencethat the disease is genetically heteroge-neous: multiple genetic factors provide dif-ferent pathways to the same disease.

It is important to note here that thevast majority of people who have first-degree relatives with schizophrenia donot end up with the disease themselves.

Something besides genes is at play, but itis not clear what that is. So another ques-tion is, what environmental factorsinteract with susceptibility genes tolaunch the onset of schizophrenia?

Researchers are exploring variouscausal theories. Viral infections that alterbrain chemistry are suspected to play arole in some, but perhaps not all,instances of this disease. Head injuries areanother possible factor, in some cases. So are prenatal infections such as rubella,developmental problems triggered bycomplications at birth, and drug abuse. In short, what we call schizophrenia mayhave many different causes and is prob-ably several distinct diseases. The searchfor genetic components to schizophreniais merely one track in the manifold inves-tigations into this tragic and disablingform of mental disorder.


A significant percentage of thehomeless in the U.S. today sufferfrom schizophrenia or some othermental disorder. It is not yetknown which environmental factors interact with genetics to cause these mental disordersto emerge.

Bipolar disorder, also polygenicLike schizophrenia, bipolar disorder is apolygenic mental disorder with no cleargenotype-phenotype relationship. Bipolar,also known as manic-depressive illness,causes extreme swings in mood.

In a depressed state, an affected personis overwhelmingly sad, disinterested inlife, indecisive in the extreme, and unableto sleep or, alternatively, unable to stayalert. The person may feel worthless andbe filled with despair, leading to suicidalimpulses. It is estimated that 15 percent

to 20 percent of patients suffering frombipolar disorder kill themselves, eventhough many are on medication.

In the manic state of bipolar disorder,the same person is highly elated and mayalso be extremely talkative, distractable,hypersexual, irresponsibly extravagantfinancially, and unable or unwilling tosleep. The person may feel extremely self-important and be willing to take extraor-dinary and dangerous risks.

For the person with bipolar disorder,extreme moods alternate with periods ofmore stable emotions. The mood swings


Persons with bipolar disordersuffer from extreme swings inmood. In the manic state, theymay be highly creative but alsoerratic, over-energetic, and irre-sponsible. In the depressed state,they may be sad, disinterested,and even suicidal.

may occur months or weeks apart, or they may cycle rapidly. The frequencyof these mood swings tends to increaseover time.

About one in every 100 persons hassevere bipolar, and another one in 100has a milder form of the disease. It occursequally often in men and women and hasits onset primarily in adulthood, thoughresearchers believe it may be underdiag-nosed in adolescents. Bipolar disorder istreated with medication and counseling,but these treatments are not effective in all cases nor to the same degree. Each physician has to experiment withtreatments until one is found that works.

From this description of bipolar dis-order, it should be apparent that its phe-notype varies in each affected person.This is because the pathway from causeto disease varies in each person.Systematic studies of families, twins, andadoptees show that the risk of havingbipolar disorder is far higher for personswho have close relatives with the disorder, compared to members of thegeneral population.

As has been the case for schizophrenia,finding the specific genes involved inbipolar disorder has proven to be difficult.A pair of scientists writing about thisodyssey have referred to it as a “manicdepressive history.” 4 Researchers usinglinkage analysis have identified more thana dozen different chromosomal regions orgenes with lod scores high enough to sug-gest they are relevant to bipolar disorder.

Later investigations (called replications)have produced lower lod scores for thesame genes, suggesting that perhaps theyare not so relevant after all. A recentmeta-analysis of genome scan studiescould find no statistical significance forany nominated site.5 One reasonable con-clusion is that no one gene has such a sig-nificant effect that it can be revealedthrough linkage analysis. Thus, the searchcontinues both for susceptibility genes formental disorders and also for bettermethods of finding them.

Research challengesThere are no recognized laboratory testsfor schizophrenia or bipolar disorder tohelp a physician confirm or disconfirm adiagnosis. Researchers know less aboutthe etiology of these disorders (the path-ways from cause to effect) than they doabout the etiology of non-psychologicaldiseases such as the various forms ofcancer and diabetes. The same relativescarcity of knowledge also holds for othermental disorders such as anxiety disorder,post-traumatic stress disorder, eating dis-orders, and phobias. The etiology ofAlzheimer’s is relatively better under-stood, but not well enough yet to providefor adequate treatments.

