early diagnosis and intervention in psychosis: perspective from turkey

early diagnosis and intervention in psychosis: perspective from turkey

Clinical Neuropsychiatry (2008) 5, 6, 290-294
EARLY DIAGNOSIS AND INTERVENTION IN PSYCHOSIS:
PERSPECTIVE FROM TURKEY
Meram Can Saka, M. KazÚm YazÚcÚ
Abstract
Schizophrenia is still one of the costliest problems of mankind on both personal and societal levels. Since
schizophrenia has been defined there had been hopes to arrest the disorder in early phases. In last 20 years there had
been a growing interest in early diagnosis and intervention area, a corresponding rise in reported studies and some
encouraging results. There are some issues demanding serious attention like non-applicability of studies to general
population, exclusion of negative and depressive symptoms from contemporary high risk definitions and treating
groups with a significant proportion not expected to have clinical disorder. After current psychiatric services and early
diagnosis and intervention efforts in Turkey are described the authors conclude that contributions to the field from
Turkey with limited resources but high levels of accessibility and attainability of medical treatment, young population,
high rates of intra-national migration between very different life circumstances, ethnic groups, different family and
social relation patterns can be of use worldwide.
Key Words: Schizophrenia – Early Intervention
Declaration of Interest: None
Meram Can Saka1, MD, M. KazÚm Yazici2*, MD
1 Ankara University, School of Medicine, Psychiatry Department
2. Hacettepe University, Faculty of Medicine, Department of Psychiatry
Corresponding Author
M. KazÚm YazÚcÚ, Hacettepe University Faculty of Medicine, Department of Psychiatry, Ankara 06100, Turkey
Email: [email protected]
The arrival of second generation antipsychotics
with fewer extrapyramidal side effects, followed
recently by others with less metabolic side effects led
psychiatrists to a relative optimism and a renewed
interest in remission in management of schizophrenia
(van Os et al. 2006) but still the results of pharmacological or psychosocial treatments are not
satisfactory and an important portion of patients are
not active in social, occupational life reporting low
levels of satisfaction (Perkins et al. 2006). Thus
schizophrenia is still one of the costliest health problems
on both personal and societal levels, causing immense
amount of suffering to the patient and the family and
high financial loads to the nation (Murray et al. 1996).
The prevalence of schizophrenia may be lower in
developing compared to developed countries (Saha et
al. 2005) the costs though can be estimated to be alike.
In the quest for etiology despite a multitude of new
findings and better results from molecular and genetic
studies we still don’t have an established model that
produces some solid intervention targets else than D2
receptors, leaving a dim hope for a more effective
treatment in short or medium term.
The hope to arrest schizophrenia in early phases
is not new. Bleuler called the prodrome phase “latent
schizophrenia” and thought that the underlying disease
process may come to a halt at any stage of its early
development (Bleuler 1911). Others followed his lead
for early diagnosis (Cameron 1938, Sullivan 1927) but
no significant intervention studies had been reported
until last decades. It has been proposed that untreated
psychosis may be “toxic”, leading to irreversible
damage affecting long term outcome (Sheitman and
Lieberman 1998) backed up with the association of
some outcome parameters with duration of untreated
psychosis (Marshall et al. 2005, Melle et al. 2004,
Perkins et al. 2005).
Last 20 years witnessed a multitude of early
diagnosis and intervention studies throughout the world
(McGorry et al. 2005) mostly from developed countries.
McGorry relates the presence of around 200 early
intervention centers worldwide (McGorry et al. 2007)
and results have been accumulating. In enriched
samples of treatment seeking subjects with subsyndromal psychosis symptoms, reported conversion
rates to schizophrenia and other psychotic clinical
disorders are around 30-40 percent and of those that
will progress to clinical disorders, up to 80 percent can
be predicted (Cannon et al. 2008, Häfner and Maurer
2005). Intervention studies using antipsychotics and/
or psychosocial interventions to prevent conversion to
schizophrenia or other psychotic disorders report
SUBMITTED JULY 2008, ACCEPTED NOVEMBER 2008
290
© 2008 Giovanni Fioriti Editore s.r.l.
