Attenuated psychosis syndrome notes

 Corcoran, C. M., Mittal, V. A., & Woods, S. W. (2021). Attenuated Psychosis Syndrome should be
moved to the main section in DSM-5-TR. JAMA Psychiatry, 78(8), 821-822.

 APS placed in disorders in need of further study

 CHR construct created in 90s to ID warning signs (putative prodrome) of schizo/psychosis
 Includes 3 sydnromes based on AP symptoms
 APS is most common CHR syndrome (85%)
 Upon first symptoms the illness has likely been underway for several years with significant
deficits in other areas
 Main goal is the prevention of a more severe disorder
 Proposed for DSM in 2010 and met most criteria including substantial evidence for validity,
clinical value and nonoverlap with existing diagnoses
 Hotly debated in relation to the benefit to harm ratio
 Concern about stigma and antipsychotic exposure, especially for false positive patients
 Effective treatments had not been developed and sig heterogeneity existed within the
psychosis risk construct and across outcomes
 Proponents emphasised the benefits and argued that risks could be mitigated
 Concern on whether clinicians could make reliable and valid diagnoses of APS due to small
field trials
 Addressing the concerns
 Stigma shown to be more about symptoms than actual diagnostic label and that stigma can
be managed through education
 Overuse of antipsychotics managed through development of treatment guidelines and
professional education
 Many in CHR who do not develop psychotic disorder still show persistent other symptms
 Lack of research would actually be fixed with inclusion as more better studies could be done
 There have been sig advancements in treatments for CHR such as CBT, cogntitive
remediation and aerobic exercise
 Other stuff like MDD also has heterogeneity
 Heterogeneity is good actually
 The proposed diagnosis must meet criteria for a mental disorder, have strong evidence of
validity, be capable of being applied reliably, manifest substantial clinical value, avoid
substantial overlap with existing diagnoses, and have a positive benefit-to-harm ratio
 Reliability wasn’t met before due to less studies but is now due to more studies

Malhi, G. S., & Bell, E. (2019). Make news: Attenuated psychosis syndrome–a premature
speculation? Australian & New Zealand Journal of Psychiatry, 53(10), 1028-1032.

 Focus on what goes wrong and when

 Pathology stypicaly v complex
 Schizophrenia fundamentally characterised by functional decline
 Typically manifests in 30s but could onset much earlier
 Defining onset is hard because source of symptoms and when they begin are unclear
 Due to absence of known detectable pathology we must rely on symptoms
 Clinical success in managing schiz is not great, especially once the illness become entrenched
  Therefore more need to diagnose early because timely interventions may improve outcomes
 Can only be defined in hindsight as we have no reliable means of anticipating psychosis
 90% of schiz describe emotional changes and changes in perception and belief from before
onset of psychotic episodes
 10-20% no symptoms before psychosis
 Nearly all experience a prodrome
 APS
 Added to further study
 Significant potential for misdiagnosis
 Stigma is bad and also unnecessary meds
 Not everyone who experiences subthreshold psychotic symptoms goes on to develop
psychosis AND not all individuals who experience a psychotic episode develop schizophrenia
 Only a third of sub go on to developing psychosis within the following 3 years and of these
only 75% develop schiz
 Therefore only a quarter of sub go on to develop schiz
 Therefore many who exhibit prodrome do not get schiz
 Therefore we must examine the pathways to examine factors and resilience
 Need a clinical threshold with robust discriminability and easily applied
 How this would work with APS is unclear
 Prodrome is useful but whether APS can meaningfully capture this seems improbable
because it is ambiguously defined
 Most disorders are judged (syndromal or subsyndromal) by severity (how many symptoms
are experienced)
 Cant do with APS cos only one symptom is needed
 Delusions and hallucinations by definition requires complete conviction and reality
 APS criteria suggests that for the purposes of attenuation they do not need this
 First time hallucinations are often reposted in a guarded manner so reality testing is often
challenging
 Therefore, evaluating nature of phenomenology is compliucated
 Reality testing is also somewhat subjective
 APS super vague so clinical practice is hard
 Frequency and duration are arbitrary
 Bad cos APS is starting to be used anyways
 Even though they have little prognostic or predictive value
 May be dangerous as it can divert the focus of research
 Prodrome is necessary but APS is not the answer
 Unable to ID biomarkers for psychosis
 Many efforst have been non specific and broad so interventions have had limited results
 Targeted approaches are needed for those who have experienced a psychotic episode
 Evidence say sthat sig permanent neurobiological changes occur once the boundary into
psychosis has been crossed
Tsuang, M. T., Van Os, J., Tandon, R., Barch, D. M., Bustillo, J., Gaebel, W., ... & Carpenter, W.
(2013). Attenuated psychosis syndrome in DSM-5. Schizophrenia research, 150(1), 31-35.

