Prospective relationship between duration of untreated psychosis and 13-year clinical outcome: a first-episode psychosis study.

BACKGROUND: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined. OBJECTIVE: To explore the relationship between DUP and long-term symptomatic remission. METHODS: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤30days), medium (31-180days) and long (>180days) DUP groups. RESULTS: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission. CONCLUSION: The findings support the threshold theory that DUP longer than 30days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment.

Longitudinal changes in semantic categorization performance after symptomatic remission from first-episode psychosis: a 3-year follow-up study.

Semantic categorization abnormalities have been observed in schizophrenia, but studies have rarely focused on the longitudinal trajectory. In this study, we consider semantic performance and the relationship with symptomatic changes during recovery from a first-episode of schizophrenia over a period of 3 years. Thirty-seven first-episode patients with schizophrenia were compared to thirty-seven matched controls in a categorization task. Patients were assessed at first episode, after clinical stabilization, and annually for the subsequent 3 years. In the task, participants indicated whether a word belonged to a given category. Each category contained words of varying degrees of semantic relatedness: typical, atypical, borderline, related-but-outside, and unrelated. Reaction times and proportion of 'yes' responses were analyzed. At first assessment, semantic categorization abnormalities were observed in first-episode patients. Patients assigned more semantically-dissimilar words to the categories than controls. As patients stabilized from acute states, their semantic categorization performance improved and then remained stable throughout the entire follow up period of 3 years. Interestingly, semantic performance deficits, particularly a diminished typicality effect, correlated with negative symptoms in the initial episode, but not at stabilization when symptoms subsided. No significant associations between positive and negative symptoms, or pre-defined categorization measures were identified. The data demonstrated semantic memory abnormalities in first-episode schizophrenia. However, an improvement of semantic categorization performance was observed in stabilized schizophrenia patients. Overall, the data are suggestive of a state effect in semantic abnormalities rather than a trait effect. The correlation between degree of impairment and symptoms may explain previous inconsistent findings.

Antipsychotics and risk of cerebrovascular events in treatment of behavioural and psychological symptoms of dementia in Hong Kong: a hospital-based, retrospective, cohort study.

OBJECTIVE: The purpose of this study was to investigate the risk of cerebrovascular adverse events (CVAEs) in patients with behavioural and psychological symptoms of dementia (BPSD) treated with typical or atypical antipsychotics in Hong Kong METHOD: This was a retrospective cohort study. Patients aged 65 or above, diagnosed with Alzheimer's disease, vascular or mixed dementia, and first attended the psychiatric service of our unit between 1st January 2000 to 30th June 2007 were studied. The patients were divided into three groups according to their antipsychotic usage. They were compared on sociodemographic and clinical characteristics. The risk of CVAEs was studied by means of Cox regression analysis. RESULTS: The studied cohort consisted of 1089 patients. The antipsychotic non-user, typical and atypical users groups consisted of 363, 654 and 72 patients, respectively. Incidence rate of CVAE for the three groups were 44.6/1000, 32.7/1000 and 49.6/1000 person years, respectively. The risk of developing CVAEs did not differ in typical or atypical antipsychotic user groups compared with non-user group. The adjusted hazard ratio of typical and atypical antipsychotic user groups were 0.964 (95% CI = 0.584-1.591) and 1.036 (95% CI = 0.350-3.066), respectively. Subgroup analyses of individual antipsychotic did not show a significant increase in risk of CVAEs. CONCLUSION: This study showed that there was no statistical difference in risk of cerebrovascular events in treatment of BPSD with typical and atypical antipsychotics compared with non-user group. Nonetheless, given the side effects of antipsychotics, prescription of antipsychotics should be reserved for severe and distressing symptoms with careful consideration.

A case-control study of bipolar depression, compared with unipolar depression, in a regional hospital in Hong Kong.

OBJECTIVE: To determine the characteristics of diagnostic conversion from unipolar depression to bipolar depression in psychiatric outpatients, and to compare the profiles of the 2 groups of patients. METHOD: This is a case-control study in which outpatients newly diagnosed with unipolar depression were reviewed. Outpatients who had polarity conversion to bipolar depression were recruited as subjects and control subjects were matched. The diagnostic validity was enhanced by clinical interview, review of case records by an independent specialist psychiatrist, and administration of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders. Multivariate conditional logistic regression was carried out to identify the predictors of bipolar switch. RESULTS: Eighty-eight subjects among those who maintained regular outpatient clinic follow-up (n = 823) showed bipolar switch during the period under study. The incidence of polarity conversion was 10.7%. Bipolar switch was associated with family history of bipolar affective disorder, use of 3 or more different types of antidepressants in the first 5 years after presentation, an earlier age at presentation of depressive symptoms of less than 37 years, and males. CONCLUSIONS: Change in diagnostic polarity is not uncommon in Chinese psychiatric outpatients initially presenting with unipolar depression. They share some common risk factors as identified in Western studies. These can be helpful to clinicians as guidance for identification of patients with depression at high risk for a bipolar course.

The incidence and characteristics of clozapine- induced fever in a local psychiatric unit in Hong Kong.