Early Diagnosis and Intervention in Psychosis: Perspective from Turkey
significant results, like reducing the conversion risk
around 20% which corresponds to a more than half of
the total risk (McGlashan et al. 2006, McGorry et al.
2002, Morrison et al. 2004).
Though encouraging, there are some points to
consider to interpret those results. The predictive values
of prodromal criteria are mediated by the structure of
the early detection services in which they are embedded
and applied. The patient samples investigated in
mentioned studies (Häfner et al. 1999, McGlashan et
al. 2006, McGorry et al. 2002) are highly enriched
patient samples, filtered at two or more assessment steps
to be directed to the speciality clinics (van Os and
Verdoux 2003). This is a serious shortcoming for
applicability of these results to general population for
achievement of public health targets. Cannon et al., in
the biggest study to date, stated that “The results are
not expected to be useful in general population
screening” (Cannon et al. 2008).
Depressive and negative symptoms seem to be the
first symptoms in the prodromal period (Häfner et al.
1999). Their importance is highlighted by the well
established association with younger age and poor
prognosis (Gillberg et al. 1993, Remschmidt 2002).
Negative symptoms are not included in contemporary
high risk definitions (Simon et al. 2007), maybe leaving
out the most poor prognosis future patients from
prevention efforts. Cornblatt and colleagues have
recently proposed a high risk definition with negative
symptoms (Cornblatt et al. 2003) but leading those
subjects with high withdrawal to seek treatment may
prove out to be quite problematic.
Even the most systematic programs today are
exceptions in general health services (Yung et al. 2007).
Prevention programs must be implemented to all health
system to have a substantial effect on schizophrenia
prevalence but a significant proportion of even
schizophrenia patients are not getting required medical
attention not only in countries like Turkey with
insufficient funds for health services but also in
developed countries like USA.
In intervention studies %30-50 of groups converts
to psychosis leaving a 50-70 percent without a clinical
diagnosis, which may well be the case for the rest of
their lives. Treating subjects with the chance to never
become clinically disturbed raises a number of ethical
challenges, in particular the imperative to do no harm.
Unnecessary additional stress for the patient and the
family, stigma and unwanted consequences are possible
effects of both psychosocial and medical treatments.
Medication side effects like EPS and metabolic changes
and possible effects on developing adolescent brain
should be assessed meticulously for the risk-benefit
ratio. In the only intervention study using antipsychotics
as the sole intervention (McGlashan et al. 2006), high
dropout rate due to weight gain and sedation is alerting.
Focusing early diagnosis and intervention (EDI)
efforts to subjects with considerable positive symptoms,
if not highly disabling negative and depressive ones
(Häfner and Maurer 2005), means we are trying to reduce risk of progression and severity rather than the
disorder itself. The perfect prevention should take place
before any symptoms and relieve those at risk or all the
population by an innocuous intervention. To reach such
prevention measures, risk factors for the disorder and
Clinical Neuropsychiatry (2008) 5, 6
their timing (prenatal, adolescence etc) must be defined
clearly. Population attributable risks of 10.5% for winter
spring birth, 36.5% for urban effect, 14% for cannabis
use and 5-10% for birth complications are quite
impressing (McGrath 2003, Moore et al. 2007,
Mortensen et al. 1999) but as those risk factors are
proxies for real risk modifying factors and the real
factors responsible like infectious agents, psychosocial
effects etc. are to be clarified, they are not suitable for
intervention targets yet.
Efforts for perfect prevention may be delayed until
we know a lot more about real risk factors but McGrath
reminds us about the miasma theory that led to the
improved sanitation long before the discovery of
microorganisms and the consumption of limes on long
sea voyages to prevent scurvy before understanding of
ascorbic acid (McGrath 2003). The long delay between
a possible prenatal risk factor and the onset of psychotic
disorder and the complex nature of schizophrenia
including gene-environment interaction and multiple
etiopathogenic processes under the psychosis title may
limit our hope for such a shortcut to be discovered but
we think this should be a target kept alive. Progress
from risk factors study can always be expected. Results
from cannabis studies alerted the United Kingdom
authorities and their stance on cannabis changed.
