Attenuated psychosis syndrome, at risk mental state and ultra high risk
AT RISK MENTAL STATE (ARMS),
ULTRA HIGH RISK (UHR) AND
ATTENUATED PSYCHOSIS SYNDROME
What is ARMS?
• Refer to these individuals who appear to be at risk of psychosis but
in whom psychosis is not inevitable. (McGorry and Singh, 1995)
• Not all people with operationally defined subthreshold forms of
psychosis will go on to develop a diagnosable psychotic disorder
such as schizophrenia.
• The ‘‘natural history’’ of the ARMS criteria was examined. A
transition rate of 41% was demonstrated. (Yung et al., 2003)
• Factors that predict an increased likelihood of the development of
psychosis are –
▫ Long duration of subthreshold (‘prodromal’) symptoms
▫ Poor functioning at presentation
▫ High levels of depressive symptoms
▫ Higher attenuated symptoms (c/f attenuated syndrome)
ARMS and “Prodrome”
• Prodromal means all the people who have it, WILL develop
psychosis (100% certainty).
• Prodrome of schizophrenia has initially been defined as “an
early or premonitory manifestation of impending disease, before
specific symptoms begin”
• So prodrome is a retrospective concept rather than a prospective
• If it is not clear 100% at the time of their presentation whether
psychosis will follow or not, then “ARMS” should be used.
• So ARMS is a prospective concept introduced for early identification
of psychotic patients.
• People with ARMS are whom intervention at an early stage, before
onset of frank psychosis, could be justified in order to prevent
further deterioration and suffering.
Why is ARMS/Prodrome important?
• Can lead to severe functional impairment, stigmatizing
disabilities and life-threathening consequences.
• Persistence of those disabilities prior to the onset of full positive
psychotic syndrome may lower the possibility of eventual
recovery (Schultze-Lutter et al. 2008, Marshall et al. 2005,
Perkins et al. 2005, Fusar-Poli et al. 2009)
• Preventive treatment could minimize alterations in brain structure,
as well as neurobiological changes, which could lead to substantial
improvement of the prognosis (Nelson et al. 2008)
for Detection of Patients at High Risk
1. UHR criteria (Personal assessment and crisis
evaluation clinic, Melbourne)
2. Basic symptoms criteria
ULTRA HIGH RISK (UHR)
Because of the non-specific nature of the ARMS as
well as absence of the “Prospective” definition of
prodrome (Yung et al., 1996), the concept of
“Ultra high risk” for psychosis was introduced by
researchers in Melbourne, Victoria in 2003,
which has subsequently undergone many
changes, and further studies, the recent one
being in early 2014.
This concept of “Ultra High Risk” is a
refined extension of ARMS
• Subjects were recruited into this study from the
Personal Assessment and Crisis Evaluation
(PACE) Clinic, Melbourne, Australia (Yung et al.,
• All referrals to the Clinic between March 1995
and January 1999 were screened for inclusion.
• Referral sources included general practitioners,
psychiatric services, school and university
counseling services, and other support agencies
working with young people, such as drug and
Subjects were included in the research program if
(a) were aged between 14 and 30 years
(b)Met criteria for one or more of the groups
(c) had not experienced a previous psychotic
(d)were living in the Melbourne metropolitan area
Exclusion criteria were: intellectual disability, lack
of fluency in English, and presence of known
organic brain disorder or previous psychosis
Essentially there are three sets of separate intake
criteria FOR UHR people :
Group 1: Attenuated psychotic symptoms (APS)
Group 2: ‘‘Brief Limited Intermittent Psychotic
Group 3: Trait and State risk factors
Scales used in this study -
• Brief Psychiatric Rating Scale 24 item version
(BPRS) (McGorry et al., 1988)
• the Comprehensive Assessment of Symptoms
and History (CASH) (Andreasen, 1987) which
were used to measure the intensity of a psychotic
BPRS SUBCOMPONENTS included in
• 11 – UNUSUAL THOUGHT CONTENT
• 10 – HALLUCINATIONS
• 9 – SUSPICIOUSNESS
• 15 – CONCEPTUAL DISORGANISATION
CASH rating scale – delusional
subcomponent included in PACE
Group 1 - Attenuated Psychotic Symptoms
• Symptoms that deviate from normal phenomena but which are not yet
frankly psychotic eg. Overvalued idea.
