Acta Psychiatr Scand 2010: 122: 173–183
All rights reserved
DOI: 10.1111/j.1600-0447.2010.01589.x
Editorial
The failure of the schizophrenia concept and
the argument for its replacement by
hebephrenia: applying the medical model for
disease recognition
The present DSM and ICD delineations of schizo-
phrenia do not identify homogeneous populations,
and patients with different presentations satisfy the
official criteria. Treatment response, illness course,
and biological findings vary widely, indicating
heterogeneity and not a common pathophysiology.
The DSM ⁄ ICD construct of schizophrenia does
not meet the standard of the medical model. This
model for disease recognition delineates syndromes
and then attempts to validate them by course and
prognosis, response to treatment, and laboratory
tests that ultimately lead to a clear picture of the
pathophysiology and its etiology. This model has
been successfully employed for centuries (1). We
examine the historical record and empirical data
for schizophrenia from this perspective and find
that hebephrenia is a more homogeneous construct
with distinctive and reliably identified clinical
features and better fits the application of the
medical model.
The present situation
Much of the literature on schizophrenia is based on
samples that are heterogeneous in constitution.
The non-specific findings are best summarized by
Tandon et al.: Of 77 variables considered Ôimpor-
tantÕ in schizophrenia, only 23 met the standard of
support from Ôindependent studies with consistent
replication and no contradictory findingsÕ (2). The
annual incidence and prevalence of schizophrenia
varies fivefold across countries. The condition is
highly heritable but with great genetic variability.
Several environmental factors of Ôsmall effectÕ play
a role. Persons with the diagnosis have reduced
brain volume with larger lateral and third ventri-
cles than non-ill comparison groups. Dopamine
agonists exacerbate and dopamine D2 antagonists
ameliorate hallucinations and delusions. The het-
erogeneity in neurobiology, clinical manifestations,
severity, course, and treatment response is great.
 2010 John Wiley & Sons A/S
ACTA PSYCHIATRICA
SCANDINAVICA
No single feature is pathognomonic, and nosologic
Ôboundaries between schizophrenia and other psy-
chiatric disorders are indistinctÕ. The diagnosis is
Ôcharacterized by an admixture of positive, nega-
tive, cognitive, and mood symptomsÕ. Generalized
intellectual impairments occur. ÔThere is a higher
occurrence of obesity and cardiovascular diseaseÕ,
an Ôincreased prevalence of cigarette smoking and
other substance use disordersÕ, and Ôincreased
suicidalityÕ. The onset of psychotic symptoms
usually occurs during adolescence or early child-
hood and is earlier in men. Mortality risk is
doubled. This olio of non-specific observations
does not support a syndrome or a disease.
Genetic studies yield few positive results despite
four decades of effort (3). The most accepted
haplotype or allele for the cell protein dysbindin
accounts for only 2% of the variance in individual
differences in illness presentation (4). In these
investigations, the laboratory procedures are better
detailed and refined than are the descriptions of the
patients studied. Unless a better defined phenotype
is delineated, progress is unlikely in identifying an
endophenotype or gene for schizophrenia.
Traditional subtyping of schizophrenia into
paranoid, disorganized, catatonic, undifferenti-
ated, and residual forms focusing on the most
prominent feature at the time of examination has
not been productive (5, 6). Such sorting is mostly
ignored in clinical practice and research studies.
Many patients with manic depression are para-
noid, catatonic, and behaviourally disorganized,
but few exhibit the signs of emotional blunting,
avolition, and formal thought disorder, the fea-
tures that better define a syndrome and prognosis
(7–12).
The positive–negative symptom dichotomy also
yields muddled results (11–13). Positive and nega-
tive features are frequently mixed. Patients identi-
fied by the presence of positive features also have
negative features, resulting in substantial overlap.
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Editorial
Formal thought disorder (considered a positive
feature) is commonly associated with negative
features, guaranteeing a mixture of symptoms in
many patients (11). The suggestion of dividing
schizophrenia into paranoid and non-paranoid
forms, the latter to include catatonia and hebe-
phrenia, has not been adopted (14, 15).
