From: Neuropsychiatric Department of Osaka Medical College, Osaka-Takatsuki, Japan

(Prof. H. Mitsuda)

T H E C O N C E P T OF ”ATYPITAL PSYCHOSES” F R O M
T H E A S P E C T OF C L I N I C A L G E N E T I C S

HISATOSHI
MITSUDA

The designation “atypical psychoses” seems to be quite a bold one. Label-

ling an illness as “atypical” may appear to be similar to applying the same
term to an internal disease or a neuropathia. However, within the group of
psychiatric speciality, the designation “atypical” is routinely used without
much hesitation. It has even become a main subject of symposiums during
academic meetings. Such a fact indicates clearly at what level nosology,
especially classification system of psychoses, is today.
As is well known, the criteria of diagnosis, hence of classification, that we
have today were originated by E. Kraepelin and developed subsequently by
E . Bleuler. The “two-entities-principle’’ (Zweiteilungsprinzip) has, since the
time of Kraepelin, when the so-called endogenous psychoses were identified
with schizophrenia and manic-depressive illness (M. D. I.), remained, if
epilepsy is not taken into account for the moment, the most concrete founda-
tion for the classification system of psychoses till today. However, it is at the
same time almost always with respect to this very principle that the classifica-
tion of psychoses has been a subject of repeated controversy, and the problem
as to “atypical” psychoses is representative. Schematically speaking, “atyp-
ical” psychoses can be placed on the borderline or overlapping area between
schizophrenia and M. D. I. Naturally, they constitute the cases that are
problematical in terms of differential diagnosis according to the “two-enti-
ties-principle”.
A brief account of clinical features manifest in “atypical” psychoses may
be relevant here. The clinical pictures of these cases are usually characterized
by kaleidoscopic appearences and rapid fluctuation, which make a sharp con-
trast to the monotonous symptoms with little fluctuation seen in “typical”
schizophrenia, especially in hebephrenic form. At the initial stage of the ill-
ness, the foreground picture not infrequently consists of emotional disturb-
ances such as those seen in the manic or depressive, but confusional or
oneiroid states accompanying active delusion or paranoid-hallucinatory ex-
periences become soon apparent. I n other words, some impairment of con-
ciousness, clouding or modification, is frequently in the background. This
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again is in good contrast with the symptoms of typical schizophrenia where

some regressive processes of personality can be presumed in the background.
H . Ey, in an attempt to classify psychoses, proposed two groups, namely,
acute psychoses as “pathologie de la conscience” on the one hand and
chronic psychoses as “pathologie de la personnalitk”, a classification which
bears resemblance with the relation between “atypical” psychoses and schizo-
phrenia as described above.
The clinical course of “atypical” psychoses is, in most cases, episodic or
periodic and prognoses is usually favourable. In this respect too, they are
quite distinct from “typical” schizophrenia where the course is largely chronic
with a relatively strong tendency to deterioration. Complete healing does not
always follow however. Although it is often taken for granted that these
atypical psychoses are characterized by a recovery without noticeable trace,
I consider it doubtful. Clearly, some degree of personality defect becomes
apparent especially in some of the cases where the illness recurs frequently.
In addition, it has been noted in the cases of siblings with “atypical” symp-
toms that one of the siblings attained complete healings while the other was
left with some personality defect. At any rate, I consider it somewhat hasty
to regard “atypical” psychoses as being totally curable, and to identify a
case as schizophrenia without any reservation when some personality defect
becomes apparent. Moreover, the defective features seen in “atypical” psy-
choses are somewhat distinct from those of schizophrenia, displaying little
autistic tendency together with slowing of speech and behavior; in a sense the
feature bears some resemblance to organic dementia seen in epilepsy or other
d’iseases.
What then confronts us next is the problem of how we consider nosolog-
ically the cases of “atypical” psychoses that show such clinical features as
above described. This problem no doubt constitutes the key point in establish-
ing a classification system in psychiatry. So far, a number of hypotheses have
been advanced. These can be divided roughly into two standpoints, though
each has some discrepancy as against the another. The one holds the view
that, sticking straight to the “two-entities-principle” of Kraepelin, the prob-
lem of “atypical” cases should be solved within the scope of the principle.
According to this view, typical cases of schizophrenia and M. D. I. can be
regarded as two extreme poles, between which the various stages or transitions
are to be placed, as advocated for example by E. Bleuler and more recently
by Pauleikhoff and many others. There are some, e. g. those of the Tubingen
School, who try to explain “atypical” cases by the use of the concept of
“mixed psychoses” ( “Mischpsychose” ) which presumes a combination of
the genetic dispositions of both schizophrenia and M. D. I. or mixture of
various constitutions. The holders of this view also try to be loyal to Kraepe-
lin’s principle.
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The other view, in contrast, regards “atypical” cases as a whole to be an

