Duration of untreated psychosis and neuropsychological function in first episode psychosis

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.     

The patient with first episode psychosis

The authors describe their approach to the patient presenting with a first episode of psychosis. This approach differs from the treatment of established/chronic patients and is critical in insuring proper assessment and initial treatment and may possibly influence the prognosis. Using prototypical cases, the authors give an overview of the first encounter, working with the family, differential diagnosis, treatment, and prognosis.     

First rank symptoms in first episode psychosis and their relationship to the duration of untreated illness

Most studies of First Rank Symptoms (FRS) are based on cross-sectional inpatient samples of people with schizophrenia at various stages of illness. We sought to examine the prevalence of FRS in a representative sample of first episode psychosis patients and compare those with and without FRS clinically and in terms of duration of untreated illness. Information was gathered from 158 consecutive cases of first episode psychosis presenting in a defined geographical region through semi-structured interview tools. Of this sample, 40.5% of cases received a diagnosis of schizophrenia. The prevalence of FRS among the entire group was 52.5%. After controlling for multiple testing, no FRS contributed significantly to predicting a diagnosis of schizophrenia. There was no significant relationship between the duration of untreated illness and FRS.     

Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.     

Structural changes in the hippocampus and amygdala at first episode of psychosis

Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ.     

The key to reducing duration of untreated first psychosis: information campaigns

The TIPS early intervention program reduced the duration of untreated psychosis (DUP) in first-episode schizophrenia from 16 to 5 weeks in a health care sector using a combination of easy access detection teams (DTs) and a massive information campaign (IC) about the signs and symptoms of psychosis. This study reports what happens to DUP and presenting schizophrenia in the same health care sector when the IC is stopped. METHODS: Using an historical control design, we compare 2 cohorts of patients with first-episode Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, non-affective psychosis at admission to treatment. The first cohort (N = 108) was recruited from January 1997 to December 2000, using an IC to raise awareness about recognizing psychosis to the public, the schools, and to general practitioners. The second cohort (N = 75) was recruited from January 2002 to June 2004 with no-IC. Easy access DTs were available to both cohorts. RESULTS: In the no-IC period, DUP increased back up to 15 weeks (median) and fewer patients came to clinical attention through the DTs. No-IC patients were diagnosed less frequently with schizophreniform disorder, more Positive and Negative Syndrome Scale positive and total symptoms, and poorer Global Assessment of Functioning (symptom) Scale scores. CONCLUSIONS: Intensive education campaigns toward the general public, the schools, and the primary health care services appear to be an important and necessary part of an early detection program. When such a campaign was stopped, there was a clear regressive change in help-seeking behavior with an increase in DUP and baseline symptoms.     

Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis

BackgroundDelay in treatment of psychosis is associated with poor clinical and social outcome and is measured as the duration of untreated psychosis (DUP) prior to treatment of the first episode. It has been suggested that this may be mediated through toxic effects of psychosis on the structure and function of the brain. Equivocal evidence exists regarding association between longer DUP and neuro-anatomical changes such as, reduced grey matter volume in specific regions in the brain and deficits in neurocognitive functions.ObjectiveTo examine if duration of untreated psychosis (DUP) preceding treatment of a first episode of psychosis is associated with structural brain abnormalities and deficits in neurocognitive functions.MethodWe investigated the relationship between DUP and grey matter volume using voxel-based morphometry techniques and with multiple domains of cognition. Eighty patients with a first episode of psychosis were separated into two equal sized groups based on a median split (18 weeks) of their DUP.ResultsCompared to the short-DUP group (mean DUP 7.9 weeks ± 5.6), the long-DUP group (mean 113.7 weeks ± 170.4) showed significant grey matter volume reductions in orbital–frontal regions (bilateral medial frontal gyrus and bilateral rectal gyrus, BA 11) and parietal regions (postcentral gyrus and superior parietal lobule) as well as a significant reduction in whole brain grey matter volume (p < 0.04). For schizophrenia spectrum cases only these findings were confined to left rectal gyrus. There were no differences in white matter or cerebral spinal fluid volumes or on cognitive functions. Results are controlled for antipsychotic medication exposure.LimitationsThe inherent difficulty in separating slow and insidious onset from long-DUP may limit the interpretation of our results and there may be an overlap between DUP and duration of illness (including the prodrome).ConclusionPatients with a longer delay in treatment of psychosis show a significant reduction in overall grey matter volume with specific reductions in the inferior-orbital region. These results provide some support to a possible neurotoxic effect of prolonged untreated psychosis.     

Suicidality in first episode psychosis

Many studies have confirmed that the risk of suicide is high in the period after first presentation. There is relatively little information about the risk of suicide using illness onset as the starting point. We assessed suicidality in a cohort of 166 individuals from an urban catchment area during the period of untreated psychosis and at 4 year follow up. Nearly 10% of individuals attempted suicide prior to presentation. Four years later 18% had made a suicide attempt and 3% completed suicide. Suicide attempts prior to presentation were associated with a longer duration of untreated psychosis.     

Extended duration of hospitalization in first episode psychosis: An evaluation of its clinical justification

Short periods of hospitalization for first episode psychosis are generally considered preferable, although research evidence is inconsistent. Clinical and social determinants of length of hospital stay (LOS) were examined in 121 admissions for first episode psychosis using standardized assessment measures, in five clinical units of a French psychiatric hospital. LOS varied from 4 to 371 days, and considerably between units. LOS was examined both as a continuous variable and dichotomized comparing short (<31 days) to long (>31 days) stays. In the multivariate analyses, change in antipsychotic medication and the unit head psychiatrist's preference for longer stays were significantly associated with both measures of LOS, indicating effects on LOS per SE and not only with respect to a threshold duration of stay. Of the clinical factors at admission, the only borderline significant association found was between the severity of negative symptoms and LOS on a continuum. Despite some justification for longer stays with respect to discharge conditions, the persisting association with the head psychiatrist's preference for long or short stays strongly suggests a need for greater evidence-based rationalization of practice.