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Reviews and Overviews

http://ajp.psychiatryonline.org

Toward a Philosophical Structure for Psychiatry

Kenneth S. Kendler, M.D.

This article, which seeks to sketch a coher-

ent conceptual and philosophical frame-

work for psychiatry, confronts two major

questions: how do mind and brain interre-

late, and how can we integrate the multi-

ple explanatory perspectives of psychiatric

illness? Eight propositions are proposed

and defended: 1) psychiatry is irrevocably

grounded in mental, first-person experi-

ences; 2) Cartesian substance dualism is

false; 3) epiphenomenalism is false; 4) both

brain

→mind and mind→brain causality

are real; 5) psychiatric disorders are etio-

logically complex, and no more “spiro-

chete-like” discoveries will be made that

explain their origins in simple terms; 6) ex-

planatory pluralism is preferable to monis-

tic explanatory approaches, especially bio-

logical reductionism; 7) psychiatry must

move beyond a prescientific “battle of

paradigms” to embrace complexity and

support empirically rigorous and pluralis-

tic explanatory models; 8) psychiatry

should strive for “patchy reductionism”

with the goal of “piecemeal integration” in

trying to explain complex etiological path-

ways to illness bit by bit.

(Am J Psychiatry 2005; 162:433–440)

Many a psychiatrist has said that he did not want to

burden himself with a philosophy…but the exclusion

of philosophy would…be disastrous for psychiatry.

—K. Jaspers (1, p. 769)

Whether we know it or not, to practice or to do re-

search in the field of mental health requires us to assume

certain positions on several philosophical issues, two of

which are particularly central. The first such issue is the

nature of the interrelationship of the brain and the mind.

The second is to understand how the various explanatory

approaches that can be taken toward psychiatric disorders

can best be interrelated.

Because our field deals with fundamental questions of

what it means to be human, psychiatry is particularly sus-

ceptible to preconceptions that can strongly color the

value we assign to differing methodological perspectives.

With the growth of neuroscience and molecular biology,

psychiatry is set to inherit rich insights into the basic

workings of the human brain. To maximally use this new

information, however, will require that we have our con-

ceptual house in order.

This article seeks to sketch a coherent conceptual and

philosophical framework for psychiatry that consists of

eight major propositions:

1. Psychiatry is irrevocably grounded in mental, first-

person experiences.

2. Cartesian substance dualism is false.

3. Epiphenomenalism is false.

4. Both brain→mind and mind→brain causality are

real.

5. Psychiatric disorders are etiologically complex, and

we can expect no more “spirochete-like” discoveries

that will explain their origins in simple terms.

6. Explanatory pluralism is preferable to monistic ex-

planatory approaches, especially biological reduc-

tionism.

7. Psychiatry needs to move from a prescientific “battle

of paradigms” toward a more mature approach that

embraces complexity along with empirically rigorous

and pluralistic explanatory models.

8. Finally, we need to accept “patchy reductionism”

with the goal of piecemeal integration in trying to ex-

plain the complex etiological pathways to psychiatric

illness a little bit at a time.

Grounding in the Mental World

Foundational to this framework is the view that the field

of psychiatry is deeply and irreversibly wedded to the

mental world. The questions that have played such a

prominent role in the history of psychology—whether

mental processes can or ought to be studied (2)—are sim-

ply not relevant for psychiatry. Our central goal as a medi-

cal discipline is the alleviation of the human suffering that

results from dysfunctional alterations in certain domains

of first-person, subjective experience, such as mood, per-

ception, and cognition. Our nosological constructs are

largely composed of descriptions of first-person experi-

ences (e.g., sad mood, hallucinations, and irrational fears).

The clinical work of psychiatry constantly requires us to

assess and interpret the first-person reports of our pa-

tients. Many of the target symptoms that we treat can only

be evaluated by asking our patients about their subjective

experiences. While we want to take advantage of the many

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advances in the neurosciences and molecular biology, this

cannot be done at the expense of abandoning our ground-

ing in the world of human mental suffering.