First episode psychosis and first few years may
bear an important opportunity to effect long term
compliance and outcome. Specialized services with
intensive and sometimes assertive care may be more
efficient and economical on the long run (McGorry et
al. 2007). This field is still demanding, in both research
and services.
Epidemiology is offering us new risk factor
gradients and large scale epidemiological studies with
multiple approaches addressing neurobiology, genetics
with the power of animal models and molecular
strategies may have the highest yield. Field studies of
subjects with sub-clinical positive and negative
symptoms, including those who do not demand
treatment can be expected to be most informative.
Representative sample sizes which will lead to
population attributable risk estimates should be
targeted. Follow up of such samples concentrating on
environmental factors, functional changes and geneenvironment interactions are surely needed.
It should be remembered that the revelation of risk
factors for cardiovascular disorders were possible not
only after progress in related basic sciences but after
field studies including thousands and thousands of
subjects. Though not affecting such a big percentage
of the population, psychosis is associated with very high
personal and societal burdens and the priority it deserves
should be addressed in funding and design of EDI
studies.
Turkish psychiatry has been aware of the now
strongly established cannabis psychosis association for
quite a while. Mazhar Osman Uzman, one of the
founders of modern psychiatry in Turkey, defined a
“schizophrenic reaction” elicited by cannabis use and
drew attention to the association more than 50 years
ago (Songar 1971). In Turkey cannabis use is neither
prevalent in the community nor in schizophrenics.
Alptekin et al. (2005) screened general population for
psychotic symptoms and reported a rate of 3.6%, which
291
Meram Can Saka, M. KazÚm YazÚcÚ
is lower than most of the similar studies and cannabis
use was reported in only 3 of 1268 subjects. Fortunately
right now it is not an important risk factor for Turkey
however in the light of rising substance problems and
high international and intra-national migration, it is a
factor to keep in mind as it may become more important
in the near future.
It is obvious that we need consensus prodrome
criteria with high predictive values convenient for
public health practice, more robust data about
antipsychotics efficacy for preventing or delaying
conversion to psychosis and especially associated
disability, long term extrapyramidal, metabolic and
developmental side effects. Still clinician facing
functional deterioration and increasing positive or negative symptoms must intervene. In Turkey early
psychotic symptoms are traditionally approached with
antidepressants, supportive and family oriented
psychotherapy, in compliance with the current data and
guidelines. But when the psychotic break seems
imminent antipsychotics are considered. At this point
the risk benefit ratio must be assessed for each patient
individually, taking into account all the listed
disadvantages; which seems to be the case in Turkish
psychiatry too. Almost all the population of Turkey is
covered by Health Insurance System, with different
agencies for different professions (civil servants,
workers, tradesmen) and other government funds for
people with low income - no profession and atypical
antipsychotics became available in Turkey almost
immediately after they are introduced in USA and EU.
Thus prodromal patients from every walk of life have
been treated with atypical antipsychotics since they are
available.
Contrary to the availability of medications, there
are almost no specialized rehabilitation services or
community treatments in psychiatry with the exception
of a few short lived examples, built on some personal
efforts. The number of psychiatrists, psychiatric beds
and supporting personnel (psychologist, social worker
etc.) are way below the preferred levels. Indeed a big
majority of the psychiatric services in Turkey are
provided by the government with eight big mental
health hospitals located throughout the country
supplying most of the psychiatric beds. Government
hospitals in most cities have psychiatrists but few have
inpatient facilities. Thus accessing outpatient treatments
may be difficult for a part of the community, especially
to those who live in the rural areas but inpatient facilities
are inadequate for everyone alike.
