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Articles- Part XV

On Narcissism: An Introduction
Sigmund Freud (1914)

The term narcissism is derived from clinical description and was chosen by Paul Nacke in 1899 to denote the attitude of a person who treats his own body in the same way in which the body of a sexual object is ordinarily treated-who looks at it, that is to say, strokes it and fondles it till he obtains complete satisfaction through these activities. Developed to this degree, narcissism has the significance of a perversion that has absorbed the whole of the subject's sexual life, and it will consequently exhibit the characteristics which we expect to meet with in the study of all perversions.
     Psychoanalytic observers were subsequently struck by the fact that individual features of the narcissistic attitude are found in many people who suffer from other disorders-for instance, as Sadger has pointed out, in homosexuals--and finally it seemed probable that an allocation of the libido such as deserved to be described as narcissism might he present far more extensively, and that it might claim a place in the regular course of human sexual development. Difficulties in psychoanalytic work upon neurotics led to the same supposition, for it seemed as though this kind of narcissistic attitude in them constituted one of the limits to their susceptibility to influence. Narcissism in this sense would not be a perversion, but the libidinal complement to the egoism of the instinct of self-perservation, a measure of which may justifiably be attributed to every living creature.
     A pressing motive for occupying ourselves with the conception of a primary and normal narcissism arose when the attempt was made to subsume what we know of dementia praecox (Kraepelin) or schizophrenia (Bleuler) under the hypothesis of the libido theory. Patients of this kind, whom I have proposed to term paraphrenics, display two fundamental characteristics: megalomania and diversion of their interest from the external world-from people and things. In consequence of the latter change, they become inaccessible to the influence of psychoanalysis and cannot be cured by our efforts. But the paraphrenic's turning away from the external world needs to be more precisely characterized. A patient suffering from hysteria or obsessional neurosis has also, as far as his illness extends, given up his relation to reality. But analysis shows that he has by no means broken off his erotic relations to people and things. He still retains them in phantasy; i.e. he has, on the one hand, substituted for real objects imaginary ones from his memory, or has mixed the latter with the former; and on the other hand, lie has renounced the initiation of motor activities for the attainment of his aims in connection with those objects. It is otherwise with the paraphrenic. He seems really to have withdrawn his libido from people and things in the external world, without replacing them by others in phantasy. When he does so replace them, the process seems to be a secondary one and to be part of an attempt at recovery, designed to lead the libido back to objects.
     The question arises: What happens to the libido which has been withdrawn from external objects in schizophrenia? The megalomania characteristic of these states points the way. This megalomania has no doubt come into being at the expense of object-libido. The libido that has been withdrawn from the external world has been directed to the ego and thus gives rise to an attitude which may be called narcissism. But the megalomania itself is no new creation; on the contrary, it is, as we know., a magnification and plainer manifestation of a condition which had already existed previously. This leads us to look upon the narcissism which arises through the drawing in of object-cathexes as a secondary one, superimposed upon a primary narcissism that is obscured by a number of different influences.