Shedding the Chains of Descartes

An initial task is to confront one large piece of historical

baggage. No philosophical concept has been as widely in-

fluential in our field or as potentially pernicious in its ef-

fects as that of Cartesian dualism. While individual psychi-

atrists may, for their own personal or religious reasons,

continue to advocate mind-body dualism, it is time for the

field of psychiatry to declare that Cartesian substance du-

alism is false. We need to reject definitively the belief that

mind and brain reflect two fundamentally different and

ultimately incommensurable kinds of “stuff.” Rather, in

accord with an overwhelming degree of clinical and scien-

tific evidence, we should conclude that the human first-

person world of subjective experience emerges from and

is entirely dependent upon brain functioning. The mental

world does not exist independently of its physical instanti-

ation in the brain. To reject Cartesian dualism (and accept

monism, the view that mental and physical processes are

both reflections of the same fundamental stuff) means to

no longer consider the mental (or functional) to be a fun-

damentally different thing from the biological (or or-

ganic). Rather, the mental and the biological become dif-

ferent ways of viewing and/or different levels of analysis of

the mind-brain system.

This rejection of Cartesian dualism requires a signifi-

cant shift in our way of thinking. Although American psy-

chiatry officially abandoned the functional-organic di-

chotomy—one of the many echoes of Cartesian dualism—

with DSM-IV (3), and the abandonment of dualism has

been recently called for by Kandel (4), dualistic thinking

and vocabulary remain deeply entrenched in our ap-

proach to clinical and research problems. From the ways

we organize our clinical presentations to our categoriza-

tions of risk factors, we remain deeply imbedded in the

Cartesian framework of seeing the mind and brain as re-

flecting fundamentally different spheres of reality.

One immediate beneficial consequence of a rejection of

Cartesian dualism is our confrontation with the misun-

derstandings that can arise from the claims of what might

be called weak biological explanation. The rejection of

Cartesian dualism logically leads to the conclusion that all

psychiatric disorders are biological. Although we should

not belittle this claim (that, for example, would eliminate

primary spiritual causes of mental illness), the greater

danger now is a tendency to exaggerate its significance. By

rejecting dualism, we accept that all psychiatric disorders

are biological. But so then are all mental processes, patho-

logical or otherwise. The very ubiquity of this claim of

weak biology robs it of much of its gravitas. Indeed, if the

rejection of Cartesian dualism is correct, then the declara-

tion that a particular psychiatric disorder is biological is a

tautology and is as informative as saying, “This circle is

round.” Nothing new is learned by this claim that was not

already evident by the acceptance of a monistic view of

mind-brain functioning.

Facing Down Epiphenomenalism

Having rejected Cartesian dualism, we are not yet home

free philosophically. Another major viewpoint on the

mind-body problem would, if true, also have a profound

impact on the field of psychiatry. The core assertion of

epiphenomenalism is that the mental world is without

causal efficacy, our mental life being simply froth on the

wave or steam from the engine. Thoughts, feelings, and

impulses occur within our subjective experience, but they

do nothing. All the causal action occurs at the level of

brain function. Whether and how this assertion can be for-

mally disproven is a subject beyond the bounds of this es-

say. For the present purposes, I wish to simply assert its

falsity and argue that thoughts, feelings, and impulses

matter not only because they are responsible for huge

amounts of human suffering but because they do things.

Acceptance of Bidirectional

Mind→Brain and Brain→Mind

Causality

Given our rejection of Cartesian dualism and our accep-

tance of an integrated mind-brain system, it becomes nec-

essary to accept the concept of brain-to-mind causality.

That is, changes in the brain can directly affect mental

functioning. In our rejection of epiphenomenalism, we

commit ourselves to the concept of mind-to-brain causal-

ity. In ways we can observe but not yet fully understand,

subjective, first-person mental phenomena have causal

efficacy in the world. They affect our brains and our bodies

and through them the outside world. (In asserting the

causal efficacy of mental phenomena, I am not reintro-

ducing dualism “through the back door.” Rather, consis-

tent with several philosophical positions—in particular,

nonreductive materialism [5, 6]—I argue that mental pro-

cesses carry critical causal information about human be-

havior. For two recent thoughtful treatments of this prob-

lem, see references 7 and 8.)

Stop Searching for Big,

Simple Explanations

Our strongly held desires to find the explanation for in-

dividual psychiatric disorders are misplaced and counter-

productive. Psychiatry has historically seen a few big ex-

planations, most notably the discovery of the spirochete

for general paresis. It is highly unlikely that spirochete-like

big explanations remain to be discovered for major psy-

chiatric disorders. We have hunted for big, simple neuro-

pathological explanations for psychiatric disorders and

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have not found them. We have hunted for big, simple neu-

rochemical explanations for psychiatric disorders and

have not found them. We have hunted for big, simple ge-

netic explanations for psychiatric disorders and have not

found them.

