REVIEW ARTICLE

Early detection and intervention of

psychosis. A review
RAIMO KR SALOKANGAS, THOMAS H MCGLASHAN

Salokangas RKR, McGlashan TH. Early detection and intervention of psychosis. A review.
Nord J Psychiatry 2008;62:92. Oslo. ISSN 0803-9488.

The vulnerability and hybrid models for the onset of psychosis are presented. Familial liability,
perinatal and developmental factors, and decreased cognitive performance associate with
psychosis in adolescence and young adulthood. Genetic predisposition connected with
behavioural deviances and/or mental symptoms associate with psychotic development so
strongly that monitoring and intervention are indicated. Especially, in families where one or
both parents or other family members are severely mentally ill, early family-centred assessments
and interventions is needed. Together with familial psychosis, deficits in adolescent and young
adult social development indicate thorough assessment, intensive monitoring and often also
preventive interventions. During the prodromal phase of psychosis, patients often display
unspecific symptoms, such as anxiety and depression, personality disorders, abuse of alcohol or
drugs. Social decline, possibly associated with neurocognitive deficits, frequently occurs in the
prodromal phase or in the early course of schizophrenia. Among help-seeking patients,
occurrence of the Basic Symptoms represent the early initial prodromal state, while the late
initial prodome state includes attenuated psychotic symptoms, brief limited intermittent
psychotic symptoms, and a first degree relative with psychotic disorder, or a schizotypal
personality disorder, together with decrease global functioning. These patients suffer also from
other mental symptoms and functional decline, and are clearly in need of psychiatric assessment
and treatment. Intervention trials have shown that patients suffering from prodromal syndromes
can be successfully treated, and onset of psychosis prevented or delayed. However, more large-
scale studies and clinical case descriptions of treatment of patients with sub-threshold psychotic
symptoms are needed.
Early detection, Early intervention, Vulnerability to psychosis, Basic symptoms, Prodomal
syndromes.
Raimo K.R. Salokangas, M.D., Ph.D., M.Sc., Professor of Psychiatry, Department of
Psychiatry, University of Turku and Psychiatric Clinic, Turku University Central Hospital,
Turku Psychiatric Clinic, Turku City Psychiatry, FIN-20520 Turku, Finland, E-mail:
Raimo.K.R.Salokangas@tyks.fi; Accepted 13 June 2007.

chizophrenia is still one of the most severe mental
S illnesses. It begins at a young age, causes delay or
decrease in the individuals psychosocial development, as
well as great human suffering and severe stress to the ill
person him/herself and to his/her caring relatives. The
economic losses, both direct and indirect, caused by
schizophrenia are extensive (1, 2). Since the introduction
of neuroleptic drugs, the proportion of those who
improve has increased, but mortality among schizophre-
nia patients is still about twice as high as in the general
population (3).
Despite the favourable development in psychosocial
treatment methods, the outcome of schizophrenia is still
too often poor and, in some areas, it seems to be worse
than it was some 15 years ago (4). One possible reason
why results in the treatment of schizophrenia are so
limited is that the initiation of adequate treatment is often
delayed. Several studies have demonstrated that the
duration of untreated psychosis is 1
2 years (5
7), that
a great majority of patients suffer for several years from
non-psychotic prodromal symptoms prior to psychotic
symptoms (6) and that psychosocial development starts
to be delayed or to decline already years before the first
psychotic symptoms and the initiation of treatment (8, 9).
Long duration of untreated psychosis is associated with
poorer clinical prognosis and psychosocial functioning

# 2008 Taylor & Francis DOI: 10.1080/08039480801984008


(e.g. 10
15), even when the effect of premorbid adjust-
ment has been taken into account (16). In one study,
temporal grey matter reductions were more marked in
patients with a long duration of illness, suggesting a
progressive pathological process prior to treatment or a
more insidious onset of illness and a later presentation to
services (17).
Thus, it is reasonable to expect that if we can prevent
schizophrenia in its very early phase or before the
occurrence of its psychotic stage, or even if we can
shorten the duration of untreated psychosis, we can
protect the individual from severe suffering and from
clinical and psychosocial consequences. Preventive mea-
sures can be taken during the premorbid period of
illness, i.e. before any symptoms or behavioural deviance
appear (primary prevention), or during the so-called
prodromal phase, i.e. when the first symptoms or signs
indicating vulnerability to schizophrenia have occurred
(secondary prevention). What we need are reliable
methods for detecting vulnerability to psychosis in
general and to schizophrenia specifically, as well as the
timing of onset of psychosis. Thus, we should be able to
detect people who are vulnerable to and at current risk
of psychosis.
Models for the onset of psychosis
Vulnerability model
According to the diathesis or vulnerability stress model,
a certain proportion of vulnerable individuals, when
exposed to stress factors, develop an overt psychosis,
whereas the remaining individuals are either asympto-
matic or exhibit only sub-clinical manifestations (18). In
the vulnerability model developed by Meehl (19),
specific genetic factors are considered to form a neces-
sary aetiological background, with the possible mod-
ulating role of a polygenic background. Environmental
factors can be of direct aetiological significance, usually
designated as formative factors. The vulnerability to
schizophrenia can manifest as cognitive slippage, anhe-
donia, ambivalence and interpersonal aversion resem-
bling Bleulers fundamental symptoms (20). According
to Meehl (19), the schizotypal (schizotaxia) disorders
represent a direct manifestation of vulnerability. Overt
schizophrenic psychosis is a superimposed condition or
decompensation state of the schizotype, caused by
additional environmental and/or pathogenic or normal
maturation of the central nervous system promoting
genetic factors. In this model, the schizotypal state
equals the premorbid state of schizophrenia.
Hybrid model
Yung and McGorry (21) have proposed a hybrid or
interactive model of prodromal changes. Instead of
following one certain pattern of changes, psychotic
prodromes can be a combination of many patterns,
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
and people can move in and out of symptomatic periods
of both the non-specific type and the attenuated
psychosis type. Both types of symptoms may precede
psychosis and either may occur primarily. Reactive
symptoms, such as anxiety, can occur in response to
prodromal and psychotic symptoms, and behavioural
changes may occur in response to any of these three
groups of symptoms. The hybrid/interactive model is
more or less an equilibrium model in which vulnerable
individuals have possibilities to move in any direction
between an asymptomatic and symptomatic state. It is
less specific than other models, which are more or less
uni-directional, indicating an evolution from an asymp-
tomatic state via certain specific stages to the frankly
psychotic outcome. From the theoretical and practical
point of view, the hybrid/interactive prodromal model
seems to offer important possibilities, although the term
prodrome in this connection may be misleading
because these symptoms do not always lead to psychosis.
Therefore, the authors have suggested the term at-risk
mental state (22).
Premorbid period; early risk factors of psychosis
Familial liability
Family, twin and adoption studies strongly suggest that
genetic transmission accounts for most of the familial
aggregation in schizophrenia (23, 24). About 80% of the
variance in susceptibility to the disorder is explained by
genetic factors (25). The risk is about 10 times higher if a
first-degree relative is ill, and decreases from close to
more distant relatives (26). In the Finnish Adoptive
Family Study of Schizophrenia (27), the relative risk of
index adoptees of schizophrenia spectrum disorders was
5.2, and for all psychotic disorders 4.4 times higher than
for control adoptees. There was also a strong interaction
between genetic disposition and family atmosphere. The
risk of schizophrenia spectrum disorders, compared with
genetically non-predisposed adoptees (4.8% and 5.3%,
respectively), was not increased in genetically predis-
posed subjects if they were reared in families with a
favourable atmosphere (5.8%), while in adoptees reared
in an unfavourable family atmosphere, the risk was
strongly increased (36.8%). In their later study, the high-
risk group was found to be distinguishable from the low-
risk group on the basis of deviant scores on the Hostility,
Hypomania and Lie scales in the Minnesota Multiphasic
Personality Inventory, suggesting that these scales may
measure genetic vulnerability, and may also possibly be
indicative of psychometric deviance predicting future
onset of schizophrenia (28).
If the familial risk is associated with symptomatology
or behavioural problems, the risk of psychosis is clearly
increased. The Copenhagen High Risk for Schizophre-
nia Project showed that pre-schizophrenic children had
more psychic symptoms and behavioural problems, as
93
RKR SALOKANGAS, TH MCGLASHAN
well as thought disorders, eccentricity and defective
emotional rapport than their controls (18, 29), and
teachers were able to correctly predict 35% of students
who developed schizophrenia during the following
25 years (30).
In the Edinburgh High Risk Study of 163 young high-
risk adults, 20 developed schizophrenia within 2 years.
They were more isolated and suffered more from partial
psychotic symptoms. The entire high-risk sample dif-
fered from the control group on developmental and
neuropsychological variables. At entry, when still well,
high-risk individuals who subsequently became ill scored
significantly higher on situational anxiety, nervous handle that they do not offer a feasible measure for
tension, depression, changed perception and hal- primary prevention of schizophrenia (48, 49). Addition-
lucinations than those remaining well and normal
controls, who did not differ. With illness onset, affective
symptomatology remained high but essentially stable.
The finding suggests that the genetic component of
schizophrenia affects many more individuals than will
develop the illness and partial impairment can be found
in such individuals. In genetically predisposed indivi-
duals, affective and perceptual disorders are prominent
before any behavioural or subjective change that usually
characterizes the shift to schizophrenic prodrome
or active illness (31, 32). In their review, Owens &
Johnstone summarize that familial high-risk studies have
established multiple biological markers relating to neu-
romotor development and cognition, especially aspects
of memory/learning. Although most of them are prob-
ably not specific, they support a neurodevelopmental
hypothesis. However, pre-illness, non-specific affective
symptomatology may have greater predictive power than
most psychotic phenomena (33).
In a study of 35 adolescents and young-adult first-
degree relatives of patients with schizophrenia or schi-
zoaffective disorder and 55 control subjects, high-risk
participants older than 17 years showed more physical
anhedonia, less positive involvement with peers, and
more problems with peers, siblings, and the opposite sex.
Older high-risk individuals were also less cooperative,
less self-directed and less reward-dependent. Problems
with peers and the opposite sex, as well as reward
dependence, were related linearly associated with genetic
loading (34). At population level, the predictive power of
childhood risk factors has been low (35, 36).
Perinatal and developmental risk factors
Numerous studies indicate that many people who
develop schizophrenia are exposed to a variety of
stressful perinatal events such as extreme maternal stress,
maternal antenatal depression, prenatal exposure to
influenza and other viral infection, maternal immune
response, living in an urban area, obstetrical complica-
tions, poor maternal nutrition, famine, and general
foetal distress as signalled by foetal hypoxia (37). In
94
two large birth cohort studies (38, 39), schizophrenia was
positively associated with multiparity, maternal bleeding
during pregnancy and birth in late winter, as well as with
pre-eclampsia after control for potentially confounding
factors. However, associations were small and a few
specific pregnancy and perinatal factors were associated
with subsequent development of schizophrenia. There
are also more psychoses and psychotic symptoms among
people living in big cities (40
42), and among immi-
grants (43
46). However, the predictive power of these
early risk factors of psychosis is low [e.g. birth complica-
tions, see Geddes & Lawrie (47)], and so difficult to
ally, obstetric complications seem not to be associated
with later development of psychosis in the ultra-high-
risk subjects (50). The same is true for minor physical
anomalies, neurological abnormalities and abnormalities
detected in motor co-ordination (37). In cohort studies,
schizophrenics have reached all the milestones of sitting,
standing, walking and talking later than controls (35,
51), and their performance in sports and handicrafts
during elementary school has been poorer (52). More-
over, central nervous system infections during childhood
carry an increased risk of adult-onset schizophrenia
(OR 4.8) or other psychoses (OR 6.9) (53). Because
of the long risk period and the low risk level, the value of
these markers in predicting occurrence of psychosis at
clinical level is questionable.
Cognitive performance
Population-based studies have shown that a low intelli-
gence quotient (IQ) is a risk factor for schizophrenia and
other psychoses, but its positive predictive value has
been low (54). However, healthy male draftees who were
later hospitalized for schizophrenia had deficits in social
functioning, organizational ability and intellectual func-
tioning. In a matched group of patients and non-
patients, the positive predictive value of the prediction
model was 72%, while in another sample of draftees, the
model yielded a positive predictive value of 43% (9).
Thus, together with behavioural dysfunction, low in-
tellectual performance may be of value in detecting
persons vulnerable to schizophrenia and other psy-
choses. In another study of male conscripts, poor
intellectual performance at 18 years associated with
early-onset psychotic disorder, particularly with schizo-
phrenia (55).
Premorbid risk factors as a whole
To summarize, pre-, peri- and postnatal complications
and childhood premorbid developmental or behavioural
deviances alone, although they have statistically signifi-
cant associations with adulthood schizophrenia or other
psychoses, are not specific enough for reliably predicting
NORD J PSYCHIATRYVOL 62 NO 2 2008