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This extension of the libido theory--in my opinion, a legitimate one--receives reinforcement from a third quarter, namely, from our observations and views on the mental life of children and primitive peoples. In the latter we find characteristics which, if they occurred singly, might be put down to megalomania: an over-estimation of the power of their wishes and mental acts, the 'omnipotence of thoughts', a belief in the thaumaturgic force of words, and a technique for dealing with the external world-'magic'-which appears to be a logical application of these grandiose premises. In the children of to-day, whose development is much more obscure to us, we expect to find an exactly analogous attitude towards the external world. Thus we form the idea of there being an original libidinal cathexis of the ego, from which some is later given off to objects, but which fundamentally persists and is related to the objectcathexes much as the body of an amoeba is related to the pseudopodia which it puts out. In our researches, taking, as they did, neurotic symptoms for their starting-point, this part of the allocation of libido necessarily remained hidden from us at the outset. All that we noticed were the emanations of this libido--the object-cathexes, which can be sent out and drawn back again. We see also, broadly speaking, an antithesis between ego-libido and object-libido. The more of the one is employed, the more the other becomes depleted. The highest phase of development of which object-libido is capable is seen in the state of being in love, when the subject seems to give up his own personality in favour of an object-cathexis; while we have the opposite condition in the paranoic's phantasy (or self-perception) of the `end of the world'. Finally, as regards the differentiation of psychical energies, we are led to the conclusion that to begin with, during the state of narcissism, they exist together and that our analysis is too coarse to distinguish between them; not until there is object-cathexis is it possible to discriminate a sexual energy--the libido--from an energy of the ego-instincts.
      What is the relation of the narcissism of which we are now speaking to auto-erotism, which we have described as an early state of the libido? Secondly, if we grant the ego a primary cathexis of libido, why is there any necessity for further distinguishing a sexual libido from a non-sexual energy of the ego-instincts? Would not the postulation of a single kind of psychical energy save us all the difficulties of differentiating an energy of the ego-instincts from ego-libido, and ego-libido from object-libido?
     As regards the first question, I may point out that we are bound to suppose that a unity comparable to the ego cannot exist in the individual from the start; the ego has to be developed, The auto-erotic instincts, however, are there from the very first; so there must be something added to auto-erotism--a new psychical action--in order to bring about narcissism.
     To be asked to give a definite answer to the second question must occasion perceptible uneasiness in every psychoanalyst. One dislikes the thought of abandoning observation for barren theoretical controversy, but nevertheless one must not shirk an attempt at clarification. It is true that notions such as that of an ego-libido, an energy of the ego-instincts, and so on, are neither particularly easy to grasp, nor sufficiently rich in content; a speculative theory of the relations in question would begin by seeking to obtain a sharply defined concept as its basis. But I am of opinion that that is just the difference between a speculative theory and a science erected on empirical interpretation. The latter will not envy speculation its privilege of having a smooth, logically unassailable foundation, but will gladly content itself with nebulous, scarcely imaginable basic concepts, which it hopes to apprehend more clearly in the course of its development, or which it is even prepared to replace by others. For these ideas are not the foundation of science, upon which everything rests: that foundation is observation alone. They are not the bottom but the top of the whole structure, and they can be replaced and discarded without damaging it. The same thing is happening in our day in the science of physics, the basic notions of which as regards matter, centres of force, attraction, etc., are scarcely less debatable than the corresponding notions in psychoanalysis.
     The value of the concepts 'ego-libido' and 'object-libido' lies in the fact that they are derived from the study of the intimate characteristics of neurotic and psychotic processes. A differentiation of libido into a kind which is proper to the ego and one which is attached to objects is an unavoidable corollary to an original hypothesis which distinguished between sexual instincts and ego-instincts. At any rate, analysis of the pure transference neuroses (hysteria and obsessional neurosis) compelled me to make this distinction and I only know that all attempts to account for these phenomena by other means have been completely unsuccessful.
     In the total absence of any theory of the instincts which would help us to find our bearings, we may be permitted, or rather, it is incumbent upon us, to start off by working out some hypothesis to its logical conclusion, until it either breaks down or is confirmed. There are various points in favour of the hypothesis of there having been from the first a separation between sexual instincts and others, ego-instincts, besides the serviceability of such a hypothesis in the analysis of the transference neuroses. I admit that this latter consideration alone would not be unambiguous, for it might be a question of an indifferent psychical energy which only becomes libido through the act of cathecting an object. But, in the first place, the distinction made in this concept corresponds to the common popular distinction between hunger and love. In the second place, there are biological considerations in its favour. The individual does actually carry on a twofold existence: one to serve his own purposes and the other as a link in a chain, which he serves against his will, or at least involuntarily. The individual himself regards sexuality as one of his own ends; whereas from another point of view he is an appendage to his germ-plasm, at whose disposal he puts his energies in return for a bonus of pleasure. He is the mortal vehicle of a (possibly) immortal substance--like the inheritor of an entailed property, who is only the temporary holder of an estate which survives him. The separation of the sexual instincts from the ego-instincts would simply reflect this twofold function of the individual. Thirdly, we must recollect that all our provisional ideas in psychology will presumably some day be based on an organic substructure. This makes it probable that it is special substances and chemical processes which perform the operations of sexuality and provide for the extension of individual life into that of the species. We are taking this probability into account in replacing the special chemical substances by special psychical forces.
     I try in general to keep psychology clear from everything that is different in nature from it, even biological lines of thought. For that very reason I should like at this point expressly to admit that the hypothesis of separate ego-instincts and sexual instincts (that is to say, the libido theory) rests scarcely at all upon a psychological basis, but derives its principal support from biology. But I shall be consistent enough [with my general rule] to drop this hypothesis if psychoanalytic work should itself produce some other, more serviceable hypothesis about the instincts. So far, this has not happened. It may turn out that, most basically and on the longest view, sexual energy-libido-is only the product of a differentiation in the energy at work generally in the mind. But such an assertion has no relevance. It relates to matters which are so remote from the problems of our observation, and of which we have so little cognizance, that it is as idle to dispute it as to affirm it; this primal identity may well have as little to do with our analytic interests as the primal kinship of all the races of mankind has to do with the proof of kinship required in order to establish a legal right of inheritance. All these speculations take us nowhere. Since we cannot wait for another science to present us with the final conclusions on the theory of the instincts, it is far more to the purpose that we should try to see what light may be thrown upon this basic problem of biology by a synthesis of the psychological phenomena. Let us face the possibility of error; but do not let us be deterred from pursuing the logical implications of the hypothesis we first adopted of an antithesis between ego-instincts and sexual instincts (a hypothesis to which we were forcibly led by analysis of the transference neuroses), and from seeing whether it turns out to be without contradictions and fruitful, and whether it can be applied to other disorders as well, such as schizophrenia.
     It would, of course, be a different matter if it were proved that the libido theory has already come to grief in the attempt to explain the latter disease. This has been asserted by C. G. Jung (1912) and it is on that account that I have been obliged to enter upon this last discussion, which I would gladly have been spared. I should have preferred to follow to its end the course embarked upon in the analysis of the Schreber case without any discussion of its premises. But Jung's assertion is, to say the least of it, premature. The grounds he gives for it are scanty. In the first place, he appeals to an admission of my own that I myself have been obliged, owing to the difficulties of the Schreber analysis, to extend the concept of libido (that is, to give up its sexual content) and to identify libido with psychical interest in general. Ferenczi, in an exhaustive criticism of Jung's work, has already said all that is necessary is correction of this erroneous interpretation. I can only corroborate his criticism and repeat that I have never made any such retraction of the libido theory. Another argument of Jung's, namely, that we cannot suppose that the withdrawal of the libido is in itself enough to bring about the loss of the normal function of reality, is no argument but a dictum. It `begs the question', and saves discussion; for whether and how this is possible was precisely the point that should have been under investigation.
      How little this inapt analogy can help us to decide the question may be learnt from the consideration that an anchorite of this kind, who `tries to eradicate every trace of sexual interest' (but only in the popular sense of the word `sexual'), does not even necessarily display any pathogenic allocation of libido. He may have diverted his sexual interest from human beings entirely, and yet may have sublimated it into a heightened interest in the divine, in nature, or in the animal kingdom, with his libido having undergone an introversion on to his phantasies or a return to his ego. This analogy would seem to rule out in advance the possibility of differentiating between interest emanating from erotic sources and from others. We may repudiate Jung's assertion, then, that the libido theory has come to grief in the attempt explain dementia praecox, and that it is therefore disposed of for the other neuroses as well.

II

In estimating the influence of organic disease upon the distribution of libido, I follow a suggestion made to me orally by Sandor Ferenczi. It is universally known, and we take it as a matter of course, that a person who is tormented by organic pain and discomfort gives up his interest in the things of the external world, in so far as they do not concern his suffering. Closer observation teaches us that he also withdraws libidinal interest from his love-objects: so long as he suffers, he ceases to love. The commonplace nature of this fact is no reason why we should be deterred from translating it into terms of the libido theory. We should then say: the sick man withdraws his libidinal cathexes back upon his own ego, and sends them out again when he recovers. "Concentrated is his soul', says Wilhelm Busch of the poet suffering from toothache, 'in his molar's narrow hole'." Here libido and ego-interest share the same fate and are once more indistinguishable from each other. The familiar egoism of the sick person covers both. We find it so natural because we are certain that in the same situation we should behave in just the same way. The way in which a lover's feelings, however strong, are banished by bodily ailments, and suddenly replaced by complete indifference, is a theme which has been exploited by comic writers to an appropriate extent.
     The condition of sleep, too, resembles illness in implying a narcissistic withdrawal of the positions of the libido on to the subject's own self, or, more precisely, on to the single wish to sleep. The egoism of dreams fits very well into this context. In both states we have, if nothing else, examples of changes in the distribution of libido that are consequent upon a change in the ego.

