Optimal haloperidol dosage in first-episode psychosis.

OBJECTIVE: To determine optimal doses of haloperidol for the treatment of a first episode of psychosis. METHOD: A 4-week prospective controlled clinical trial with "optimal dose" defined as the dose at which either of the following occurs: 1) significant improvement, defined as a 15% or greater decrease in scores on the Positive And Negative Syndrome Scale (PANSS), or 2) the onset of extrapyramidal symptoms. Beginning with 2 mg daily, haloperidol was increased weekly to 5 mg, 10 mg, and finally 20 mg daily until either 1) or 2) occurred. RESULTS: Optimal doses for the 36 subjects were 2 mg daily for 15 subjects, 5 mg daily for 11, 10 mg daily for 7, and 20 mg daily for 3. On average, subjects whose optimal dose was 2 mg daily showed the greatest improvement. Among the 27 subjects evidencing clinical response to treatment, 20 had plasma haloperidol levels below 5 ng/ml. CONCLUSION: Many people suffering a first psychotic episode respond to haloperidol doses well below levels in common use.     

Self-harm in first-episode psychosis

BACKGROUND: Little is known about self-harm occurring during the period of untreated first-episode psychosis. AIMS: To establish the prevalence, nature, motivation and risk factors for self-harm occurring during the untreated phase of first-episode psychosis. METHOD: As part of the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study, episodes of self-harm were identified among all incident cases of psychosis presenting to services in south-east London and Nottingham over a 2-year period. RESULTS: Of the 496 participants, 56 (11.3%) had engaged in self-harm between the onset of psychotic symptoms and first presentation to services. The independent correlates of self-harm were: male gender, belonging to social class I/II, depression and a prolonged period of untreated psychosis. Increased insight was also associated with risk of self-harm. CONCLUSIONS: Self-harm is common during the pre-treatment phase of first-episode psychosis. A unique set of fixed and malleable risk factors appear to operate in those with first-episode psychosis. Reducing treatment delay and modifying disease attitudes may be key targets for suicide prevention.     

Mentalizing in first-episode psychosis

Mentalizing deficits have often been observed in people with schizophrenia and a few recent studies suggest that such deficits are also present in patients with first episode psychosis (FEP). It is not clear, however, whether these mentalizing deficits in FEP can be accounted for by underlying processes such as social cue recognition, social knowledge and general reasoning. In this study, we assessed mentalizing abilities in 31 people with FEP and 31 matched controls using a novel, comprehensive mentalizing task validated through the present study. We also assessed social cue recognition, social knowledge and non-social (or general) reasoning performance in the same participants in order to determine if the mentalizing deficits in FEP can be at least partly explained by performance in these three underlying processes. Overall, the mentalizing task revealed the greatest impairment in FEP, an impairment that remained significant even after controlling for social cue recognition, social knowledge and non-social reasoning performance. Interestingly, non-social reasoning and social knowledge were both shown to contribute to mentalizing performance. In addition, social cognition measures were linked to social functioning in the FEP group, with the strongest correlation observed with mentalizing performance. Taken together, these results show that mentalizing is an aspect of social cognition that is particularly affected in FEP and might contribute to functional impairments in these patients. These deficits could be a prime target for cognitive remediation in FEP, and our results suggest that this could be done either directly or through improvement of related social and non-social cognitive skills such as social knowledge and general reasoning.     

EEG abnormalities and outcome in first-episode psychosis.

OBJECTIVE: There is widespread consensus that the EEG is not useful for the detection of clinically relevant abnormalities in patients with psychosis. Given that the EEG records brain dysfunction, this study examines whether an abnormal EEG in first-episode psychosis patients is associated with poorer prognosis, compared with a normal EEG. METHOD: At their initial assessment, 61 patients with first-episode psychosis had an EEG classified according to the following modified Mayo Clinic system: normal, essentially normal (that is, one or more elements of questionable normality), or dysrhythmia (grade I to V). We assessed psychiatric symptoms using the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS) on entry and after 1 year of treatment. Psychosis is considered to have remitted if there are no, or minimal, psychotic symptoms (that is, a rating of 2 or less on every SAPS global rating), maintained for 1 month. RESULTS: At the end of 1 year, 19/21 (90.5%) patients with a normal EEG had a remission of their positive symptoms, compared with 18/28 (64.3%) of those with an essentially normal EEG and only 7/12 (58.3%) of those with dysrhythmia. Negative symptoms were reduced by more than 50% in 11/18 (61.1%) patients with a normal EEG, compared with 10/28 (35.7%) patients with an essentially normal EEG. None of the 8 patients with dysrhythmia on their EEG experienced reduced negative symptoms. CONCLUSION: The above findings suggest that an abnormal EEG in patients with first-episode psychosis is associated with a poorer prognosis.     