Our current knowledge, although incomplete, strongly

suggests that all major psychiatric disorders are complex

and multifactoral. What we can best hope for is lots of

small explanations, from a variety of explanatory per-

spectives, each addressing part of the complex etiological

processes leading to disorders. It will be particularly chal-

lenging to understand how these many different small ex-

planations all fit together.

In grieving for our loss of big explanations, we similarly

have to give up our hope for simple, linear explanatory

models. It will not be “A→B→C→D.” Etiological pathways

will be complex and interacting, more like networks than

individual linear pathways.

Acceptance of Explanatory Pluralism

Introduction to Levels of Explanation

Multiple explanatory perspectives can be adopted in

our attempts to understand most natural phenomena.

Furthermore, for any given phenomenon, these perspec-

tives will differ in their informativeness and efficiency. It is

possible to study scientific questions from perspectives

that are both too basic and too abstract. However, cur-

rently, the former is a greater concern and so will be the fo-

cus of this discussion. The concept of “levels of explana-

tion” is so central to this argument that I will illustrate it

with three scenarios.

Scenario 1

Jackie is a physiologist studying hormonal regulation.

She accepts that the large biological molecules she is ex-

amining are constituted of atoms that are made up of

particles that are in turn made up of subatomic particles.

However, in seeking to alter certain aspects of a hor-

monal system that she is studying, she might consult with

a biochemist or pharmacologist but not with a particle

physicist. Why? Because the kind of effects she wants to

produce—the stimulation of particular hormonal recep-

tors—results from the actions of large biological mole-

cules. Knowing what quarks are doing in these molecules

will not help her achieve her desired goal.

Scenario 2

Bill is performing a statistical analysis on his com-

puter and is getting the wrong result because he has

made a mistake in his statistical program. Being a down-

to-earth kind of guy, Bill decides to take off the back of

his computer, pull out the motherboard, and reach for

his soldering iron, hoping to find a loose connection to

solder, thereby solving his programming problem. Why

is this the wrong approach? After all, a computer is re-

ally just a bunch of circuits and electrons. Using a sol-

dering iron is a highly inefficient approach because it is

an intervention directed at the wrong explanatory level

in the complex system. The cause of the dysfunction is

at the level of high-order computer code and could not

be easily perceived or repaired at the level of circuits on

a motherboard.

Scenario 3

Kathy, a young psychiatrist, is asked by a distressed

parent to consult with her about her son, Brian, who has

decided to leave a career in science to enter the priest-

hood. The upset parent insists that Kathy order a brain

scan to find a way to change his decision. “There must be

something the matter with his brain, doctor. How could

he throw away such a promising scientific career?” Kathy

sees the young man, who appears thoughtful and ma-

ture, and he describes the deep satisfaction and inspira-

tion he feels in the Catholic religion. He understands the

possible hardships ahead of him but feels he is making

the right decision. Kathy tells the parent that she is not

going to order a magnetic resonance imaging scan.

There is no evidence, she states, that there is anything

the matter with his brain, and no interventions that

would act directly on his brain are indicated in this situ-

ation. She feels that he has reached his decision in a rea-

sonable way, but the mother should feel free, if she

wants, to try to argue her son out of his decision.

What is going on in these three scenarios? In each case,

we have a higher-order system that is completely consti-

tuted from lower-order elements. That is, Jackie’s macro-

molecules are made up of subatomic particles. Bill’s com-

puter is made up of circuits and electrons. Brian’s mental

processes are expressed in the biology of his brain. How-

ever, in each of these scenarios, an intervention at the level

of the lower-order elements is likely to be, at best, ineffi-

cient and, at worst, ineffective and possibly harmful.

The Limits of Biological Reductionism

There is no such thing as a psychiatry that is too

biological.

—S.B. Guze (9)

The last several decades have seen a rise to prominence

within psychiatry of a biological reductionist perspective.

Advocates of this point of view argue that the only valid

approach to understanding psychiatric disorders or, more

broadly, psychological functioning is in terms of basic

neurobiological processes (10). Multilevel models, espe-

cially those including mental and social explanatory per-

spectives, are typically rejected (sometimes with the epi-

thet of being nonscientific or “soft-headed”) or accepted

only with the caveat that all the “real” causal effects occur

at the level of basic biology.