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Hypochondria, like organic disease, manifests itself in distressing and painful bodily sensations, and it has the same effect as organic disease on the distribution of libido. The hypochondriac withdraws both interest and libido--the latter specially markedly--from the objects of the external world and concentrates both of them upon the organ that is engaging his attention. A difference between hypochondria and organic disease now becomes evident: in the latter, the distressing sensations are based upon demonstrable [organic] changes; in the former, this is not so. But it would be entirely in keeping with our general conception of the processes of neurosis if we decided to say that hypochondria must be right: organic changes must be supposed to be present in it, too.
     But what could these changes be? We will let ourselves be guided at this point by our experience, which shows that bodily sensations of an unpleasurable nature, comparable to those of hypochondria, occur in the other neuroses as well. I have said before that I am inclined to class hypochondria with neurasthenia and anxiety-neurosis as a third `actual' neurosis. It would probably not be going too far to suppose that in the case of the other neuroses a small amount of hypochondria was regularly formed at the same time as well. We have the best example of this, I think, in anxiety neurosis with its superstructure of hysteria. Now the familiar prototype of an organ that is painfully tender, that is in some way changed and that is yet not diseased in the ordinary sense, is the genital organ in its states of excitation. In that condition it becomes congested with blood, swollen and humected, and is the seat of a multiplicity of sensations. Let us now, taking any part of the body, describe its activity of sending sexually exciting stimuli to the mind as its `erotogenicity', and let us further reflect that the considerations on which our theory of sexuality was based have long accustomed us to the notion that certain other parts of the body--the 'erotogenic' zones--may act as substitutes for the genitals and behave analogously to them. We have then only one more step to take. We can decide to regard erotogenicity as a general characteristic of all organs and may then speak of an increase or decrease of it in a particular part of the body. For every such change in the erotogenicity of the organs there might then be a parallel change of libidinal cathexis in the ego. Such factors would constitute what we believe to underlie hypochondria and what may have the same effect upon the distribution of libido as is produced by a material illness of the organs.
     We see that, if we follow up this line of thought, we come up against the problem not only of hypochondria, but of the other `actual' neuroses--neurasthenia and anxiety neurosis. Let us therefore stop at this point. We may suspect that the relation of hypochondria to paraphrenia is similar to that of the other `actual' neuroses to hysteria and obsessional neurosis: we may suspect, that is, that it is dependent on ego-libido just as the others are on object-libido, and that hypochondriacal anxiety is the counterpart, as coming from ego-libido, to neurotic anxiety. Further, since we are already familiar with the idea that the mechanism of falling ill and of the formation of symptoms in the transference neuroses--the path from introversion to regression--is to be linked to a damming-up of object-libido, we may come to closer quarters with the idea of a damming-up of ego-libido as well and may bring this idea into relation with the phenomena of hypochondria and paraphrenia.
     At this point, our curiosity will of course raise the question why this damming-up of libido in the ego should have to be experienced as unpleasurable. I shall content myself with the answer that unpleasure is always the expression of a higher degree of tension, and that therefore what is happening is that a quantity in the field of material events is being transformed here as elsewhere into the psychical quality of unpleasure. Nevertheless it may be that what is decisive for the generation of unpleasure is not the absolute magnitude of the material event, but rather some particular function of that absolute magnitude. Here we may even venture to touch on the question of what makes it necessary at all for our mental life to pass beyond the limits of narcissism and to attach the libido to objects. The answer which would follow from our line of thought would once more be that this necessity arises when the cathexis of the ego with libido exceeds a certain amount. A strong egoism is a protection against falling ill, but in the last resort we must begin to love in order not to fall ill, and we are bound to fall ill if, in consequence of frustration, we are unable to love. This follows somewhat on the lines of Heine's picture of the psychogenesis of the Creation, "God is imagined as saying: 'Illness was no doubt the final cause of the whole urge to create. By creating, I could recover; by creating I became healthy'"- Heinrich Heine.
      We have recognized our mental apparatus as being first and foremost a device designed for mastering excitations which would otherwise be felt as distressing or would have pathogenic effects. Working them over in the mind helps remarkably towards an internal draining away of excitations which are incapable of direct discharge outwards, or for which such a discharge is for the moment undesirable. In the first instance, however, it is a matter of indifference whether this internal process of working-over is carried out upon real or imaginary objects. The difference does not appear till later-if the turning of the libido on to unreal objects (introversion) has led to its being dammed up. In paraphrenics, megalomania allows of a similar internal working-over of libido which has returned to the ego; perhaps it is only when the megalomania fails that the damming-up of libido in the ego becomes pathogenic and starts the process of recovery which gives us the impression of being a disease.

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A third way in which we may approach the study of narcissism is by observing the erotic life of human beings, with its many kinds of differentiation in man and woman. Just as object-libido at first concealed ego-libido from our observation, so too in connection with the objectchoice of infants (and of growing children) what we first noticed was that they derived their sexual objects from their experiences of satisfaction. The first autoerotic sexual satisfactions are experienced in connection with vital functions which serve the purpose of self-preservation. The sexual instincts are at the outset attached to the satisfaction of the ego-instincts; only later do they become independent of these, and even then we have an indication of that original attachment in the fact that the persons who are concerned with a child's feeding, care, and protection become his earliest sexual objects: that is to say, in the first instance his mother or a substitute for her. Side by side, however, with this type and source of object-choice, which may be called the anaclitic' or `attachment` type, psychoanalytic research has revealed a second type, which we were not prepared for finding. We have discovered, especially clearly in people whose libidinal development has suffered some disturbance, such as perverts and homosexuals, that in their later choice of love-objects they have taken as a model not their mother but their own selves. They are plainly seeking themselves as a loveobject, and exhibiting a type of object-choice which must be termed narcissistic'. In this observation we have the strongest of the reasons which have led us to adopt the hypothesis of narcissism.
     We have, however, not concluded that human beings are divided into two sharply differentiated groups, according as their object-choice conforms to the anaclitic or to the narcissistic type; we assume rather that both kinds of object-choice are open to each individual, though he may show a preference for one or the other. We say that a human being has originally two sexual objects--himself and the woman who nurses him--and in doing so we are postulating a primary narcissism in everyone, which may in some cases manifest itself in a dominating fashion in his object-choice.
     A comparison of the male and female sexes then shows that there are fundamental differences between them in respect of their type of objectchoice, although these differences are of course not universal. Complete object-love of the attachment type is, properly speaking, characteristic of the male. It displays the marked sexual overvaluation which is doubtless derived from the child's original narcissism and thus corresponds to a transference of that narcissism to the sexual object. This sexual overvaluation is the origin of the peculiar state of being in love, a state suggestive of a neurotic compulsion, which is thus traceable to an impoverishment of the ego as regards libido in favour of the love-object. A different course is followed in the type of female most frequently met with, which is probably the purest and truest one. With the onset of puberty the maturing of the female sexual organs, which up till then have been in a condition of latency, seems to bring about an intensification of the original narcissism, and this is unfavourable to the development of a true object-choice with its accompanying sexual overvaluation. Women, especially if they grow up with good looks, develop a certain self-contentment which compensates them for the social restrictions that are imposed upon them in their choice of object. Strictly speaking, it is only themselves that such women love with an intensity comparable to that of the man's love for them. Nor does their need lie in the direction of loving, but of being loved; and the man who fulfils this condition is the one who finds favour with them. The importance of this type of woman for the erotic life of mankind is to be rated very high. Such women have the greatest fascination for men, not only for aesthetic reasons, since as a rule they are the most beautiful, but also because of a combination of interesting psychological factors. For it seems very evident that another person's narcissism has a great attraction for those who have renounced part of their own narcissism and are in search of object-love. The charm of a child lies to a great extent in his narcissism, his self-contentment and inaccessibility, just as does the charm of certain animals which seem not to concern themselves about us, such as cats and the large beasts of prey. Indeed, even great criminals and humorists, as they are represented in literature, compel our interest by the narcissistic consistency with which they manage to keep away from their ego anything that would diminish it. It is as if we envied them for maintaining a blissful state of mind-an unassailable libidinal position which we ourselves have since abandoned. The great charm of narcissistic women has, however, its reverse side; a large part of the lover's dissatisfaction, of his doubts of the woman's love, of his complaints of her enigmatic nature, has its root in this incongruity between the types of object-choice.
     Perhaps it is not out of place here to give an assurance that this description of the feminine form of erotic life is not due to any tendentious desire on my part to depreciate women. Apart from the fact that tendentiousness is quite alien to me, I know that these different lines of development correspond to the differentiation of functions in a highly complicated biological whole; further, I am ready to admit that there are quite a number of women who love according to the masculine type and who also develop the sexual overvaluation proper to that type.
     Even for narcissistic women, whose attitude towards men remains cool, there is a road which leads to complete object-love. In the child which they bear, a part of their own body confronts them like an extraneous object, to which, starting out from their narcissism, they can then give complete object-love. There are other women, again, who do not have to wait for a child in order to take the step in development from (secondary) narcissism to object-love. Before puberty they feel masculine and develop some way along masculine lines; after this trend has been cut short on their reaching female maturity, they still retain the capacity of longing for a masculine ideal--an ideal which is in fact a survival of the boyish nature that they themselves once possessed.
     What I have so far said by way of indication may be concluded by a short summary of the paths leading to the choice of an object. A person may love:

I) According to the narcissistic type:

(a) what he himself is (i.e. himself),
(b) what he himself was,
(c) what he himself would like to be,
(d) someone who was once part of himself.

(a) the woman who feeds him,
(b) the man who protects him,

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The primary narcissism of children which we have assumed and which forms one of the postulates of our theories of the libido, is less easy to grasp by direct observation than to confirm by inference from elsewhere. If we look at the attitude of affectionate parents towards their children, we have to recognize that it is a revival and reproduction of their own narcissism, which they have long since abandoned. The trustworthy pointer constituted by overvaluation, which we have already recognized as a narcissistic stigma in the case of object-choice, dominates, as we all know, their emotional attitude. Thus they are under a compulsion to ascribe every perfection to the child--which sober observation would find no occasion to do--and to conceal and forget all his shortcomings. (Incidentally, the denial of sexuality in children is connected with this. Moreover, they are inclined to suspend in the child's favour the operation of all the cultural acquisitions which their own narcissism has been forced to respect, and to renew on his behalf the claims to privileges which were long ago given up by themselves. The child shall have a better time than his parents; he shall not be subject to the necessities which they have recognized as paramount in life. Illness, death, renunciation of enjoyment, restrictions on his own will, shall not touch him; the laws of nature and of society shall be abrogated in his favour: he shall once more really be the centre and core of creation--'His Majesty the Baby', as we once fancied ourselves. The child shall fulfil those wishful dreams of the parents which they never carried out--the boy shall become a great man and a hero in his father's place, and the girl shall marry a prince as a tardy compensation for her mother. At the most touchy point in the narcissistic system, the immortality of the ego, which is so hard pressed by reality, security is achieved by taking refuge in the child. Parental love, which is so moving and at bottom so childish, is nothing but the parents' narcissism born again, which, transformed into object-love, unmistakably reveals its former nature.

III

Psychoanalytic research ordinarily enables us to trace the vicissitudes undergone by the libidinal instincts when these, isolated from the ego-instincts, are placed in opposition to them; but in the particular field of the castration complex, it allows us to infer the existence of an epoch and a psychical situation in which the two groups of instincts, still operating in unison and inseparably mingled, make their appearance as narcissistic interests. It is from this context that Adler [1910] has derived his concept of the 'masculine protest', which he has elevated almost to the position of the sole motive force in the formation of character and neurosis alike and which he bases not on a narcissistic, and therefore still a libidinal, trend, but on a social valuation. Psychoanalytic research has from the very beginning recognized the existence and importance of the 'masculine protest', but it has regarded it, in opposition to Adler, as narcissistic in nature and derived from the castration complex. The 'masculine protest' is concerned in the formation of character, into the genesis of which it enters along with many other factors, but it is completely unsuited for explaining the problems of the neuroses, with regard to which Adler takes account of nothing but the manner in which they serve the ego-instincts. I find it quite impossible to place the genesis of neurosis upon the narrow basis of the castration complex, however powerfully it may come to the fore in men among their resistances to the cure of a neurosis.