OBJECTIVE: To determine the incidence, characteristics, and predictors of clozapine-induced fever in a sample of patients in a local psychiatric unit. METHOD: A retrospective review of case notes of 227 inpatients newly started on clozapine from March 2003 to December 2006 was conducted. Demographic characteristics, presence of fever, investigations carried out, fever characteristics, and complications of fever were recorded and analyzed. Patients with clozapine-induced fever were compared with their fever-free counterparts on demographic and clinical factors. Multivariate logistic regression was performed to identify predictors of clozapine-induced fever. RESULTS: Thirty-one out of 227 patients (13.7%) developed clozapine-induced fever. The means for day of onset of clozapine-induced fever after clozapine initiation and duration of fever were 13.7 and 4.7 days, respectively. The mean highest body temperature was 38.8 degrees C. Fever resolved within 48 hours after clozapine discontinuation in 79% of the patients with clozapine-induced fever. One out of 7 patients (14.3%) had fever on re-challenge. Clozapine-induced fever was associated with rate of titration more than 50 mg/wk (OR 18.9; 95% CI 5.3 to 66.7; P < 0.01), concomitant use of valproate (OR 3.6; 95% CI 1.5 to 8.9; P = 0.01), and presence of physical illnesses (OR 3.2; 95% CI 1.2 to 8.3; P = 0.02). CONCLUSION: Clozapine-induced fever is common. Temporary withdrawal of clozapine may result in resolution of fever, and clozapine re-challenge may be considered after fever subsides. Slower rate of clozapine titration may be helpful in patients with underlying physical illness and concomitant valproate treatment.

A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients.

BACKGROUND: Cognitive predictors of relapse have been extensively explored only in few long term longitudinal studies of first-episode schizophrenia. METHOD: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform disorder, and schizoaffective disorder for 3 years after their first-episode illness. Cognitive domains including verbal intelligence, verbal and visual memory, verbal fluency, and Wisconsin Card Sorting Test performance were investigated as potential predictors of relapse. RESULTS: We found that by the first year 21% patients had relapsed, by the second year 33% had relapsed, and by the third year 40% had relapsed. There was a significant difference in the relapse rate between patients with good adherence and patients with poor adherence to medication regimes. A multiple logistic regression analysis revealed that after controlling for medication adherence, perseverative error in the Wisconsin Card Sorting Test was the only cognitive function that significantly predict relapse with an odds ratio of 2.4. CONCLUSIONS: Cognitive flexibility in set shifting is related to tendency towards relapse in first-episode schizophrenic patients. Other cognitive factors appear not to be related to relapse. Possible mechanisms included the link between prefrontal dysfunction and sub-cortical dopamine system stability, as well as the effects of executive dysfunction on insight impairment and adherence behavior.

The impact of family experience on the duration of untreated psychosis (DUP) in Hong Kong.

BACKGROUND: Previous family experience of psychotic illness may play an important role in whether and when a patient seeks help in first-episode psychosis. This study investigated the relationship between family experience of psychosis and the duration of untreated psychosis in a prospective sample of first-episode psychosis patients in Hong Kong. We also studied the effects of pre-morbid adjustment, educational level, living alone, and mode of onset as potential determinants of the duration of untreated psychosis (DUP). METHODS: A total of 131 first-episode psychosis patients in Hong Kong were recruited in a study of the DUP and related factors. The Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS) was used to measure the DUP and to provide a structured assessment of family history, educational level, household arrangement, and mode of onset. RESULTS: Previous family experience of psychiatric illness (the presence of another family member who has been receiving psychiatric treatment) and an acute mode of onset were significant predictors of a shorter DUP. Educational level had a modest effect on its own, but was not significant in the binary logistic regression model. Living alone had a moderate effect size, but was non-significant, possibly because of the small proportion of single-person households in the sample. The symptom profile, pre-morbid adjustment, and other demographic factors were not significantly related to the DUP. CONCLUSION: In addition to the mode of onset, previous family experience plays an important role in the presentation of early psychosis. Educational efforts that target the family should be an important part of any strategy for the early detection of psychosis.

A 3-year prospective study of neurological soft signs in first-episode schizophrenia.

Neurological soft signs are biological traits that underlie schizophrenia and are found to occur at higher levels in at-risk individuals. The expression of neurological soft signs may be modifiable during the onset of the first psychotic episode and the subsequent evolution of the illness and its treatment. This study investigates neurological soft signs in 138 patients with first-episode schizophrenia and tracks the expression of motor soft signs in the following 3 years. For the 93 patients who have completed the 3-year follow-up, we find that neurological soft signs are stable in the 3 years that follow the first psychotic episode, and that neurological soft signs are already elevated at the presentation of first-episode psychosis in medication-naive subjects. The level of neurological soft signs at clinical stabilization is lower for patients with a shorter duration of untreated psychosis. Although the quantity of neurological soft signs does not significantly change in the 3 years that follow the first episode, the relationship between neurological soft signs and negative symptoms does not become apparent until 1 year after the initial episode. A higher level of neurological soft signs is related to a lower educational level and an older age at onset, but the level of neurological soft signs does not predict the outcome in terms of relapse or occupational functioning.