Temporal relationship of first-episode non-affective psychosis with cannabis use: A clinical verification of an epidemiological hypothesis

Background

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.

Method

We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57 years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use.

Results

We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank χ² = 23.43, df = 1, p < 0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5 years (27, 45) (for log-transformed AOPT, t = 5.6, df = 110, p < 0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05).

Conclusions

Our results are in favor of a catalytic role for cannabis use in the onset of psychosis.     

Premorbid functioning of patients with first-episode nonaffective psychosis: a comparison of deterioration in academic and social performance, and clinical correlates of Premorbid Adjustment Scale scores

BACKGROUND: Motivated by a previous study among male veterans [Allen, D.N., Frantom, L.V., Strauss, G.P., van Kammen, D.P., 2005. Differential patterns of premorbid academic and social deterioration in patients with schizophrenia. Schizophr. Res. 75, 389-397], the present analysis examined: (1) patterns of premorbid academic and social functioning during childhood, early adolescence, and late adolescence, and (2) associations between these premorbid functioning dimensions and a number of clinical variables. METHODS: Data on premorbid functioning were collected using the Premorbid Adjustment Scale (PAS) in 95 hospitalized first-episode patients. Analyses were similar to those conducted by Allen and colleagues (2005). RESULTS: Deterioration was evident in both academic and social functioning from childhood to early adolescence, along with a pronounced/accelerated deterioration in academic functioning from early adolescence to late adolescence, occurring in both male and female patients. Age at onset of prodromal symptoms was predicted by childhood/early adolescent/late adolescent academic functioning scores, and age at onset of psychotic symptoms was significantly associated only with childhood academic functioning. Severity of negative symptoms was predicted by childhood and late adolescent social functioning scores, and severity of general psychopathology symptoms was predicted by late adolescent academic functioning, as well as childhood and late adolescent social functioning scores. CONCLUSIONS: Consistent with prior findings, deterioration in premorbid functioning appears to be more pronounced in the academic than social dimension of the PAS. Some PAS scores are predictive of ages at onset of prodrome/psychosis and severity of psychotic symptoms. Ongoing research on premorbid adjustment in schizophrenia may have implications for future prevention goals.     

Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis in schizophrenia. The objective of this study is to evaluate whether DUP and premorbid level of social functioning are related to treatment response in acute treatment of first-episode schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed with BPRS, SAPS, and SANS on admission and discharge during their first hospitalisation. Percentage of the difference between admission and discharge in total scores of all scales were taken as measures of absolute symptom reduction. The median DUP was 6 months (mean=8.6). DUP was correlated with reduction in BPRS and SAPS scores but not SANS scores. Patients with a short DUP (n=41) also showed a higher reduction in BPRS, and SAPS scores than those with a long DUP. Premorbid Adjustment Scale (PAS) scores were inversely correlated with age at onset and positively correlated with BPRS scores at admission. We did not find any relationship between PAS scores and response to treatment. Our findings suggest that DUP may be an important predictor of response in acute treatment of first-episode schizophrenia and thus, attempts for early diagnosis may also have a positive effect on acute treatment response.     

Relapse prevention and remission attainment in first-episode non-affective psychosis. A randomized, controlled 1-year follow-up comparison of haloperidol, risperidone and olanzapine

The effectiveness of antipsychotics in preventing relapses and attaining symptomatic remission is a relevant topic of psychopharmacological research. The purpose of the present study was to compare the relapse and symptomatic remission rates during the first year of treatment between low doses of haloperidol and SGAs (olanzapine and risperidone) in drug-naïve first-episode non-affective psychosis individuals. This is a prospective, randomized, open-label study conducted from February 2001 to February 2006. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 1 year. Primary effectiveness measures were the time up to relapse and rates of relapse and symptomatic remission. There were no significant differences in the relapse rate between treatments (11.1% haloperidol; 18.5% olanzapine, and 13.8% risperidone) (χ² = 1.230; p = 0.541) or in the time up to relapse (Log Rank χ² = 0.308; p = 0.857). The rates of relapse for adherent (11.2%) and non-adherent (26.9%) patients were significantly different (χ² = 4.215; df = 1; p = 0.040). The remission rate did not differ significantly between treatment groups (χ² = 2.760; p = 0.252) and adherence to medication did not seem to significantly influence remission rates. We conclude that haloperidol, olanzapine and risperidone show a similar effectiveness in relapse prevention or in remission attainment during the first year of treatment.     