This position might be seen as a logical consequence of

the rejection of Cartesian dualism. After all, if we agree

that there are no mental processes that are independent of

brain function, then should not all the causes of psychiat-

ric disorders be reduced to brain processes? Although this

reductionist perspective is understandable in sociological

terms as a reaction to prior radical mentalistic programs

within psychiatry (e.g., some forms of dynamic psychia-

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try) and is appealing because of the ease with which it fits

into a medical model, this approach is too narrow to en-

compass the range of causal processes that are operative

in psychiatric disorders.

The limits of biological reductionism are well illustrated

by the three scenarios just outlined. Contrary to Guze’s as-

sertion, psychiatry can be too biological in the same sense

that it would be an error for Jackie to focus on subatomic

particles in her physiological research, for Bill to try to fix

his problem with statistical analysis by using a soldering

iron, or for Kathy to employ psychopharmacology to re-

verse Brian’s career decision. Note that I do not contest

that ultimately (in the sense of “weak biology”) all psychi-

atric illness is biological. What is at issue here is the opti-

mal level in the causal processes underlying psychiatric

illness at which intervention can be best focused and un-

derstanding most easily achieved.

Explanatory Pluralism

In the tradition of other thoughtful commentators (es-

pecially Engel [11] and McHugh and Slavney [12]), in place

of biological reductionism, I advocate explanatory plural-

ism (13–17) as the approach best suited to understanding

the nature of psychiatric illness. Explanatory pluralism hy-

pothesizes multiple mutually informative perspectives

with which to approach natural phenomena. Typically,

these perspectives differ in their levels of abstraction, use

divergent scientific tools, and provide different and com-

plementary kinds of understanding. Explanatory plu-

ralism is especially appropriate for psychiatry because

psychiatric disorders are typically influenced by causal

processes operating at several levels of abstraction.

A clear example of explanatory pluralism comes from

biology, where it is useful to distinguish between “how”

questions and “why” questions (18). For example, in ex-

amining the large and colorful tail of the male peacock, we

could study its developmental biology to clarify physio-

logically how such a tail develops. Alternatively, we could

seek, in the evolutionary history of the peacock, an answer

about why the tail develops, presumably through mecha-

nisms of sexual selection. Neither the how/physiological

nor the why/evolutionary explanatory perspective can

easily replace or invalidate the other. It is simply in the

nature of the phenomenon that it can be usefully ap-

proached scientifically from two different perspectives.

(The pluralistic explanatory approach outlined in this es-

say assumes the natural science perspective that Jaspers

termed “explanation” [1]. I do not here address another

highly relevant question—how does the information ac-

quired from this perspective relate to knowledge obtained,

through empathy, from human relationships, through the

process termed “understanding” by Jaspers [1]?)

Arguments for Explanatory Pluralism

and Against Biological Reductionism

I will now review eight arguments in favor of explana-

tory pluralism and against biological reductionism or

other unimodal perspectives on psychiatric illness (in-

cluding radical mentalistic accounts). These arguments

assume the conclusive demonstration that specific bio-

logical processes that are manifest, for example, at the

level of genetic risk factors or neurochemical alterations

play a significant causal role in all psychiatric disorders.

First, a long clinical tradition and much empirical evi-

dence of increasing methodological rigor point to the im-

portance of first-person mental processes in the etiology

of psychiatric disorders. Of the many possible studies, one

recent investigation will illustrate this point (19). In a large

epidemiological sample of twins, severely stressful life

events and onsets of major depression and generalized

anxiety were studied. Descriptions of the severely stressful

life events were blindly reviewed by trained raters and

scored for their level of loss, humiliation, entrapment, and

danger. Even though only highly threatening life events

were studied, these ratings further predicted the risk of de-

pression and anxiety.

Humiliation and loss are classical, subjective, first-

person experiences that humans can recognize in them-

selves and in others. Although humiliation is ultimately

expressed in the brain, this does not mean that the basic

neurobiological level is necessarily the most efficient level

at which to observe humiliation. Trying to understand hu-

miliation by looking at basic brain biology may be like Bill

trying to fix his statistical analyses with his soldering iron.

It may be the wrong explanatory level.

Second, a large body of descriptive literature shows con-

vincingly that cultural processes affect psychiatric illness.