Present DSM diagnostic criteria guarantee
sample heterogeneity. Should most patients with
hallucinations and delusions and without mood
disorder or identifiable neurologic disease be
labeled schizophrenic? Is schizophrenia a develop-
mental disorder emerging early in life before
psychosis or a disease afflicting any age group? Is
a residual decline in function always present or can
the illness remit? Is a 17-year-old isolating person
with long-standing problems of emotional expres-
sion, volition, and social and motor awkwardness
suffering from the same illness as a 50-year-old
person with adequate premorbid functioning, if
both meet the cross-sectional criteria? A person
with preserved personality and normal emotional
expression but experiencing persistent auditory
hallucinations of first rank (e.g. voices comment-
ing) and a person with catatonia and delusions of
grandeur or disorganized speech both meet the
criteria. Do they suffer from the same illness? Any
two features permit the DSM diagnosis: hallucina-
tions, delusions, ÔdisorganizedÕ speech, Ôdisorga-
nizedÕ behaviour or catatonia, and negative
symptoms. A ÔbizarreÕ delusion (e.g. being con-
trolled by electromagnetic waves) or a hallucina-
tion of sustained voices discussing or commenting
in the third person about the patient is each
sufficient alone; but reliance on a single feature to
diagnose schizophrenia harkens back to Kurt
SchneiderÕs notion of first rank symptoms (16).
These features, while characteristic, are not patho-
gnomonic of schizophrenia, even in the absence of
coarse brain disease, nor do they predict treatment
response or long-term prognosis (11, 17, 18).
These weaknesses in the present formulation of
schizophrenia led to our review.
HebephreniaÕs historical origins and the notion of
dementia praecox
Applying general paresis as a model for a single
disease frequently expressed as several syndromes,
Wilhelm Griesinger (1817–1868) championed the
mid-nineteenth century notion of what was later
called a Ôunitary psychosisÕ – different syndromes
considered stages of a single disease rather than
expressions of different pathophysiologies (19).
Sufferers were believed to pass through stages of
melancholia, mania, and amentia (delirium),
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ending in dementia, although it was understood
that some patients experienced several forms, while
others experienced only one (20). With only one
form of psychosis to consider, the professionÕs
energies were directed at determining etiology, not
classification.
Karl Ludwig Kahlbaum (1828–1899) rejected
the unitary model and re-focused attention on
delineating specific syndromes, seeking to link
psychiatric disorders to biological turning points
in life (21–23). ÔParaphrenia hebeticaÕ was identified
as the psychosis of youth and adolescence. He
coined the term ÔhebephreniaÕ.
Kahlbaum classified behaviour disorders by
symptom patterns and illness course in 1863.
Basing his studies on the 19th centuryÕs tripartite
image of the mind consisting of will, emotion, and
intellect, he recognized an idiopathic progressively
deteriorating condition affecting all spheres that
became KraepelinÕs model for dementia praecox.
He defined a postpubescent circumscribed illness
affecting only emotion that is recognized in todayÕs
mood disorders. Melancholia was included in this
category, but he used the term ÔdysthymiaÕ for it.
The concept of ÔcyclothymiaÕ was introduced as a
low-grade form of what became Ômanic-depressive
illnessÕ. His disorders of intellect (e.g. paranoia,
dementia paranoides) are todayÕs delusional disor-
der, and his disorders of will are exemplified by
catatonia (23).
At the Reimer Sanitarium in Görlitz, Kahlbaum
was joined in 1866 by Ewald Hecker, a junior
clinician (21, 22). In 1874, Kahlbaum published his
monograph on catatonia, separating catatonia and
hebephrenia (24). He presented catatoniaÕs distinc-
tive clinical features, course, and a variety of non-
specific brain autopsy findings as validation for
catatonia being a discrete disease. Catatonia is now
recognized as a syndrome associated with many
conditions (25). A chronology is cited in Table 1.