the onset of psychosis. The period from the occurrence
of these risk markers and onset of psychosis is also very
long. For these reasons, preventive interventions based
on the occurrence of some premorbid risk factor seem
not to be feasible. Of the premorbid risk factors, genetic
predisposition connected with behavioural deviances
and/or mental symptoms seems to predict psychotic
development so strongly that monitoring and possibly
also intervention are indicated. We need to have more
specific information from the immediate period preced-
ing the onset of psychosis.
Prodromal period; clinical vulnerability markers
Prodromal symptoms and disorders
Symptoms preceding the outburst of manifest psychosis
are called prodromal symptoms. In clinical practice, the
prodrome of psychosis is a retrospective concept refer-
ring mostly to the period from the first noticeable
symptoms or unusual experiences to the first prominent
psychotic symptoms (12, 21, 56). At the early stage,
when a subject has psychotic-like experiences or isolated
psychotic symptoms, it would be better to speak about
vulnerability to psychosis. In the case when psychotic
symptoms have reached a certain level of severity or
otherwise fulfil the criteria of a prodromal syndrome, the
subject is at current or high risk of psychosis.
Schizophrenia is often preceded by milder psychiatric
diagnoses. According to Meehl (57), the schizotypal
disorders represent a direct manifestation of vulnerabil-
ity, a primary or fundamental disorder in schizophrenia.
These types of disorders are rather stable, however.
Hoch et al. (58) found that 20% of the patients suffering
from pseudoneurotic schizophrenia became schizophre-
nic. In two follow-up studies, out of 39 patients
diagnosed as having pseudoneurotic schizophrenia at
first admission, six or 15.4% became psychotic (four or
10.2% schizophrenic) during the 8-year follow-up (59,
60). In a recent intervention study of patients with
schizotypal disorder, conversion rates to psychosis were
much higher, being, during the first year, three out of 37
(8.1%) among patients with integrated treatment, and 10
out of 30 (33.3%) among patients with standard treat-
ment, while at the end of the second year, the corre-
sponding figures were 9/26 (25.0%) and 14/29 (48.3%)
(61).
In a sample of Swedish draftees, there was an
increased risk of schizophrenia in those with ICD-8
diagnoses of neurosis (OR 4.6), personality disorder
(OR 8.2), alcohol abuse (OR 5.5) or substance abuse
(OR 14.0) at age 18. Of those who developed schizo-
phrenia, 38% received a diagnosis of non-psychotic
psychiatric disorder at age 18. Personality factors could
reflect an underlying vulnerability to schizophrenia,
while other diagnoses occurring before schizophrenia
may reflect a prodromal phase of the illness (62). In
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
another study of male draftees (63), 1.03% of the
adolescents assigned a non-psychotic, non-major affec-
tive psychiatric diagnosis, compared with 0.23% of the
adolescents without any psychiatric diagnosis, were later
hospitalized for schizophrenia. Of the patients with
schizophrenia, 26.8%, compared with only 7.4% in the
general population, had been assigned a non-psychotic,
non-major affective psychiatric diagnosis in adolescence
(OR 4.5), ranging from OR 21.5 for schizophrenia
spectrum personality disorders to OR 3.6 for neurosis.
These results reflect the relatively common finding of
impaired functioning in patients later hospitalized for
schizophrenia, and the relatively low power of these
disorders in predicting schizophrenia. Similar results
were also obtained in from female draftees with self-
reported mental difficulties (64).
In clinical retrospective first-episode studies, the
average duration of symptoms before the first admission
has varied between 1 and 2 years (12, 56, 60, 65). Hafner
and co-workers (66) found that, on average, negative
symptoms dated back to 6.5 years before the first
admission, and the earliest positive symptoms reported
dated back on average about 2 years (maximum
24 years). In about 70% of cases, negative symptoms
developed before positive ones, in 20% they developed at
the same time, and only in 10% did positive symptoms
develop before negative symptoms. Depressive symp-
toms, which formed the earliest symptom category,
occurred on average more than 5 years prior to first
admission (67). Recently, Hafner et al. (68) have shown
that during the period before the first hospitalization,
the symptom profiles of patients with schizophrenia and
major depression were very similar. The only significant
difference concerned positive psychotic symptoms just
before the first admission. Depression can be seen as an
integral part of the disease process leading to psychosis
(69).
SYMPTOM PROFILE
The symptom profile of prodromals is extremely vari-
able. The most frequent features such as disturbances of
attention or inability to concentrate, apathy or loss of
drive, depression, sleep disturbances, anxiety, social
withdrawal, suspiciousness, deterioration in school,
work or other functioning, anger or irritability, are
clearly non-specific to schizophrenia and are very often
seen, for example, in the early phase of depression (21).
The prodrome to schizophrenia usually begins with non-
specific, neurotic-like symptoms, followed by more
specific prepsychotic symptoms, eventually leading to
frank psychosis. Subjective symptoms are accompanied
by deterioration in role functioning and other beha-
vioural changes. However, Chapman (70) proposed that
specific subjective changes occur first and are followed,
as a reaction to these, by neurotic symptoms and
95
RKR SALOKANGAS, TH MCGLASHAN
behavioural changes. The fundamental early symptoms
of schizophrenia are disturbances of attention caused by
the inability of the central nervous system to filter out
irrelevant stimuli and to concentrate selectively on
relevant information only. Persons may subjectively
experience disturbances of attention, perception,
thought, speech and motility before overt signs of
established disease appear, and long before the person
actually complains of symptoms to others.
DOPAMINE SENSITIVITY
Following the modern dopamine theory, Kapur (71) has
recently suggested that a central role of dopamine is to
mediate the salience of environmental events and
internal representations. In psychosis, there is a dysre-
gulated dopamine transmission that leads to stimulus-
independent release of dopamine and to aberrant
assignment of salience to external objects and internal
representations. In other words, a dysregulated, hyper-
dopaminergic state, at brain level, leads to an aberrant
assignment of salience to the elements of ones experi-
ence, at mind level. Before psychosis, subjects experi-
ence a novel and perplexing stage marked by the
exaggerated importance of certain perceptions and ideas
which they try to explain. Delusions are cognitive efforts
by the patient to make sense of these aberrantly salient
experiences, whereas hallucinations reflect direct experi-
ence of the aberrant salience of internal representations.
Once the subject arrives at such an explanation, it
provides an insight relief or psychotic insight. function connected with familial risk. It seems, however,
Selten & Cantor-Graae (72) have emphasized the
significance of environmental factors. They suggest
that chronic and long-term experience of social defeat
may increase the risk of schizophrenia by sensitization of
the mesolimbic dopamine system and/or increasing the
baseline activity of this system.
PSYCHOTIC SYMPTOMS IN THE GENERAL
POPULATION
At the level of the general population, the specificity and
the predictive value of prodromal features can be
questioned, as they are so prevalent especially in
adolescents (40). McGorry et al. (73) found that among
young students, 75% indicated the presence of one or
more, and 50% two or more of the DSM-III-R defined
nine prodromal symptoms. The most prevalent symp-
toms were magical ideation and unusual perceptual
experiences. If only the subjects who had had these
features during the previous 5 years were included,
around 10
15% belonged to the group with prodromal
features. At the community level, interventions based on
occurrence of psychotic symptoms seem to be question-
able (74). However, later studies have showed rather
strong associations between occurrence of psychotic
symptoms and psychotic disorders. In a prospective
96
birth cohort study (75, 76), self-reported psychotic
symptoms at age 11 years predicted a very high risk of
a schizophreniform diagnosis at age 26 years (OR 
16.4) suggesting continuity of psychotic symptoms
from childhood to adulthood. In a long-term follow-
up study of a general population sample, prevalence of
continuous psychotic experiences was 5.8% for schizo-
phrenia nuclear symptoms, 2.8% for schizotypal signs
and 1.7% for both dimensions simultaneously (77).
Delusional ideations and hallucinatory experiences
seems to be more prevalent among patients with
anxiety/depression than normal controls (78). Thus, in
mental healthcare users, self-reported psychotic experi-
ences may give useful information for preventive inter-
ventions (74).
Decrease in functioning
Social decline, possibly associated with neurocognitive
deficits, frequently occurs in the premorbid phase or in
the early course of schizophrenia (8, 9, 79
82). The
premorbid psychosocial dysfunction is usually mild in
childhood but more manifest and progressive in the
adolescence of persons who later develop schizophrenia
(83, 84). A significant decrease in psychosocial function-
ing, especially in young people, may be the first sign of
severe mental illness and deserves attention in the
assessment of possible prodromal states. The assessment
scales developed for detecting persons at high risk
of psychosis (21, 85), include the criterion, decreased
that decline in functioning is an independent but
unspecific risk factor, which may increase conversion
to psychosis without familial risk, i.e. with psychotic-like
experiences. Quality of life and everyday functioning in
patients at risk of psychosis are lower than in patients
without risk of psychosis, and nearly as low as patients
with psychosis (86). Yung et al. (87) showed that bizarre
experiences and persecutory ideas of psychotic-like
experiences were associated with distress, depression,
and poor functioning, and suggested that these may be
more malignant forms of psychotic symptoms, as they
are associated with current disability, and may confer
increased risk of development of full-blown psychotic
disorder. Preliminary findings also suggest that in ultra-
high-risk patients, early age of onset of psychiatric
symptoms and low functioning at baseline significantly
predict conversion to psychosis (87
89).
Neuropsychological findings
Schizophrenic patients exhibit prominent impairments
in attention, memory and executive functions, indicating
impairments in frontal and medial temporal cerebral
regions (90). These deficits, preceding the onset of
psychotic symptoms for many years (91), indicate
deterioration at some higher level of functioning and
NORD J PSYCHIATRYVOL 62 NO 2 2008