In addition to the limited accessibility of
psychiatric services, primary health services also
provide limited care for people with mental illness
(KÚlÚc et al. 1994). Low rate of mental health referrals
in general health care (YÚldÚz M et al. 2003) also
contributes to low service utilization in Turkey. In YÚldÚz
et al’s (2003) study, designed to assess general
practitioners’ attitudes and behavior towards psychotic
disorders, practitioners in primary care settings report
encountering patients with psychosis rarely. To us, the
reasons behind this may be either the dysfunctional
referring system causing psychosis patients to apply to
specialty clinics and psychiatrists first or they are not
recognized by general practitioners. Likewise in the
community survey conducted by SaXduyu et al. (2001)
292
on a wide sample in Turkey, the majority of participants
identified schizophrenia as a mental illness (76.5%),
the most commonly endorsed causes being stressful
life events (54.3%) and weak mental constitution
(52%). Three quarters of the sample chose medical
treatment as the first thing to do and 90% of those
assessed psychiatry as the proper address and only %3.5
thought traditional or local treatments beneficial. Those
results also stress that there are a lot to do for the
utilization of primary care for mental disorders. Yet the
possibility of practitioners’ failure to recognize
psychosis is important for mental disorders that are not
prominent and especially for prodrome. In YÚldÚz et al’s
above mentioned study (2003), almost a half of GPs
sought structured and advanced education about
psychosis, supporting this possibility.
Governmental and other professional authorities
had organized some educational activities for
practitioners aiming to raise recognition and treatment
rates of depression and, PTSD after big earthquakes,
but none for schizophrenia. Ucok et al. (2006) report a
small scale study on education against stigma related
to schizophrenia, where practitioners developed a more
favorable view on availability and their capability of
participating to the treatment of schizophrenia. Thus,
primary health care remains at the central stage for
mental health promotion activities in Turkey (Uçok et
al. 2006).
There are no specialized centers or government
funds for EDI studies in Turkey yet. A serious drawback
to EDI studies is the scarceness of epidemiological data
on schizophrenia and psychosis. Previously mentioned
study of Alptekin et al. (2005) gave an opinion on
psychotic symptoms. A large scale study to assess
incidence and prevalence as well as treatment and
service use has been started recently with first results
expected in 2010 (Binbay et al., personal
communication, June 1, 2008). Some groups are
working on early psychosis (Atbasoglu et al. 2005) and
highly cited DUP studies have been reported (Uçok et
al. 2004). The first completed high risk study in Turkey,
to our knowledge, is Aydin and Ucok’s study in that
the changes in the brains of high risk subjects were
investigated by using magnetic resonance spectroscopy
(Aydin et al. 2008). To our knowledge, there are no
reported EDI studies. Schizophrenia Proneness
Instrument Adult Version (SPI-A) (Schultze-Lutter et
al. 2006) has recently been adapted to Turkish,
supervised by one of the authors (MKY) and is about
to be submitted by the group who are conducting a
psychosis prediction project in adolescents with high
genetic loading for schizophrenia with structural and
metabolic brain imaging and electrophysiological
testing. Another big scale follow-up of normal young
adults with assessment of sub-clinical psychosis,
academic and social functioning is also going on with
results expected soon by the group of the other author
(MCS). The same group have adapted the Chapman
Magical Ideation scale and adopting other Wisconsin
schizotypy scales to Turkish (Atbasoglu et al. 2003).
As seen EDI studies are in infancy in Turkey. After
accumulation of some epidemiological data, experience
with research in this group and with hopefully more
positive results from the world, we can hope to create
public opinion, governmental support and funds for EDI
Clinical Neuropsychiatry (2008) 5, 6
Early Diagnosis and Intervention in Psychosis: Perspective from Turkey
studies.
Extensive early diagnosis and intervention systems
may be seen as an overambitious target for Turkey for
now, considering very limited resources for
rehabilitation and almost no community treatments like
halfway houses or assertive community treatments for
schizophrenia. EDI is expected to be cost effective in
both personal and financial burdens of the disorder, if
disabling and chronic nature of the disorder can be
overcome. Results from a country like Turkey with
limited resources but high levels of accessibility and
attainability of medical treatment, young population,
high rates of intra-national migration between very
different life circumstances, ethnic groups, different
family and social relation patterns can be of use for the
area worldwide.
References
Alptekin K, Semin S, Akdede BB, Ergor G, Akvardar Y, Demiral
Y, et al. (2005). Risk factors and prevalance of psychotic
symptoms in the general population in Izmir-Turkey.
Schizophr Bull 31, 215.
Atbasoglu EC, Kalaycioglu C, Nalcaci E (2003). [Reliability
and validity of Turkish version of magical ideation scale
in university students]. Turk Psikiyatri Derg 14, 31-41.