In 1871, Ewald Hecker (1843–1909) described
ÔhebephreniaÕ as a discrete illness by its symptoms
and course, acknowledging Kahlbaum as the
originator of the concept (26, 27). Hecker wrote:
ÔOf course, not all mental illness appearing at
puberty show the same development. Nearly all
the clinical forms (mania, melancholia, etc.) can be
found in this age group without appearing much
different than they do at other ages. Hebephrenia,
however, stands out as possessing both a specific
course and a distinct symptomatologyÕ. After
presenting a typical case history, he concluded
that ÔHebephrenia… is a disease that always rises in
connection with the development of pubertyÕ (27).
Among his patients, the onset was between ages
18 and 22, the course distinctive, always ending in
 Editorial

Table 1. Errors in schizophrenia formulations

Theorist Formulation Error

Kahlbaum (1874) Catatonia is a distinct disease
Hecker (1871) Hebephrenia is a distinct disease with adolescent onset that affects the
tripartite mind and which ends in dementia
Kraepelin (1896) Dementia praecox is a distinct disease of adolescent onset that includes
catatonia, hebephrenia and several other conditions, each affecting all
domains of the tripartite mind and having a deteriorating course
Bleuler (1911) Dementia praecox is a valid illness best defined by fundamental
dysfunctions of the tripartite mind and not by hallucinations or delusions
Schneider (1929) Certain clinical features are pathognomonic of schizophrenia regardless of
the presence of sufficient signs of mood disorder
DSM-IV Uses a few features to define schizophrenia, but offers no construct for
what kind of illness the condition is; implicitly accepts the first rank
symptom notion
Catatonia is a syndrome not a distinct disease and is associated with
many conditions
The tripartite mind is not a valid construct
The tripartite mind is not a valid notion and the idea that conditions with
the same course share the same pathophysiology is not supported;
catatonia and hebephrenia are not the same disease; without effective
treatments many of his manic-depressive patients appeared demented
and remained chronically ill forcing the incorrect diagnosis of dementia
praecox
KraepelinÕs foundation for schizophrenia was not valid, nor is the notion of
fundamental and accessory features; BleulerÕs terms encourage
idiosyncratic application
There are no pathognomonic features for schizophrenia
The few cross-sectional features are poorly drafted and lead to
heterogeneity of diagnosis; without an overarching construct of the
nature of schizophrenia, any combination of features and type of illness
course is accepted

Ôhebephrenic dementiaÕ; the disease process Ôlimits
further intellectual and emotional development
and produces a particular form of mental disabil-
ityÕ. The disease began with symptoms of melan-
cholia but then psychosis set in. Amidst the
symptoms of melancholia, Ôthese patients often
exhibit an irrepressible impulse to laugh and tell
silly jokesÕ. [Witzelsucht] After discharge from the
hospital, many subjects became vagabonds. Some
philosophized grandly about life and science. Non-
sequiturs and poorly constructed logical sentences
crept into their speech. Some spoke and wrote in
strange jargons. While all the symptoms would not
be present in every patient, Ôthe characteristic
course that is invariably present, the early onset
that is unmistakable, and the peculiarly silly form
of dementia together make for a secure delineation
of this type of illnessÕ. As the illness advanced, the
silliness was replaced by Ôhebephrenic dementiaÕ, a
state that did not approach the dementia of
neurosyphilis (which was well recognized), but
which corresponded to Ôan intermediate level of
mental deteriorationÕ. Hallucinations emerged.
Later, listless apathy replaced the silliness.
The distinctive and historically new element in
HeckerÕs description was the downhill course of an
illness that began as melancholia, rapidly ending in
intellectual deterioration, often over a period of a
few months (26, 27). This concept was quickly
accepted (28–30).
Hebephrenia and catatonia become the core of dementia
praecox
Emil Kraepelin (1856–1926) adopted KahlbaumÕs
classification system: ÔI got the starting point of
the line of thought which in 1896 led to dementia
praecox being regarded as a distinct disease, on the
one hand from the overpowering impression of the
states of dementia quite similar to each other
which developed from the most varied initial
clinical symptoms, on the other hand from the
experience connected with the observations of
Hecker that these peculiar dementias seemed to
stand in near relation to the period of youthÕ (31).