• The duration of attenuated psychotic symptoms should be <5 years.
• This limit on the duration of the attenuated psychotic features was
included as long duration trait phenomena (schizotypal personality
disorder) rather than acute mental state change.
• However, subjects meeting this criterion might well have other
symptoms, such as depressed mood or anxiety, lasting over 5 years.
• Thus the maximum duration of symptoms applies only to the actual
Group 2: ‘‘Brief Limited Intermittent Psychotic
• Symptoms of psychotic intensity but which have a total
duration of <7 days before resolving spontaneously.
• A recency criterion is included for this group: symptoms
must have occurred within the last year.
• Someone with a brief psychotic experience which
occurred over 1 year ago would be excluded from
the study as the period of risk is thought to be no longer
Group 3 ‘‘Trait and State Risk Factors’’
• Have nonspecific symptoms such as
lowered mood or anxiety
some trait risk factor for psychotic disorder (schizotypal PD) or a family
history of a psychotic disorder in a first-degree relative
at least 1 month to not longer than 5 years (to exclude trait
• Have marked disability or decrease in functioning.
• This severity criterion is necessary to exclude otherwise normal relatives
of patients with psychotic illnesses who have a brief period of mild
• A recency criterion of deterioration within the last year is also included
so that people who deteriorate but who then recover are not labeled as high
risk as the period of risk is thought to be no longer current.
When does subject become psychotic?
• If it is a delusion, it is acquisition of delusional conviction and
preoccupation with the belief.
• Essentially the definition of psychosis describes a clinical picture of
frank delusions, hallucinations, or formal thought disorder present
most of the time and for at least one week (Exclusion criteria in
• NOTE – This definition used here is for antipsychotic rx
rather than a diagnostic category as endpoint, and does
not conform to DSM-IV standards
• Thirty-six subjects (34.6%) developed frank
psychotic symptoms within 12 months.
• Measures of symptom duration, functioning,
disability and psychopathology were made at
intake, 6 and 12 months.
• Poor functioning, long duration of symptoms,
high levels of depression and reduced attention
were all predictors of psychosis
RESULTS of 2006 study
• UHR+ individuals were significantly more likely
to become psychotic than UHR- individuals
(Odds Ratio 19.3, 95% CI 2.5, 150.5).
• Low functioning at baseline was associated with
psychosis onset in the whole sample and in the
A.R. Yung et al. / Schizophrenia Research 84 (2006) 57–66
RECENT STUDIES in UHR criteria
• More recent studies (Yung et al. 2007, McGorry et al. 2008,
Cannon et al. 2007) tends to show a lower rate of annual transition
(20-35%), which could be due to earlier detection, improved
efficacy of intervention and a “dilution effect” (greater portion of
• 30-35 % risk of psychosis within 1 to 2 years of follow-up among
UHR cases, a rate definitively higher that the incidence rate of
psychosis in the general young population (Cannon et al. 2007)
• A large longitudinal North American study published in 2009
shows that 40% of the 377 patients assessed by the Structured
Interview for Prodromal Syndromes (SIPS) as meeting criteria for
prodromal syndromes, converted to fully psychotic illness during
the 2.5 years of follow-up (Woods et al. 2009)
BASIC SYMPTOMS CRITERIA
(Koch et al. 2010,
Nelson et al. 2008)
• The annual conversion rate for sample meeting basic symptoms
criteria is around 25% (Koch et al. 2010)
• Rate of conversion reaches 70% in a study with a 110 patient’s
follow-up of 9.6 years, with a mean time to onset of 5.6 years
(Nelson et al. 2008)
• Some authors consider that the Basic (Cognitive) Symptoms
precede the onset of APS and BLIPS according to according to
Comprehensive Assessment of At Risk Mental States (CAARMS)
criteria (Koutsouleris et al. 2009)
• A 2010 German retrospective study exploring the time-related
syndromic sequence preceding the onset of full-blown psychosis
(Shultze-Lutter et al. 2010) DID NOT CONFIRM ABOVE
• In a naturalistic 48-month follow-up study, the conversion rate to
ﬁrst-episode psychosis was studied in 246 outpatients of an early
detection of psychosis service (FETZ); thereby, the association
between conversion, and the combined and singular use of UHR
criteria and COGDIS was compared.
