Jay Joseph Psy.D. The Missing Gene Chapters

CHAPTER ONE

Introduction. The Twin Method: Science or Pseudoscience?

The Missing Gene: Psychiatry, Heredity, and the Fruitless Search for Genes

sychologist Jay Joseph

challenges the widely

disseminated view

that the major

psychiatric disorders have an important underlying genetic

basis. The main

pillar supporting this

view

is a research

technique called the

twin

method

, which is utilized mainly

by the fields

of behavior genetics

[1]

and psychiatric

genetics

[

]

. The twin

method compares the resemblance of

reared-

together identical twin

pairs

(also known as monozygotic, or MZ),

who share 100%

genetic similarity,

versus

the

resemblance of reared-

together same-sex fraternal twin

pairs

(also known as

dizygotic, or DZ), who

average a

50% genetic similarity. (Twin resemblance is usually

measured with concordance rates or

correlations.)

Based

on the

assumption that the childhood and adult environments of both types of twins

are

comparable, known

the “equal environment

assumption” or “EEA,”

[3]

twin researchers attribute to genetic

factors the usual

finding

of a

significantly

greater resemblance among

identical versus same-sex fraternal twin

pairs.

In his previous book,

he Gene Illusion: Genetic Research in Psychiatry and Psychology Under the

Microscope

, Joseph

showed that the

equal environment assumption of the twin method,

egardless of how

has

been

defined, is false.

Thus, it is likely

that the twin method records nothing more than the greater environmental

similarity, the greater psychological association, and the

more similar treatment of identical versus

same-sex

fraternal twin pairs.

In Chapter 1 of

The Missing Gene

, Joseph elaborates on

his previous

critique of the twin

method, and shows

that the arguments

presented by Kenneth S. Kendler,

leading defender

the

twin method,

do not hold up to critical examination.

Like most contemporary twin researchers, Kendler recognizes that identical

twin

pairs

experience more similar environments than

fraternal twin pairs, yet continues to uphold the validity of

the twin method.

Joseph suggests that, because it rests on at least one clearly false theoretical assumption, the twin

method

can be

understood

within

the framework others have created to separate science from

pseudo

science.

[4]

As one

example, when faced

with evidence

that runs counter to

their claims,

pseudoscience

proponents often reverse the

burden of proof for demonstrating the

validity of their

claims

from themselves

onto

their critics. Unidentified flying

object (UFO) proponents, for example, sometimes

demand that skeptics

explain every report of an abnormal

event

in the sky. However, “because it is essentially

impossible to prove a

universal negative,

this tactic incorrectly

places the burden of proof on

the skeptic

rather than the claimant.”

[5]

Similarly, it is common for defenders of the twin method to state or imply that critics of the twin method bear

the burden of proof

for demonstrating that identical twins’ more similar environments invalidate the twin method. As

others who have attempted to

distinguish science from pseudoscience have pointed out, however, “a basic tenet

of science is that the burden of proof always falls

squarely on the claimant, not the critic...Consequently, it is up to

the proponents of these techniques to demonstrate that they work,

not up to the critics of these techniques to

demon

trate the converse.”

[6]

But since the twin method would indeed be relegated to

the museum of

pseudosciences if twin researchers bore the burden of proof for demonstrating the validity of the twin method, they

frequently place this burden on critics.

In 1983, Kendler wrote, “For a familial-environmental bias in twin studies of schizophrenia to be a tenable

hypothesis,

nongenetic familial

factors must be shown to be of major etiologic importance in the disorder.”

[7]

When he wrote that familial-

environmental factors “must be

shown,” Kendler clearly meant that these factors

must

be shown

y critics

. Kendler does this even

though (1) shifting the burden of proof to

critics runs counter

to a

“basic tenet of science,” (2) family environment is a major factor in

non-genetic explanations of

schizophrenia and

other

psychiatric disorders, and (3) he takes the opposite position when discussing

potential environmental

confounds in psychiatric

family

studies. In

he latter

case, Kendler does not require critics

to show that

“familial

factors” are of “major etiologic importance in the disorder” to invalidate

conclusions in

favor of genetics.