Also: ÔI kept KahlbaumÕs and HeckerÕs ideas in
mind and tried to collect those cases, which
inclined toward dementia as Ômental degeneration
processesÕ. Apart from KahlbaumÕs catatonia,
I differentiated between dementia praecox, which
essentially corresponded with hebephrenia, [our
emphasis] and dementia paranoides with halluci-
nations, which quickly developed into mental
deficiencyÕ (32, 33).
Relying heavily on illness course, Kraepelin
conflated the syndromes of catatonia, paranoia,
and hebephrenia into the single condition: ÔI was
forced to realize that in a frighteningly large
number of patients, who at first seemed to have
the syndrome of mania, melancholia, insanity,
amentia or madness, the syndrome changed fairly
quickly into a typical progressive dementia and in
spite of some differences, the syndromes became
increasingly similar. I soon realized that the
abnormalities at the beginning of the disease had
no decisive importance compared to the course of
the illnessÕ (32).
KraepelinÕs interpretation of dementia as a
necessary outcome compounded a faulty reliance
on catatonia and hebephrenia as one disorder.
Many patients with severe mood disorder appear
demented, and a large number become chronically

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dysfunctional when inadequately treated. Without
effective treatments, severity and chronicity were
common in KraepelinÕs experience, encouraging
him to incorporate manic and melancholic patients,
particularly those with catatonia, into his notion of
dementia praecox.
Outcomes for the different variations of demen-
tia praecox were grim: ÔI must consider excluding
the possibility of any recovery from this illnessÕ.
He reserved the label of hebephrenia only for
those cases in which the presence of ÔagitationÕ
creates Ôthe more unfavorable kinds of prognosesÕ
(34).
The image shifted in successive editions of his
textbook. In the sixth edition, Kraepelin divided
dementia praecox into hebephrenic, catatonic, and
paranoid forms. He retained HeckerÕs ideas of
hebephrenia (35). In 1899, he included de´lire
chronique (36) within dementia praecox. In the
seventh edition (1904), he added all disorders that
led to chronic behavioural and intellectual impair-
ment (37). Otto DiemÕs dementia simplex was
included (38), but the paraphrenias were separated
by delusions without avolition or loss of emotional
expression.
In the eighth edition (1913), Kraepelin introduced
the unfortunate term Ôsilly dementiaÕ (läppische
Verblödung) to characterize hebephrenia. The term
has misled the profession, as ÔsillyÕ did not mean
jocularity but rather a lapse into immaturity in
socialization and thinking with blunting of emo-
tional expression (this was also HeckerÕs under-
standing of the term). Kraepelin added descriptions
of psychosis, highly changeable moods, isolation in
relations with others, and Ôirrational and confusedÕ
actions. Almost all ended in dementia with few
recoveries. The patients with silly dementia (hebe-
phrenia) amounted to thirteen per cent of the cases
of dementia praecox (39). Among other patients
with dementia praecox, Kraepelin recognized that
some recovered (31).
The validity of KraepelinÕs concept of dementia
praecox rested on both catatonia and hebephrenia
being aspects of a single disease with a deteriorat-
ing course. By the end of his career, he had
conceptually merged dementias occurring before
age 50 and all forms of mania, melancholia, and
circular mood disorders into the two ÔfunctionalÕ
psychoses of dementia praecox and manic-depres-
sive insanity. This formulation became the bedrock
of the ICD and DSM classifications. Its weak logic
(all conditions with the same longitudinal course
have similar etiology) and faulty construct (the
effect of the illness on the tripartite mind deter-
mining grouping) shape present-day efforts to
delineate psychiatric illness.
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The transformation of dementia praecox into schizophrenia
Eugen Bleuler (1857–1939), professor of psychiatry
in Zurich, transformed KraepelinÕs concept of
dementia praecox in 1908 renaming it Ôschizophre-
niaÕ (40). Fundamental symptoms were identifiable
in all the patients, with fluctuating accessory
secondary symptoms in some. Kraepelin saw one
disease. Bleuler acknowledged the possibility of
several disorders, with ÔhebephreniaÕ as the princi-
pal form (41). In 1911, Bleuler argued that
dementia was too narrow a view of the condition.