首次发作精神分裂症患者出院服药情况1年调查

目的 了解首次发作(以下简称首发)精神分裂症患者出院服用抗精神病药的特点.方法 对137例首发精神分裂症患者出院后的服药情况进行问卷式跟踪随访调查1年,并比较服用第1代抗精神病药患者(64例)和第2代抗精神病药患者(73例)的差异.结果 首发精神分裂症患者服药依从性随时间推延逐渐降低,与所服药物类型无关.第1代抗精神病药组出院后第1、3、6、12个月的停药率分别为0%、7%、18%、50%,第2代抗精神病药组的停药率依次为3%、11%、21%、55%,2组各时点的差别无统计学意义.第1代抗精神病药锥体外系不良反应明显多于第2代抗精神病药,随访第12个月时分别为30%、7%, χ2=12.310,P<0.01.而后者在随访第12个月时出现内分泌系统不良反应比例(40%)高于第1代抗精神病药(5%)(χ2=13.433,P<0.05).结论 如何提高首发精神分裂症长期维持治疗的依从性是精神卫生服务的重要内容.     

Pathways to care and treatment delays in first and multi episode psychosis

BACKGROUND: In contrast to findings from the developed world where general practitioners and mental health professionals are central in first episode psychosis pathways, studies from Africa have found GPs to play a less prominent role with other help providers such as traditional healers being more important. METHODS: We compared pathways to care, treatment delays and gender differences in patients with first versus multi episode psychosis. RESULTS: Private sector GPs were first contacts in first episode patients in as many as 38% of patients and were significantly more likely to be the first contact (odds ratio = 4.5, 95% CI = 1.38-14.67) and final referring agent (odds ratio = 6.8, 95% CI = 1.56-25.12) in first episode patients. Female multi episode patients were significantly more likely to make first contact with primary care practitioners whereas male multi episode patients were more likely to first come into contact with the police (P = 0.003) and be admitted compulsorily (P = 0.009). Only 5.6% (n = 4) of patients contacted traditional healers at some point in their pathway to care. Treatment delays and DUP in first episode patients were longer and reached a median of 4.5 versus 2.5 months in multi episode patients. Treatment discontinuation of antipsychotics occurred in 82% of multi episode patients. Despite significantly longer overall treatment delays in first episode patients the distribution of treatment delays in multi episode patients followed a similar pattern to DUP in first episode patients with a subgroup having very long delays. CONCLUSIONS: Pathways to care in this treatment setting correspond more to findings from first world and newly industrialized countries. A subgroup of multi episode patients had very long periods of untreated illness. Limitations include small sample size and the retrospective nature of data collection.     

Predictors of schizophrenia in patients with a first episode of psychosis

Early identification of schizophrenia in patients with a first episode of psychosis (FEP) may help to avoid inappropriate treatment and may enhance long-term outcome by addressing issues such as family network, treatment adherence and functional and symptomatic outcome. It was the aim of the study to determine baseline variables that significantly predicted a diagnosis of schizophrenia in patients with FEP. The sample consisted of 133 FEP patients hospitalized for at least 6 weeks, in whom a DSM-IV diagnosis was confirmed after 1 year follow-up. Patients were divided into two groups, those with a diagnosis of schizophrenia (Schizophrenia group, n = 63; 47.8%), and those with other psychosis, who were grouped under Non-Schizophrenic Psychosis (NSP, n = 70; 52.2%). Sociodemographic (marital status, educational level) and clinical variables were recorded for each patient. Substance use (alcohol, cannabis and cocaine) did not statistically differ between the two groups. Absence of characteristics defined as criteria for good prognosis, lack of ≥ 20% improvement in the total Positive and Negative Syndrome Scale score at 6 weeks, and a poor premorbid adjustment as determined by the Premorbid Adjustment Scale score significantly predicted the presence of schizophrenia. The regression model including these three variables achieved a predictive value of 76.3%, with a sensitivity of 74.6% and a specificity of 77.9%.     