then stabilization. Patients with schizotypal personality
disorder are also impaired in their attentional function-
ing, and they display deficits that are similar to the
pattern characterising schizophrenic patients (92).
Relatives of schizophrenia patients have also shown
impaired performance in neurocognitive tests, especially
in attention, executive functions, working memory and
verbal learning tests (93
101). Cornblatt (102) has
suggested that attention deficits detected at age 12
persist and can predict the occurrence of psychosis
with high specificity.
Healthy relatives of patients with schizophrenia have
produced a considerable number of the Rorschach
Schizophrenia signs (103), indicating genetic vulner- Test, although greater in ultra-high-risk subjects than in
ability to psychotic reactions. Similarly, the Ego Impair-
ment Index (EII), a Rorschach-derived measure,
increased stepwise in a continuum from normal controls,
to first-degree relatives of schizophrenia, students with
elevation in perceptual aberrations, magical ideation and
physical anhedonia, schizotypal personality disorder,
outpatients with schizophrenia and finally inpatients
with schizophrenia (104). Among psychiatric adolescent
patients, in patients with prodromal symptoms, EII was
at the same level as in patients with psychotic diagnosis
but clearly at a higher level than in patients with non-
psychotic diagnosis (105). In another study, first-degree
relatives without a lifetime diagnosis differed from
normal controls in a similar but less marked way to
schizophrenic patients on the Bonn Scale for Assessment
of Basic Symptoms (106), and there is some evidence
that these self-experienced cognitive deficits also predict
the occurrence of schizophrenic psychosis (107).
Compared with healthy controls, young people with
prodromal symptoms have extensive deficits in their
neuropsychological performance, especially on measures
of attention, memory and executive functions (108
110).
Young patients presently at ultra-high-risk of psychosis
demonstrated a significant reduction in current IQ, smell
identification, attention, memory and executive function
compared to controls, and 32% of them converted to
psychosis within 8 months (111, 112). In a later study of
ultra-high-risk patients, there was a significant impair-
ment in olfactory identification ability in those of the
ultra-high-risk group that later developed a schizophre-
nia spectrum disorder but not in those who did not
become psychotic (113). In a study of the RAP
programme, 62 adolescent patients were divided into
three clinical high-risk groups, characterized by 1)
negative and non-specific symptoms (CHR ), 2) emer-
ging attenuated positive symptoms of moderate intensity
(CHRmod), and 3) severe attenuated positive symp-
toms (CHRsev). In the Continuous Performance Test,
there was no significant difference between the groups,
while Perservative Errors in the Wisconsin Card Sorting
Test were in the CHRsev patients significantly more
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
frequent than in other groups, and during an approxi-
mately 1-year follow-up, seven (47%) out of 15 CHR
sev patients converted to psychosis, while the corre-
sponding figure in the CHRmod group was one (11%)
out of 19, and in the CHR  group none out of 14 (114).
In their later study, the CHR adolescents showed deficits
in spatial WM compared with controls (115). In another
study of ultra-high-risk individuals, participants showed
significant deficits in speed of processing, verbal learning
and memory, and motor speed. Poorer verbal learning
and memory performance were significantly associated
with poorer social functioning (116). Impaired sustained
attention, measured by the Continuous Performance
healthy controls, did not predict transition to psychosis
in an ultra-high-risk group (117). Other studies have
suggested greater (spatial) verbal memory impairment in
high-risk subjects who go on to develop schizophrenia
(118, 119). Visuospatial processing impairment and
logical memory deficits seem to become apparent before
the full expression of psychosis in ultra-high-risk
patients. Cognitive performance on more complex tasks
requiring rapid registration and efficient recall may be
compromised before development of first-episode psy-
chosis (120).
To sum up, on neuropsychological tests, healthy
relatives of schizophrenia patients and young people
with prodromal symptoms seems to exhibit greater
deficits than controls, but smaller than psychotic
patients. Deficits in attention, working memory, and in
executive functioning have been found most frequently.
These deficits appear to be associated with functional
disability in a manner parallel to that observed in
patients with established psychotic illness (115). Of these
cognitive deficits, particularly deficits in spatial working
memory, olfactory identification ability and certain
perceptional deviances seem to have predictive power
for developing psychosis, while impaired olfactory
identification ability seems to specifically predict the
occurrence of schizophrenia (121).
Addictive behaviour
Addictive behaviour also seems to be prevalent in the
prodromal phase of psychosis. Among Swedish army
recruits, those consuming cannabis on more than 15
occasions were six times more likely to develop schizo-
phrenia than less frequent users and non-users (122). In
five prospective population studies, cannabis use was
estimated to confer an overall twofold increase in the
relative risk of later schizophrenia (123).
Among a young population, after adjustment for
several possible confounding factors, cannabis use at
baseline increased the cumulative incidence of psychotic
symptoms at follow-up 4 years later (OR 1.67). The
effect of cannabis use was much stronger in those with
97
RKR SALOKANGAS, TH MCGLASHAN
any predisposition to psychosis at baseline (23.8% vs.
5.6%) than in those without. There was a dose
response
relation with increasing frequency of cannabis use, but
predisposition to psychosis at baseline did not signifi-
cantly predict cannabis use 4 years later (124). Thus,
cannabis use seems to moderately increase the risk of
psychotic symptoms in young people but has a much
stronger effect in those with evidence of predisposition
to psychosis. Cannabis smokers with polymorphism in
the catechol-O-methyltransferase gene are at increased
risk of psychosis (125).
Alcohol abuse also seems to be a risk factor for
psychosis. In schizophrenia, the rates of alcohol and
drug abuse were twice the rates in the general population.
Alcohol abuse usually started during the prodromal
phase, but before the first positive symptoms, while drug
abuse emerged before the first symptoms in one third,
simultaneously with them in another third, and during
the prodromal phase in the last third of patients (126).
Prodromal syndromes
Early initial prodromal state; basic symptoms
In the early 1960s, Huber studied subjective anomalous
experiences in patients with schizophrenia at various
stages of the illness, and developed a concept of basic
symptoms. These symptoms can become manifest either
in prodromes that continuously develop into psychosis
or in outpost syndromes, which resolve spontaneously
without immediately progressing to psychosis (127
130).
The Bonn Scale for the Assessment of Basic Symptoms
(BSABS) (131) includes more than a hundred detailed
descriptions and questions on subjective impairments in
cognitive, emotional, motor and autonomic functioning,
bodily sensation, energy, external perception and toler-
ance to normal stress, and represents the immediate
experience of a special vulnerability to schizophrenia
In their prospective study dealing with patients with
neurotic or personality disorders, Klosterkotter et al.
(132) followed 110 patients with and 50 without initial
prodromal symptoms, assessed by the BSABS, for an
average of 9.6 years, and found that 79 (49.4%) of the
160 patients developed schizophrenia; 77 (70.0%) pa-
tients with and two (4.0%) patients without initial
prodromal symptoms. The absence of initial prodromal
symptoms excluded a subsequent schizophrenia with
a probability of 96% (sensitivity: 0.98; false-negative
predictions: 1.3%), whereas their presence predicted
schizophrenia with a probability of 70% (specificity:
0.59; false-positive predictions: 20%). Recently, Bechdolf
et al. (133) reported that in a comparison group with
basic symptoms and receiving supportive counselling the
conversion rate to schizophrenia was 12.1% in
12 months. Roughly calculated, the conversion rate for
patients with basic symptoms is about 10% in
12 months.
98
Late initial prodrome state; prodromal syndrome
THE CAARMS
Another approach to the assessment of clinical vulner-
ability to psychosis is defining prodromal syndromes.
Using a combination of symptoms, changes in function-
ing and family history, an Australian group developed
an instrument called the Comprehensive Assessment of
At-Risk Mental States or CAARMS (134) for diagnos-
ing young prodromal people (21, 135, 136). The
CAARMS includes three states of prodrome:
1) Patients with attenuated psychotic symptoms have
at least one of the following symptoms: ideas of
reference, odd beliefs or magical thinking, percep-
tual disturbances, odd thinking and speech, para-
noid ideation and odd behaviour and appearance as
defined in DSM-IV schizotypal personality disor-
der.
2) Patients with transient psychosis demonstrated brief
limited intermittent psychotic symptoms (BLIPS),
including hallucinations, delusions or disorganized
speech*severity of symptoms assessed by the Brief
Psychiatric Rating Scale and the Comprehensive
Assessment of Symptoms and History rating
scale*for less than 1 week before spontaneous
resolution.
3) The definition of the third group includes (a) a first
degree relative with a history of any psychotic
disorder, or a schizotypal personality disorder, as
defined by DSM-IV, and (b) any change in mental
state or functioning, which results in a loss of
30 points or more on the Global Assessment of
Functioning (GAF).
In addition, for all groups, the risk factor of age between
16 and 30, the period of maximum risk of becoming
psychotic, was added.
In a follow-up, the Australian group observed a 40%
annual rate of conversion to psychosis among young
people who attended the Personal Assessment and Crisis
Evaluation (PACE) clinic and who were identified as
prodromals with the CAARMS criteria (135). However,
in a later sample, the transition to psychosis rate has
been lower (137). In a sample of 150 non-psychotic help-
seekers, the CAARMS has displayed good to excellent
concurrent, discriminant and predictive validity, and
excellent inter-rater reliability (138).
THE SIPS/SOPS
The Yale group, McGlashan et al. (85, 139), have
developed an instrument to assess the prodrome called
The Scale of Prodromal Symptoms or SOPS, and a
structured interview for rating the SOPS and other
information essential for categorizing the prodrome
called the Structured Interview for Prodromal Symptoms
NORD J PSYCHIATRYVOL 62 NO 2 2008

