Because 40% of individuals with a psychotic prodrome develop schizophrenia, detecting and preventing this transition could improve many patients’ lives. Unfortunately:
- psychotic prodrome lacks clear-cut symptoms and is difficult to identify
- little evidence exists to help clinicians select psychotropics and decide how long to use them
- treating all prodromal patients would expose those who never develop psychosis to the risk of psychotropics’ side effects.
How, then, can psychiatrists help patients who present with possible prodromal symptoms? Based on research and our experience, this article describes the psychotic prodrome and offers a pragmatic, evidence-based approach to diagnosis and treatment.
WHAT CAUSES PSYCHOTIC CONVERSION?
Reduced gray matter volumes in certain brain regions may be associated with conversion to psychosis (Box 1). Stress also may play a role; elevated stress-reactive cortisol levels are associated with positive symptom severity in the prodrome.1 Other factors being investigated include obstetric complications at birth, maternal age >30, premorbid schizotypal personality disorder, and impaired olfaction.
Symptoms. Nearly 80% of patients with schizophrenia experience a psychotic prodrome that lasts a few months to several years.2 Common features include:
- gradual worsening of perceptual disturbance
- referential thinking
- paranoia
- mild cognitive deficits
- mood lability
- impulsivity
- suicidality
- declining social function and academic performance.3,4
A premorbid phase often precedes the prodrome, with symptoms such as impaired attention, soft neurologic signs, and subtle social deficits. These changes may be harbingers of the prodrome but are too nonspecific to be diagnostic. Other functional impairments—including anxiety, depression, drug abuse, and psychosocial factors such as school stress—may mimic schizophrenic prodrome.
Prognosis. Studies of patients’ first schizophrenia episodes suggest that prodrome duration may predict outcome. A longer prodrome is thought to indicate a poor prognosis,6 such as in patients who wait a year before seeking treatment.7 A review of 22 studies of first-episode psychosis found early psychosocial and pharmacologic interventions improved long-term prognosis, and medication discontinuation predicted more-severe and chronic disease.8
Reduced gray matter volumes in certain brain regions may be associated with conversion to psychosis. Imaging studies have found medial temporal lobe changes—specifically, hippocampal volume alterations—in persons with schizophrenia, genetic high-risk groups, and those thought to be at risk for imminent psychosis.11
MRI imaging of patients with prodromal signs has shown less gray matter in the right medial temporal, lateral temporal, inferior frontal cortex, and bilateral cingulate regions in those who have developed psychosis, compared with those who have not. In the psychotic patients, 12-month longitudinal follow-up has found reduced gray matter in the left hippocampal, fusiform, orbitofrontal, cerebellar cortices, and cingulate gyrus.12
Brain structure is related to genetic liability for schizophrenia in high-risk patients, who seem to have smaller right and left prefrontal lobes and smaller right and left thalami. These findings are consistent with the prodrome’s neurocognitive deficits, which are less than those reported in schizophrenia and greater than those seen in healthy subjects.
Pioneering work by McGorry et al10 identified an “ultra high-risk group” with a psychotic conversion rate of 40% to 60%. These patients present with three symptom patterns:
- attenuated positive symptoms
- brief intermittent psychotic episodes
- genetic risk and recent deterioration syndrome (Table 1).
3 patient groups considered at ‘ultra high risk’ to develop schizophrenia
Patients with… | Symptoms |
---|---|
Attenuated psychotic symptoms | Overvalued ideas, perceptual disorders |
Present at least 1 week; not >5 years | |
At least 1 symptom several times a week | |
Brief intermittent psychotic episodes | Frank psychotic features |
Resolve spontaneously within 7 days | |
Can be drug-induced | |
Genetic risk and recent deterioration syndrome | Psychotic disorder in a first-degree relative |
Schizotypal personality disorder | |
Present at least 1 month; not >5 years | |
Significant functional decline | |
Source: Adapted from reference 10 |
The Edinburgh High Risk Study of 162 individuals ages 16 to 25 showed more marked psychopathology in those with at least two close relatives with schizophrenia, compared with control groups. A direct correlation was seen between genetic liability and poor neurocognitive performance.11
PRODROME RATING SCALES
Researchers are using outcome measures to diagnose prodromal symptoms and assess their severity. Operational, validated assessment tools include:
- Bonn Scale for the Assessment of Basic Symptoms (BSABS): captures subtle changes in thinking, feeling, and perception.
- Schizophrenia Prediction Instrument for Adults (SPI-A): defines prepsychotic deviations and rates symptoms that are subjectively experienced by the patient.
- Comprehensive Assessment of At Risk Mental State (CAARMS): defines ultra high-risk criteria and incorporates eight dimensions of psychopathology.
- Scale of Prodromal Symptoms (SOPS): rates psychosis severity. When embedded within the Structured Interview for Prodromal Syndromes (SIPS), the SOPS determines the presence or absence of psychosis and predicts progression to psychopathology.
- Criteria for Prodromal Symptoms (COPS): defines ultra high-risk categories.
- Presence of Psychosis Scale (POPS): rates severity, intensity, and duration of positive prodromal symptoms.12