He rejected the notion of Ôpubertal insanityÕ and
said hebephrenia could occur at any age (42). By
1916, Bleuler rejected silly adolescent behaviour as
a criterion for the diagnosis and dismissed the
concept of adolescent insanity inevitably ending in
terminal dementia. He retained the term Ôhebe-
phreniaÕ nevertheless, Ôalthough it no longer applies
to the current conceptÕ (43).
Bleuler accepted and expanded the dementia
praecox notion. He used the never validated idea of
fundamental and accessory features to characterize
the illness. His terminology and constructs were
easily misunderstood. And he had the mischance to
write in German just before two world wars that
resulted in things German being shunned and the
emergence of English as the dominant language of
science and medicine. His writings were not avail-
able in English until 1950 and are not commonly
studied in psychiatric training centers.
The heterogeneity of samples identified by Ble-
ulerÕs approach led to efforts to separate ÔgoodÕ
from ÔbadÕ prognosis schizophrenic patients (44),
the construction of the hybrid schizoaffective
disorder (45), and proposing schizophreniform
disorder (46) and reactive psychosis (47) each of
Ôpsychogenic originÕ with good outcomes. These
constructs are now conflated as brief psychotic
disorder. None has been empirically validated.
Recognizing the heterogeneity among patients
with schizophrenia, some writers sought to recap-
ture the image of hebephrenia. In the 1920s, Karl
Kleist, professor of psychiatry at the University of
Frankfurt, found hebephrenia to be among schizo-
phreniaÕs core symptoms. Kleist wrote of Ôaffective
atrophyÕ in hebephrenia, an illness whose cardinal
symptom is affective flattening, not silliness.
Schizophrenia was not a group of syndromes but
a single disease, the Ôprocess of progressive demen-
tia with deficit symptomsÕ. Hebephrenia and cata-
tonia were its core symptoms (48).
KleistÕs student Karl Leonhard, professor of
psychiatry at the Charité Hospital in East-Berlin,
regarded Ôaffective flatteningÕ and being Ôaffectively
deadenedÕ as the prime characteristic of hebephre-

nia, one of his ÔsystematicÕ psychoses (meaning
non-fluctuating psychoses)Õ (49, 50). While Leon-
hardÕs overall schema has not been accepted, his
description of systematic psychosis of hebephrenia
is consistent with HeckerÕs model.
Kurt Schneider (1887–1967) proposed the notion
of Ôfirst rank symptomsÕ as specific features that, in
the absence of coarse brain disease, were patho-
gnomonic of ÔtrueÕ schizophrenia with its poor
prognosis (51). Although first rank symptoms are
found in mania and melancholia (9, 16, 52, 53) as
well as in schizophrenia, they form the basis for the
DSM Ôcriterion AÕ for schizophrenia. Their occur-
rence is de facto considered pathognomonic as the
schizophrenia diagnosis is permitted if the patient
only exhibits the hearing of sustained voices
discussing or commenting in the third person
about the patient or has a ÔbizarreÕ delusion (e.g.
believing a transmitter has been placed in a tooth
that reveals oneÕs thoughts).
Delineating the modern syndrome of hebephrenia
The features of hebephrenia are displayed in
Table 2. Individual features are not independent.
They have been historically associated with hebe-
phrenia, and the motor and cognitive features are
linked to brain frontal circuitry dysfunction. Loss
of emotional expression, avolition, and indifference
are classic features of the frontal lobe apathetic
syndrome (54, 55). Executive function difficulties
are an accepted aspect of frontal circuitry, the
brain region particularly vulnerable to such envi-
Table 2. The defining features of hebephrenia
Cross-sectional psychopathology
Loss of emotional expression
(monotone, no facial expression, reduced gestures)
Avolition
(no interests or plans, reduced interactions, apathy)
Indifference to present situation
Formal thought disorder
(fluctuating paraphasic speech with agrammatisms, derailments, neologisms, and
non-sequiturs)
Delusions of passivity
(controlled by outside forces, thought insertion and withdrawal)
Complete auditory hallucinations
(sustained, clear voices perceived as originating from outside the patientÕs mind)
Cognitive and motor deficits
Executive function and other cognitive deficits
(Poor sustained attention and working memory, cognitive inflexibility, new learning
problems, difficulties in reasoning, planning and self-monitoring)
Motor disturbances
(Poor sequential and fine hand movement, stereotypy, poor coordination,
past-pointing, dystonia, dyspraxia, poor eye tracking)
Prodrome
Childhood cognitive, emotional, and neuromotor problems; socialization
difficulties; and occasional perceptual distortions
Editorial
ronmental impacts as maternal starvation, viral
infection, and anoxia, experiences reported in
persons who later develop schizophrenia (56, 57).