or SIPS. The SOPS consists of five Positive Symptom
items, six Negative items, four Disorganization Symptom
items, and four General Symptom items. Each item has a
severity scale rating from 0 to 6 (140). Patients are also
rated according to their Global Assessment of Function-
ing (GAF) rating, a Schizotypal Personality Disorder
rating, and family history data. The SOPS/SIPS attempts
to be both categorical and dimensional, allowing a
categorization of the prodrome according to the Austra-
lian sub-types, as well as being a measure of severity for
longitudinal assessment of course and treatment re-
sponse.
In a follow-up study of 29 prodromal patients,
agreement in differentiating prodromal from non-pro-
dromal patients was 93%, and the conversion rate to
schizophrenic psychosis was 46% at 6 months, and 54%
at 12 months (139). In another sample, the 1-year-
conversion rate of psychosis in the SIPS-positive patients
was 45.7% (141). Sensitivity of the SIPS instrument was
100%, specificity 74% and positive predictive power 50%
(142).
To distinguish them from the risk stage defined by
basic symptoms, patients fulfilling the prodrome criteria
of the CAARMS or SIPS/SOPS have been termed being
in an at-risk-mental-state (ARMS) or at ultra-high-risk
of psychosis (UHR-P). The conversion rate of psychosis
in ARMS patients has proved to be high. Schulze-Lutter
(List of studies concerning conversion of ultra-high-risk
patients to psychosis; personal communication, 2005)
has calculated from nine studies (50, 139, 143
149) that
the average conversion rate for ultra-high-risk patients
during 12 months is 38.2%.
Interventions for preventing psychosis
Preventive intervention in patients with psychotic-like
symptoms has been strongly debated (150
153). Most
authors consider that prevention is possible, and it is
ethically defensible to treat patients at high risk of
psychosis, although also the possibility of population
prevention strategies has been suggested (154). Several
studies have shown that patients at high risk of psychosis
suffer from many mental symptoms, and are reliably
diagnosed. They are cognitively and functionally im-
paired and clearly at risk of becoming overtly psychotic.
Finally, according to their definition, these patients are
seeking treatment and thus need to be helped (141). The
key question is what kind of intervention should be given
to patients at risk of psychosis, and how should we
define standards of care for such patients.
Neuroleptic treatment
So far, two randomized controlled drug-treatment trials
for prevention of onset of psychosis in UHR patients
have been reported. The first trial dealt with 59 ultra-
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
high-risk patients and was carried out in the PACE
(Personal Assessment and Crisis Evaluation) clinic by
McGorry et al. (145). The study compared specific
intervention, comprising low-dose risperidone (mean
1.3 mg/day) and cognitive
behavioural therapy (31 pa-
tients), with a need-based treatment (28 patients) for a
period of 6 months followed by another 6-month
observation period. After the 6-month intervention
period, three (9.7%) patients in the specific intervention
group had converted to psychosis, while the correspond-
ing figure in the need-base treatment group was 10
(35.7%; P 0.03). After the observation period, this
difference was no longer significant (P 0.24) because of
three new psychoses in the specific intervention group.
However, no new psychoses occurred among those in the
specific intervention group who continued medication. It
is difficult to say to what extent the efficacy of the
specific intervention was due to risperidone or cognitive

behavioural therapy. The results from the observation
period suggest that drug treatment could prevent
psychotic progression. Administration of low-dose ris-
peridone was well tolerated, with minimal adverse
effects. Of the 16 psychoses occurring during the
12 months, seven were schizophrenic or schizoaffective,
three major depressive, three bipolar, one psychotic
disorder NOS, one brief psychotic disorder and one
substance-induced psychotic disorder. Thus, about two-
fifths of the psychoses were schizophrenic and another
two-fifths affective psychoses (Lisa Phillips, 2002, per-
sonal communication).
In a placebo-controlled double-blind trial reported by
McGlashan et al. (147, 155), 60 ultra-high-risk patients
were treated with olanzapine (31 patients) or placebo (29
patients) for a year and followed for another year. In the
placebo group, 11 (37.9%) converted to psychosis, while
the corresponding figure in the olanzapine group was 5
(16.1%; P 0.08). The psychoses were either schizo-
phreniform or non-specific psychoses. It is noteworthy
that all psychoses in the olanzapine group occurred
within the first 4 weeks of the clinical trial when the daily
doses of olanzapine were low. Post-hoc analyses revealed
that by week 8, prodromal symptoms had decreased
more in the olanzapine group (mean dose 8 mg/day)
than in the placebo group (PB0.05) (156). During
this period, there was a marked weight gain in the
olanzapine group (8.79 kg) vs. the placebo group
(0.30 kg) (PB0.001).
In a German controlled multicentre open-label study,
patients with early prodromal symptoms were treated
with amisulpride. According to the results, in the
patients receiving drug treatment, attenuated psychotic
and negative symptoms decreased and functioning
increased more than in the control patients (157, 158).
99
RKR SALOKANGAS, TH MCGLASHAN
In an open study, 52 persons who fulfilled the PACE
criteria of ultra-high risk of psychosis received low-dose
antipsychotic treatment (haloperidol or risperidone, 0.5

2 mg/day) for 6 months together with psychoeducation
and supportive psychotherapy. Participants were as-
sessed at baseline, 6 months and 12 months. Forty-two
persons completed the study, of whom three (7.1%)
developed schizophrenia during the 6-month treatment
period, with no new psychotic episodes being observed
during the 6-month follow-up period. Side-effects were
mild and transient, appearing in the first 4 weeks of
treatment, and the participants were satisfied with the
treatment. The low conversion rate suggested that low-
dose antipsychotic treatment is effective in the preven-
tion or delay of psychosis (159). In another open study,
ultra-high-risk patients received 5
15 mg aripiprazole.
Of 11 patients who completed on average 52 days on the
drug, none developed psychosis (160). There are some
case studies on patients with prodromal symptoms
treated successfully with antipsychotic medication (161,
162).
Cognitive psychotherapy
Two controlled intervention studies have been carried
out on the effect of cognitive psychotherapy. The first
controlled trial compared cognitive therapy with treat-
ment as usual in 58 ultra-high-risk patients. Therapy was
provided for 6 months and all patients were monitored
for 12 months (163). About 70% of both groups
completed the therapy. Conversion to psychosis was
assessed by PANSS scores, antipsychotic medication and
a DSM-IV psychosis diagnosis. According to all these
criteria, two (6%) of the cognitive therapy group
progressed to psychosis, while in the comparison group,
between five and seven, depending on the criteria,
became psychotic. The difference was significant in all
criteria (P B0.05) in favour of cognitive therapy. Of the
eight DSM-IV psychoses, all were schizophrenic (six
schizophrenia, one schizophreniform and one schizoaf-
fective).
The second controlled randomized trial compared
comprehensive cognitive
behavioural therapy with sup-
portive counselling in 128 patients with an early initial
prodomal state of psychosis (basic symptoms) (133). In
all, 110 patients could be followed for 12 months. By
month 12, transitions to sub-threshold psychotic symp-
toms (38% vs. 17.3%; P 0.024) and schizophrenia (1.9
vs. 12.1; P 0.041) were statistically significantly lower
in the cognitive therapy group than in the comparison
group. The numbers of patients who would need to be
treated with cognitive therapy to prevent one making the
transition were seven for transition to sub-threshold
psychotic symptoms, and 10 for transition to schizo-
phrenia. Both cognitive therapy and supportive counsel-
ling resulted in significant symptomatic and functional
100
improvements post-treatment with no significant be-
tween-group differences. Later, the same researchers
reported that Kaplan
Meier estimates of the risk of
transition to sub-threshold psychosis (5.3% vs. 18.5%,
P 0.032), psychosis (1.6% vs. 13.8%, P 0.020) and
schizophrenia (none vs. 13.8%, P 0.005) were signifi-
cantly lower for cognitive
behavioural therapy than for
supportive counselling (164). Preliminary results from
the German Research Network on Schizophrenia pro-
gramme suggested that both the early-recognition in-
ventory plus cognitive tests and the two therapy
strategies (psych- and pharmacotherapy) are feasible
and effective in reducing positive and negative symptoms
and improving global functioning compared with con-
trols who had received normal clinical treatment (165).
Integrated treatment
A randomized study included in the OPUS trial
examined whether integrated treatment, compared with
standard treatment, reduced transition to psychosis for
first-contact patients diagnosed with schizotypal disor-
der. During the first year, three out of 37 (8.1%) patients
with integrated treatment and 10 out of 30 (33.3%)
patients with standard treatment were diagnosed with
psychotic disorder during the first year, while at the end
of the second year the corresponding figures were 9/26
(25.0%) and 14/29 (48.3%) respectively. In multivariate
analysis, integrated treatment was associated with re-
duced risk (RR 0.36) of psychosis (61). There was no
statistical difference in the proportion of patients
receiving neuroleptic drug treatment, but among pa-
tients without transition to psychosis, significantly more
patients in integrated treatment than in standard treat-
ment were treated with neuroleptics.
Concluding remarks
Following the conclusions in an earlier review (37), from
the literature update we can draw the following conclu-
sions on predicting and detecting, as well as on inter-
ventions for preventing, onset of psychosis:
1) Heredity is an important factor related to schizo-
phrenia. The risk of psychosis among the first-
degree relatives of patients with schizophrenia or
other psychoses is about 10%. If the familial risk is
associated with psychic, cognitive and/or beha-
vioural disturbances, the risk of psychosis is much
higher, and clearly indicates a need for intensive
monitoring and preventive interventions. It is im-
portant to remember, however, that the population-
attributable risk of familial schizophrenia is only
about 5%, so that, on the general population level,
sporadic schizophrenia is more prevalent than
familial schizophrenia.
NORD J PSYCHIATRYVOL 62 NO 2 2008

