Schizophrenia prodrome: An optimal approach

In studies of schizophrenia, one of the more striking findings is the delay in the initiation of treatment. That delay ranges from 1 to 2 years for patients experiencing psychotic symptoms to several years if the prodromal phase is taken into account.¹ Yet duration of untreated psychosis has been found to be a critical factor in prognosis, including psychosocial functioning, in patients with schizophrenia.^2,3 Identification of individuals in the prodromal phase not only offers an opportunity to intervene at an earlier symptomatic stage, but might be associated with a better response to antipsychotics and a better overall treatment outcome as well.

What’s in a name?

Several terms, including ultra high risk, clinical high risk, at-risk mental state, psychosis risk syndrome, and schizophrenia/psychosis prodrome, have been used to describe the prodromal phase of schizophrenia. The proposal to include attenuated psychosis syndrome (APS) in the DSM-5—originally intended to capture those with subthreshold delusions, hallucinations, or disorganized behavior, occurring at least once a week for the past month and worsening over the past year—generated a debate about the validity of such a diagnostic category^4,5 that culminated in the inclusion of APS as a condition for further study but not as a term for clinical use.⁶ Its presence in the DSM-5 brings to the forefront the importance of early clinical intervention in patients at risk of developing psychotic illness.

Schizophrenia is not inevitable

The prodromal phase can be viewed as a sequence of evolving symptoms⁷ (Box 1^8,9), starting with subtle differences evident only to the person experiencing them and often progressing to brief limited intermittent psychosis (BLIPS) or attenuated psychosis.⁸

In fact, prodrome is a retrospective diagnosis. The predictive power of conversion to psychosis has been found to fluctuate from as low as 9% to as high as 76%,¹⁰ prompting ethical concerns about a high false-positive rate, the assumption of inevitability associated with the term “schizophrenia prodrome,”⁹ and the potential for overdiagnosis and misdiagnosis. Concerns about psychosocial stigma and exposure to antipsychotic medications have been expressed as well.¹¹

A case for early engagement

In retrospect, patients who eventually progress to psychotic illness are commonly found to have been in the prodromal phase for several years. Yet many patients’ first contact with psychiatric services occurs during a florid episode of acute psychosis. Identifying patients in the early prodromal period offers the opportunity to more effectively engage them and form a therapeutic alliance.¹² Any young adult who presents with a decline in academic or occupational function, social withdrawal, perplexity, and apparent distress or agitation (Table 1^13-16) without a clear precipitating factor should therefore be closely monitored, particularly if he (she) has a family history of psychosis.

Screening tools. A variety of interviews and rating scales (Table 28) have been developed to assess and monitor at-risk persons, a number of which have been designed to detect basic symptoms in the early phase of prodrome. In addition to the structured scales, several self-report tools—including the Prodromal Questionnaire-Brief (PQ-B), Youth Psychosis At Risk Questionnaire-Brief (YPARQ-B), Prime Screen-Revised, and PROD-screen (Screen for prodromal symptoms of psychosis)—have been found to be useful in screening a large sample to identify those who might need further evaluation.¹⁷

Increased risk of conversion. Several clinical factors are associated with an increased risk of conversion to psychotic illness.9 In addition to family history, these include:

• greater severity and longer duration of attenuated positive symptoms
• presence of bizarre thoughts and behavior
• paranoia
• decline in global assessment of functioning score over the previous year
• use of either Cannabis or amphetamines.

A history of childhood trauma, increased sensitivity to psychosocial stressors, and dysregulation of the hypothalamicpituitary axis also have been associated with progression to psychosis.¹⁸

Recent evidence suggests that the prodromal phase is a predictor not only for psychosis but also for other disabling psychiatric illnesses, such as bipolar disorder and obsessive-compulsive disorder.¹⁹

From a phenomenological standpoint, disturbance of the sense of self—characterized by features such as depersonalization, derealization, decreased reactivity to other people and the environment, and intense reflectivity to oneself or others—has been proposed as a critical marker for progression to psychosis.²⁰ Another predictor is the perception of negativity of others toward oneself. Examples include heightened sensitivity to rejection or shame, which seems to emerge from a pattern of insecure attachment, and the outsider status experienced by immigrants faced with multiple social, cultural, and language barriers.²¹ The presence of obsessivecompulsive symptoms during the prodromal phase has been linked to significant impairment in functioning, an acute switch to psychosis, and an increased risk of suicide.²²