Atbasoglu EC, Ozguven HD, Saka MC, Olmez S (2005). Relative sparing of executive functions in the early phase of
schizophrenia. J Neuropsychiatry Clin Neurosci 17, 510516.
Aydin K, Ucok A, Guler J (2008). Altered Metabolic Integrity
of Corpus Callosum Among Individuals at Ultra High Risk
of Schizophrenia and First-Episode Patients. Biol
Psychiatry, in press.
Bleuler E (1911). Dementia praecox oder Gruppe der
Schizophrenien. Deuticke, Leipzig, pp 1-420.
Cameron DE (1938). Early diagnosis of schizophrenia by the
general practitioner. N Engl J Med 218, 221-224.
Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington
J, Walker E, et al. (2008). Prediction of psychosis in youth
at high clinical risk: a multisite longitudinal study in North
America. Arch Gen Psychiatry 65, 28-37.
Cornblatt BA, Lencz T, Smith CW, Correll CU, Auther AM,
Nakayama E (2003). The schizophrenia prodrome
revisited: a neurodevelopmental perspective. Schizophr
Bull 29, 633-651.
Gillberg IC, Hellgren L, Gillberg C (1993). Psychotic disorders
diagnosed in adolescence. Outcome at age 30 years. J Child
Psychol Psychiatry 34, 1173-1185.
Häfner H, Loffler W, Maurer K, Hambrecht M, an der Heiden
W (1999). Depression, negative symptoms, social
stagnation and social decline in the early course of
schizophrenia. Acta Psychiatr Scand 100, 105-118.
Häfner H, Maurer K (2005). Prodromal Symptoms and Early
Detection of Schizophrenia. In Maj M (ed) Early detection
and management of mental disorders. Wiley, Chichester,
pp 1-51.
Kilic C, Rezaki M, Ustun TB, Gader RA (1994). Pathways to
psychiatric care in Ankara. Soc Psychiatry Psychiatr
Epidemiol 29, 131-136.
Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace
T (2005). Association between duration of untreated
psychosis and outcome in cohorts of first-episode patients:
a systematic review. Arch Gen Psychiatry 62, 975-983.
McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T,
Woods SW, et al. (2006). Randomized, double-blind trial
of olanzapine versus placebo in patients prodromally
symptomatic for psychosis. Am J Psychiatry 163, 790-799.
McGorry PD, Edwards J, Yung AR (2005). The Management of
Clinical Neuropsychiatry (2008) 5, 6
Early Psychosis. In: Maj M editor. Early detection and
management of mental disorders. Wiley, Chichester, pp
51-109.
McGorry PD, Killackey E, Yung AR (2007). Early intervention
in psychotic disorders: detection and treatment of the first
episode and the critical early stages. Med J Aust 187, S810.
McGorry PD, Yung AR, Phillips LJ, Yuen HP, Francey S,
Cosgrave EM, et al. (2002). Randomized controlled trial
of interventions designed to reduce the risk of progression
to first-episode psychosis in a clinical sample with
subthreshold symptoms. Arch Gen Psychiatry 59, 921-928.
McGrath J (2003). Prevention of schizophrenia – not an
impossible dream. In Murray R (ed) The epidemiology of
schizophrenia. Cambridge University Press, Cambridge,
pp 427-439.
Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO,
Opjordsmoen S, et al. (2004). Reducing the duration of
untreated first-episode psychosis: effects on clinical
presentation. Arch Gen Psychiatry 61, 143-150.
Moore THM, Zammit S, Lingford-Hughes A, Barnes TRE, Jones
PB, Burke M, Lewis G (2007). Cannabis use and risk of
psychotic or affective mental health outcomes: a systematic
review. The Lancet 370, 319-328.
Morrison AP, French P, Walford L, Lewis SW, Kilcommons A,
Green J, et al. (2004). Cognitive therapy for the prevention
of psychosis in people at ultra-high risk: randomised
controlled trial. Br J Psychiatry 185, 291-297.