 Schizophrenia is hectic and debilitating and lifelong

 Overall outcome is directly correlated with functional ability prior to onset of psychosis and
inversely correlated with duration of untreated psychosis
 Therefore we need early intervention
 Existing early ID has had moderate effects but these could be even better if we get them
earlier
 Psychosis risk symptom before APS but not moved ahead due to most people not going on
to develop a psychotic disorder and most with this had additional relevant clinical deeds
 Attenuated psychosis syndrome focuses on current clinical need
 Focus on other clinical needs besides psychosis
 Shows DSM criteria
 Rationale
 Most schiz exhibit high range of psychiatric symptoms prior to initial psychotic epidofe
 Declines may be difficult to reverse after psychosis
 No criteria for these people
 Proposed to fill this gap
 Current gap prevents people from getting appropriate clinical attention which may help now
and prevent psychosis
 Other measures to find these people have been made
 1/3 ultra high risk people develop psychosis
 Some interventions have been effective but not adequately differentiated
 Close follow up is important, should include assessment for conversion to psychosis and also
assessment for development of persistence of other psychiatric disorders and provision of
appropriate treatment
 Little is known about prevalence
 About 5% of genpop exhibit symptoms, few of thse seek help and would be eligible for
diagnosis
 Reliability seems fine but lack of data and small sample size
 Data on validity
 Limited antecedent validity
 Some research shows subjects were impaired in general cognitive stuff
 Transition to psychosis was associated with deficits in the verbal fluency and memory
domains
 HR groups had less gray matter volumes in the frontal region, those in HR who developed
psychosis had less grey matter volume in the parahippocampal cortex
 There is an association between elevation of pre-synaptic dopamine synthesis capacity and
transition to psychosis
 Multimodal fMRI-PET and fMRI-MRS data also support the validity of an HR diagnosis
 Predictive validity
 Higher rate of conversion than genpop (22% vs 0.015%) increasing with time
 Studies with HR show that 73% converted to schizophrenia spectrum disorder and 11% to
psychotic mood disorders affective (psychotic depression and bipolar psychosis
 Lack of data on clinical trials testing interventions (also small SS)
 Mixed results regarding interventions
 Recommendation of work group
 Some argue for inclusion, others for development of a general early syndrome of significant
psychopathology
 Consensus that APS warrants systematic attention, but arguments about whether it should
be placed in the main body of the DSM or as an appendix as a condition for further study
 Arguments include
 1. Many people with APS have comorbidities which need treatment, but these symptoms
are common in many disorders and are not relevant to APS
2. Most APS don’t ger full blown schiz, however, many still have symptoms and impairment
which merit attention and the value of id aps is not just to avoid schiz, though that is
nice as well
3. Relationship to schizotypal personality disorder is not clear, however people with APS
don’t qualify for SPD, also many SPD don’t progress to schiz or full psychosis
4. Unclear if help seeking is due to APS or comorbidity, however APS requires help seeking
to be related to the symptom criteria, comorbidities would be judged as secondary
5. Concern about stigma and inappropriate anti-psychotic utilisation, however, new APS
category will educate clinicians about relative lack of utility of antipsychotics in this
population and may actually reduce inappropriate antipsychotic use among youth,
furthermore, any stigma is principally related to behaviours associated with a diagnosis
of APS rather than the diagnosis itself, therefore, the category may reduce traumatic
experiences
 Despite validating research, failed field trials preclude further consideration for inclusion in
the main
 Research has focuses on prodrome
 Further studies will likely broaden the definition and change the proportion of transition
cases that belong on the schiz spectrum
 Work group decided that more work was necessary before full inclusion
 We need to know 1. How APS works in ordinary clinical setting in terms of reliability and
predictive utility. 2. At what stage in development of APS related pathology is it optimal to
defina a disorder. 3. Does the disorder enhance acquisition of therapeutic knowledge
 Work group concluded there are strong reasons for continued evaluation, early detection
and intervention are really good and allow for secondary prevention
 APS is now assigned to section 3 for further study
Yung, A. R., Woods, S. W., Ruhrmann, S., Addington, J., Schultze-Lutter, F., Cornblatt, B. A., ... &
McGlashan, T. H. (2012). Whither the attenuated psychosis syndrome?. Schizophrenia bulletin, 38(6),
1130-1134.

 Formerly known as psychosis risk syndrome

 Based on criteria developed in the 1990s informed by a comprehensive review of
retrospective studies on the prodromal phase of nonaffective psychosis
 Aim to ID people in the prodrome of schiz and other psychotic disorders and have been
titled UHR and CHR and ARMS and prodromal stage
 Criteria associated with higher rates of PD onset
 Possibility of early intervention vs risk of unnecessary diagnosis
 Possibility of stigma and discrimination
 Increased use of antipsychotics
 Absence of an APS category has led clinicians to use the term psychosis NOS, which may lead
to antipsychotic prescription
 APS criteria will enable EB treatments to be developed, including psychological therapies
and could therefore decrease antipsychotic use
 Ultimately was excluded only because of lack of data on the diagnostic reliability of APS
 Points of consensus
 Strong consensus that people who come in for help have symptoms which warrant care
 These people fulfil the broad definition of a mental disorder
  Agreement that this treatment should include monitoring of mental state, supportive
therapy and attention to current practical needs
 CB and omega 3 fatty acids may be helpful
 Antipsychotics not effective
 Consensus that people with APS are at risk of PD
 Within a brief time frame
 Consensus that more research is needed
 Searching for markers
 Need to do longitudinal research to ID bio markers
 Stigma
 Must research harms and benefits of a diagnosis
 Look at stigma and desire for distance
 Reliability and clinical utility
 Reliability of assessment has been demonstrated but not for routine practice
 Must research routine practice reliability,
 Little is known about effects of comorbidities on help seeking
 Lack of research on adolescent and adults and in the general community
 Treatment trials
 Omega 3 fatty acids have been v good but needs more evidence, vitamin d, glycine and
other neuroprotective agents are also worth testing
 Possibility of a pluripotent risk syndrome
 APS could be extended to a broader early intervention thing for other disorders
Trask, C. L., Kameoka, V. A., Schiffman, J., & Cicero, D. C. (2019). Perceptions of attenuated
psychosis in a diverse sample of undergraduates. Early intervention in psychiatry, 13(4), 922-927.

 Stigma not so bad