For example, a recent meta-analysis (20) concluded that

rates of bulimia have meaningfully increased in Western

countries in recent years. Furthermore, in non-Western

countries, the prevalence of bulimia is strongly related to

the degree of contact with Western culture (20). One study

in Fiji (21) has shown a substantial rise in eating disorder

pathology in adolescent girls after the introduction of tele-

vision and the associated intense exposure to Western ide-

als about body image. These results suggest that the risk for

bulimia is related to cultural models of ideal body size.

While culture ultimately exists as belief systems in the

brains of individual members of a cultural group, it is un-

likely that cultural forces that shape psychopathology can

be efficiently understood at the level of basic brain biology.

Third, our first two examples illustrate that, in addition

to neurobiological and genetic risk factors, a full etiologi-

cal understanding of at least some psychiatric disorders

will require consideration of psychological and cultural

factors. We have, however, been naively assuming a model

in which biological, psychological, and cultural factors

each independently affect risk. However, the reality is

more complex, thereby posing further difficulties for the

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reductionist biological model. The impact of genetic fac-

tors on the risk for psychiatric disorders or drug use can be

modified by the rearing environment (22, 23), stressful life

experiences (24, 25), and exposure to cultural forces (26).

Recent work in bulimia suggests that this disorder arises

given a combination of a biological/genetic predisposi-

tion and cultural factors encouraging slim body ideals.

The actions of basic biological risk factors for psychiatric

illness are modified by forces acting at higher levels of

abstraction.

Furthermore, gene expression is extensively modified

by both simple (e.g., light-dark cycle) and complex (e.g.,

learning tasks, maternal separation) environmental stim-

uli (27), and even relatively gross aspects of neuronal and

brain anatomy can be modified by experience (28). A bot-

tom-up hard reductionist approach to psychiatric illness

will be futile if basic neurobiological risk factors are fre-

quently modified by higher-order processes, including en-

vironmental, psychological, and cultural experiences.

Fourth, biological reductionists assume that neuro-

biological risk factors for psychiatric disorders operate

through physiological “inside-the-skin” pathways. How-

ever, an emerging body of research suggests that this as-

sumption is false. Part of the way in which genetic risk

factors influence the liability to psychiatric disorders is

through “outside-the-skin” pathways that alter the proba-

bility of exposure to high-risk environments. For example,

genetic risk factors for major depression increase the

probability of interpersonal and marital difficulties, which

are known risk factors for depression (29). This is not a

theoretical issue. If the impact of genetic risk factors is me-

diated through environmental processes, this opens up

new possible modes of prevention.

Fifth, hard reductive models in science strive for clear

“one-to-one” relationships between basic processes and

outcome variables. Such simple relationships are not

plausible for psychiatric illnesses. For example, individual

genetic risk factors probably predispose to a range of dif-

ferent psychiatric disorders, depending on other genetic,

developmental, and environmental factors (30), and many

different DNA variants probably predispose to one disor-

der (31). This pattern of many-to-many causal links be-

tween basic etiological processes and outcomes is more

compatible with pluralistic than with monistic reductive

etiological models.

Sixth, a series of important questions in psychiatry are

historical in nature and not plausibly subject to reductive

biological explanations. Why are humans prone to de-

velop depression when exposed to social adversity? Why

do genetic risk factors for schizophrenia persist in human

populations? Like the puzzle of the peacock’s tail, these

questions are best answered at historical/evolutionary

and not physiological levels.

Seventh, how, using a hard reductive biological ap-

proach toward psychiatry, can we define dysfunction (14)?

While certain psychiatric symptoms may be pathological

at a basic biological level (e.g., hallucinations), many

symptoms are dysfunctional only in certain contexts. At a

physiological level, a panic attack during a near-fatal

climbing accident in a psychiatrically healthy individual

or in a crowded shopping mall in a patient with agorapho-

bia are probably the same. Since many psychiatric disor-

ders include, by definition, some degree of psychosocial

dysfunction (32), explanation at the level of biology alone

is unlikely to be sufficient.

Eighth, biological systems generally and mind-body sys-

tems more specifically have goals and generate processes

to address these goals, such as the maintenance of blood

pressure or self-esteem and the acquisition of food, sexual

partners, or status. As argued persuasively by Bolton and

Hill (7), these information-based systems cannot be re-

duced to their molecular constituents without a loss of

explanatory power. After all, the biology of a neural im-

pulse—the influx and efflux of sodium, potassium, and

calcium ions—is essentially the same all over the brain.