Genetic research will help fill in theblanks, and here’s how. As each suscepti-bility gene of large or small effect is iden-tified, lab techniques can be used toentice the gene to express itself and


Many studies have sought to identify the susceptibility genesfor bipolar (the genes that playsome role in the disease), but sofar none has been confirmed.Finding them may be difficult ifthere are many genes, each ofsmall effect.

reveal the amino acids for which it codesand the proteins that result. Through avariety of techniques, researchers canthen figure out what the proteins dowhen they are functioning properly andwhat happens when they malfunction.Following this trail for each gene,researchers hope to put together a betterpicture of what happens inside the bodyto cause the paranoia of schizophrenia,the mood swings of bipolar disorder, and the memory loss of Alzheimer’s.Researchers are also attempting to discover more about the mostly unknownfactors that regulate variability in geneexpression. With such knowledge couldcome medicines that substitute for proteins the body needs, but is not able to produce properly itself or producesinsufficiently due to problems in geneticcoding.

The environmental part of the storymay be neglected through this approach,but that is mainly because researchershave not yet found a good way to isolateand study each contributing environ-mental factor the way a gene can be iso-lated and studied. The complex interplaythat occurs between biological processesand environments also gets neglected,though it is argued that approachingmental disorders through individualgenes — as piecemeal and artificial asthat may be — is a pragmatic and doableway to get started on this difficult puzzle.

Lamar’s dilemmaDespite the considerable effort beingexpended in behavioral genetic research,results so far offer little practical help tothe patient who already has a mental dis-order. Very little can be done for Adele,who already suffers from Alzheimer’s,nor for Lamar, who worries that he him-self may someday be afflicted with thisdisease.

Alzheimer’s affects about 4 millionAmericans. That number is growingbecause people are living longer and thedisease appears late in life. The biggestrisk factor for expression of the disease isaging. It is estimated that perhaps asmany as 10 percent of all people age 65and older have the disease and up to 50 percent of all people age 85 and older.People with relatives affected byAlzheimer’s are at somewhat higher risk


By finding the genes at work inAlzheimer’s disease, scientistshope to obtain clues to the environmental factors that alsoplay a role.

themselves for acquiring the disease. The form of Alzheimer’s that has a late

onset is what afflicts former U.S.President Ronald Reagan. It is a complexdisorder, with many genes contributing.One gene identified as a contributingfactor sits on Chromosome 19 and iscalled apoE (for apolipoprotein class E).Although the details remain unclear,researchers believe that the protein asso-ciated with this gene repairs connectionsbetween cells in the brain. This suggeststhat the problems of Alzheimer’s occurwhen these repairs are no longer madeproperly.

ApoE appears in three different allelescalled apoE2, apoE3, and apoE4. Peoplewho inherit one copy of apoE4 (about aquarter of the population) have about fourtimes the risk of developing Alzheimer’scompared to the general population.People who inherit two copies of apoE4,one from each parent (about 2 percent ofthe population) are at a ten-fold increasein risk. The risk declines for people withapoE3 alleles, and it declines even morefor people with apoE2 alleles.

About 5 percent of Americans withAlzheimer’s have the rare early-onset vari-eties that strike people before age 65. Thisis the form of the disease that has affectedLamar’s mother, Adele. Three differentloci have been implicated in earlyAlzheimer’s, and they are located onChromosomes 1, 14, and 21. It is a dom-inant, single-locus disorder, which meansthat just one copy of a disease-related

allele at any one of these three loci isenough to trigger the disease.

A diagnosis of Alzheimer’s, both late-onset and early-onset, rests on a variety offactors, such as tests of cognitive func-tioning and mood (to gauge symptoms),blood and urine tests (to rule out otherhealth problems), and brain scans (to ruleout strokes). As yet there is no cure forAlzheimer’s, although there are drugsthat can delay the problems for somepeople.

Lamar’s mother, with early-onsetAlzheimer’s, has obviously inherited oneof the alleles associated with the disease.Recall that each person has a pair ofalleles for every gene and passes only one


Former U.S. President RonaldReagan is among the millions ofAmericans who suffer fromAlzheimer’s, the most commonform of dementia.

of them down to each child. Lamar mayhave inherited the problem allele from hismother, in which case he has inheritedthe disease, or he may have inherited abenign allele from her, in which case hewill escape the early onset form of the dis-ease. (He would still share the generalpopulation’s risk for the late onset form.)

Lamar could get a genetic test to findout whether he has inherited an alleleassociated with early-onset Alzheimer’s. Ifthe test shows he is free from such alleles,perhaps his fiancée Marta will reconsidermarriage and life will be back to usual.