The diagnosis of hebephrenia requires four ele-
ments: i) loss of emotional expression and avoli-
tion; ii) formal thought disorder (defined as speech
and language difficulties); iii) delusions of passivity
or ÔcompleteÕ auditory hallucinations; and iv)
deficits in executive functioning or motor distur-
bances. Childhood cognitive, emotion, and neuro-
motor problems are commonly present. Catatonia
is not a feature of the designation because it is
independently defined and is effectively treated. Its
presence assumes priority in treatment. Hypoma-
nia, mania, or melancholia in the psychopathology
of the present illness or in the personal history
directs attention to the mood disorders and
precludes the diagnosis of hebephrenia.
The validation of hebephrenia
There is little historical and experimental support
for schizophrenia as a single disease. The historical
record, however, encourages the singular concept
of hebephrenia and indicates its specific criteria.
Cross-sectional image
HeckerÕs model of hebephrenia was of a brain
illness with deficits in emotional expression, voli-
tion, motor regulation, executive functioning,
speech and language, and perceptual integration.
Onset in childhood with emerging neuromotor and
socialization difficulties was followed in adoles-
cence and young adulthood by hallucinations and
other perceptual disturbances and delusions and
then by a persistent but not progressive decline in
cognitive, social, interpersonal, and employment
functioning. The syndrome is recognizable today
(57, 58). The hallmark negative features and formal
thought disorder are found together in 60–80% of
psychotic patients who have neither mood disorder
nor defined neurologic disease (59–62). Carpenter
distinguished such patients as having Ôdeficit syn-
drome schizophreniaÕ (63).
Cluster and factor analytic studies support the
descriptive validity of hebephrenia but find samples
of schizophrenics to be heterogeneous (64–71). In a
latent class analysis of a large proband and relative
sample, Kendler et al. identify Ôclassic schizophre-
niaÕ as characterized by both ÔpositiveÕ and Ônega-
tiveÕ symptoms, chronicity, poor outcome with
deterioration, no depressive or manic symptoms,
low rates of marriage and employment, and a
family illness pattern of little manic depression but
more schizophrenia (72). Oddly, they describe a
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ÔhebephreniaÕ group with a mixed pattern of
psychosis, deterioration, and excited or ÔdeliriousÕ
mania. The former class better fits the hebephrenia
appellation.
While deficit syndrome schizophrenia offers a
consistent picture, other classes of psychotic dis-
orders exhibit class instability (73, 74). Negative
features are stable over time, even between exac-
erbations of psychosis (75). Such patients have
deficits in executive functioning (76), with pro-
longed poor social and work performance, and
failure to respond to modern pharmacotherapy
(77). Formal thought disorder, i.e. aphasic-like
speech and language abnormalities, is also associ-
ated with dysfunction in frontal lobe executive
functions, poor response to pharmacotherapy,
chronic illness course, and similar pathology in
relatives (61, 78–81). HeckerÕs detailed formal
thought disorder was characterized by the speech
patterns of his patients.
Course
Patients with hebephrenia function poorly in their
daily lives (82). Yet, many function well enough to
lead independent existences, work productively,
and contribute to the community. Those with
negative features and early onset of illness are most
likely to become chronically ill (77). Patients with
poor socialization, low libido, psychosocial isola-
tion, and reduced interests before exhibiting psy-
chosis fail to respond to pharmacotherapy, have
persistent symptoms, and chronically function
poorly (77, 83).