• Patients that met UHR criteria and COGDIS (n = 127) at baseline
had a signiﬁcantly higher risk of conversion (hr = 0.66 at month
48) and a shorter time to conversion than patients that met only
UHR criteria (n = 37; hr = 0.28) or only COGDIS (n = 30; hr = 0.23)
UHR positivity PLUS COGDIS positivity =
GREATER RISK FOR CONVERSION to
PSYCHOSIS within 6 years.
Where is it actually in DSM-5?
• At first glance, it seems to be included in “Conditions for further
study” in Page 783.
• Is it there in the main text? YES. It is given as an example 3 in
Other Specified Schizophrenia Spectrum and Other
Psychotic disorder 298.8 (F28 in ICD-10 as Other nonorganic
psychotic disorder) in Page 122.
• As an “Other” disorder with its own numerical code, APS can now
be diagnosed and used to bill for insurance reimbursement,
although the DSM-5 Psychosis task group initially promised it
would not include it.
• So technically, ATTENUATED PSYCHOSIS SYNDROME is very
much an already existing diagnosis.
Why should it not have been included in
• Many attenuated symptoms are quite stable and do not lead to more
severe illness, as in individuals who have schizotypal personality
disorder, who rarely become psychotic, or in the nearly 10% of
normal individuals who believe in sorcery or aliens or hear voices.
• No proven treatment for this syndrome. Attempts to institute early
antipsychotic treatment have shown no long-lasting effect and only
exposed these individuals to drug side effects.
• Research also requires a consensus among researchers and funding
agencies that a population of affected persons can be identified.
• Premature diagnosis may have negative consequences on the
expectations and acceptance of others in the individual’s social
environment (People diagnosed are young).
• Field testing will assess whether the diagnosis can be made reliably
over time by different clinicians on the same patient and in
agreement with those who have conducted the initial research.
• ULTIMATELY, WHY IT should not have been INCLUDED IS
BECAUSE OF INSUFFICIENT FIELD TESTING AS WELL AS
INCONCLUSIVE TREATMENT PLANS AND/OR
• Diminution of the transition rate about 15% in favor of the
antipsychotics which reached statistical significance only in
the studies using risperidone and amisulpride (McGorry et al.
2002, Rurhmann et al. 2007).
• A randomized, placebo-controlled trial (Amminger et al. 2010)
involving long chain omega-3 FA with a 12-week intervention
and 40-weeks monitoring period showed a reduction of 22.6% (28%
to 5%) of the cumulative risk of progression to full-threshold
psychosis for the intervention group.
• Long-chain Ω-3 fatty acids also significantly reduced positive,
negative and general symptoms and improved functioning,
compared with placebo.
• A randomized study (Morrison et al. 2004) comparing CBT
over 6 months with monthly monitoring in 58 patients meeting
UHR criteria showed a 15% reduction of the rate of conversion
to full blown psychosis.
• Seventy-nine patients were randomized to Integrated model
treatment (Modified Assertive Community Treatment, Social
skills training, and Psycho-education in multiple-family groups). At
two-year follow-up, the proportion diagnosed with a psychotic
disorder was 25.0% for patients randomized to integrated
treatment vs standard treatment (48.3%) (Nordentoft et al. 2006).