Developing Criteria for Atrisk Mental States and Ultrahigh Risk

The ideas expressed by Bell [23] were first translated into practice in Melbourne, Australia in 1994 at the Personal Assessment and Clinical Evaluation (PACE) Clinic [24]. This approach has now been adopted in a number of other clinical research programmes across the world (e.g. 25-27). These studies have been referred to as ''ultra-high-risk'' (UHR) studies to differentiate them from the traditional high-risk studies that rely on family history as the primary inclusion criteria. Intake criteria for such studies were initially developed from information gleaned from literature reviews and clinical experience with first-episode psychosis patients and have been evaluated and refined in the PACE Clinic over the past eight years. Although the UHR studies ostensibly seek to identify individuals experiencing an initial psychotic prodrome, infallible criteria have not yet been developed towards this end. In addition, ''prodrome'' is a retrospective concept that can only be applied once the full illness develops. Therefore, criteria used in these studies are collectively referred to as at-risk mental state (ARMS) criteria [28,29] or ''precursor'' signs and symptoms [30], while the UHR criteria are the operationally defined subset which accurately predicts transition. This terminology does not imply that a full threshold psychotic illness such as schizophrenia is inevitable, but suggests that an individual is at risk of developing a psychotic disorder by virtue of his/her current mental state. This terminology is more conservative than the use of the term prodrome which, as mentioned, can only be accurately applied in retrospect if and when the disorder in question fully emerges. Additionally, the ARMS concept acknowledges current limitations in our knowledge and understanding about psychosis. This frankness is arguably superior in an ethical sense, and it should be noted that participants in this approach are voluntary and help-seeking, i.e. they are concerned about changes in their mental state and functioning and are requesting some assistance to address these changes. Indeed, in many cases, the young people are concerned about the possibility that they may be developing a psychotic disorder.

UHR criteria currently in operation at the PACE Clinic require that the person falls into one or more of the following groups: (a) attenuated psychotic symptoms group (they have experienced subthreshold, attenuated positive psychotic symptoms during the past year); (b) brief limited or intermittent psychotic symptoms (BLIPS) group (they have experienced episodes of frank psychotic symptoms that have not lasted longer than a week and have spontaneously abated); or (c) trait and state risk factor group (they have a first-degree relative with a psychotic disorder or the identified client has a schizotypal personality disorder and they have experienced a significant decrease in functioning during the previous year). Operationa-lized criteria are shown in Table 2.4. As well as meeting the criteria for at least one of these groups, subjects are aged between 14 and 30 years, have not experienced a previous psychotic episode and live in the Melbourne metropolitan area. Thus, the UHR criteria identify young people in the age range with peak incidence of onset of a psychotic disorder (late adolescence/early adulthood) who additionally describe mental state and functional changes that are suggestive of an emerging psychotic process and/or may have a strong family history of psychosis. Thus, the multiple-gate screening and close-in strategies recommended by Bell [23] have been translated into practice. Despite the paucity of knowledge about causal risk factors, clinical and functional changes have been utilized to fill this gap and connote increased levels of risk. Exclusion criteria are intellectual disability, lack of fluency in English, presence of a known organic brain disorder, and a history of a prior psychotic episode, either treated or untreated. It is recognized that some subthreshold cases, in particular those meeting BLIPS criteria, might meet criteria for DSM-IV brief psychotic disorder. However, such a diagnosis does not necessarily require the prescription of antipsychotic medication.

Criteria have also been developed to define the onset of psychosis in the UHR group (Table 2.4). These are not identical to DSM-IV criteria, but are designed to define the minimal point at which antipsychotic treatment is indicated. This definition of onset of psychosis might be viewed as somewhat arbitrary, but does at least have clear treatment implications and applies equally well to substance-related symptoms, symptoms that have a mood component - either depression or mania - and schizophrenia spectrum disorders. The predictive target is first-episode psychosis which is judged to require antipsychotic medication, arbitrarily defined by the persistence of frank/severe psychotic symptoms for over 1 week. Schizophrenia is a subset or subsidiary target, since although the majority of progressions from the ARMS ultimately fall within the schizophrenia spectrum (schizophreniform disorder or schizophrenia), a significant minority do not. In fact, the broader first-episode psychosis target is a more proximal and therapeutically salient one than schizophrenia, which can be considered a subtype to which additional patients can graduate distal to first-episode psychosis (as well as being one of the proximal categories). This logic applies to the early intervention field generally, where first-episode psychosis is a more practical, flexible and safer concept than first-episode schizophrenia (again best considered as a subtype).