According to twin researchers Michael Lyons and colleagues, “it would seem that the burden of proof

rests

with critics of the twin

method to

demonstrate that ‘trait-relevant’ environmental factors are more similar

for

identical than same-sex fraternal twins.”

[8]

Although they wrote,

without any justification, that the burden

proof

“seems” to fall on critics, twin researchers bear this burden

because

they

are responsible for

demonstrating the

validity of their research method.

Similarly, according to twin researcher Thomas J. Bouchard, Jr.,

“It is certainly true that MZ twins experience more similar environments than do DZ twins, but it is also

true, if

perhaps

surprising, that no

one has been able to show that such imposed similarities in

treatment are trait-

relevant.”

[9]

Elsewhere Bouchard argued, in response to criticisms of the EEA by psychologist Louise Hoffman,

“The equal environment assumption is required only for trait relevant features of the environment;

features of

the environment

that have

causal status. Causal status must be demonstrated, not

assumed.... It is

absolutely mandatory

that Hoffman

demonstrate

that the

differential treatments she

cites have a causal

influence on the traits whose similarity she is trying to

explain. This is a very difficult

task

[emphasis added].”

[10]

And in response to an earlier criticism of the EEA by Joseph, psychiatric genetic researchers Ste

en Faraone

and Joseph

Biederman attempted to reverse the burden of proof for demonstrating the validity of the twin method

onto Joseph

“The second claim made by Joseph is that twin studies of ADHD are flawed by the equal environment

assumption, which holds

that the

trait-relevant environments of identical and fraternal twins are the

same. He

finds this assumption untenable for two

reasons. First, several

studies have shown that,

compared with

fraternal twins, identical twins are treated more alike, spend

more time together, have

common friends,

and experience greater levels of identity confusion. Second, he

infers

from

these

data that identical twins are

more likely

to be similarly exposed to

trait-relevant

environmental factors.

Notably, Joseph

presents no data

to support his inference. Thus, readers

should view it as a

hypothesis to be tested rather than a conclusion

be accepted [emphasis in original].”

[11]

It is clear to most people (including most twin researchers), and backed up by research, that identical

twin

pairs experience

much more

similar environments than do

same-sex

fraternal twin pairs. Therefore, regardless of

how twin researchers have

attempted to

validate the twin method (see

the discussion of Chapter 10), the

simple

fact that identical twin pair environments are

more similar is

sufficient to conclude that the twin method,

like a

family study (see below), is unable to disentangle potential genetic

and

environmental influences on

psychiatric

disorders.

CHAPTER TWO

ADHD Genetic Research: Activity Deserving of Attention, or

Studies

Disordered by

Deficits?

Chapter 2 examines the argument that attention-deficit hyperactivity disorder (ADHD)

as an underlying

genetic basis.

Here,

Joseph

highlights the invalidating flaws of family, twin, and adoption research in this

area,

and argues that, contrary to the

ominant

view in

psychiatry, there is little scientifically

acceptable evidence

supporting a genetic basis for the condition. ADHD

molecular

genetic research, which

thus far has failed to identify

any “ADHD genes,” is discussed in Chapter 11.

Research suggests that ADHD, like most psychiatric disorders, tends to aggregate in families. However,

although many

behavioral

tendencies may be

familial

in the sense that they “run” or cluster in families, we

cannot

determine whether this clustering

is caused by the

greater

genetic

resemblance of family members,

since families

are also exposed to similar environmental factors.

As schizophrenia genetic

researchers

Irving

Gottesman and

James

Shields have written, “that a disease is familial does not

necessarily imply that

it is genetic.

Familial

clustering can

also be transmitted through culture, infectious sources, or learning.”