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Observation of normal adults shows that their former megalomania has been damped down and that the psychical characteristics from which we inferred their infantile narcissism have been effaced. What has become of their ego-libido? Are we to suppose that the whole amount of it has passed into object-cathexes? Such a possibility is plainly contrary to the whole trend of our argument; but we may find a hint at another answer to the question in the psychology of repression.
   We have learnt that libidinal instinctual impulses undergo the vicissitude of pathogenic repression if they come into conflict with the subiect's cultural and ethical ideas. By this we never mean that the individual in question has a merely intellectual knowledge of the existence of such ideas; we always mean that he recognizes them as a standard for himself and submits to the claims they make on him. Repression, we have said, proceeds from the ego; we might say with greater precision that it proceeds from the self-respect of the ego. The same impressions, experiences, impulses and desires that one man indulges or at least works over consciously will be rejected with the utmost indignation by another, or even stifled before they enter consciousness. The difference between the two, which contains the conditioning factor of repression, can easily be expressed in terms which enable it to be explained by the libido theory. We can say that the one man has set up an ideal in himself by which he measures his actual ego, while the other has formed no such ideal. For the ego the formation of an ideal would be the conditioning factor of repression.
     This ideal ego is now the target of the self-love which was enjoyed in childhood by the actual ego. The subject's narcissism makes its appearance displaced on to this new ideal ego, which, like the infantile ego, finds itself possessed of every perfection that is of value. As always where the libido is concerned, man has here again shown himself incapable of giving up a satisfaction he had once enjoyed. He is not willing to forgo the narcissistic perfection of his childhood; and when, as he grows up, he is disturbed by the admonitions of others and by the awakening of his own critical judgement, so that he can no longer retain that perfection, he seeks to recover it in the new form of an ego ideal. What he projects before him as his ideal is the substitute for the lost narcissism of his childhood in which he was his own ideal.
     We are naturally led to examine the relation between this forming of an ideal and sublimation. Sublimation is a process that concerns objectlibido and consists in the instinct's directing itself towards an aim other than, and remote from, that of sexual satisfaction; in this process the accent falls upon deflection from sexuality. Idealization is a process that concerns the object; by it that object, without any alteration in its nature, is aggrandized and exalted in the subject's mind. Idealization is possible in the sphere of ego-libido as well as in that of object-libido. For example, the sexual overvaluation of an object is an idealization of it. In so far as sublimation describes something that has to do with the instinct and idealization something to do with the object, the two concepts are to be distinguished from each other.
     The formation of an ego ideal is often confused with the sublimation of instinct, to the detriment of our understanding of the facts. A man who has exchanged his narcissism for homage to a high ego ideal has not necessarily on that account succeeded in sublimating his libidinal instincts. It is true that the ego ideal demands such sublimation, but it cannot enforce it; sublimation remains a special process which may be prompted by the ideal but the execution of which is entirely independent of any such prompting. It is precisely in neurotics that we find the highest differences of potential between the development of their ego ideal and the amount of sublimation of their primitive libidinal instincts; and in general it is far harder to convince an idealist of the inexpedient location of his libido than a plain man whose pretensions have remained more moderate. Further, the formation of an ego ideal and sublimation are quite differently related to the causation of neurosis. As we have learnt, the formation of an ideal heightens the demands of the ego and is the most powerful factor favouring repression; sublimation is a way out, a way by which those demands can be met without involving repression.
     It would not surprise us if we were to find a special psychical agency which performs the task of seeing that narcissistic satisfaction from the ego ideal is ensured and which, with this end in view, constantly watches the actual ego and measures it by that ideal. If such an agency does exist, we cannot possibly come upon it as a discovery-we can only recognize it; for we may reflect that what we call our 'conscience' has the required characteristics. Recognition of this agency enables us to understand the so-called 'delusions of being noticed' or more correctly, of being watched, which are such striking symptoms in the paranoid diseases and which may also occur as an isolated form of illness, or intercalated in a transference neurosis. Patients of this sort complain that all their thoughts are known and their actions watched and supervised; they are informed of the functioning of this agency by voices which characteristically speak to them in the third person ('Now she's thinking of that again', 'now he's going out'). This complaint is justified; it describes the truth. A power of this kind, watching, discovering and criticizing all our intentions, does really exist. Indeed, it exists in every one of us in normal life.
     Delusions of being watched present this power in a regressive form, thus revealing its genesis and the reason why the patient is in revolt against it. For what prompted the subject to form an ego ideal, on whose behalf his conscience acts as watchman, arose from the critical influence of his parents (conveyed to him by the medium of the voice), to whom were added, as time went on, those who trained and taught him and the innumerable and indefinable host of all the other people in his environment-his fellow-men-and public opinion.
     In this way large amounts of libido of an essentially homosexual kind are drawn into the formation of the narcissistic ego ideal and find outlet and satisfaction in maintaining it. The institution of conscience was at bottom an embodiment, first of parental criticism, and subsequently of that of society-a process which is repeated in what takes place when a tendency towards repression develops out of a prohibition or obstacle that came in the first instance from without. The voices, as well as the undefined multitude, are brought into the foreground again by the disease, and so the evolution of conscience is reproduced regressively. But the revolt against this 'censoring agency' arises out of the subject's desire in accordance with the fundamental character of his illness) to liberate himself from all these influences, beginning with the parental one, and out of his withdrawal of homosexual libido from them. His conscience then confronts him in a regressive form as a hostile influence from without.
     The complaints made by paranoics also show that at bottom the selfcriticism of conscience coincides with the self-observation on which it is based. Thus the activity of the mind which has taken over the function of conscience has also placed itself at the service of internal research, which furnishes philosophy with the material for its intellectual operations. This may have some bearing on the characteristic tendency of paranoics to construct speculative systems.

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We may here recall that we have found that the formation of dreams takes place under the dominance of a censorship which compels distortion of the dream-thoughts. We did not, however, picture this censorship as a special power, but chose the term to designate one side of the repressive trends that govern the ego, namely the side which is turned towards the dream-thoughts. If we enter further into the structure of the ego, we may recognize in the ego ideal and in the dynamic utterances of conscience the dream-censor as well. If this censor is to some extent on the alert even during sleep, we can understand how it is that its suggested activity of self-observation and self-criticism-with such thoughts as, `now he is too sleepy to think', `now he is waking up'--makes a contribution to the content of the dream.
     At this point we may attempt some discussion of the self-regarding attitude in normal people and in neurotics. In the first place self-regard appears to us to be an expression of the size of the ego; what the various elements are which go to determine that size is irrelevant. Everything a person possesses or achieves, every remnant of the primitive feeling of omnipotence which his experience has confirmed, helps to increase his self-regard.
     Applying our distinction between sexual and ego-instincts, we must recognize that self-regard has a specially intimate dependence on narcissistic libido. Here we are supported by two fundamental facts; that in paraphrenics self-regard is increased, while in the transference neuroses it is diminished; and that in love-relations not being loved lowers the self-regarding feelings, while being loved raises them. As we have indicated, the aim and the satisfaction in a narcissistic object-choice is to be loved.
     Further, it is easy to observe that libidinal object-cathexis does not raise self-regard. The effect of dependence upon the loved object is to lower that feeling: a person in love is humble. A person who loves has, so to speak, forfeited a part of his narcissism, and it can only be replaced by his being loved. In all these respects self-regard seems to remain related to the narcissistic element in love.
     The realization of impotence, of one's own inability to love, in consequence of mental or physical disorder, has an exceedingly lowering effect upon self-regard. Here, in my judgement, we must look for one of the sources of the feelings of inferiority which are experienced by patients suffering from the transference neuroses and which they are so ready to report. The main source of these feelings is, however, the impoverishment of the ego, due to the extraordinarily large libidinal cathexes which have been withdrawn from it-due, that is to say, to the injury sustained by the ego through sexual trends which are no longer subject to control.
     Adler is right in maintaining that when a person with an active mental life recognizes an inferiority in one of his organs, it acts as a spur and calls out a higher level of performance in him through overcompensation. But it would be altogether an exaggeration if, following Adler's example, we sought to attribute every successful achievement to this factor of an original inferiority of an organ. Not all artists are handicapped with bad eyesight, nor were all orators originally stammerers. And there are plenty of instances of excellent achievements springing from superior organic endowment. In the aetiology of neuroses organic inferiority and imperfect development play an insignificant part-much the same as that played by currently active perceptual material in the formation of dreams. Neuroses make use of such inferiorities as a pretext, just as they do of every other suitable factor. We may be tempted to believe a neurotic woman patient when she tells us that it was inevitable she should fall ill, since she is ugly, deformed or lacking in charm, so that no one could love her; but the very next neurotic will teach us better-for she persists in her neurosis and in her aversion to sexuality, although she seems more desirable, and is more desired, than the average woman. The majority of hysterical women are among the attractive and even beautiful representatives of their sex, while, on the other hand, the frequency of ugliness, organic defects and infirmities in the lower classes of society does not increase the incidence of neurotic illness among them.
     The relations of self-regard to erotism--that is, to libidinal object-cathexes--may be expressed concisely in the following way. Two cases must be distinguished, according to whether the erotic cathexes are egosyntonic, or, on the contrary, have suffered repression. In the former case (where the use made of the libido is ego-syntonic), love is assessed like any other activity of the ego. Loving in itself, in so far as it involves longing and deprivation, lowers self-regard; whereas being loved, having one's love returned, and possessing the loved object, raises it once more. When libido is repressed, the erotic cathexis is felt as a severe depletion of the ego, the satisfaction of love is impossible, and the re-enrichment of the ego can be effected only by a withdrawal of libido from its objects. The return of the object-libido to the ego and its transformation into narcissism represents, as it were, a happy love once more; and, on the other hand, it is also true that a real happy love corresponds to the primal condition in which object-libido and ego-libido cannot be distinguished.