On the other hand, if the test shows hehas an early-onset Alzheimer’s allele, thenLamar has brought upon himself fore-knowledge of a sorry fate. Because early-onset Alzheimer’s is a single-gene,dominant disorder, Lamar will most likelysuccumb to the slow destruction of hismind. How would such information affecthis life in the meantime? Probably notwell, based on reports in the medical literature on people who have obtainedthis knowledge.

Lamar may or may not want to knowwhat his future holds, but at least he canchoose whether or not to find out. Thatchoice is not available to people con-cerned about their risks for the predomi-nant forms of Alzheimer’s. Because thoseforms of the disease are polygenic, thepresence of apoE4 or any other alleleassociated with the disease would onlyindicate level of risks, not certain diag-nosis. No professional medical society rec-

ommends screening for the apoE4 allele. But, as Lamar probably realizes, there

is little to be gained from getting tested forany form of Alzheimer’s so long as nocure is known and treatment is palliativeat best. In fact, there is much to be risked.Suppose, for example, that Lamar’semployer obtains access to his medicalrecords and learns he has an early-onsetAlzheimer allele. The employer couldmisunderstand the information and pre-sume Lamar is already diseased. Lamarcould find himself moved to a position ofless responsibility, cut off from promotion.The employer might even be tempted tofire Lamar out of fears that insurance pre-miums will climb if Lamar stays. Thiswould all be quite unfair for Lamar sincehe may have left twenty or more years ofhealthful living.

Lamar’s fiancée, of course, did not evenwait for a test before jumping to conclu-sions and abandoning him. So perhapsLamar has been spared marriage tosomeone so flighty. There’s little else positive to see about his situation. Butwho knows? Before the disease appears inLamar — if it does — researchers mayhave found the cure. They may have dis-covered the environmental factors Lamarshould avoid to delay onset of the disease.They may have figured out how to synthesize the proteins his body needs inorder to compensate for those his bodyinadequately produces. They may evenknow how to repair or replace unwantedalleles through gene therapy.


Normal and abnormal traitsThere are opposing ways to look atmental disorder. One view is that they areall-or-none states, like pregnancy ormeasles. The other view is that disordersrepresent the extreme end of a con-tinuum ranging from healthy tounhealthy or, to put it in psychologicalterms, from the normal to the patholog-

ical. These competing possibilities lead tosuch questions as whether the sad orintroverted person differs in kind ordegree from the depressed person,whether or not someone with an exu-berant personality is just a few shadesaway from being uncontrollably manic,and whether absentmindedness is a pre-liminary form of dementia.

If a disorder is on a continuum with“order,” then the location of the dividingline becomes important. Otherwise, treat-ment for disorder could someday extendinto treatment for normal conditions.

One way to distinguish mental disorderfrom normal mental functioning is to saythat a disorder is one that has a detri-mental effect on a person’s ability to getalong in society. But sometimes that’shard to say. Vincent Van Gogh sufferedgreatly from severe mental problems, yethe was one of the greatest artists of the19th century. Many have pointed to aputative link between creative genius andmental disorder. Some researchers saythat a feature common to both is greateremotional range. If this is the case, thenthe quest to eliminate mental disorder

could have the unintended effect of elim-inating positive traits as well. For a mentaldisorder such as Alzheimer’s, it is hard toimagine what the related positive traitmight be, but someday scientists mayprove that it is simply the extreme oppo-site of some beneficial protein processesrather than a unique aberration.

Notes

1 National Institutes of Health (2000), p. 10.

2 See Enns et al. (1999). See Dipple (2000) which quotes

Enns.

3 See for example Williams, H. J. et al. (2003), disconfirming

the association between the PRODH gene on Chromosome

22 and schizophrenia. See also the vague conclusion of the

abstract for a genome scan meta-analysis by Lewis, C. M.

et al. (2003), p. 34: “The results suggest that some or all of

[more than a dozen chromosomal] regions contain loci that

increase susceptibility to schizophrenia in diverse popula-

tions.”

4 See Risch, N. and D. Botstein (1996).

5 Segurado, R. et al. (2003).


Vincent Van Gogh suffered frommental disorder, possibly bipolar.This self-portrait reveals his indis-putable talent, yet also hints athis internal disturbance. Someresearchers believe that theremay be a relationship betweenmental illness and creativity.

R E S O U R C E S F O R C H A P T E R 5

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