[12]

Researchers’ understanding that the familial clustering of ADHD can be explained on environmental

grounds

led them to seek

other

methods to determine whether genetic factors play a role. Most have turned

to the twin

method to answer this question.

However, since the

evidence overwhelmingly suggests that

identical twin pairs

are treated more alike, spend considerably more

time together, and experience

greater

levels of identity confusion

and closeness than fraternal pairs, we would expect identical

twins—on purely

environmental grounds—to

correlate higher than same-sex fraternals on ADHD-related measures. Thus, as

have seen, the twin method is

unable to disentangle the

potential influences of genes and environment,

and therefore supplies no

evidence

supporting a genetic basis for ADHD. It in also noteworthy

that most

ADHD twin researchers (more than 25 ADHD

twin

studies have been published) did not discuss the merits of

the equal environment

assumption in their

research publications.

Another method used to assess

for

genetic influences on ADHD and other syndromes is the study of

adopted individuals. In

theory, an

adoption study is able to disentangle

otential

genetic and environmental

influences on psychiatric disorders because

adoptees receive their

genes from one family, but are raised in

the

environment of another family. Six ADHD adoption studies have

been published by to date. The

results of

these

studies are frequently cited in textbooks, review articles, and scientific papers as

supporting genetic

theories of

ADHD. However,

these studies contain several invalidating flaws. The main problems in ADHD

adoption research

include (1) in contrast to schizophrenia adoption

research, ADHD adoption researchers

were unable to study

adoptees’ biological relatives; (2) the researchers used non-blinded diagnoses

in all but one of the studies

which

they sometimes

made on the basis of

relatives’ recollections; (3) ADHD was not adequately defined in most

studies; (4) the researchers

were often

unable to control for

environmental confounds; (5) the researchers

did not

control for the status of adoptive parents as a population

screened for

psychiatric disorders; (6) there

was

potential researcher bias; and (7) the researchers used late-separated adoptees.

Unfortunately, ADHD genetic researchers and subsequent review authors usually fail to discuss the

severe

limitations of ADHD

adoption

models unless compelled to do so by critics.

[13]

As Joseph documents,

they

sometimes obscure the fact that—unlike the

schizophrenia

adoption studies before them—ADHD

adoption

researchers were unable to study adoptees’ biological relatives. This

by itself calls into question

any

conclusions

in favor of genetics. In subsequent chapters, Joseph shows that the problem of secondary

sources’ potentially

misleading

accounts of psychiatric genetic research is by no means limited to ADHD. In

fact, the

misrepresentation

of psychiatric genetic research

in influential texts

is a

running theme throughout the entire book.

Joseph assesses of the total weight of the evidence put forward in favor of a genetic basis or

predisposition

for ADHD, and

concludes that a

role for genetic factors is not supported, and that future

research should be

directed towards psychosocial causes.

Of course, this conclusion

lends support to the

increasing number of

people who question the validity of the ADHD concept itself.

CHAPTER THREE

A Critique of the Spectrum Concept as Used in the Danish-

American

Schizophrenia

Adoption Studies.

Studies validating the dominant theories in psychiatry usually are not the subject of in-depth critical

examination by those who

defend them.

This is particularly true about research cited in support of genetic

influences on the major psychiatric disorders. Yet,

conclusions in favor of

genetics frequently depend on the

investigators’ decision-making process during the course of their studies.

Whom should they count as cases?

How

should they define the disorder in question? What statistical procedures should they use?

Which

comparisons

should they emphasize? Too

often, studies have been published in which the methods, results,

and conclusions

appear together for the first time, allowing researchers to

present the study as a neat

package.

This can occur because there is no procedure in psychiatry requiring researchers to submit and/or

publish

their methods

before

they collect

data. Thus, even highly ethical investigators might be tempted to

pick and

choose results enabling them to find

statistically significant results,

which are often a prerequisite for

having their

study published.

[14]

These problems could be reduced

the establishment of a system

requiring researchers to

submit a description of their methods prior to the collection and

analysis of

data, and

requiring journals to agree to

publish the results regardless of whether statistical significance is achieved.