2) Predictive factors such as pregnancy and delivery
complications, CNS infections or traumas, child-
hood family, or rearing environment, may play a
role as additional information in assessing an
individuals vulnerability to schizophrenia. Their
positive predictive value for schizophrenia or other
severe psychiatric disorders, without other concur-
rent risk factors or markers, is too low for specific
preventive interventions.
3) The childhood family or rearing environment seems
to have an interactive effect on an individuals
genetic vulnerability, suggesting that a favourable
childhood rearing environment may decrease and
an unfavourable environment increase, the risk of
familial schizophrenia. This clearly indicates early
family-centred assessments and interventions if
needed in families where one or both parents or
other family members are severely mentally ill.
These families are often in need of multiprofes-
sional help and support in their family life and
rearing duties. In addition to need-specific inter-
ventions in family members, the creation and
supporting of a favourable rearing atmosphere for
developing children in these families is of utmost
importance.
4) Together with familial psychosis, deficits in adoles-
cent and young adult social development and
cognitive performance, especially if the preceding
development has been normal, are such strong
indicators of severe psychiatric disorder that thor-
ough assessment, intensive monitoring and, if
psychic symptoms and functional decline occurs,
preventive interventions are indicated.
5) At the general population level, the diagnosing of
current risk of psychosis is not reliable enough, and
therefore prevention of psychosis at this level is not
feasible. However, among help-seeking patients,
those who are at current risk of psychosis can be
fairly reliably diagnosed. Occurrence of basic
symptoms indicates early risk of psychosis, while
the patients fulfilling the criteria of the CAARMS
or SIPS/SOPS are at very high risk of sliding into
psychosis. Additionally, these patients suffer from
other mental symptoms and functional decline, and
are thus in need of psychiatric assessment and
treatment.
6) Subjects vulnerable to and at risk of psychosis
display deficits in many neurocognitive examina-
tions and their functioning is decreased. In the
future, some of these examinations may contribute
the diagnosis of prodromals and their conversion to
psychosis. Sudden decrease in functioning and
deficits in spatial working memory and smell
identification seem to be rather reliable indicators
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
of conversion from prodrome to psychosis. Drug
abuse may also precipitate the onset of psychosis.
7) During the past 5 years, intervention trials have
shown that patients suffering from prodromal
symptoms can be successfully treated, and onset
of psychosis prevented or delayed. However, the
number of these published studies is still very few,
and they have not included very many patients.
Therefore, more large-scale studies are needed.
Clinical case descriptions of treatment of patients
with sub-threshold psychotic symptoms would also
be welcome.
References
1. Knapp MRJ, Almond S, Percudani M. Costs of schizophrenia, a
review. In: May M, Sartorius N, editors. Schizophrenia. Chiche-
ster: John Wiley & Sons; 1999. p. 407
54.
2. Knapp M, Mangalore R, Simon J. The global costs of schizo-
phrenia. Schizophr Bull 2003;30:279
93. / /
3. Joukamaa M, Heliovaara M, Knekt P, Aromaa A, Raitasalo R,
Lehtinen V. Mental disorders and cause-specific mortality. Br J
Psychiatry 2001;179:498
502.
/ /
4. Kelly C, McCreadie RG, MacEwan T, Carey S. Nithsdale
schizophrenia surveys. 17. Fifteen year review. Br J Psychiatry
1998;172:513
7.
/ /
5. Johnstone EC, Crow TJ, Johnson AL, Macmillan JF. The
Northwick Park study of first episodes of schizophrenia: I.
Presentation of the illness and problems relating to admission. Br
J Psychiatry 1986;148:115
20.
/ /
6. Hafner H, Maurer K, Loffler W, Riecher-Rossler A. The
influence of age and sex on the onset and early course of
schizophrenia. Br J Psychiatry 1993;162:80
6.
/ /
7. Larsen TK, Johannessen JO, Opjordsmoen S. First-episode
schizophrenia with long duration of untreated psychosis. Br J
Psychiatry 1998;172 Suppl 33:45
52.
/
8. Hafner H, Loffler W, Maurer K, Hambrecht M, an der Heiden W.
/
Depression, negative symptoms, social stagnation and social
decline in the early course of schizophrenia. Acta Psychiat Scand
1999;100:105
18.
/ /
9. Davidson M, Reichenberg A, Rabinpwitz J, Weiser M, Kaplan Z,
Mark M. Behavioral and intellectual markers for schizophrenia in
apparently healthy male adolescents. Am J Psychiatry 1999;156: / /
1328
35.
10. Crow TJ, MacMillan JF, Johnson AL, Johnstone EC. A
randomised controlled trial of prophylactic neuroleptic treatment.
Br J Psychiatry 1986;148:120
7. / /
11. Helgason L. Twenty years follow up of first psychiatric pre-
sentation for schizophrenia: What could have been prevented?
Acta Psychiatr Scand 1990;81:231
5. / /
12. Loebel AD, Lieberman JA, Alvir JM, Mayerhoff DI, Geisler SH,
Szymanski SR. Duration of psychosis and outcome in first
episode schizophrenia. Am J Psychiatry 1992;149:1183
8. / /
13. Edwards J, Maude D, McGorry PD, Harrigan SM, Cocks JT.
Prolonged recovery in first-episode psychosis. Br J Psychiatry
Suppl 1998;172:107
16.
/ /
14. Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace
T. Association between duration of untreated psychosis and
outcome in cohorts of first-episode patients: A systematic review.
Arch Gen Psychiatry 2005;62:975
83. / /
15. Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship
between duration of untreated psychosis and outcome in first-
episode schizophrenia: A critical review and meta-analysis. Am J
Psychiatry 2005;162:1785
804. Review.
16. Keshavan MS, Haas G, Miewald J, Montrose DM, Reddy R,
Schooler NR, et al. Prolonged untreated illness duration from
prodromal onset predicts outcome in first episode psychoses.
Schizophr Bull 2003;29:757
69. / /
101
RKR SALOKANGAS, TH MCGLASHAN
17. Lappin JM, Morgan K, Morgan C, Hutchison G, Chitnis X,
Suckling J, et al. Gray matter abnormalities associated
with duration of untreated psychosis. Schizophr Res 2006;83:145

53.
18. Parnas J. From predisposition to psychosis: Progression of
symptoms in schizophrenia. Acta Psychiatr Scand 1999;99 Suppl:
20
9.
19. Meehl PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol
1962;17:827
38.
/ /
20. Bleuler E. Dementia Praecox oder die Gruppe der Schizophre-
nien. Translation Dementia Praecox or the group of schizophre-
nias. New York: International University Press; 1911/1950.
21. Yung AR, McGorry PD. The prodromal phase of first episode
psychosis: Past and current conceptualizations. Schizophr Bull
1996;22:353
70.
/ /
22. McGorry PD, Singh BS. Schizophrenia: Risk and possibility. In:
Raphael B, Burrows GD, editors. Handbook of preventive
psychiatry. New York: Elsevier; 1995. p. 492
514.
23. Gottesman II. Schizophrenia genesis: The origin of madness. New
York: Freeman; 1991.
24. Kendler KS, Diehl SR. The genetics of schizophrenia: A current,
genetic
epidemiologic perspective. Schizophr Bull 1993;19:261

