First-episode Non-affective Psychosis Research Articles

DOPAMINE D3 RECEPTOR OCCUPANCY AND D3 RECEPTOR-MEDIATED ACTIONS OF CARIPRAZINE, A DOPAMINE D3/D2 RECEPTOR PARTIAL AGONIST ANTIPSYCHOTIC CANDIDATE

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

NOVEL TREATMENT OPTIONS FOR IMPAIRED COGNITION IN SCHIZOPHRENIA: COMBINING DIFFERENT MODES OF COGNITIVE REMEDIATION

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

A Disrupted-in-Schizophrenia 1 Gene Variant is Associated with Clinical Symptomatology in Patients with First-Episode Psychosis.

ObjectiveDISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis.MethodsTwo hundred and thirteen Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects.ResultsPatients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers.ConclusionDISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorder.

A naturalistic, randomized, controlled trial combining cognitive remediation with cognitive–behavioural therapy after first-episode non-affective psychosis

Cognitive remediation (CR) preceding cognitive-behavioural therapy for psychosis (CBTp) was trialled within routine clinical services, with the hypothesis that following first-episode non-affective psychosis CR would enhance CBTp efficacy by improving neuropsychological performance. A total of 61 patients with DSM-IV non-affective psychoses waiting for routine CBTp were randomized to computerized CR over 12 weeks, supported by a trained support worker, or time-matched social contact (SC). Primary outcome was the blind-rated Psychotic Symptoms Rating Scale (PSYRATS). Secondary outcomes included measures of CBTp progress, cognition, symptoms, insight and self-esteem: all at baseline, after CR (12 weeks) and after CBTp (42 weeks). PSYRATS and global neuropsychological efficacy were tested using mixed-effects models with a group×time interaction term. Measures of CBTp progress and some neuropsychological measures were modelled by regression. There was no significant difference between the CR and SC groups in PSYRATS (group×time coefficient 0.3, 95% confidence interval -0.4 to 1.1, p=0.39). However, after CR CBTp was shorter [median 7 sessions, interquartile range (IQR) 2-12 after CR; median 13, IQR 4-18 after SC; model p=0.011] and linked to better insight (p=0.02). Global cognition did not improve significantly more after CR (p=0.20) but executive function did (Wisconsin Card Sort, p=0.012). CBTp courses preceded by CR were far shorter but achieved the same outcome as CBTp preceded by an active control, consistent with neuropsychological improvement enhancing CBTp. CR was delivered by staff with minimal training, offering the potential to reduce the costs of CBTp considerably.

Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year

Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment. The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year. From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants. First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.

Course of cognitive deficits in first episode of non-affective psychosis: A 3-year follow-up study

Cognitive dysfunctions are critical determinants of the quality of life and functionality in schizophrenia. Whether the cognitive deficits present at an early stage, are static or change across one's lifespan is still under debate. This study aims to investigate the long-term (3years) course of cognitive deficits in a large and representative cohort of first episode schizophrenia spectrum patients (N=155),and evaluate their influence on disability. In addition, a healthy control sample (N=43) was also studied for comparison. This study evaluates the performance of patients and controls in a battery of cognitive assessments using baseline, 1-year and 3-year follow-up designs. The results show that, although cognitively outperformed by the controls at any time, the cognitive performance of the patients improved similar to the controls in all cognitive functions except verbal and visual memory. Even though the course of cognitive performance across the sample as a whole was stable, the subgroup of patients who experienced a cognitive decline had worse functionality and lesser amelioration of negative symptoms. Overall, there is no significant deterioration in the cognitive function in a group of first episode schizophrenia spectrum disorder patients, with the possible exception of tasks that were associated with episodic memory. However, patients whose cognitive performance demonstrated a declining trend may present with a poorer progression in terms of clinical and disability variables.

Prospective study of the course of delusional themes in first-episode non-affective psychosis

The stability of delusional themes in psychotic disorders is only sparsely lit. The study aims to investigate the stability of delusional themes over a period of time in patients with first-episode non-affective psychosis. The data were drawn from a randomized controlled trial of 547 first-episode patients with schizophrenia spectrum disorders, the OPUS trial. A subsample of 411 patients met our inclusion criteria. They were interviewed at the time of first treatment contact, and at years 1, 2 and 5 after onset. The delusional themes of the 411 patients were classified by applying principal component analysis to the patients' scores on 12 items of delusions from the Scale for the Assessment of Positive Symptoms in Schizophrenia, SAPS. The course of the patients' predominant delusional themes was analysed afterwards. The 12 delusional themes from SAPS were converted into five groups using principal component analysis. At all three follow ups there were almost equal proportions of patients with the predominant delusion being from the same group of delusional themes as at baseline and of patients with the predominant delusion being from another group of delusional themes than at baseline. The predominant delusional theme at the time of first treatment contact was seen to be only of some predictive value to the predominant delusional theme at the later follow-up points in patients with first-episode non-affective psychosis. This stresses the importance of a systematic assessment of different delusional themes in the continued monitoring of early signs of psychotic relapse and at each psychotic episode.