Although it is

understood that there

“is a cardinal rule in

experimental design that any decision regarding the

treatment of data must

be made

prior

an inspection of the data,”

[15]

accountability in

psychiatric research,

as well as research in other fields, is

inadequate.

The Danish-American adoption studies of the 1960s and 70s played a crucial role in establishing

schizophrenia as psychiatry’s

paradigmatic

genetic disorder. Yet, although the results depended on greatly

expanding the definition of schizophrenia, there is no

evidence that Seymour

Kety, David Rosenthal, Paul

Wender, and their Danish associates agreed on this expanded definition before

they collected and analyzed

their

data. Furthermore, Joseph shows that these investigators made faulty calculations of their

published

data, which

led them, mistakenly, to

conclude in favor of genetic influences on schizophrenia.

Having provided a detailed critical review of the Danish-American adoption studies in Chapter 7 of

The

Gene

Illusion

Chapter 3

The

Missing Gene

Joseph takes a close look a crucial aspect of schizophrenia

adoption

research:

the

“schizophrenia

spectrum” concept. In doing so,

he shows that the spectrum concept

does not hold

up to

critical examination, and that the

researchers should have limited their definition of

schizophrenia to the

chronic form as it was understood at the time they performed

their research. His analysis

is relevant today for

two

main

reasons: (1) because these adoption studies remain the most frequently

cited

evidence in support of

genetic

theor

ies

of schizophrenia, and

(2) as an example of how a close examination

of one aspect of

genetic research

can uncover serious and invalidating flaws—even in studies

that form the

basis of existing

scientific paradigms.

Interestingly, Eugen Bleuler, the founder of the schizophrenia concept, argued against diagnosing people

manifesting milder

symptoms

ith schizophrenia.

“Only a few isolated psychotic symptoms

can be utilized in

recognizing the disease,” wrote Bleuler,

“and these

too, have a very high diagnostic threshold value.”

[16]

Moreover, it was improper for the

investigators to

count as

schizophrenia “uncertain” cases in general, and

“uncertain borderline

schizophrenia” cases in

particular.

Joseph suggests that the Danish-American schizophrenia spectrum was created not on the basis of

theoretical or empirical

soundness, but

rather to enable the researchers (1) to have enough subject to study,

and

(2) to be able to find statistically significant

results in the genetic

direction. He concludes that the

“schizophrenia

spectrum” concept, as the Danish-American researchers

defined it, is invalid on several

grounds. Thus, “chronic

schizophrenia” is the only diagnosis they should have used in their studies,

implying that the Danish-American

schizophrenia adoption studies, and their authors’ conclusions in favor of

genetics, should be

reassessed on this

basis.

CHAPTER FOUR

Pellagra and Genetic Research.

In Chapter 4, Joseph engages in a bit of historical speculation by predicting the results of twin and

adoption

studies of pellagra,

an early

20th century often fatal disease characterized by severe skin rash,

gastrointestinal

problems, and mental disturbance.

Pellagra was ultimately

discovered to be caused by a

vitamin deficiency linked

to malnutrition.

Joseph discusses pellagra as the subject of genetic research, both real and hypothetical, as a way of

illustrating how psychiatric

genetic

research methods are potentially confounded by environmental factors,

and

how the “genetic predisposition” concept is often

irrelevant and

even potentially harmful.

Joseph discusses an

early 20th century published family pedigree study of pellagra, and

speculates about what pellagra twin and

adoption studies might have found.

Although there is currently a widespread consensus in

psychiatry that

individuals

diagnosed with mental disorders are

genetically predisposed to develop them, many of the

environmental

factors thought

to trigger these disorders are either controversial or are

unknown. However, the

cause of

pellagra

known

and, as

Joseph argues,

psychiatric genetic methods would be expected to point to the

operation of genetic factors in a condition known to

be caused not by

genes, but by a dietary deficiency.