Low-activity allele of Catechol-O-Methyltransferase (COMTL) is associated with increased lateral ventricles in patients with first episode non-affective psychosis

BACKGROUND: Structural brain anomalies are present at early phases of psychosis. The objective was to examine the impact of Catechol-O-Methyltransferase (COMT) gene variations on brain morphology in first-episode non-affective psychosis. We hypothesized that the low activity-COMT (COMT(L)) allele would be associated with the presence of structural brain changes as assessed by quantitative magnetic resonance imaging (MRI). METHODS: Fifty-two males and 23 females underwent COMT genotyping and MRI. Patients were categorized into three genetic subgroups: COMT(H/H), COMT(L/H) and COMT(L/L). MRI data were analyzed using BRAINS2. Global and lobar volumes of grey matter (GM) and cerebrospinal fluid (CSF) were compared among the three groups after controlling for total intracranial volume and age of illness onset. RESULTS: COMT(L) carriers showed a significant enlargement of the lateral ventricles (F = 7.13, p = 0.009), right lateral ventricle (F = 5.99, p = 0.017) and left lateral ventricle (F = 6.22, p = 0.015). No other significant differences in any of the brain structures were found among subgroups. CONCLUSIONS: Our findings suggest that genetic variations of COMT can contribute to the enlargement of the lateral ventricles described in early phases of non-affective psychosis.     

Early prediction of clinical response in first episode schizophrenia (FES) patients receiving olanzapine

Abstract

Background: At present, schizophrenia guidelines recommend waiting for 8?weeks before considering a patient as non-responder. This study aims to detect the optimal early response threshold that best predict the final outcome of olanzapine.

Methods: The study was conducted for 8-week, four points follow up (week 2,3,4, and 8) prospective observational study. A reduction of 20, 25, 30% in Positive and Negative Syndrome Scale (PANSS) score from the base line at week 2,3, and 4 respectively were considered as early response. A reduction of 50% at week 8 was considered as responders. Receiver Operating Characteristics (ROC) curves were performed to detect the optimal threshold.

Results: Mean total baseline PANSS score was 106.66(95% CI; 100.4, 112.9). Week 2 (AUC = 50.5%, p?>?0.964) and week 3 (AUC = 64.9, p?>?0.13) responses failed to predict the 8th week response. Week 4 response (AUC = 92%, p?<?0.001) can be taken for the prediction of 8th week response (specificity = 72%, sensitivity = 100%, Positive Predictive Value = 61.1%, Negative Predictive Value = 100% and Optimum Early Response (OER) = 29.4%). 25 patients (69%) achieved more than 50% reduction (responders) in PANSS score after 8?weeks of treatment.

Conclusions: Our study suggests that patients with early response at week 4 are likely to achieve positive response after 8?weeks. This may help in appropriate clinical decision making for early non-responders.

• Key Points

• The early response can forecast the outcome at the endpoint for the treatment of FES

• A reduction of baseline PANSS score by 30% or more after four weeks are likely to have remission after week 8 with olanzapine therapy.

     

Prosody abilities in a large sample of affective and non-affective first episode psychosis patients

ObjectiveProsody comprehension deficits have been reported in major psychoses. It is still not clear whether these deficits occur at early psychosis stages.The aims of our study were to investigate a) linguistic and emotional prosody comprehension abilities in First Episode Psychosis (FEP) patients compared to healthy controls (HC); b) performance differences between non-affective (FEP-NA) and affective (FEP-A) patients, and c) association between symptoms severity and prosodic features.MethodsA total of 208 FEP (156 FEP-NA and 52 FEP-A) patients and 77 HC were enrolled and assessed with the Italian version of the "Protocole Montréal d'Evaluation de la Communication” to evaluate linguistic and emotional prosody comprehension. Clinical variables were assessed with a comprehensive set of standardized measures.ResultsFEP patients displayed significant linguistic and emotional prosody deficits compared to HC, with FEP-NA showing greater impairment than FEP-A. Also, significant correlations between symptom severity and prosodic features in FEP patients were found.ConclusionsOur results suggest that prosodic impairments occur at the onset of psychosis being more prominent in FEP-NA and in those with severe psychopathology. These findings further support the hypothesis that aprosodia is a core feature of psychosis.     

Remission after first-episode schizophrenia: results of a long-term follow-up

The aim of this study was to identify the rate and predictors of remission after first episode of schizophrenia (FES). Ninety-three FES patients were followed for at least 12 months and up to 12 years (mean = 58.4 months) including monthly assessments with the Brief Psychiatric Rating Scale-Expanded (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative Symptoms (SANS). We also administered the Premorbid Adjustment Scale (PAS). We used the remission criteria recently defined by Andreasen et al. (2005). Fifty-six (59.5%) patients met the remission criteria in the first 24 months of the follow-up period, but 40 (71.5%) of these patients could not maintain their status. However, 23 (57%) of these patients later met the remission criteria again. The remission group patients achieved a higher rate of employment both in the first year and overall. In the logistic regression analysis, lower negative and higher positive symptoms at admission, lower positive symptoms at month 3 of the follow-up, medication compliance in the first 6 months, and occupational status during the last month before admission were found related to remission status. Our findings suggest that the remission group has advantages in terms of occupational status and symptom severity compared with their counterparts who did not achieve or maintain a state of remission.     