HeckerÕs reports of pre-existing childhood dif-
ficulties in hebephrenia are consistent with
modern reports (84–87). Bleuler described
reduced emotional expression and volition,
social and motor awkwardness, and isolation as
prepsychotic features of schizophrenia. About
half the persons diagnosed with schizophrenia
exhibit these childhood behaviours (88, 89). The
traits are modestly heritable (90, 91). Children
who exhibit abnormal emotional expression,
inappropriate social interactions, cognitive inflex-
ibility, and neuromotor problems experience a
characteristic deficit syndrome later in life.
Genetic and intra-uterine factors (e.g. maternal
malnutrition, influenza) (56) contribute to the
condition. The more salient these factors, the
more severe are the childhood abnormalities and
the later psychotic episodes.
While poor neuromotor and social functioning
are associated with hebephrenia, the validating
value of a chronic course after the first episode
is unclear. When patients with schizophrenia,
178
schizoaffective, and manic depression are com-
pared on these criteria, no points of rarity among
the groups are found (92). Long-term outcome is
variable in each group with substantial chronicity
in persistence of symptoms and decline in func-
tioning in those with a deficit syndrome (92–96).
Mortality rates are higher than expected (97, 98).
KraepelinÕs concept of a poor prognosis dementia
praecox and a good prognosis manic depression is
found only at the extremes of a continuum when
the present DSM criteria are applied to patient
populations (99).
While dementia is neither inevitable nor even the
most common outcome of DSM-defined schizo-
phrenia, cognitive difficulties are recognized early,
particularly those consistent with hebephrenia. The
deficits, even when mild, involve cognitive pro-
cesses, with executive functions the most dramat-
ically affected. The deficits are associated with
negative features and formal thought disorder, but
not with hallucinations and delusions (76, 100,
101). Some researchers propose cognitive deficits to
be a diagnostic criterion for schizophrenia, but
while most sufferers have cognitive problems con-
sistent with frontal circuitry dysfunction, these are
not pathognomonic (102).
Synthesizing the attributes of hebephrenia to a
class of patients and then predicting course has not
been often assessed, but several recent efforts
suggest the value of considering psychotic disor-
ders from a non-DSM perspective. Koutsouleris
et al. used MRI-derived neuroanatomic patterns
(consistent with the features described in the next
section) in a small sample to successfully predict
transition to psychosis over a 4-year follow-up in
persons with a positive family history for psycho-
sis. Subjects had clinical features such as previous
prenatal and obstetrical problems, thought inter-
ference, receptive language difficulties, and acous-
tic and visual perceptual disturbances (103).
Ruhrmann et al. describe a clinical model for
predicting future psychosis in a sample of adoles-
cents and young adults also at high risk of
psychosis. Those at greatest risk of future psycho-
sis were likely unmarried or divorced, had obstet-
rical difficulties, and were said to have ÔschizotypalÕ
traits. These patterns are consistent with the image
of hebephrenia (104).
Treatment response
While modern treatments for schizophrenia ame-
liorate symptoms to some degree, none leads to
remission of the illness. Both typical and atypi-
cal antipsychotic drugs and electroconvulsive
therapy (ECT) relieve the ÔpositiveÕ symptoms of

hallucinations and delusions (105). No treatment
effectively limits the ÔnegativeÕ symptoms of apathy,
loss of emotional expression, and avolition (106).
Of the present subtypes of schizophrenia, effec-
tive treatments are known for the catatonic and
paranoid types. Patients with catatonia respond
remarkably well to benzodiazepines and to ECT,
usually fully remitting the signs of catatonia, and
often the associated signs of psychiatric illness (25).
It was the reformulation of catatonia as a syn-
drome and not as a type of schizophrenia that
encouraged clinical trials, which developed its
present successful treatment algorithms (107,
108). Persecutory delusions may be ameliorated
by classical antipsychotic agents and by ECT
although less effectively than the relief afforded
catatonia. Definitive studies of treatment response
in hebephrenia are lacking, but classifying it
separately would encourage such efforts.
Biological findings
We lack a biochemical or physiological marker
identifying hebephrenia. The omission likely
results from such patients being lumped with
others. Neuromotor difficulties consistent with
abnormal development are reported for the deficit
syndrome. Kraepelin described basal ganglia and
cerebellar motor signs in his patients and discussed
a Ôcerebellar formÕ of dementia praecox (109).