These impulses have specific causal efficacy only through

the particular neuronal system in which they are imbed-

ded. Critical causal processes in the mind-brain system

can only be captured though an understanding of the

higher organizational levels of these goal-directed systems.

What Kind of Explanatory Pluralism

Do We Need?

As outlined in an illuminating chapter by Mitchell et al.

(33), explanatory pluralism can come in several “flavors,”

two of which interest us here. Compatible pluralism recog-

nizes the existence of distinct and independently mean-

ingful levels of analysis. However, for scientific and/or so-

ciological reasons, research in these distinct levels occurs

largely in isolation. In integrative pluralism, by contrast,

active efforts are made to incorporate divergent levels of

analysis. This approach assumes that, for most problems,

single-level analyses will lead to only partial answers.

However, rather than building large theoretical structures,

integrative pluralism establishes small “local” integrations

across levels of analysis.

Our field may be in particular need of integrative plural-

ism, where scientists, without abandoning conceptual

rigor, cross borders between different etiological frame-

works or levels of explanation. Such efforts may be unusu-

ally scientifically fruitful and work bit by bit toward broader

integrative paradigms. Recent examples of integrative plu-

ralism in psychiatric research would include the incorpo-

ration by Gutman and Nemeroff (34) of early traumatic

events into neurobiological models for depression and the

efforts by Caspi and colleagues to include specific geno-

types in an epidemiological study examining the develop-

ment of antisocial behavior (35) and depression (25) after

exposure to environmental adversity.

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Problems With Implementation

of Explanatory Pluralism

In mental health research, explanatory orientations are

too often adopted for ideological rather than empirical

reasons. At its worst, our field consists of mutually antago-

nistic, noninteracting theoretical camps. One approach to

this cacophony of divergent explanatory orientations

would be to impose rigidly one methodological perspec-

tive, such as biological reductionism. However, this is un-

feasible and would be unlikely to succeed even if it could

be accomplished.

Rather, our task, the difficulty of which is hard to overes-

timate, is to establish a methodologically rigorous but

conceptually open-minded scientific playing field. Advo-

cating explanatory pluralism for psychiatry should not be

construed as a vacuous invitation to treat all methodolo-

gies as of equal value. As divergent perspectives compete

for resources and students, the deciding factors should

not be the orientation of the methods but rather the power

of the designs, the replicability of the results, and their rel-

evance to understanding the causal pathways to psychiat-

ric disorders.

Thomas Kuhn (36), the famous philosopher of science

who stressed the degree to which science was intrinsically

a social activity, would suggest that this agenda may be a

fool’s quest. He might argue that the competing scientific

paradigms within psychiatry are “incommensurable,” that

their advocates have such widely divergent viewpoints

that they effectively inhabit different professional worlds.

Furthermore, he would assert that data in our field are

heavily theory-laden and deeply intertwined with theo-

retical assumptions. In such circumstances, effective

communication across paradigms and finding a common

ground on which the various paradigms might fairly com-

pete would be difficult.

These arguments have force. I recall too many sterile ar-

guments between psychoanalysts, social psychiatrists,

and biological psychiatrists in the late 1970s to lightly dis-

miss Kuhn’s contention of the incommensurability of dif-

ferent theoretical perspectives. Furthermore, I remember

with surprise the growing realization that in earlier gener-

ations, researchers from divergent perspectives had taken

the same set of data—evidence that schizophrenia ran in

families—and assumed that it proved biological (37) or

family-dynamic (38) etiological theories of schizophrenia.

However, Kuhn’s perspective may be too pessimistic.

Many philosophers of science now disagree with the more

radical versions of his claims (39). Getting researchers

from different perspectives to agree on broadly similar in-

terpretations of data is not impossible. Within the field of

mental health research, we have seen increasing “cross-

paradigm” discussions and collaborations. The ideological

rancor that characterized earlier debates may be lessen-

ing, and the optimists among us might ascribe that to a

maturation of the field.

Kuhn argues that to be considered a mature science, a

field has to agree on a basic scientific paradigm (36).

Psychiatry, by this criterion, would be in an immature

“preparadigmatic” state. Although vastly underspecified

and in need of being “filled in” in different ways for each of

the major psychiatric and drug abuse disorders, explana-

tory pluralism might form the substrate of such a shared

paradigm.