首发精神分裂症未治时间对神经认知功能P300和P50预后的影响研究

目的DUP（duration of unmedicated psychosis）指精神疾病患者首次正式开始抗精神病治疗以前其精神病状态持续存在的时间。本研究探讨首发精神分裂症DUP对其神经认知功能的影响。方法收集从未服药首次发作精神分裂症患者70例和正常对照者54例,并对50例患者完成为期2个月随访。应用诺丁汉发病量表评估患者的DUP,应用DUP中位值将患者分为长DUP组和短DUP组。应用事件相关电位P300和感觉门控P50抑制评估神经认知功能。结果与对照者相比,分裂症患者P300波幅降低（P〈0．01）,P300潜伏期延迟（P〈0．01）,感觉门控P50抑制值异常升高（P〈0．01）。治疗前,长DUP组的P300潜伏期较短DUP组有延迟（352．1ms±36．7ms,336．0ms±29．0ms;F=4．2,P〈0．05）。治疗2个月后,仅短DUP组患者的P300波幅有明显改善（5．41xV±3．01．LV,7．31．LV±2．6uV,F=8．1,P〈0．01）。同时,两组患者的感觉门控P50抑制改善均不显著。结论DUP对首发精神分裂症患者神经认知功能预后有显著影响。如何预防长DUP的发生,值得关注。     

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project

PurposeIn patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment.MethodsIn all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed.ResultsDuring the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model.ConclusionA great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.     

Prognosis and outcome in a cohort of patients with non-affective functional psychosis

Summary Over a period of 3 years since the first in a lifetime onset of an episode of non-affective functional psychosis a cohort of 82 Dutch patients was studied at set intervals with regard to prognosis and outcome. Prognostic statements on remission, relapse, duration of episode, length of stay in hospital, and occupational, family and overall social adjustment were checked against actual outcome after I year. In general, the research team of three psychiatrists, a psychologist and a sociologist began quite optimistically, but became slightly more pessimistic with time. However, their predictions proved hardly better than chance statements. The team appeared to be more pessimistic about the diagnosis of schizophrenia than about that of reactive psychosis, although they were not correct with one diagnostic category more often than with the other.     

The relationship of early premorbid adjustment with negative symptoms and cognitive functions in first-episode schizophrenia: A prospective three-year follow-up study

Premorbid adjustment is an important prognostic factor of schizophrenia. The relationships between sub-components of premorbid adjustment and outcomes on symptoms and cognition in first-episode schizophrenia were under-studied. In the current study, we prospectively followed up 93 patients aged 18–55 years presenting with first-episode schizophrenia-spectrum disorder. Psychopathological and cognitive assessments were conducted at baseline, clinical stabilization, 12, 24 and 36 months. Premorbid adjustment was sub-divided into discrete functional domains, developmental stages and premorbid-course types based on ratings of the Premorbid Adjustment Scale (PAS). The study focused on early developmental stages to minimize contamination by prodromal symptoms. Results indicated that gender differences in premorbid functioning were primarily related to early-adolescence adjustment and academic domain. Social domain was more strongly related to negative symptoms, while academic domain was more consistently linked to cognitive outcome (Wisconsin Card Sorting test and verbal fluency). Patients with stable-poor premorbid course had more severe negative symptoms and cognitive impairment. In conclusion, in a Chinese cohort of first-episode schizophrenia-spectrum disorder, sub-components of early premorbid adjustment were shown to be differentially related to clinical and cognitive measures. The results highlighted the importance of applying a more refined delineation of premorbid functioning in studying illness outcome.     

Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients

The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP’s.We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment.This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.     

Chronology of panic and avoidance,age of onset in panic disorder,and prediction of treatment response

Summary The relevance of the chronology between panic disorder and avoidance behavior and of an early, medium or late onset of panic disorder was tested. Groups from the sample of the cross-national collaborative panic study (CNCPS) were compared for differences in basic characteristics and for the ability to predict treatment response. Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment. Patients with an early onset of panic disorder suffered more often from agoraphobia. The treatment response was similar in the groups with early, medium or late onset of panic disorder. Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or impiramine.