entirely independent psychosis. According to this view, a third psychosis is to
be recognized, as exemplified by the terms “Degenerationspsychose” of Kleist,
Binswanger, “zykloide Psychose” of Leon hard, “schizophreniform psychosis”
of Langfeldt and “Oneirophrenia” of Meduna etc.
To determine the validity of the two mutually distinct view points just
described is in all the probability impossible and of no significance as long
as the criteria of classification are based on the level of clinical feature or
psychopathology. In fact, the daily practice of clinical diagnosis does not
warrant a clear distinction as to whether these “atypical” cases are a
transitional form between, or mixed form of, schizophrenia and M. D. I., or
an independent psychosis.
However, the situation is of course different in the view of clinical genetics
which deals with both clinical and genetic aspects simultaneously. The object
here is not mere “type” but “genotype” and differential nosology instead
of differential typology becomes the target of classification. If, then, inquiry
is made as to whether “atypical” psychoses are a mere phenotypical variant
of typical psychoses genetically or possess an independent genotype, some
solution to the aforementioned controversy regarding the nosology of atypical
psychoses may be expected.
Since 1941, when I published my work “on the heterogeneity of schizo-
phrenia”, I have conducted clinico-genetic studies of the endogenous psy-
choses in toto. Of the results obtained, some deal with the relation between
“typical” schizophrenia and “atypical” psychoses. First of all both are
distinct with respect to the mode of inheritance; whereas schizophrenia is
mostly recessive, the “atypical” psychoses are both dominant and recessive
at about equal rates. Secondly, more important is the demonstration of a
strong homotype tendency as observed in the study of intrafamilial variabil-
ity of hereditary traits; the pedigree of schizophrenia reveals no case of
“atypical” psychoses, and conversely, that of “atypical“ psychoses contain
scarcely any cases of schizophrenia. In order to verify these findings of our
pedigree survey, we have also conducted twin study. Although the number of
twin pairs studied was only 16 (MZ 15, DZ l ) , there was no such case as
that propositus suffering typical schizophrenia and the partner atypical psy-
choses. The result of schizophrenic twin studies made extensively by Inouye
seems to be in general agreement on this point.
From these findings it is clear that the genotype of “atypical” psychoses
is distinct from, and independent of, that of schizophrenia. A relation of
similar sort is seen also between the “atypical” psychoses and M. D. I., al-
though the difference between them is not as clear as that which is seen
with schizophrenia, with respect not only to the mode of inheritance but also
to the intrafamilial variability. However, it is noted here again that the
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“nuclear” group of M. D. I., consisting of relatively pure or uncomplicated

cases, show intrafamilially a tendency to homotype and the incidence of
“atypical” psychoses rarely occur, as has been recently reported by Asam.
In any case, it is reasonably certain from the view point of clinical genetics
that “atypical” psychoses are not mere phenotypical variants of typical
psychoses but they belong to a genetically different category, to an independ-
ent genetic circle.
Mention should be made here regarding the problem of “mixed psychosis”.
As is pointed out earlier, pupils of the Tubingen School such as Gaupp,
Kretschmer, Maur etc. consider that a mixture of genetic dispositions or of
constitution, gives birth to “atypical” psychoses which may appear as a mix-
ture of clinical pictures. Of such conceptions, “mixture of genetic disposi-
tion” seems to emerge from the notion of a so-called intermediary bastard
which assumes production of a pink flower to result from the mating of red
and white flowers. However, such an intermediary bastard can naturally be
brought forth only through the mating of alleles. Therefore, it is highly un-
likely that “atypical” psychoses become manifest as an intermediary bastard
when genetic dispositions of both schizophrenia and M. D. I., mutually not
in the relation of alleles of nature, get into an individual simultaneously by
accident. I n fact, within the scope of our own investigation, it was only
exceptionally seen that “atypical” psychotics showed the taints of schizo-
phrenia and M. D. I. separately on the paternal and maternal sides.
The notion of “mixture of constitution” is based on Kretschmer’s idea of
psychoses and body type. I t claims that “atypical” pictures are brought
about by a combination of psychoses with body type which has basically no
mutual affinity (for example of schizophrenia with the pycnic or of M. D. I.
with the leptosome). The picture of a psychosis is no doubt modified to some
extent, and influenced pathoplastically, by the constitution. However, the
constitution p e r se possess no potential capacity to be a pathogenetic factor;
hence it is too-far-going to regard the disposition of M. D. I. as residing in the
pycnic constitution. We know that many patients of M. D. I. are pycnic, but
surely we do not know the fact that the incidence of M. D. I. is high in
the pycnic.
Finally, “the relation between atypical psychoses and epilepsy” will be
considered. Thus far, attention has been drawn only to the relationship be-
tween schizophrenia and M. D. I., my having disregarded epilepsy for the
sake of simplicity. However, “atypical” psychoses seem to be related also to
epilepsy. As is described above, symptoms of L‘atypical” psychoses are charac-
terized frequently by disturbance of conciousness. I n addition, the onset is
usually acute and clinical course takes an episodic or even ictal form. At the
EEG level also, paroxysmal dysrhythmia has been recorded (Sawa, Y a m a d a ) .
What is of particular importance here, from the view of clinical genetics, is
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that the pedigrees of “atypical” psychoses show a relatively high incidence

of epilepsy as compared with those of schizophrenia or M. D. I. The epileptics
seen in such pedigrees were shown to display relatively frequently psycho-
motor seizure as I had observed in my earlier investigation. Such findings
are compatible with the fact that at least some “atypical” psychotics are in
some way closely related to epilepsy clinico-genetically. From all the foregoing,
it is self-evident that many problems are left unsolved with respect to the
“atypical” psychoses so long as we remain loyal only to the “two-entities-
principle” held hitherto.
Hoche once made a statement of bitter irony that searching for disease
entities in the field of psychoses is something like chasing after phantoms.
We must admit that even today this statement is relevant to some extent.
Even if the genetic independence of “atypical” psychoses can be confirmed,
it does not follow immediately that such a genetic independence also carries
with it the significance of a genetic entity or a disease entity. Common sense
of general human genetics today points to the fact that “atypical” psychoses
are in all the probability heterogenous themselves. I n order to develop the
current classification system of psychoses into a more rational and natural
one, it seems of paramount importance that the independence of “atypical”
psychoses must be recognized and that, at the same time, the labelling of
schizophrenia or M. D. I. should be confined to typical forms as strictly as
possible. Such an endeavor will be an indispensable promise in advancing
our step forwards in the research of the somatic pathology involved therein.

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Hisatoshi Mitsuda,
Dept. of Neuropsychiatry,
Osaka Medical College,
Osaka - Takatsuki,
Japan.