85. Review.
25. Asherson P, Mant R, McGuffin P. Genetics and schizophrenia.
In: Hirsh ST, Weinberger DR, editors. Schizophrenia. Cambridge:
Blackwell Science; 1995. p. 253
74.
26. Gottesman II. Schizophrenia epigenesis: Past, present, and future.
Acta Psych Scand 1994;90:26
33. / /
27. Tienari P, Wynne LC, Moring J, Lahti I, Naarala M, Sorri A, et
al. The Finnish adoptive family study of schizophrenia. Implica-
tions for family research. Br J Psychiatry 1994;23 Suppl:20
6.
28. Siira V, Wahlberg KE, Miettunen J, Tienari P, Laksy K.
Differentiation of adoptees at high versus low genetic risk for
schizophrenia by adjusted MMPI indices. Eur Psychiatry 2006;21:
245
50.
29. Olin SS, John RS, Mednick SA. Assessing the predictive value of
teacher reports in a high risk sample for schizophrenia: A ROC
analysis. Schizophr Res 1995;16:53
66.
/ /
30. Olin SS, Mednick SA, Cannon T, Jacobsen B, Parnas J, Schul-
singer F, et al. School teacher ratings predictive of psychiatric
outcome 25 years later. Br J Psychiatry 1998;172 Suppl 33:7
13.
31. Owens DG, Miller P, Lawrie SM, Johnstone EC. Pathogenesis of
schizophrenia: A psychopathological perspective. Br J Psychiatry
2005;186:386
93.
/ /
32. Johnstone EC, Ebmeier KP, Miller P, Owens DG, Lawrie SM.
Predicting schizophrenia: Findings from the Edinburgh High-
Risk Study. Br J Psychiatry 2005;186:18
25.
33. Owens DG, Johnstone EC. Precursors and prodromata of
schizophrenia: Findings from the Edinburgh High Risk Study
and their literature context. Psychol Med 2006;36:1501
14.
34. Glatt SJ, Stone WS, Faraone SV, Seidman LJ, Tsuang MT.
Psychopathology, personality traits and social development of
young first-degree relatives of patients with schizophrenia. Br J
Psychiatry 2006;189:337
45.
/ /
35. Jones P, Rodgers B, Murray R, Marmot MG. Child develop-
mental risk factors for adult schizophrenia in the British 1946
birth cohort. Lancet 1946;344:1398
402. / /
36. Jones PB, van Os JJ. Predicting schizophrenia in teenagers:
Pessimistic results from the British 1946 birth cohort. Abstract of
the 7th International Congress on Schizophrenia Research,
Colorado Springs; 1997. p. 11.
37. Salokangas RKR. Precursors and markers of psychosis*Scien-
tific basis for examinations and intervention. Neurol Psychiat
Brain Res 2001;9:105
26.
/ /
38. Hultman CM, Sparen P, Takei N, Murray RM, Cnattingius S.
Prenatal and perinatal risk factors for schizophrenia, affective
psychosis, and reactive psychosis of early onset: Case
control
study. BMJ 1999;318:421
6.
/ /
39. Dalman C, Allebeck P, Cullberg J, Grunewald C, Koster M.
Obstetric complications and the risk of schizophrenia: A long-
itudinal study of a national birth cohort. Arch Gen Psychiatry
1999;56:234
40.
/ /
102
40. van Os J, Hanssen M, Bijl RV, Vollebergh W. Prevalence of
psychotic disorder and community level of psychotic symptoms:
/ /
An urban
rural comparison. Arch Gen Psychiatry 2001;58:663
8. / /
41. van Os J, Pedersen CB, Mortensen PB. Confirmation of synergy
between urbanicity ja familial liability in the causation of
/ /
psychosis. Am J Psychiatry 2004;161:2312
4. / /
42. Holloway J, Hutchinson G, Leff JP, Mallett RM, Harrison GL,
Murray RM, Jones PB. Heterogeneity in incidence rates of
schizophrenia and other psychotic syndromes: Findings from the
3-center AeSOP study. Arch Gen Psychiatry 2006;63:250
8. / /
43. Selten JP, Veen N, Feller W, Blom JD, Schols D, Camoenie W, et
al. Incidence of psychotic disorders in immigrant groups to The
Netherlands. Br J Psychiatry 2001;178:367
72. / /
44. Hjern A, Wicks S, Dalman C. Social adversity contributes to high
morbidity in psychoses in immigrants*A national cohort study
in two generations of Swedish residents. Psychol Med 2004;34: / /
1025
33.
45. Kirkbridge JB, Fearon P, Morgan C, Dazzan P, Morgan K,
Tarrant J, et al. Heterogeneity in incidence rates of schizophrenia
and other psychotic syndromes: Findings from the 3-center
AeSOP study. Arch Gen Psychiatry 2006;63:250
8. / /
46. Leao TS, Sundquist J, Frank G, Johansson LM, Johansson SE,
Sundquist K. Incidence of schizophrenia or other psychoses in
first- and second-generation immigrants: A national cohort study.
J Nerv Ment Dis 2006;194:27
33. / /
47. Geddes JR, Lawrie SM. Obstetric complications and schizo-
phrenia: A meta-analysis. Br J Psychiatry 1995;167:786
93. / /
48. Hafner H, Maurer K, Ruhrmann S, Bechdolf A, Klosterkotter J,
Wagner M, et al. Early detection and secondary prevention of
psychosis: Facts and visions. Eur Arch Psychiatry Clin Neurosci
2004;254:117
28.
/ /
49. Maki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P,
/ /
et al. Predictors of schizophrenia*A review. Br Med Bull 2005; /
73
74:1
15. /
50. Yung Y, Phillips LJ, Cotton S, Yung AR, Francey SM, Yuen HP,
/ /
et al. Obstetric complications and transition to psychosis in an
ultra high risk sample. Aust N Z J Psychiatry 2005;39:460
6.
/ /
51. Jones PB, Done DJ. From birth to onset: A developmental
perspective of schizophrenia in two national birth cohorts. In:
Keshavan MS, Murray RM, editors. Neurodevelopment and
adult psychopathology. Cambridge: Cambridge University Press;
1997. p. 119
36.
/ /
52. Cannon M, Jones P, Huttunen MO, Tanskanen A, Huttunen T,
Rabe-Hesketh S, et al. School performance in Finnish children
and later development of schizophrenia: A population-based
longitudinal study. Arch Gen Psychiatry 1999;56:457
63.
/ /
53. Rantakallio P, Jones P, Moring J, von Wendt L. Association
/ /
between central nervous system infections during childhood and
adult onset schizophrenia and other psychoses: A 28-year follow-
up. Int J Epidemiology 1997;26:837
43. / /
/ /
54. David AS, Malmberg A, Brandt L, Allebeck P, Lewis G. IQ and
risk for schizophrenia: A population-based cohort study. Psychol
Med 1997;27:1311
23./ /
55. Gunnell D, Harrison G, Rasmussen F, Fouskakis D, Tynelius P.
Associations between premorbid intellectual performance, early-
life exposures and early-onset schizophrenia. Cohort study. Br J
Psychiatry 2002;181:298
305./ /
56. Beiser M, Erickson D, Fleming JAE, Iacono WG. Establishing
the onset of psychotic illness. Am J Psychiatry 1993;150:1349
54. / /
57. Meehl PE. Toward an integrated theory of schizotaxia, schizotypy
and schizophrenia. J Pers Dis 1990;4:1
99. / /
58. Hoch PH, Cattel JP, Strahl MO, Pennes HH. The course and
outcome of pseudoneurotic schizophrenia. Am J Psychiatry 1962; /
119:106
15.
/
59. Salokangas RKR. Skitsofreniaan sairastuneiden psykososiaali-
nen kehitys. (The psychosocial development of schizophrenic
patients.) Kansanelakelaitoksen julkaisuja AL 7, Turku; 1977.
60. Salokangas RKR. Skitsofrenian hoito ja ennuste. (Treatment and
outcome in schizophrenia.) Kansanterveystieteen julkaisuja M
89/85. Tampereen yliopiston kansanterveystieteen laitos, Turun
yliopiston Psykiatrian klinikka, Tampere; 1985.
61. Nordentoft M, Thorup A, Petersen L, .O hlenschlaeger J, Malau
M, O stergaard C, et al. Transition rates from schizotypal disorder
NORD J PSYCHIATRYVOL 62 NO 2 2008
 EARLY DETECTION AND INTERVENTION OF PSYCHOSIS

to psychotic disorder for first-contact patients included in the 82. Goldberg T, David A, Gold JM. Neurocognitive deficits in
OPUS trial. A randomized clinical trial of integrated treatment schizophrenia. In: Hirsch SR, Weinberger DR, editors. Schizo-
and standard treatment. Schizophr Res 2006;82:29
40. / /

phrenia, 2nd edition. London: Blackwell; 2003. p. 168
84.

62. Lewis G, David AS, Malmberg A, Allebeck P. Non-psychotic 83. Larsen TK, McGlashan TH, Johannessen JO, Vibe-Hansen L.
psychiatric disorder and subsequent risk of schizophrenia. Cohort First-episode schizophrenia: II. Premorbid patterns by gender.
study. Br J Psychiatry 2000;177:416
20. / /

Schizophr Bull 1996;22:257
69. / /

63. Weiser M, Reichenberg A, Rabinowitz J, Kaplan Z, Mark M, 84. MacEwan TH, Athawes RWB. The nithsdale schixophrenia
Bodner E, et al. Association between nonpsychotic psychiatric surveys XV. Social adjustment in schizophrenia: Associations
diagnoses in adolescent males and subsequent onset of schizo- with gender, symptoms and childhood antecedents. Acta Psy-
phrenia. Arch Gen Psychiatry 2001;58:959
64. / /

chiatry Scand 1997;95:254
8. / /

64. Reihenberg A, Goldenberg J. Self-reported mentl health difficul- 85. McGlashan TH, Miller TJ, Woods SW, Hoffman RE, Davidson
ties and subsequent risk for schizophrenia in females: A 5-year L. Instrument for the assessment of prodromal symptoms and
follow-up cohort study. Schizophr Res 2006;82:233
9. / /

states. In: Miller T, Mednick SA, McGlashan TH, Libiger J,

65. Salokangas RKR. Psychosocial prognosis in schizophrenia. Johannessen JO, editors. Early intervention in psychotic dis-
Formation of the prognosis for schizophrenic patients: A multi- orders. Dordrecht: Kluwer Academic; 2001. p. 135
49.
variate analysis. Annales Univ Turkuensis Ser. D 9, Turku; 1978. 86. Salokangas RKR, Heinimaa M, Huttunen J, Klosterkotter J,
66. Hafner H, Riecher-Rossler A, Hambrecht M, Maurer K, Ruhrmann S, von Reventlow H, et al. Quality of life in psychiatric
Meissner S, Schmiedtke A, et al. IRAOS: An instrument for the patients vulnerable to psychosis. Results of the EPOS study.
assessment of onset of early course of schizophrenia. Schizophr Presentaion in the 14th AEP Congress 4
8 March 2006, Nice. Eur
Res 1992;6:209
23. / /

Psychiatry 2006;21 Suppl 1:S58.