Cognitive functioning in stabilized first-episode psychosis patients.

This paper describes the cognitive functioning of a community cohort of individuals presenting with a first episode of a schizophrenia spectrum psychosis. Data were obtained for 107 patients (mean age 25 years) following stabilization of acute psychotic symptoms, mostly with the use of novel antipsychotics, on measures of intellectual, memory, attentional and executive functioning using a standardized battery of cognitive measures, including WAIS III and WMS III. While patients generally performed in the average range across the majority of measures, deficits (Z-scores >1.0 S.D.) were observed on measures of speed of information processing (PASAT, WAIS III) and executive functions (Stroop Test and Trails B), with the greatest deficits observed on tests of processing speed (PASAT). Discrepancy scores between the NART and the WAIS suggest subtle but statistically significant declines in full scale and performance IQ following onset of psychosis. Differences in cognitive functioning between diagnostic groups were not supported. Comparison of the highest and lowest functioning patients with respect to the cognitive measures also did not support any demographic or clinical differences between these two subgroups. Our results suggest a relatively benign cognitive profile in first-episode schizophrenia spectrum psychosis, regardless of diagnosis, when most potential incidence cases in the community are included. The most severe deficits reported were on measures of speeded information processing, and level of performance did not distinguish between patients demographically or clinically.     

Subgenual cingulate cortex volume in first-episode psychosis.

OBJECTIVE: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. METHOD: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. RESULTS: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. CONCLUSIONS: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.     

Functional neuroimaging in first-episode psychosis

Single photon emission computed tomography (SPECT) is a valuable tool for evaluating regional cerebral blood flow (rCBF) in patients with schizophrenia. Recently, various neuropharmacological studies using SPECT in patients with schizophrenia have also characterized dopamine D₂ receptors, their correlation with symptoms, as well as receptor occupancy after treatment with atypical antipsychotics.^1,2 We studies changes in rCBF in first-episode psychosis (FEP) before and after pharmacological treatment.     

Measuring quality of life in first-episode psychosis.

Quality of life (QoL) measures are increasingly recognized as necessary parts of outcome assessments in psychosis. The present paper is a comprehensive study of patients with first-episode psychosis where QoL is measured by the commonly used Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI maintain its original structure when used in a group of patients with first-episode psychosis, and to investigate what determines global subjective QoL with a specific emphasis on premorbid adjustment, duration of untreated psychosis (DUP) and clinical symptoms. The study indicates that the psychometric properties of the L-QoLI do not change significantly when used in first-episode samples. The patients report subjective and objective QoL in the fair to good range, with only a moderate association between the objective and subjective measures. Poor global satisfaction is predicted by being single, abusing drugs, being depressed, having a diagnosis of psychotic affective disorder, having poor premorbid social adjustment and DUP over 10 weeks. The study supports the notion that patients with first-episode psychosis construct QoL in the same way as other groups, and that longer durations of compromised function at this stage produces poor satisfaction with life rather than a downward readjustment of expectations.     

Early intervention in first-episode psychosis

OBJECTIVE: Substantial delays in providing access to treatment in first-episode psychosis have been well documented. The present study examines the impact of strategies aimed at improving access and reducing delays. METHOD: A pilot community education campaign was conducted with the aim of reducing the duration of untreated psychosis (DUP) in a geographically defined intervention sector located in the northwestern region of Melbourne, Australia. Utilising a quasi-experimental design, a comparison sector with similar demographics was selected from another part of the north-western region. A mobile early detection team and the same treatment system served both sectors. RESULTS: While there was no significant difference between the mean DUP for intervention and comparison sectors, the distributional features of DUP between the two regions were significantly different. In the intervention sector, disproportionately more cases with very long DUP were detected. When a small number of outliers were removed, the mean and median DUP in the intervention sector was reduced. CONCLUSION: These findings highlight the complexity of treatment access and delay and suggest that efforts to reduce DUP may have two effects, not one. Firstly, a different sample of cases is treated through the detection of hidden "long DUP" cases that otherwise may have remained untreated. Secondly, the DUP for the remainder may indeed be reduced. More research with larger samples and more potent campaign strategies is clearly required. It may also be worth considering whether there is a safe and ethical way to undertake a RCT of early versus delayed antipsychotic treatment to perhaps settle the DUP debate once and for all.     

White-matter hyperintensities in first-episode psychosis

BACKGROUND: White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. AIMS: To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. METHOD: T(2)-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons. RESULTS: There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. CONCLUSIONS: White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings.     

Spontaneous parkinsonism in antipsychotic-naive patients with first-episode psychosis.