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The importance and extensiveness of the topic must be my justification for adding a few more remarks which are somewhat loosely strung together.
     The development of the ego consists in a departure from primary narcissism and gives rise to a vigorous attempt to recover that state. This departure is brought about by means of the displacement of libido on to an ego ideal imposed from without; and satisfaction is brought about from fulfilling this ideal.
     At the same time the ego has sent out the libidinal objectcathexes. It becomes impoverished in favour of these cathexes, just as it does in favour of the ego ideal, and it enriches itself once more from its satisfactions in respect of the object, just as it does by fulfilling its ideal.
     One part of self-regard is primary--the residue of infantile narcissism; another part arises out of the omnipotence which is corroborated by experience (the fulfilment of the ego ideal), whilst a third part proceeds from the satisfaction of object-libido.
     The ego ideal has imposed severe conditions upon the satisfaction of libido through objects; for it causes some of them to be rejected by means of its censor, as being incompatible. Where no such ideal has been formed, the sexual trend in question makes its appearance unchanged in the personality in the form of a perversion. To be their own ideal once more, in regard to sexual no less than other trends, as they were in childhood--this is what people strive to attain as their happiness.
     Being in love consists in a flowing-over of ego-libido on to the object. It has the power to remove repressions and re-instate perversions. It exalts the sexual object into a sexual ideal. Since, with the object type (or attachment type), being in love occurs in virtue of the fulfilment of infantile conditions for loving, we may say that whatever fulfils that condition is idealized.
     The sexual ideal may enter into an interesting auxiliary relation to the ego ideal. It may be used for substitutive satisfaction where narcissistic satisfaction encounters real hindrances. In that case a person will love in conformity with the narcissistic type of object-choice, will love what he once was and no longer is, or else what possesses the excellences which lie never had at all (cf. (c) [p. 90]). The formula parallel to the one there stated runs thus: what possesses the excellence which the ego lacks for making it an ideal, is loved. This expedient is of special importance for the neurotic, who, on account of his excessive object-cathexes, is impoverished in his ego and is incapable of fulfilling his ego ideal. He then seeks a way back to narcissism from his prodigal expenditure of libido upon objects, by choosing a sexual ideal after the narcissistic type which possesses the excellences to which he cannot attain. This is the cure by love, which he generally prefers to cure by analysis. Indeed, he cannot believe in any other mechanism of cure; he usually brings expectations of this sort with him to the treatment and directs them towards the person of the physician. The patient's incapacity for love, resulting from his extensive repressions, naturally stands in the way of a therapeutic plan of this kind. An unintended result is often met with when, by means of the treatment, he has been partially freed from his repressions: he withdraws from further treatment in order to choose a loveobject, leaving his cure to be continued by a life with someone he loves. We might be satisfied with this result, if it did not bring with it all the dangers of a crippling dependence upon his helper in need.
     The ego ideal opens up an important avenue for the understanding of group psychology. In addition to its individual side, this ideal has a social side; it is also the common ideal of a family, a class or a nation. It binds not only a person's narcissistic libido, but also a considerable amount of his homosexual libido,' which is in this way turned back into the ego. The want of satisfaction which arises from the non-fulfilment of this ideal liberates homosexual libido, and this is transformed into a sense of guilt (social anxiety). Originally this sense of guilt was a fear of punishment by the parents, or, more correctly, the fear of losing their love; later the parents are replaced by an indefinite number of fellow-men. The frequent causation of paranoia by an injury to the ego, by a frustration of satisfaction within the sphere of the ego ideal, is thus made more intelligible, as is the convergence of ideal-formation and sublimation in the ego ideal, as well as the involution of sublimations and the possible transformation of ideals in paraphrenic disorders.

Today the word "schizophrenia" brings to mind such names as John Nash and Andrea Yates. Nash, the subject of the Oscar-winning film A Beautiful Mind, emerged as a mathematical prodigy and eventually won a Nobel Prize for his early work, but he became so profoundly disturbed by the brain disorder in young adulthood that he lost his academic career and floundered for years before recovering. Yates, a mother of five who suffers from both depression and schizophrenia, infamously drowned her young children in a bathtub to "save them from the devil" and is now in prison.
     The experiences of Nash and Yates are typical in some ways but atypical in others. Of the roughly 1 percent of the world's population stricken with schizophrenia, most remain largely disabled throughout adulthood. Rather than being geniuses like Nash, many show below- average intelligence even before they become symptomatic and then undergo a further decline in IQ when the illness sets in, typically during young adulthood. Unfortunately, only a minority ever achieve gainful employment. In contrast to Yates, fewer than half marry or raise families. Some 15 percent reside for long periods in state or county mental health facilities, and another 15 percent end up incarcerated for petty crimes and vagrancy. Roughly 60 percent live in poverty, with one in 20 ending up homeless. Because of poor social support, more individuals with schizophrenia become victims than perpetrators of violent crime.
     Medications exist but are problematic. The major options today, called antipsychotics, stop all symptoms in only about 20 percent of patients. (Those lucky enough to respond in this way tend to function well as long as they continue treatment; too many, however, abandon their medicines over time, usually because of side effects, a desire to be "normal" or a loss of access to mental health care). Two thirds gain some relief from antipsychotics yet remain symptomatic throughout life, and the remainder show no significant response.
     An inadequate arsenal of medications is only one of the obstacles to treating this tragic disorder effectively. Another is the theories guiding drug therapy. Brain cells (neurons) communicate by releasing chemicals called neurotransmitters that either excite or inhibit other neurons. For decades, theories of schizophrenia have focused on a single neurotransmitter: dopamine. In the past few years, though, it has become clear that a disturbance in dopamine levels is just a part of the story and that, for many, the main abnormalities lie elsewhere. In particular, suspicion has fallen on deficiencies in the neurotransmitter glutamate. Scientists now realize that schizophrenia affects virtually all parts of the brain and that, unlike dopamine, which plays an important role only in isolated regions, glutamate is critical virtually everywhere. As a result, investigators are searching for treatments that can reverse the underlying glutamate deficit.