67. Hafner H, Maurer K. Are there two types of schizophrenia? True 87. Yung AR, Buckby JA, Cotton SM, Cosgrave EM, Killackey EJ,
onset and sequence of positive and negative syndromes prior to Stanford C, et al. Psychotic-like experiences in nonpsychotic help-
the first admission. In: Marneros A, Andreasen NC, Tsuan MT, seekers: Associations with distress, depression, and disability.
editors. Negative versus positive schizophrenia. Berlin: Springer; Schizophr Bull 2006;32:352
9. / /

1991. p. 134
59. 88. Amminger GP, Leicester S, Yung AR, Phillips LJ, Berger GE,
68. Hafner H, Maurer K, Trendler G, an der Heiden W, Schmidt M, Francey SM, et al. Early-onset of symptoms predicts conversion
Konnecke R. Schizophrenia and depression: Challenging the to non-affective psychosis in ultra-high risk individuals. Schi-
paradigm of two separate diseases*A controlled study of zophr Res 2006;84:67
76.
schizophrenia, depression and healthy controls. Schizophr Res
/ /

89. Woods S Effects of Olanzapine in those at high risk of psychosis.

2005;77:11
24.
/ /

Presentation in an international conference, The early phase of

69. Hafner H, Maurer K. Early detection of schizophrenia. Current psychosis*Research and treatment, 3
4 April 2006, London.
evidence and future perspectives. World Psychiatry 2006;5:130
8. / /

90. Goldberg TE, Gold JM. Neurocognitive deficits in schizophrenia.

70. Chapman JP. The early symptoms of schizophrenia. Br J
In: Hirsch SR, Weinberger DR, editors. Schizophrenia. Cam-
Psychiatry 1966;112:225
51.
bridge: Blackwell Science; 1995. p. 146
62.
/ /

71. Kapur S. Psychosis as a state of aberrant salience: A framework

91. Lawrie SM. The neuropsychology of schizophrenia. In: Johnstone
linking biology, phenomenology, and pharmacology in schizo-
ED, Humphreys MS, Lang FH, Lawrie SM, Sandler R, editors. .
phrenia. Am J Psychiatry 2003;160:13
23.
Schizophrenia. Concepts and clinical management. Cambridge:
/ /

72. Selten JP, Cantor-Graae E. Social defeat: Risk factor for

Cambridge University Press; 1999. p. 129
44.
schizophrenia? Br J Psychiatry 2005;187:101
2.
92. Roitman SE, Cornblatt BA, Bergman A, Obuchowski M,
/ /

73. McGorry PD, McFarlane C, Patton GC, Bell R, Hibbert ME,

Jackson H, et al. The prevalence of prodromal features of Mitropoulou V, Keefe RS, et al. Attentional functioning in
schizophrenia in adolescence: A preliminary survey. Acta Psy- schizotypal personality disorder. Am J Psychiatry 1997;154:655

chiatr Scand 1995;92:241
9. 60. Published erratum appears in Am J Psychiatry 1997;154:1180.
93. Franke P, Maier W, Hain C, Klingler T. Wisconsin Card Sorting
/ /

74. Hanssen MS, Bijl RV, Vollebergh W, van Os J. Self-reported

psychotic experiences in the general population: A valid screening Test: An indicator of vulnerability to schizophrenia? Schizophr
tool for DSM-III-R psychotic disorders? Acta Psychiatr Scand Res 1992;6:243
9.
/ /

2003;107:369
77.
/ /
94. Cornblatt BA, Keilp JG. Impaired attention, genetics, and
75. Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, the pathophysiology of schizophrenia. Schizophr Bull 1994;20:31
/ /

Harrington H. Childrens self-reported psychotic symptoms and 46.

adult schizophreniform disorder: A 15-year longitudinal study. 95. Bryne M, Hodges A, Grant E, Johnstone EC. Evidence for
Arch Gen Psychiatry 2000;57:1053
8. / /
executive dysfunction in young people at high genetic risk for
76. Cannon M, Caspi A, Moffitt TE, Harrington H, Taylor A, schizophrenia? Results of the Hayling Sentence Completion Test.
Murray RM, et al. Evidence for early-childhood, pan-develop- Schitzophr Res 1998a;29:43. / /

mental impairment specific to schizophreniform disorder: Results 96. Toulopoulou T, Morris RG, Murray RM. Spatial working
from a longitudinal birth cohort. Ach Gen Psychiatry 2002;59: / /
memory and strategy formation in schizophrenic patients and
449
56. their first degree relatives. Schitzophr Res 1998;29:138. / /

77. Rossler W, Riecher-Rossler A, Angst J, Murray R, Gamma A, 97. Cannon TD, van Erp TGM, Finklestein JRJ, Huttunen M,
Eich D, et al. Psychotic experiences in the general population: A Kaprio J, Lonnqvist J, et al. Disturbance in a frontal lobe-
twenty-year prospective community study. Schizophr Res 2007; /
working memory circuit as an inherited neurobiological substrate
92:1
14.
/
in schizophrenia: Results from a controlled twin study. Schizophr
78. van Os J, Verdoux H, Maurice-Tison S, Gay B, Liraud F, Res 1999;36:88.
/ /

Salamon R, et al. Self-reported psychosis-like symptoms and the 98. Byrne M, Hodges A, Grant E, Owens DC, Johnstone EC.
continuum of psychosis. Soc Psychiatry Psychiatr Epidemiol Neuropsychological assessment of young people at high genetic
1999;34:459
63.
/ /
risk for developing schizophrenia compared with controls: Pre-
79. Hafner H, Nowotny B, Loffler W, an der Heiden W, Maurer K. liminary findings of the Edinburgh High Risk Study (EHRS).
When and how does schizophrenia produce social deficits? Eur Psychol Med 1999;29:1161
73./ /

Arch Psychiatry Clin Neurosci 1995;246:17
28. / /

99. Finklestein JRJ, Cannon TD, Huttunen T, Tuulio-Henrikson A,
80. Hafner H, an der Heiden W. Course and outcome of schizo- Kaprio J, Lonnqvist J, et al. The viability of attention deficit as
phrenia. In: Hirsch SR, Weinberger DR, editors. Schizophrenia, markers of genetic vulnerability to schizophrenia: A discordant
2nd edition. London: Blackwell; 2003. p. 101
41. twin study. Schizophr Res 1999;36:90. / /

81. Jablensky A. The epidemiological horizon. In: Hirsch SR, 100. Egan MF, Goldberg TE, Gscheidle T, Bigelow L, Weinberger
Weinberger DR, editors. Schizophrenia, 2nd edition. London: DR. Hereditability estimates for independent domains of cogni-
Blackwell; 2003. p. 203
31. tive dysfunction in schizophrenia. Schizophr Res 2000;41:89
90. / /

NORD J PSYCHIATRY VOL 62NO 22008 103

RKR SALOKANGAS, TH MCGLASHAN
101. Trandafir A, Meary A, Schurhoff F, Leboyer M, Szoke A.
Memory tests in first-degree adult relatives of schizophrenic
patients: A meta-analysis. Schizophr Res 2006;81:217
26. / /
102. Cornblatt B. High-risk research: Implications for new interven-
tions. Plenary presentation, International Congress on Schizo-
phrenia Research, 21 April 1999.
103. Meurice EE. Rorschach Schizophrenia Signs in healthy first
degree family members of patients with schizophrenia. A study of
three complete families. Schitzophr Res 1998;29:59
60.
/ /
104. Perry W, Minassian A, Cadenhead K, Sprock J, Braff D. The use
of the Ego Impairment Index across the schizophrenia spectrum.
J Pers Assess 2003;80:50
7. / / Harrington H, et al. Moderation of the effect of adolescent-onset
105. Ilonen T. Is it possible to differentiate patients vulnerable to
psychosis? Presentation at the XVIII International Congress of
Rorschach and Projective Methods, 25
30 July 2005, Barcelona.
Abstracts. p. 333.
106. Klosterkotter J, Schultze-Lutter F, Steinmeyer EM, Wieneke A.
Are self-experienced neuropsychological deficits able to indicate
liability to schizophrenia? Results of a comparative study of 1st-
degree relatives of schizophrenics. Schitzophr Res 1998;29:64.
107. Schulze-Lutter F. Basic symptoms. Presentation in an interna-
tional conference, The early phase of psychosis*Research and
treatment, 3
4 April 2006, London.
108. Bartok E, Berecz R, Glaub T, Degrell I. Cognitive functions in
prepsychotic patients. Prog Neuropsychopharmacol Biol Psy-
chiatry 2005;29:621
5.
/ /
109. Tabraham P, Brett C, Johns L, Valmaggia L, Broome M, Woolley
J, et al. Spatiel working memory is impaired in individuals at high
risk for psychosis. Schizopr Res 2006;81 Suppl:271.
110. Pflueger MO, Gschwandtner U, Aston J, Borgwardt S, Stieglitz
RD. The neuropsychological assessment of the risk for psychosis
in the Basel FEPSY study. Eur Psychiatry 2006;21 Suppl 1:S48. / /
111. Brewer W, Francey S, Yung A, Velakoulis D, Anderson V,
McGorry P, et al. Cognitive and olfactory deficits: Course from
high risk to first-episode psychosis. Schitzophr Res 1998;29:54
5.
112. Brewer W, Francey S, Yung A, Velakoulis D, Anderson V,
McGorry P, et al. Cognitive and related olfactory deficits in young
people at high risk for psychosis. Abstract of the 7th International
Congress on Schizophrenia Research. Schizophr Res 1999;36:125.
113. Brewer WJ, Wood SJ, McGorry PD, Francey SM, Phillips LJ,
Yung AR, et al. Impairment of olfactory identification ability in
individuals at ultra-high risk for psychosis who later develop
schizophrenia. Am J Psychiatry 2003;160:1790
4.
/ /
114. Cornblatt BA, Lencz T, Smith CW, Correll CU, Auther AM,
Nakayama E. The schizophrenia prodrome revisited: A neuro-
development perspective. Schizophr Bull 2003;29:633
51. /
115. Smith CW, Park S, Cornblatt B. Spatial working memory deficits
in adolescents at clinical high risk for schizophrenia. Schizophr
Res 2006;81:211
5.
/ /
116. Niendam TA, Bearden CE, Johnson JK, McKinley M, Loewy R,
OBrien M, et al. Neurocognitive performance and functional
disability in the psychosis prodrome. Schizophr Res 2006;84:100