Aripiprazole, Ziprasidone and Quetiapine in the treatment of first-episode nonaffective psychosis: A 12-week randomized, flexible-dose, open-label trial

BackgroundDifferences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second generation antipsychotics (SGAs) are scarce. We aimed to compare the clinical effectiveness in the short-term of Aripiprazole, Ziprasidone and Quetiapine in the treatment of first-episode schizophrenia-spectrum disorders. MethodFrom October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. 202 first-episode drug-naïve patients were randomly assigned to Aripiprazole (N=78), Ziprasidone (N=62), or Quetiapine (N=62) and followed-up for 3months. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat populations was conducted in the analysis for clinical efficacy. ResultsThe overall dropout rate at 3months was small (13.86%). The treatment discontinuation rate differed significantly between treatment groups (Aripiprazole=23.1%, Ziprasidone=37.1% and Quetiapine=61.3%) (χ2=21.334; p<0.001). Insufficient efficacy in the group of Quetiapine is the main reason for discontinuation rate differences (χ2=20.223; p<0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank=23.467 p<0.001). Aripiprazole and Quetiapine were associated with a greater depressive symptoms improvement (p=0.043). The profile of side-effects varies between treatments. Patients on Quetiapine were less likely to be prescribed hypnotics. ConclusionsPatients treated with Quetiapine had a higher risk of treatment discontinuation in the short-term after a first episode due to insufficient efficacy. Establishing differences between SGAs may help clinicians in prescribing decisions for the treatment of individuals presenting with first-episode schizophrenia.

Aripiprazole, Ziprasidone, and Quetiapine in the Treatment of First-Episode Nonaffective Psychosis

Differences among antipsychotics in effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second-generation antipsychotics are scarce. From October 2005 to March 2011, a prospective, randomized, open-label study comparing the effectiveness of aripiprazole, ziprasidone, and quetiapine in the short-term treatment of first-episode schizophrenia-spectrum disorders was undertaken. Two hundred two patients were randomly assigned to aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 6 weeks. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The overall dropout rate at 6 weeks was small (6.4%). The treatment discontinuation rate differed significantly between treatment groups (aripiprazole, 15%; ziprasidone, 19%; and quetiapine, 35%; χ(2) = 8.529; P = 0.014). Insufficient efficacy in the group of quetiapine is the main reason for discontinuation rate differences (χ = 10.139; P = 0.006). The mean time to all-cause discontinuation was significantly different between the groups (log-rank, 12.783; P = 0.001). Quetiapine was associated with a greater depressive symptoms improvement than ziprasidone (P = 0.045). The rate of responders at 6 weeks differed between the groups (F = 6, 116; P = 0.047), with a higher rate of the responders with aripiprazole. The profile of adverse effects varies between the treatments. Patients on quetiapine were less likely to be prescribed concomitant medications. Treatment with quetiapine was associated with a higher risk of treatment discontinuation during treatment owing to insufficient efficacy. Differences in effectiveness between second-generation antipsychotics would determine their position in everyday clinical practice and could help physicians choose the more efficacious antipsychotics.

Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis

Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone

The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Prediction of acute clinical response following a first episode of non affective psychosis: Results of a cohort of 375 patients from the Spanish PAFIP study

Predicting response to antipsychotic treatment might optimize treatment strategies in early phases of schizophrenia. We aimed to investigate sociodemographic, premorbid and clinical predictors of response to antipsychotic treatment after a first episode of non-affective psychosis. 375 (216 males) patients with a diagnosis of non affective psychosis entered the study. The main outcome measure was clinical response at 6 weeks and variables at baseline were evaluated as predictors of response. ANOVA for continuous and chi-square for categorical data were used to compare responders and non-responders. Multivariate logistic regression was used to establish a prediction model. 53.3% of study subjects responded to antipsychotic treatment. The following variables were associated with an unfavorable response: 1.--lower severity of symptoms at baseline; 2.--diagnosis of schizophrenia; 3.--longer DUI and DUP; 4.--poorer premorbid adjustment during adolescence and adulthood; 5.--family history of psychosis, and 6.--hospitalization. Patients with a family history of psychosis, longer DUP, poor premorbid functioning and lower severity of psychotic symptoms at intake have a reduced likelihood of responding to antipsychotic treatment. Helping clinicians to identify those first episode patients with a lower probability of having a favorable clinical response is meant as a first step to achieve a successful initial treatment.