Cerebellar volume loss is reported in patients with
schizophrenia exhibiting negative features, even in
never-medicated persons (110). Cerebral cortical
and subcortical abnormalities in structure and
metabolic function are also reported (111–113),
and basal ganglia signs are seen in never-medicated
schizophrenics (114). The abnormalities are asso-
ciated with the negative features of the condition
(115).
Schizophrenic patients with negative features
also exhibit delayed and jerky pursuit eye move-
ments, a difficulty linked to frontal circuitry disease
(116). The difficulties are found early in the
condition (117). The basal ganglia and cerebellum
are part of a motor-cognitive system that also
controls eye movements. All the motor features of
the severe forms of schizophrenia can be under-
stood as expressions of dysfunction in this system
(118).
Genetic findings
Despite the successful definition of the human
genome, progress is poor in identifying putative
genes of vulnerability for schizophrenia. Few
associational strategies yield positive results (4).
Editorial
The genome-wide association studies for schizo-
phrenia reveal no clear findings (3). The results are
confounded by the inclusion of patients with the
schizoaffective designation (6).
The difficulty in detecting the genes for schizo-
phrenia has been attributed to the modest and
polygenic heritability presumed for the condition,
the putative involvement of several different chro-
mosomal sites, and the possibility that the involved
genes may be expressed as a vulnerability toward a
psychotic illness but not for a specific psychotic
condition (119). A more parsimonious criticism of
the search for Ôthe genes of schizophreniaÕ is that
schizophrenia, as now defined, is not a single
disease. The search is analogous to the quixotic
quest for the genes of mental retardation.
Kraepelin reported that 70% of his patients with
dementia praecox had a family history for psycho-
sis (39), and many recent studies report increased
morbid risks for psychosis among first-degree
relatives of psychotic patients and adopted-away
offspring of mothers diagnosed as schizophrenic.
Concordance rates among mono- and dizygotic
twins are elevated, consistent with a genetic trans-
mission (6, 120). A few studies, however, identified
patients by criteria specific for hebephrenia.
Among those that did, the heritability for hebe-
phrenia (identified as ÔcoreÕ or ÔnegativeÕ symptom
schizophrenia) is weak with a possible relationship
between the severest forms and mood disorder
(119, 120). Only additional studies that specifically
define probands by criteria for hebephrenia can
resolve this issue. Unless we isolate hebephrenia as
a syndrome, genetic and biological studies will
remain unproductive.
Conclusions
The historical record does not support schizophre-
nia as a valid diagnostic class. Psychopathologists
from Kahlbaum and Kraepelin to recent writers
conceived a disease that likely does not exist as a
single pathophysiologic process, yet which con-
sumes much psychiatric thinking and resources.
Modern efforts to delineate the notion do not
capture a homogeneous population. Clinicians and
researchers are obliged to rely on vague and non-
specific interview criteria to identify persons who
are ill and who hallucinate or who are delusional,
but who do not cluster into a clear syndrome.
Biological criteria and effective treatments to verify
the diagnosis are lacking. ÔPsychosis without mood
disorder or identified neurologic diseaseÕ would
serve equally well as the present criteria. The only
condition in the schizophrenia story that has not
been rejected by evidence is hebephrenia or Ôcore
179
Editorial
deficit syndromeÕ schizophrenia. It is a recogniz-
able syndrome and should be considered a replace-
ment for the present construct of schizophrenia.
Studies of the psychopathology of psychotic con-
ditions support the hebephrenia construct, but the
validity of the syndrome needs to be prospectively
tested. Resurrecting hebephrenia as a subtype of
schizophrenia will not suffice. Hebephrenia is not a
subtype of schizophrenia. It is schizophrenia. Its
characteristics are well defined and warrant its
replacing the construct of schizophrenia.
Acta Psychiatrica Scandinavica
Michael Alan Taylor, Edward Shorter,
Nutan Atre Vaidya and Max Fink
Invited Guest Editors
Acknowledgements
We are grateful to Susan Bélanger of the University of
Toronto who copy edited the manuscript and organized the
references.
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