Multiple Symptoms
To develop better treatments, investigators need to understand how schizophrenia arises--which means they need to account for all its myriad symptoms. Most of these fall into categories termed "positive," "negative" and "cognitive." Positive symptoms generally imply occurrences beyond normal experience; negative symptoms generally connote diminished experience. Cognitive, or "disorganized," symptoms refer to difficulty maintaining a logical, coherent flow of conversation, maintaining attention, and thinking on an abstract level.
     The public is most familiar with the positive symptoms, particularly agitation, paranoid delusions (in which people feel conspired against) and hallucinations, commonly in the form of spoken voices. Command hallucinations, where voices tell people to hurt themselves or others, are an especially ominous sign: they can be difficult to resist and may precipitate violent actions.
     The negative and cognitive symptoms are less dramatic but more pernicious. These can include a cluster called the 4 A's: autism (loss of interest in other people or the surroundings), ambivalence (emotional withdrawal), blunted affect (manifested by a bland and unchanging facial expression), and the cognitive problem of loose association (in which people join thoughts without clear logic, frequently jumbling words together into a meaningless word salad). Other common symptoms include a lack of spontaneity, impoverished speech, difficulty establishing rapport and a slowing of movement. Apathy and disinterest especially can cause friction between patients and their families, who may view these attributes as signs of laziness rather than manifestations of the illness.
     When individuals with schizophrenia are evaluated with pencil-and-paper tests designed to detect brain injury, they show a pattern suggestive of widespread dysfunction. Virtually all aspects of brain operation, from the most basic sensory processes to the most complex aspects of thought are affected to some extent. Certain functions, such as the ability to form new memories either temporarily or permanently or to solve complex problems, may be particularly impaired. Patients also display difficulty solving the types of problems encountered in daily living, such as describing what friends are for or what to do if all the lights in the house go out at once. The inability to handle these common problems, more than anything else, accounts for the difficulty such individuals have in living independently. Overall, then, schizophrenia conspires to rob people of the very qualities they need to thrive in society: personality, social skills and wit.

Beyond Dopamine
The emphasis on dopamine-related abnormalities as a cause of schizophrenia emerged in the 1950s, as a result of the fortuitous discovery that a class of medication called the phenothiazines was able to control the positive symptoms of the disorder. Subsequent studies demonstrated that these substances work by blocking the functioning of a specific group of chemical-sensing molecules called dopamine D2 receptors, which sit on the surface of certain nerve cells and convey dopamine's signals to the cells' interior. At the same time, research led by the recent Nobel laureate Arvid Carlsson revealed that amphetamine, which was known to induce hallucinations and delusions in habitual abusers, stimulated dopamine release in the brain. Together these two findings led to the "dopamine theory," which proposes that most symptoms of schizophrenia stem from excess dopamine release in important brain regions, such as the limbic system (thought to regulate emotion) and the frontal lobes (thought to regulate abstract reasoning).
     Over the past 40 years, both the strengths and limitations of the theory have become apparent. For some patients, especially those with prominent positive symptoms, the theory has proved robust, fitting symptoms and guiding treatment well. The minority of those who display only positive manifestations frequently function quite well--holding jobs, having families and suffering relatively little cognitive decline over time--if they stick with their medicines.
     Yet for many, the hypothesis fits poorly. These are the people whose symptoms come on gradually, not dramatically, and in whom negative symptoms overshadow the positive. The sufferers grow withdrawn, often isolating themselves for years. Cognitive functioning is poor, and patients improve slowly, if at all, when treated with even the best existing medications on the market.
Such observations have prompted some researchers to modify the dopamine hypothesis. One revision suggests, for example, that the negative and cognitive symptoms may stem from reduced dopamine levels in certain parts of the brain, such as the frontal lobes, and increased dopamine in other parts of the brain, such as the limbic system. Because dopamine receptors in the frontal lobe are primarily of the D1 (rather than D2) variety, investigators have begun to search, so far unsuccessfully, for medications that stimulate D1 receptors while inhibiting D2s.
     In the late 1980s researchers began to recognize that some pharmaceuticals, such as clozapine (Clozaril), were less likely to cause stiffness and other neurologic side effects than older treatments, such as chlorpromazine (Thorazine) or haloperidol (Haldol), and were more effective in treating persistent positive and negative symptoms. Clozapine, known as an atypical antipsychotic, inhibits dopamine receptors less than the older medications and affects the activity of various other neurotransmitters more strongly. Such discoveries led to the development and wide adoption of several newer atypical antipsychotics based on the actions of clozapine (certain of which, unfortunately, now turn out to be capable of causing diabetes and other unexpected side effects). The discoveries also led to the proposal that dopamine was not the only neurotransmitter disturbed in schizophrenia; others were involved as well.
     Theories focusing largely on dopamine are problematic on additional grounds. Improper dopamine balance cannot account for why one individual with schizophrenia responds almost completely to treatment, whereas someone else shows no apparent response. Nor can it explain why positive symptoms respond so much better than negative or cognitive ones do. Finally, despite decades of research, investigations of dopamine have yet to uncover a smoking gun. Neither the enzymes that produce this neurotransmitter nor the receptors to which it binds appear sufficiently altered to account for the panoply of observed symptoms.

The Angel Dust Connection
If dopamine cannot account well for schizophrenia, what is the missing link? A critical clue came from the effects of another abused drug: PCP (phencyclidine), also known as angel dust. In contrast to amphetamine, which mimics only the positive symptoms of the disease, PCP induces symptoms that resemble the full range of schizophrenia's manifestations: negative and cognitive and, at times, positive. These effects are seen not just in abusers of PCP but also in individuals given brief, low doses of PCP or ketamine (an anesthetic with similar effects) in controlled drug-challenge trials.
Such studies first drew parallels between the effects of PCP and the symptoms of schizophrenia in the 1960s. They showed, for example, that individuals receiving PCP exhibited the same type of disturbances in interpreting proverbs as those with schizophrenia. More recent studies with ketamine have produced even more compelling similarities. Notably, during ketamine challenge, normal individuals develop difficulty thinking abstractly, learning new information, shifting strategies or placing information in temporary storage. They show a general motor slowing and reduction in speech output just like that seen in schizophrenia. Individuals given PCP or ketamine also grow withdrawn, sometimes even mute; when they talk, they speak tangentially and concretely. PCP and ketamine rarely induce schizophrenialike hallucinations in normal volunteers, but they exacerbate these disturbances in those who already have schizophrenia.
     The ability of PCP and ketamine to induce a broad spectrum of schizophrenia-like symptoms suggests that these drugs replicate some key molecular disturbance in the brain of schizophrenic patients. At the molecular level the drugs impair the functioning of the brain signaling systems that rely on glutamate, the main excitatory neurotransmitter in the brain. More precisely, they block the action of a form of glutamate receptor known as the NMDA receptor, which plays a critical role in brain development, learning, memory and neural processing in general. This receptor also participates in regulating dopamine release, and blockade of NMDA receptors produces the same disturbances of dopamine function typically seen in schizophrenia. Thus, NMDA receptor dysfunction, by itself, can explain both negative and cognitive symptoms of schizophrenia as well as the dopamine abnormalities at the root of the positive symptoms.
     One example of the research implicating NMDA receptors in schizophrenia relates to the way the brain normally processes information. Beyond strengthening connections between neurons, NMDA receptors amplify neural signals, much as transistors in old-style radios boosted weak radio signals into strong sounds. By selectively amplifying key neural signals, these receptors help the brain respond to some messages and ignore others, thereby facilitating mental focus and attention. Ordinarily, people respond more intensely to sounds presented infrequently than to those presented frequently and to sounds heard while listening than to sounds they make themselves while speaking. But people with schizophrenia do not respond this way, which implies that their brain circuits reliant on NMDA receptors are out of kilter.
     If reduced NMDA receptor activity prompts schizophrenia's symptoms, what then causes this reduction? The answer remains unclear. Some reports show that people with schizophrenia have fewer NMDA receptors, although the genes that give rise to the receptors appear unaffected. If NMDA receptors are intact and present in proper amounts, perhaps the problem lies with a flaw in glutamate release or with a buildup of compounds that disrupt NMDA activity.
     Some evidence supports each of these ideas. For instance, postmortem studies of schizophrenic patients reveal not only lower levels of glutamate but also higher levels of two compounds (NAAG and kynurenic acid) that impair the activity of NMDA receptors. Moreover, blood levels of the amino acid homocysteine are elevated; homocysteine, like kynurenic acid, blocks NMDA receptors in the brain. Overall, schizophrenia's pattern of onset and symptoms suggests that chemicals disrupting NMDA receptors may accumulate in sufferers' brains, although the research verdict is not yet in. Entirely different mechanisms may end up explaining why NMDA receptor transmission becomes attenuated.