Subtyping first-episode non-affective psychosis using four early-course features: potentially useful prognostic information at initial presentation.

Heterogeneity of symptoms, course and outcomes in primary psychotic disorders complicates prognosis, treatment and diverse aspects of research. This study aimed to identify interpretable subtypes of first-episode non-affective psychosis based on four early-course features (premorbid academic functioning, premorbid social functioning, duration of the prodrome and age at onset of psychosis). Data from 200 well-characterized patients hospitalized in public-sector inpatient units for first-episode non-affective psychosis were used in latent profile analyses. Derived subtypes were then compared along a number of clinical dimensions using analyses of variance. Using four early-course features, three classes were derived. A good premorbid/short prodrome subtype was characterized by a lower severity of positive symptoms, better social/occupational/global functioning, and a shorter duration of untreated psychosis; a poor premorbid/early onset subtype demonstrated greater negative and preoccupation symptoms, as well as greater psychosocial problems; and a long prodrome/late onset subtype was characterized by greater dysphoric symptoms. Findings indicate a need for further research with first-episode samples on the utility of subtyping based on early-course (premorbid, prodromal and onset-related) characteristics. Such efforts could enhance the parsing of heterogeneity, thereby advancing clinical practice and research.

Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia

To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.

Predictors of clinical remission following a first episode of non-affective psychosis: Sociodemographics, premorbid and clinical variables

The aim of the study was to identify predictors associated with a lower likelihood of achieving a clinical remission 1 year after the first break of the illness. Participants were 174 consecutive subjects included in a first episode programme with no prior treatment with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone in a randomized, open-label, prospective clinical trial. The main outcome variable was the remission criteria developed by the Remission in Schizophrenia Working Group. Clinical variables were included in a logistic regression analysis in order to predict the remission state at 1 year. At 1 year, 31% of patients met criteria for remission. The logistic regression analysis revealed that the strongest predictors of achieving clinical remission 1 year away from a first episode of non-affective psychosis were the length of duration of untreated psychosis (DUP), the severity of negative symptomatology and the educational level attained at baseline. The results suggest that: (1) patients with a lengthy DUP, a greater severity of negative symptomatology at baseline and with a lower education level are in a higher risk of not achieving a clinical remission during the first year of treatment; and (2) early intervention clinical programs should aim to reduce the length of DUP in order to provide a better outcome for patients.

Predicting relapse after a first episode of non-affective psychosis: A three-year follow-up study

BackgroundPreventing relapse during the first years of illness has a critical impact on lifelong outcomes in schizophrenia. A better understanding and improvement in factors which influence relapse should diminish the risk of relapse and consequently improve the outcome of the illness. ObjectiveTo identify factors associated with relapse after 3 years of a first episode in a sample of non-affective psychosis patients who are representative of clinical practice in an epidemiological catchment. MethodWe analyzed socio-demographic and clinical data from a cohort of patients who were treated in a specialized early intervention service and who were at risk of relapse during a 3-year follow-up. Univariate analyses, logistic regression and survival analyses were performed. The analyzed variables included gender, age at onset, duration of untreated psychosis, clinical severity at baseline, insight at baseline, premorbid functioning, substance use, family history of psychosis and adherence to medication. ResultsOf the 140 patients considered to be at risk for relapse, 91 (65%) individuals relapsed at least once over the three-year period. The relapse rates at 1 year and 2 years were 20.7% and 40.7%, respectively. Adherence to medication was the only significant predictor of relapse after a three-year follow-up [hazard ratio (HR) 4.8, 95% confidence interval (CI) 2.9–7.7; p < 0.001]. Comparison of the mean time of relapse between adherent and non-adherent patients also revealed statistically significant differences (933 and 568 days, respectively). 50% of patients will relapse despite being categorized as treatment adherents. ConclusionNon-adherence to medication is the biggest predictive factor of relapse after a first episode of psychosis.

Long-Term Follow-Up of the TIPS Early Detection in Psychosis Study: Effects on 10-Year Outcome

Early detection in first-episode psychosis confers advantages for negative, cognitive, and depressive symptoms after 1, 2, and 5 years, but longitudinal effects are unknown. The authors investigated the differences in symptoms and recovery after 10 years between regional health care sectors with and without a comprehensive program for the early detection of psychosis. The authors evaluated 281 patients (early detection, N=141) 18 to 65 years old with a first episode of nonaffective psychosis between 1997 and 2001. Of these, 101 patients in the early-detection area and 73 patients in the usual-detection area were followed up at 10 years, and the authors compared their symptoms and recovery. A significantly higher percentage of early-detection patients had recovered at the 10-year follow-up relative to usual-detection patients. This held true despite more severely ill patients dropping out of the study in the usual-detection area. Except for higher levels of excitative symptoms in the early-detection area, there were no symptom differences between the groups. Early-detection recovery rates were higher largely because of higher employment rates for patients in this group. Early detection of first-episode psychosis appears to increase the chances of milder deficits and superior functioning. The mechanisms by which this strategy improves the long-term prognosis of psychosis remain speculative. Nevertheless, our findings over 10 years may indicate that a prognostic link exists between the timing of intervention and outcome that deserves additional study.