Early 20th century proponents of eugenics

[17]

and genetic determinism, such as Charles Davenport,

mistakenly interpreted

pellagra family

histories as showing that the condition had a genetic basis. Joseph

goes on

to argue that, had researchers then

decided to perform studies

using (1) the twin method, (2) reared-

apart twins,

and (3) adoptees, the results from these studies would

likely have “confirmed the finding” from

family research that

pellagra has a

n important

genetic basis. Although these studies would

have

appeared to provide

converging

evidence in support of

genetic theories of pellagra’s causation, these theories would have

been

mistaken.

But suppose it had been shown that some people

are

genetically more vulnerable to develop pellagra.

That

is, despite the clear

cause of

pellagra being a vitamin deficiency linked to malnutrition, suppose it was

shown that

some individuals, because of their

genetic predisposition,

were more likely to develop pellagra

following

malnutrition. Still, the discovery of a genetic predisposition for

pellagra would not have been of

major

importance.

Pellagra was wiped out in the United States by the relief programs of the 1930s,

and, more

importantly, by a

federally-

mandated World War II-era program requiring the enrichment of flour and corn

meal with the

vitamins

needed to prevent pellagra. In other

words, once the environmental factor was

identified and eliminated, any

possible

genetic predisposition had been rendered unimportant.

Perhaps this

explains why no one ever bothered

to perform a pellagra twin

or adoption study. As Joseph concludes, “For

psychiatric conditions

believed to carry a

genetic predisposition requiring an unknown

environmental trigger,

the importance researchers give to the genetic

predisposition represents little more than a recognition that

they have not identified the environmental cause or

trigger.”

The example of pellagra shows that an emphasis on genetics, and a mis

nterpretation

of the genetic

predisposition concept,

can delay

discovery of the true causes of a condition at the cost of unnecessary

suffering,

and can promote the unwarranted

stigmatization of diagnosed

individuals. For psychiatric disorders,

the claim of a

hereditary component—even if true—can have

similar consequences.

CHAPTER FIVE

A Generation Misinformed: Psychiatry and Psychology

Textbooks’

Inaccurate

Accounts of Schizophrenia Adoption Research

Textbooks are valuable tools for transmitting the knowledge and history of various academic fields to

students

and

professionals.

Unfortunately, they can also help perpetuate myths. Modern psychiatry is

dominated by the

biological/psychopharmacology paradigm, which

must show that its diagnoses are

biologically/genetically based.

Furthermore, the

prevailing views in psychiatry influence psychology and

fields.

Chapter 5 examines textbooks’ reporting of a specific area of psychiatric research: the study of adoptees

as a

means of testing

the

hypothesis that genetic factors influence schizophrenia. Joseph surveys 43

psychiatry and

psychology textbooks’ discussions of

schizophrenia

adoption research. These include fifteen

psychiatry textbooks,

eleven abnormal psychology textbooks, six books

devoted entirely to

schizophrenia, six

books whose authors

argue that genes play an important role in determining human behavioral

differences, two chapters

from annual

psychiatry reviews, two neuroscience textbooks, and the DSM-IV-TR. Simply put,

these

sources constitute the

authoritative texts of

psychiatry and abnormal psychology.

Unfortunately, textbook descriptions of

schizophrenia

adoption research are sometimes inaccurate

, and

critical analysis is largely absent.

Problems with the surveyed textbooks include:

1. They emphasize the original researchers’ conclusions at the expense of independent critical analysis.

2. They often rely on secondary sources.

3. They typically do not discuss, or mention only briefly, the views and publications of critics.

4. They

ometimes

misreport studies’ methods and results.

5. While some surveyed textbooks discuss possible environmental confounds

[18]

in schizophrenia twin

research, few discuss

the

likelihood that

genetic inferences from adoption studies are confounded by the

selective placement of adoptees with a

family history of

mental disorders.

[19]

6. Few discuss problems with the reliability and validity of a