The criteria described in Table 2.4 have been evaluated in a series of studies at the PACE Clinic between 1994 and 1996. Young people meeting the UHR criteria were recruited and their mental state was monitored over a 12-month period. At the end of the follow-up, 41% of the cohort had developed an acute

Table 2.4 Ultra-high-risk criteria according to Comprehensive Assessment of At-Risk Mental States (CAARMS) scores

Group 1: Attenuated psychotic symptoms

• Subthreshold psychotic symptoms: severity scale score of 3-5 on Disorders of Thought Content subscale, 3-4 on Perceptual Abnormalities subscale and/or 4-5 on Disorganized Speech subscales of the CAARMS; plus

• Frequency scale score of 3-6 on Disorders of Thought Content, Perceptual Abnormalities and/or Disorganized Speech subscales of the CAARMS for at least a week; or

• Frequency scale score of 2 on Disorders of Thought Content, Perceptual Abnormalities and Disorganized Speech subscales of the CAARMS on more than two occasions; plus

• Symptoms present in the past year and for not longer than five years.

Group 2: Brief limited or intermittent psychotic symptoms (BLIPS)

• Transient psychotic symptoms: severity scale score of 6 on Disorders of Thought Content Subscale, 5 or 6 on Perceptual Abnormalities subscale and/or 6 on Disorganized Speech subscales of the CAARMS; plus

• Frequency scale score of 1-3 on Disorders of Thought Content, Perceptual Abnormalities and/or Disorganized Speech subscales; plus

• Each episode of symptoms is present for less than one week and symptoms spontaneously remit on every occasion; plus

• Symptoms occurred during last year and for not longer than five years.

Group 3: Trait and state risk factors

• First-degree relative with a psychotic disorder or schizotypal personality disorder in the identified patient (as defined by DSM-IV); plus

• Significant decrease in mental state or functioning, maintained for at least a month and not longer than 5 years (reduction in Global Assessment of Functioning (GAF) scale of 30% from premorbid level); plus

• The decrease in functioning occurred within the past year and has been maintained for at least a month.

Transition to first-episode psychosis or acute psychosis criteria

• Severity scale score of 6 on Disorders of Thought Content subscale, 5 or 6 on Perceptual Abnormalities subscale and/or 6 on Disorganized Speech subscales of the CAARMS; plus

• Frequency scale score greater than or equal to 4 on Disorders of Thought Content, Perceptual Abnormalities and/or Disorganized Speech subscales; plus

• Symptoms present for longer than one week.

psychosis and had been started on appropriate antipsychotic treatment [18,19]. This occurred despite the provision of minimal supportive counselling, case management and selective serotonin reuptake inhibitor (SSRI) medication, if required. The primary diagnostic outcome of the group who developed an acute psychosis was schizophrenia (65%) [19].

The high transition rate to psychosis indicates that these criteria accurately identify young people with an extremely high risk of developing a psychotic disorder within a short follow-up period. These results cannot be easily generalized to the wider population as a whole or even to individuals with a family history of psychosis who are asymptomatic. Participants at the PACE Clinic are a selected sample, characterized perhaps by high help-seeking characteristics or other nonspecific factors. The sample undoubtedly includes only a minority of those who proceed to a first episode of psychosis, and a possibly unstable proportion of false positives, depending on sampling and detection factors, which in turn are difficult to define and measure, but which can affect the base rate of true positives in the sample. Hence the transition rate may vary and needs to be validated and monitored, because the UHR criteria are not the only variable involved. However, these criteria are now being utilized in a number of other settings around the world, with preliminary results indicating that they predict equally well in the USA, the UK and Norway as in Melbourne, Australia [26,27,31].

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