Continued Cannabis Use and Outcome in First-Episode Psychosis

Cannabis use has been found to increase the risk of psychosis. It is unclear whether, after a first psychotic episode has occurred, continued cannabis use is associated with poor functional outcome of psychosis. As part of a randomized, open-label, controlled trial, the association of cannabis use and measures for psychopathology and social role functioning after 2 years of follow-up and for the recently proposed outcome measures of symptomatic remission, functional remission, and clinical recovery was explored in a group of 124 patients suffering from nonaffective first-episode psychosis (diagnosed according to DSM-IV and included from a catchment area in the Netherlands of 3.1 million inhabitants from October 2001 through December 2002). Other patient characteristics that were expected to be independently associated with outcome, among them alcohol and other drug use, were assessed at baseline. Continued cannabis use was not associated with symptomatic or functional remission or clinical recovery. After 2 years, cannabis use was related to certain aspects of social role functioning (economic and social activities; explained variance 5.6% and 8.4%, respectively) but not to psychopathology (Positive and Negative Syndrome Scale Positive, Negative, or General symptoms). Our findings support the notion that continued cannabis use after the onset of a first-episode psychosis is correlated with worse social outcome and should be discouraged whenever possible, but its role in outcome is modest in comparison to other factors. Nederlands Trial Register: http://www.trialregister.nl (ID: NTR 374).

The Structural Neural Substrates of Persistent Negative Symptoms in First-Episode of Non-Affective Psychosis: A Voxel-Based Morphometry Study

Objectives: An important subset of patients with schizophrenia present clinically significant persistent negative symptoms (PNS). Identifying the neural substrates of PNS could help improve our understanding and treatment of these symptoms. Methods: This study included 64 non-affective first-episode of psychosis (FEP) patients and 60 healthy controls; 16 patients displayed PNS (i.e., at least one primary negative symptom at moderate or worse severity sustained for at least six consecutive months). Using voxel-based morphometry (VBM), we explored for gray matter differences between PNS and non-PNS patients; patient groups were also compared to controls. All comparisons were performed at p < 0.05, corrected for multiple comparisons. Results: PNS patients had smaller gray matter in the right frontal medial–orbital gyrus (extending into the inferior frontal gyrus) and right parahippocampal gyrus (extending into the fusiform gyrus) compared to non-PNS patients. Compared to controls, PNS patients had smaller gray matter in the right parahippocampal gyrus (extending into the fusiform gyrus and superior temporal gyrus); non-PNS patients showed no significant differences to controls. Conclusion: Neural substrates of PNS are evident in FEP patients. A better understanding of the neural etiology of PNS may encourage the search for new medications and/or alternative treatments to better help those affected.

Depression and quality of life in first-episode psychosis

AimQuality of life (QOL) has gained recognition as a valid measure of outcome in first-episode psychosis (FEP). This study aimed to determine the influence of specific groups of depressive symptoms on separate domains of subjectively appraised QOL. MethodsWe assessed 208 individuals with first-episode non-affective psychosis using measures of diagnosis (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), symptoms (Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and Calgary Depression Scale for Schizophrenia), functioning (Global Assessment of Functioning), insight (Birchwood Scale), duration of untreated psychosis (Beiser Scale), and QOL World Health Organisation Quality of Life Instrument (WHOQOL-Bref). We used multiple regression to determine the contribution of depressive symptoms to QOL domains while controlling for socio-demographic and other clinical characteristics. ResultsThere were complete data for 146 individuals with FEP. Quality-of-life domains were consistently predicted by depressive symptoms including depressive mood and hopelessness rather than biological symptoms of depression with those experiencing more depressive symptoms reporting worse QOL. Those who were treated as in-patients reported improved QOL, and hospitalization was an independent predictor of most QOL domains. In-patients displayed greater levels of positive symptoms with those involuntarily detained displaying greater levels of bizarre behavior, thought disorder, and delusions. ConclusionsThese findings suggest that QOL is heavily influenced by depressive symptoms at initial presentation; however, as QOL domains are also influenced by admission status with in-patients being more symptomatic in terms of positive symptoms, subjective QOL assessment may be compromised during the acute phase of illness by both positive and depressive symptom severity.