11.
117. Francey SM, Jackson HJ, Phillips LJ, Wood SJ, Yung AR,
McGorry PD. Sustained attention in young people at high risk of
psychosis does not predict transition to psychosis. Schizophr Res
2005;79:127
36.
/ /
118. Wood SJ, Berger G, Velakoulis D, Phillips LJ, McGorry PD,
Yung AR, et al. Proton magnetic resonance spectroscopy in first
episode psychosis and ultra high-risk individuals. Schizophr Bull
2003;29:831
43.
/ /
119. Whyte MC, Brett C, Harrison LK, Byrne M, Miller P, Lawrie
SM, et al. Neuropsychological performance over time in people at
high risk of developing schizophrenia and controls. Biol Psy-
chiatry 2006;59:730
9.
/ /
120. Brewer WJ, Francey SM, Wood SJ, Jackson HJ, Pantelis C,
Phillips LJ, et al. Memory impairments identified in people at
ultra-high risk for psychosis who later develop first-episode
psychosis. Am J Psychiatry 2005;162:71
8.
/ /
121. Pantelis C. Neuropsychological impairments in the At Risk
Mental State. Presentation in an international conference, The
early phase of psychosis*Research and treatment, 3
4 April
2006, London
104
124. Henquet C, Krabbendam L, Spauwen J, Kaplan C, Lieb R,
126. Hambrecht M, Hafner H. Substance abuse and the onset of
/ /
129. Huber G, Gross G, Schuttler R, Linz M. Longitudinal studies of
/ /
/ /
/ Suppl 33:14
20./
/ /
142. Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Ventura J,
122. Andreasson S, Allbeck P, Engstrom A, Rydberg U. Cannabis and
schizophrenia: A longitudinal study of Swedish conscripts. Lancet
1987;2:1483
6.
/ /
123. Arseneault L, Cannon M, Witton J, Murray RM. Causal
association between cannabis and psychosis: Examination of the
evidence. Br J Psychiatry 2004;184:110
7. / /
Wittchen HU, et al. Prospective cohort study of cannabis use,
predisposition for psychosis, and psychotic symptoms in young
people. BMJ 2005;330:11.
/ /
125. Caspi A, Moffitt TE, Cannon M, McClay J, Murray R,
cannabis use on adult psychosis by a functional polymorphism in
the catechol-O-methyltransferase gene: Longitudinal evidence of
a gene X environment interaction. Biol Psychiatry 2005;57:1117
/ /
27.
schizophrenia. Biol Psychiatry 1996;40:1155
63. / /
127. Huber G. Reine Defektsyndrome und Basisstadien endogener
Psychosen. Fortschr. Neurol Psychiatry 1966;34:409
26. / /
128. Huber G. Verlaufsprobleme schizophrenen Erkrankungen.
Schweiz Arch Neurol Neurochir Psychiatry 1968;101:346
68. / /
schizophrenic patients. Schizophr Bull 1980;6:592
605. / /
130. Gross G, Huber G. Prodromes and primary prevention of
schizophrenic psychoses. Neurol Psychiatry Brain Res 1998;6: / /
51
8.
131. Gross G, Huber G, Klosterkotter J, Linz M. BSABS Bonner
Skala fur die Beurtailung von Basissymptomen (Bonn Scale for
the Assessment of Basic Symptoms). Manual, Kommentar,
Dokumentationbogen. Berlin: Springer; 1987.
132. Klosterkotter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F.
Diagnosing schizophrenia in the initial prodromal phase. Arch
Gen Psychiatry 2001;58:158
64.
/ /
133. Bechdolf A, Wagner M, Veith V, Pukrop R, Berning J, Stamm E,
et al. A randomized controlled trail of cognitive
behavioral
therapy in the early initial prodromal state of psychosis.
Presentation in the 18th Biennial Winter Workshop on Schizo-
phrenia Research, Davos, 4 February 2006. Schizophr Res 2006;
81 Suppl:22
3.
134. Comprehensive Assessment of At Risk Mental States
(CAARMS) Version 2, February 1996.
135. Yung AR, Phillips LJ, McGorry PD, McFarlane CA, Francey S,
Harrigan S, et al. Prediction of psychosis: A step towards
indicated prevention of schizophrenia. Br J Psyschiatry 1998;172 /
136. Yung AR, Jackson HJ. The onset of psychotic disorder: Clinical
and research aspects. In: McGorry PD, Jackson HJ, editors. The
recognition and management of early psychosis. A preventive
approach. Cambridge: Cambridge University Press; 1999. p. 27

50.
137. Yung AR, Stanford C, Cosgrave E, Killackey E, Phillips L,
Nelson B, et al. Testing the ultra high risk (prodromal) criteria for
the prediction of psychosis in a clinical sample of young people.
Schizophr Res 2006;84:57
66.
/ /
138. Yung AR, Yuen HP, McGorry PD, Phillips LJ, Kelly D, DellOlio
M, et al. Mapping the onset of psychosis: The Comprehensive
Assessment of At-Risk Mental States. Aust NZ J Psychiatry 2005; /
39:964
71.
/
139. Miller TJ, McGlashan TH, Lifshey Rosen J, Somjee L, Marko-
vich PJ, Stein K, et al. Prospective diagnosis of the initial
prodrome for schizophrenia based on the Structured Interview for
Prodromal Syndromes: Preliminary evidence of interrater relia-
bility and predictive validity. Am J Psychiatry 2002;159:863
5. / /
140. Miller TI, McGlashan TH, Woods SW, Stein K, Driesen N,
Concran CM, et al. Symptom assessment in schizophrenic
prodromal states. Psychiat Q 1999;70:273
87. / /
141. Woods S. SIPS, SOPS & COPS. Presentation in an international
conference, The early phase of psychosis*Research and treat-
ment, 3
4 April 2006, London.
McFarlane W, et al. Prodromal assessment with the structured
interview for prodromal syndromes and the scale of prodromal
NORD J PSYCHIATRYVOL 62 NO 2 2008

symptoms: Predictive validity, interrater reliability, and training
to reliability. Schizophr Bull 2003;29:703
15.
/ /
143. Phillips LJ, Yung A, McGorry PD. Identification of young people
at risk of psychosis: Validation of the Personal Assessment and
Crisis Evaluation Clinic intake criteria. Aust N Zeal J Psychiatry
2000;34 Suppl:164
9.
144. Yung AR, Phillips LJ, Yuen HP, McGorry PD. Risk factors for
psychosis in an ultra high-risk group: Psychopathology and
clinical features. Schizophr Res 2004;67:131
42.
/ /
145. McGorry PD, Yung AR, Phillips LJ, Yuen HP, Francey S,
Cosgrave EM, et al. Randomised controlled trial of interventions
designed to reduce the risk of progression to first-episode
psychosis in a clinical sample with subthreshold symptoms. Ach
Gen Psychiatry 2002;59:921
8.
/ /
146. Morrison AP, French P, Walford L, Lewis SW, Kilcommons A,
Green J, et al. Cognitive therapy for the prevention of psychosis in
people at ultra-high risk. Randomised controlled trial. Br J
Psychiatry 2004;185:291
7.
/ /
147. McGlashan TH, Zipursky RB, Perkins DO, Addington J, Woods
SW, Miller TJ, et al. Olanzapine vs. placebo for prodromal
schizophrenia. Schizophr Res 2004;67 Suppl:6.
148. Mason O, Startup M, Halpin S, Schall U, Conrad A, Carr V. Risk
factors for transition to first episode psychosis among individuals
with at-risk mental states. Schizophr Res 2004;71:227
37. / /
149. Broome RM, Woolley JB, Johns LC, Valmaggia LR, Tabraham P,
Gafoor R, et al. Outreach and support in south London (OASIS):
Implementation of a clinical service for prodromal psychosis and
the at risk mental state. Eur Psychiatry 2005;20:372
78. Follow-
up at a maximum catamnestic interval of 30 months.
150. McGlashan TH. Early detection and intervention of schizophre-
nia: Rationale and research. Br J Psychiatry 1998;172 Suppl 33: / /
3
6.
151. Jablensky A. Prevalence and incidence of schizophrenia spectrum
disorders: Implications for prevention. ANZ J Psychiatry 2000;
34(Suppl):S26
34.
/
152. McGrath J. Universal interventions for primary prevention of
schizophrenia. Aust NZ J Psychiatry 2000;34(Suppl):S58
64.
/ /
153. Warner R. The prevention of schizophrenia: What interventions
are safe and effective? Schizophr Bull 2001;27:551
62. / /
154. Mojtabai R, Malaspina D, Susser E. The concept of population
prevention: Application to schizophrenia. Schizophr Bull 2003;
29:791
801.
/
155. McGlashan TH, Zipursky RB, Perkins DO, Addington J, Miller
TJ, Woods SW, et al. Randomized, double-blind trial of
NORD J PSYCHIATRY VOL 62NO 22008
EARLY DETECTION AND INTERVENTION OF PSYCHOSIS
Olanzapine versus placebo in patients prodromally symptomatic
for psychosis. Am J Psychiatry 2006;163:790
9. / /
156. Woods SW, Breier A, Zipursky RB, Perkins DO, Addington J,
Miller TJ, et al. Randomized trial of olanzapine versus placebo in
the symptomatic acute treatment of the schizophrenic prodrome.
Biol Psychiatry 2003;54:453
64. / /
157. Ruhrmann S, Schulze-Lutter F, Maier W, Klosterkotter J.
Pharmacological intervention in the initial prodromal phase of
psychosis. Eur Psychiatr 2005;20:1
6. / /
158. Ruhrmann S, Hoppmann B, Theyshn S, Picker H, Kuhn K-U,
Schulze-Lutter F, et al. Acute symptomatic treatment clinically at
risk for psychosis. Schizophr Res 2006;86:S8.
/ /
159. Keri S, Kelemen O, Janka Z. Therapy of mental states at high risk
for psychosis: Preliminary results from Hungary (in Hungarian)
Orv Hetil 2006;147:201
4.
/ /
160. Walsh BC, Tully E, Thomas L, McGlashan TH, Woods S.
Aripiprazole treatment of the psychosis prodrome. Schizophr Res
2006;86:S7.
/ /
161. Tsuang MT, Stone WS, Tarbox SI, Faraone SV. An integration of
schizophrenia with schizotypy: Identification of schizotaxia and
implications for research on treatment and prevention. Schizophr
Res 2002;54:169
75.
/ /
162. Chong SA, Verma SK, McGorry P. Psychosis*A need for
preemptive intervention? Singapore Med J 2003;44:426
7. / /
163. Morrison AP, French P, Walford L, Lewis SW, Kilcommons A,
Green J, et al. Cognitive therapy for the prevention of psychosis in
people at ultra-high risk. Br J Psychiatry 2004;185:291
7. / /
164. Bechdolf A, Wagner M, Veith V, Ruhrman S, Janssen B,
Bottlender R, et al. A randomized controlled multicentre trial of
cognitive behavioral therapy in the early initial prodromal state of
psychosis. Schizophr Res 2006;86:S8. / /
165. Hafner H, Maurer K, Ruhrmann S, Bechdolf A, Klosterkotter J,
/
Wagner M, et al. Early detection and secondary prevention of
psychosis: Facts and visions. Eur Arch Psychiatry Clin Neurosci
2004;254:117
28. Review.
Raimo K.R. Salokangas, M.D., Ph.D., M.Sc, Professor of Psychiatry,
Department of Psychiatry, University of Turku; Psychiatric Clinic,
Turku University Central Hospital Turku Psychiatric Clinic, Turku
/
City Psychiatry, FIN-20520 Turku, Finland.
Thomas H. McGlashan, M.D, Professor of Psychiatry, Yale
University, New Haven, Connecticut, USA.
105