Acceptance of Patchy Reductions

Leading to Piecemeal Integration

What should be our goals in seeking to understand the

extraordinarily complex casual networks within the mind-

brain system and its interaction with the psychosocial en-

vironment that lead to psychiatric illness? Another asser-

tion of the biological reductionists is that the value of a

causal explanation is directly related to how far down it

goes on the causal chain—the more basic and biological

the better (10). While tempting, this “zeitgeist” should be

resisted.

A thought experiment might help. Imagine that there

are 15 discrete levels, with the mind-brain system between

DNA on one hand and the clinical manifestations of

schizophrenia on the other. Researcher 1 is conducting

linkage and association studies that attempt to directly re-

late levels 1 and 15 but would provide no insight into the

intervening levels. Researcher 2 is trying to understand, at

a basic molecular level, the actions of a putative altered

gene transcript, thereby trying to move from level 1 to level

2 or 3. Meanwhile, researcher 3 is seeking to understand

the neuropsychological deficits in schizophrenia, trying to

clarify the link between levels 13 and 15. Although biolog-

ical reductionists might declare the work of researcher 2 to

be more “scientific” and valuable because it is more basic,

I hope that this thought experiment makes it clear that we

can make no such judgments a priori. There are many

links in the chain, and their ultimate value and scientific

fruitfulness are unlikely to bear any strong relationship

with where on the causal chain (or, more realistically, net-

work) they sit.

This thought experiment leads to a final point. Although

developing the “grand theory” is attractive and may pro-

vide a fruitful heuristic framework, we are not close to de-

veloping a full casual network for any psychiatric disorder.

Nor should this now be our primary goal. Rather, we

should settle for what we have called “bit-by-bit” efforts of

integrative pluralism. Schaffner (40, p. 282) has expressed

a similar idea in what he calls “patchy reductions” in “a

structure of overlapping interlevel causal models.” Such

efforts should, over time, result in clarification of parts of

the causal network from which it may be possible to move

toward a more complete etiological understanding of the

extremely complex mind-brain dysfunctions that it is our

task to understand and treat.

Am J Psychiatry 162:3, March 2005 439

KENNETH S. KENDLER

http://ajp.psychiatryonline.org

Integration and Conclusions

Working in the field of psychiatry inevitably involves us

in some of the most important and perplexing questions

that humans can face. Two are of paramount importance

for our field: how do mind and brain interrelate, and how

can we integrate the multiple explanatory perspectives on

psychiatric illness? I have tried to pose tentative answers

to these questions in the hope that they might contribute

toward providing, for psychiatric research, a pragmatic in-

tegrated rubric. We need to move from sterile, ideologi-

cally driven debates toward critical, creatively conceptual-

ized empirical questions. How much real explanatory

power is provided by the many possible etiological per-

spectives on a given psychiatric disorder? How can we be-

gin to understand how the various explanatory levels in-

terrelate with one another?

Our hope should be for the scientific maturation of psy-

chiatry that will in turn allow us to use and integrate the

coming scientific advances. This will require our moving

beyond the clumsy and outdated baggage left us by Carte-

sian dualism. We should not, however, thereby reject our

fundamental roots within the mental and psychosocial

spheres or succumb to the temptations of simplistic re-

ductionist models. Psychiatric disorders are, by their na-

ture, complex multilevel phenomena. We need to keep

our heads clear about their stunning complexity and real-

ize, with humility, that their full understanding will re-

quire the rigorous integration of multiple disciplines and

perspectives.

Received Feb. 4, 2004; revision received March 20, 2004; accepted

May 3, 2004. From the Virginia Institute for Psychiatry and Behav-

ioral Genetics, Departments of Psychiatry and Human Genetics, Med-

ical College of Virginia, Virginia Commonwealth University, Rich-

mond, Va. Address correspondence and reprint requests to Dr.

Kendler, Department of Psychiatry, P.O. Box 980126, Richmond, VA

23298-0126; kendler@hsc.vcu.edu (e-mail).

Supported by a Fritz Redlich Fellowship from the Center for Ad-

vanced Study in the Behavioral Sciences and the Rachel Brown Banks

Endowment Fund.

The author thanks Kenneth Schaffner, M.D., Ph.D., and John Camp-

bell, Ph.D., for discussions that aided development of the manuscript.

Little expressed in this essay is original. The author is especially in-

debted to the works of Turkheimer (41), Schaffner (40, 42), Mitchell

(13), and Zachar (14).

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