Mortensen PB, Pedersen CB, Westergaard T, Wohlfahrt J, Ewald
H, Mors O, et al. (1999). Effects of family history and
place and season of birth on the risk of schizophrenia. N
Engl J Med 340, 603-608.
Murray CJL, Lopez AD, Harvard School of Public Health, World
Health Organization, World Bank (1996). The global
burden of disease : a comprehensive assessment of
mortality and disability from diseases, injuries, and risk
factors in 1990 and projected to 2020. [Cambridge, Mass.]:
Published by the Harvard School of Public Health on behalf
of the World Health Organization and the World Bank;
Distributed by Harvard University Press.
Perkins DO, Gu H, Boteva K, Lieberman JA (2005). Relationship
between duration of untreated psychosis and outcome in
first-episode schizophrenia: a critical review and metaanalysis. Am J Psychiatry 162, 1785-1804.
Perkins DO, Miller-Andersen L, Lieberman JA (2006). Natural
History and Predictors of Clinical Course. In Lieberman
JA, Stroup TS, Perkins DO, American Psychiatric
Publishing (eds) The American Psychiatric Publishing
Textbook of Schizophrenia, 1st ed. American Psychiatric
Pub, Washington, DC, pp xvii, 435 p.
Remschmidt H (2002). Early-onset schizophrenia as a progressive-deteriorating developmental disorder: evidence from
child psychiatry. J Neural Transm 109, 101-117.
SaXduyu A, Aker T, Özmen E, Ögel K, Tamar D (2001). HalkÚn
œizofreniye BakÚÚ Ve YaklaÚmÚ Üzerine Bir Epidemiyolojik AratÚrma. Turk Psikiyatri Derg 12, 2, 99-110.
Saha S, Chant D, Welham J, McGrath J (2005). A systematic
review of the prevalence of schizophrenia. PLoS Med 2,
e141.
Schultze-Lutter F, Ruhrmann S, Picker HKJ (2006). The
Schizophrenia Proneness Instrument (SPI-A) - a tool for
the assessment of basic symptoms. European Psychiatry
21, S27.
Sheitman BB, Lieberman JA (1998). The natural history and
pathophysiology of treatment resistant schizophrenia. J
Psychiatr Res 32, 143-150.
Simon AE, Roth B, Zmilacher S, Isler E, Umbricht D (2007).
Developing services for the early detection of psychosis:
a critical consideration of the current state of the art. Eur
Child Adolesc Psychiatry 16, 96-103.
Songar A (1971). eptilâlar ve entoksikasyon PsikozlarÚ Psikiyatri.
estanbul Gül MatbaasÚ, pp 367-419.
Sullivan SH (1927). The onset of schizophrenia. Am J Psychiatry
293
Meram Can Saka, M. KazÚm YazÚcÚ
6, 105-134.
Uçok A, Soygür H, Atakli C, Kucu K, Sartorius N, Duman ZC,
et al. (2006). The impact of antistigma education on the
attitudes of general practitioners regarding schizophrenia.
Psychiatry Clin Neurosci 60, 4, 439-43.
Uçok A, Polat A, Genc A, Cakir S, Turan N (2004). Duration of
untreated psychosis may predict acute treatment response
in first-episode schizophrenia. J Psychiatr Res 38, 163168.
van Os J, Burns T, Cavallaro R, Leucht S, Peuskens J, Helldin
L, et al. (2006). Standardized remission criteria in
schizophrenia. Acta Psychiatr Scand 113, 91-95.
van Os J, Verdoux H (2003). Diagnosis and classification of
294
schizophrenia: categories versus dimensions, distributions
versus disease. In Murray R (ed) The epidemiology of
schizophrenia. Cambridge University Press, Cambridge,
New York, NY, pp 364-410.
YÚldÚz M, Onder ME, Tural U, Balta HI, Kocalim N (2003).
General practitioners’ attitudes towards psychotic disorders
and their treatment in primary health care system. Turk
Psikiyatri Derg 14, 106-105.
Yung AR, McGorry PD, Francey SM, Nelson B, Baker K, Phillips
LJ, et al. (2007). PACE: a specialised service for young
people at risk of psychotic disorders. Med J Aust 187, S4346.
Clinical Neuropsychiatry (2008) 5, 6