Ultra High Risk – fact or fiction?

An EPA 2019 debate presented the data supporting the cases both for and against abandonment of using the term Ultra High Risk (UHR) of transition to psychosis. Making the case for was Jim Van Os, Utrecht University Medical Centre, Utrecht, The Netherlands, and Franke Schultze-Lutter, Department of Psychiatry and Psychotherapy, Dusseldorf, Germany, made the case against the proposition.

An epidemiological perspective

Professor Van Os spoke first and approached at the issue from an epidemiological perspective. He stated that in the early stages of psychopathologies there exists a mixed bag of symptoms, all of which evolve between different stages during the course of the disease. Symptomatology is, therefore, ‘fuzzy’, heterogeneous and, unlike neurological conditions, there are no clear dichotomies of symptoms between diseases; substantial sharing of variant risks exist.

It is now well recognized that psychosis has attenuated threshold expression in ‘non-psychotic’ disorders (depression, anxiety, and substance abuse) and is predictive of poor outcomes for patients in all these conditions. Thus, he suggested, psychosis is a symptom of severity of multi-dimensional psychopathology – nothing more.

“Psychosis is a symptom of severity of multi-dimensional psychopathology”

Too much variety in symptomatology

Definitions of UHR vary and are based on various combinations of various symptoms. The presence of signs of psychosis seems to be classed as UHR by clinicians, who then surmise that there will, therefore, be a transition to a psychotic state. The appearance of psychosis appears to trump the non-psychotic symptoms. But what exactly is ‘transition’?

Psychosis appears to trump the non-psychotic symptoms

Concept of transition is irrelevant

In other branches of medicine, true transition occurs when risk of illness manifests as “real” illness – and where there is illness only, then a diagnosis can be made. In the transition from UHR to psychotic disorder, a diagnosis has already been made. UHR patients are seeking help, because they are experiencing psychotic symptoms. The concept of transition is, therefore, irrelevant.

Prevention paradox

However, patients with subthreshold psychosis, who never ‘transition,’ have poor outcomes just like those that do. Professor van Os believes that the vast majority of mental health disorders originate in the lower risk of psychosis group – those that never transition rather than those that do. He calls it “the prevention paradox”. And he believes that this is where the greater benefit for patients can be realized.

To reduce the levels of severe mental health problems; better access to mental health services for everyone seeking help for mental health issues, including those with early psychopathologies, will be more effective than specifically singling out those artificially classed as UHR. This approach will ameliorate the overall risk of progression to psychosis. He likened it to a national program to reduce levels of alcoholism – rather than target those at high risk of becoming alcoholic, raise the price of alcohol to make it less easily accessible to all – and in this way generate a better outcome for a higher proportion of the population.

Better access to mental health services for everyone with early psychopathologies will be more effective than specifically singling out those ‘artificially’ classed as UHR

A clinical perspective

Professor Schultze-Lutter considered the value of UHR being maintained from a clinical perspective. Psychoses, while severely debilitating, occur infrequently in the population. However, where they do occur, there is usually a long history of prodromal symptoms and functional decline, which starts well before a diagnosis is made. Earlier diagnosis and treatment are seen as imperative and preventative approaches, and should target those in the prodromal – that is, clinical/ultra-high risk – stages, who are experiencing problems and seeking help.

Such patients, who actually are experiencing attenuated psychotic symptoms, report cognitive disturbances - disturbances that could be used to predict the emergence of psychotic disorders earlier. These patients are experiencing significant problems – not a little bit of psychosis on top of everything else, as Professor van Os implied. Conversion rates to full blown psychoses are 285 times as high as those in the general population. Their problems are not insignificant - this group of patients is real.

These patients are experiencing significant problems – not a little bit of psychosis

Patients don’t seek help for psychosis per se

Professor Schultze-Lutter recognizes that UHR patients frequently experience co-morbid conditions, such as depression, bipolar disorder and anxiety; but notes that coincidentally –or not - these same comorbidities are present in those patients with schizophrenia. She noted that attenuated psychotic symptoms are related to the likelihood of help-seeking, but are never given as the main reason for help-seeking. The principal reasons normally given are mood and anxiety disorders and other disorders that cause functional impairment. It’s the functional impairment caused by the underlying psychosis that is the foundation of UHR and that is what is being seen in these patients.

Attenuated psychotic symptoms are related to the likelihood of helpseeking, but are never given as the main reason for help-seeking

Studies investigating the relationship between UHR status and non-conversion and non-psychotic disorders suggest that baseline UHR status was never significantly related to any mental health disorder other than psychosis at follow-up. Indeed, one study where UHR patients were compared to help-seeking controls suggested that UHR specifically predicts a psychosis diagnostic outcome, rather than pluripotential variety of psychotic and non-psychotic outcomes.

UHR may be over-diagnosed

Psychosis-like experiences may be mistaken for attenuated psychotic symptoms and it may be that psychoses are being over-diagnosed. Taking this into account, estimates for the risk of “true” UHR in the community are around 0.11%. This group of patients is manageable if correctly identified and should be treated.

UHR status was never significantly related to any mental health disorder other than psychosis at follow-up

If for no other reasons than those cited above, Professor Schultze-Lutter believes that the term UHR has value in identifying of those most likely to benefit from early intervention and its use should be retained.

What is apparent from both speakers’ arguments is that both are clear that patients with mental health problems should be better identified and better managed.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


Further readings

McGorry and van Os Lancet 2013;381:343-345

Van Os and Guloksuz. World Psychiatry 2017;16:200-206

Schultze-Lutter et al. World Psychiatry 2018;17:107-8

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