OBJECTIVE: The purpose of this study was to establish rates of spontaneous parkinsonism (SP) among the different types of psychosis. We hypothesized that the rate would be higher among persons with affective symptoms. METHODS: We included in the study consecutive patients admitted to a first-episode psychosis intervention program. We recorded sociodemographic data from interviews with patients and caregivers and from medical records. We used the Simpson-Angus Rating Scale at baseline to assess parkinsonism and a diagnosis of SP was established if the Simpson-Angus score was > or = 0.3. RESULTS: A total of 174 patients were examined; of these, only 4 (2.3%; 2 Chinese women, 1 Chinese man, and 1 Malay man) had SP. There was a significant difference in the rates of SP in patients with affective psychosis and schizoaffective disorder, compared with those with nonaffective psychoses (15.4% vs 1.2%; chi2 = 10.7, P = 0.001). The 2 groups did not differ significantly in age, duration of untreated psychosis, or sex distribution. CONCLUSIONS: The rate of SP in Asian patients with first-episode psychosis was low, and it was significantly higher in those with affective symptoms.     

Duration of psychosis and outcome in first-episode schizophrenia.

OBJECTIVE: This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. METHOD: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. RESULTS: The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. CONCLUSIONS: Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.     

'Jumping to conclusions' in first-episode psychosis

Aim: People with psychotic symptoms are reported to have a characteristic reasoning style in which they jump to conclusions (JTC). The aims of this research were threefold. The first was to establish how prevalent this style is in people with first‐episode psychosis. The second was to examine the specificity of JTC to delusions. The third was to examine explanatory factors that may account for the JTC style. This was investigated by attempting to replicate, with a large sample, previous studies indicating that JTC is associated with specific psychotic and non‐psychotic symptoms and processes. Methods: Seventy‐seven service users were recruited from a first‐episode service and completed measures of reasoning and psychotic and non‐psychotic symptomatologies. A well‐established criterion was used to compare the JTC performance of those people with and without JTC. Results: JTC was present in over 40% of the sample, which is consistent with previous studies of people with long‐standing psychotic symptoms. Unlike previous research, no strong associations were found in relation to symptoms and other processes. Conclusions: JTC is a phenomenon common in many people in first‐episode services. In this large cohort sample, no clear associations with symptoms or other psychological processes were evident. Hence, the reason people JTC is still unclear.     

'Social dysmetria' in first-episode psychosis patients

Waters F, Rock D, Dragovic M, Jablensky A. ‘Social dysmetria’ in first‐episode psychosis patients. Objective: The ‘embodied cognition’ hypothesis suggests a close relationship between internal self‐representations and the outward expression of social behaviours and emotions. Given self‐awareness disturbances in patients with first‐rank symptoms (FRS), we hypothesized that these patients would show abnormal social behaviours. In this study, we examined the social interactive skills of patients with first‐episode psychosis during an interview, together with changes in performance over time. Method: We analysed previously unreported data from 227 patients with first‐episode psychosis (90 with, and 137 without, FRS) who took part in the WHO multicentre study on the Determinants of Outcome of Severe Mental Disorders. They were assessed on the Psychological Impairment Rating Schedule (PIRS) and examined again after 2 years. Results: A principal component analysis on the Psychosocial Impairment Rating Schedule produced two factors (interactive skills; withdrawal from interactions). Patients with FRS showed greater impairments in the domain linked to ‘interactive skills’, which remained 2 years after the first experience of a psychotic illness. These findings were not explained by clinical characteristics, or presence of non‐FRS delusions. Conclusion: Self‐awareness deficits, as indexed by the FRS symptom cluster, are linked to deficits in social interactive behaviours. These abnormalities are indicative of ‘social dysmetria’ in this group, which involves difficulties conveying motor aspects of behaviours, volition and affect to facilitate mutual communication. These findings point to the utility of behavioural assessment scales in clinical and research settings.     

Temporal lobe abnormalities in first-episode psychosis

OBJECTIVE: The nature and time course of temporal lobe abnormalities in psychotic illness remain controversial. Confounds include disease chronicity, gender, and handedness. The present study investigated temporal substructures in right-handed male patients experiencing their first episode of psychotic illness. METHOD: Magnetic resonance imaging scans were obtained for 25 minimally treated patients experiencing their first psychotic episode and 16 healthy comparison subjects. Group differences in volumes of the hippocampus, amygdala, planum temporale, and Heschl's gyrus were tested. RESULTS: The patients had smaller bilateral hippocampal and left planum temporale volumes than the comparison subjects. Paranoid and nonparanoid patients differed in left amygdala volume. CONCLUSIONS: The authors conclude that bilateral hippocampal and left planum temporale abnormalities are present near the onset of psychosis.