New Treatment Possibilities
Regardless of what causes NMDA signaling to go awry in schizophrenia, the new understanding--and preliminary studies in patients--offers hope that drug therapy can correct the problem. Support for this idea comes from studies showing that clozapine, one of the most effective medications for schizophrenia identified to date, can reverse the behavioral effects of PCP in animals, something that older antipsychotics cannot do. Further, short-term trials with agents known to stimulate NMDA receptors have produced encouraging results. Beyond adding support to the glutamate hypothesis, these results have enabled long-term clinical trials to begin. If proved effective in large-scale tests, agents that activate NMDA receptors will become the first entirely new class of medicines developed specifically to target the negative and cognitive symptoms of the disorder.
     The two of us have conducted some of those studies. When we and our colleagues administered the amino acids glycine and D-serine to patients with their standard medications, the subjects showed a 30 to 40 percent decline in cognitive and negative symptoms and some improvement in positive symptoms. Delivery of a medication, D-cycloserine, that is primarily used for treating tuberculosis but happens to cross-react with the NMDA receptor, produced similar results. Based on such findings, the National Institute of Mental Health has organized multicenter clinical trials at four hospitals to determine the effectiveness of D-cycloserine and glycine as therapies for schizophrenia; results should be available this year. Trials of D-serine, which is not yet approved for use in the U.S., are ongoing elsewhere with encouraging preliminary results as well. These agents have also been helpful when taken with the newest generation of atypical antipsychotics, which raises the hope that therapy can be developed to control all three major classes of symptoms at once.
     None of the agents tested to date may have the properties needed for commercialization; for instance, the doses required may be too high. We and others are therefore exploring alternative avenues. Molecules that slow glycine's removal from brain synapses--known as glycine transport inhibitors--might enable glycine to stick around longer than usual, thereby increasing stimulation of NMDA receptors. Agents that directly activate "AMPA-type" glutamate receptors, which work in concert with NMDA receptors, are also under active investigation. And agents that prevent the breakdown of glycine or D-serine in the brain have been proposed.

Many Avenues of Attack
Scientists interested in easing schizophrenia are also looking beyond signaling systems in the brain to other factors that might contribute to, or protect against, the disorder. For example, investigators have applied so-called gene chips to study brain tissue from people who have died, simultaneously comparing the activity of tens of thousands of genes in individuals with and without schizophrenia. So far they have determined that many genes important to signal transmission across synapses are less active in those with schizophrenia--but exactly what this information says about how the disorder develops or how to treat it is unclear.
     Genetic studies in schizophrenia have nonetheless yielded intriguing findings recently. The contribution of heredity to schizophrenia has long been controversial. If the illness were dictated solely by genetic inheritance, the identical twin of a schizophrenic person would always be schizophrenic as well, because the two have the same genetic makeup. In reality, however, when one twin has schizophrenia, the identical twin has about a 50 percent chance of also being afflicted. Moreover, only about 10 percent of first-degree family members (parents, children or siblings) share the illness even though they have on average 50 percent of genes in common with the affected individual. This disparity suggests that genetic inheritance can strongly predispose people to schizophrenia but that environmental factors can nudge susceptible individuals into illness or perhaps shield them from it. Prenatal infections, malnutrition, birth complications and brain injuries are all among the influences suspected of promoting the disorder in genetically predisposed individuals.
      Over the past few years, several genes have been identified that appear to increase susceptibility to schizophrenia. Interestingly, one of these genes codes for an enzyme (catechol-O-methyltransferase) involved in the metabolism of dopamine, particularly in the prefrontal cortex. Genes coding for proteins called dysbindin and neuregulin seem to affect the number of NMDA receptors in brain. The gene for an enzyme involved in the breakdown of D-serine (D-amino acid oxidase) may exist in multiple forms, with the most active form producing an approximately fivefold increase in risk for schizophrenia. Other genes may give rise to traits associated with schizophrenia but not the disease itself. Because each gene involved in schizophrenia produces only a small increase in risk, genetic studies must include large numbers of subjects to detect an effect and often generate conflicting results. On the other hand, the existence of multiple genes predisposing for schizophrenia may help explain the variability of symptoms across individuals, with some people perhaps showing the greatest effect in dopamine pathways and others evincing significant involvement of other neurotransmitter pathways.
     Finally, scientists are looking for clues by imaging living brains and by comparing brains of people who have died. In general, individuals with schizophrenia have smaller brains than unaffected individuals of similar age and sex. Whereas the deficits were once thought to be restricted to areas such as the brain's frontal lobe, more recent studies have revealed similar abnormalities in many brain regions: those with schizophrenia have abnormal levels of brain response while performing tasks that activate not only the frontal lobes but also other areas of the brain, such as those that control auditory and visual processing. Perhaps the most important finding to come out of recent research is that no one area of the brain is "responsible" for schizophrenia. Just as normal behavior requires the concerted action of the entire brain, the disruption of function in schizophrenia must be seen as a breakdown in the sometimes subtle interactions both within and between different brain regions.
     Because schizophrenia's symptoms vary so greatly, many investigators believe that multiple factors probably cause the syndrome. What physicians diagnose as schizophrenia today may prove to be a cluster of different illnesses, with similar and overlapping symptoms. Nevertheless, as researchers more accurately discern the syndrome's neurological bases, they should become increasingly skilled at developing treatments that adjust brain signaling in the specific ways needed by each individual.

DANIEL C. JAVITT and JOSEPH T. COYLE have studied schizophrenia for many years. Javitt is director of the Program in Cognitive Neuroscience and Schizophrenia at the Nathan Kline Institute for Psychiatric Research in Orangeburg, N.Y., and professor of psychiatry at the New York University School of Medicine. His paper demonstrating that the glutamate-blocking drug PCP reproduces the symptoms of schizophrenia was the second-most cited schizophrenia publication of the 1990s. Coyle is Eben S. Draper Professor of Psychiatry and Neuroscience at Harvard Medical School and also editor in chief of the Archives of General Psychiatry. Both authors have won numerous awards for their research. Javitt and Coyle hold independent patents for use of NMDA modulators in the treatment of schizophrenia, and Javitt has significant financial interests in Medifoods and Glytech, companies attempting to develop glycine and D-serine as treatments for schizophrenia.