Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.

204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.

Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.

Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Évaluer la tolérance, la sécurité d’emploi et la réponse à un traitement par palmitate de palipéridone (PP) à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par un autre antipsychotique injectable à action prolongée : décanoate d’halopéridol (Déc-Hal), décanoate de flupentixol (Déc-Fpt), décanoate de fluphénazine (Déc-Flu), zuclopenthixol (Zuc) ou rispéridone à libération prolongée (RIS-LP).

Étude internationale, prospective, ouverte, de six mois, chez des patients atteints de schizophrénie, non aigus mais insuffisamment contrôlés par d’autres antipsychotiques injectables à action prolongée.

Taux de réponse (amélioration ≥ 20 % du score total à la PANSS [Positive and Negative Syndrome Scale]), score à la PSP (Personal and Social Performance scale), événements indésirables (EIs).

Les analyses ont été réalisées sur la population en intention de traiter de façon stratifiée pour chaque traitement : 53 patients Déc-Hal, 35 Déc-Fpt, 44 Déc-Flu, 42 Zuc, 56 RIS-LP. Les scores totaux moyens à la PANSS initiale variaient de 67,7 ± 20,3 [RIS-LP] à 75,7 ± 13,2 [Déc-Hal]. Entre 71,4 % [RIS-LP] et 85,7 % [Déc-Fpt] des patients ont terminé l’étude. À la fin de l’étude, 53,7 % [Zuc], 54,7 % [Déc-Hal], 59,1 % [Déc-Flu], 61,1 % [RIS-LP] et 61,8 % [Déc- Fpt] des patients ont vu leur score total à la PANSS diminuer d’au moins 20 %. Les scores moyens de PSP de base étaient de 48,7 [Déc-Hal], 59,6 [Déc-Fpt], 53,5 [Déc-Flu], 52,9 [Zuc] et 60,1 [RIS-LP], et le changement en fin d’étude était respectivement de : 5,2 ; 6,1 ; 6,0 ; 6,4 ; et 5,2 (p ≤ 0,0163 pour tous les traitements). Les EIs rapportés au moins une fois dans tous les sous-groupes : douleur au site d’injection, insomnie, trouble psychotique.

Le PP à doses flexibles a été bien toléré et a permis une réponse thérapeutique cliniquement significative chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par d’autres antipsychotiques injectables à action prolongée.

Évaluer l’amélioration fonctionnelle chez des patients atteints de schizophrénie sous palmitate de paliperidone (PP) à doses flexibles après échec d’un traitement par antipsychotiques oraux.

Analyse menée dans deux sous-groupes de patients atteints de schizophrénie : aigus (n = 202) et non aigus (n = 593) après échec d’un traitement par antipsychotiques oraux, inclus dans une étude internationale, prospective, de six mois.

Changement du score total à la PANSS (Positive and Negative Syndrome Scale), à la PSP (Personal and Psychosocial Performance scale), et à la Mini-ICF-APP (Mini International Classification of Functionality, Disability and Health Rating for Activity and Participation Disorders in Psychological Illnesses).

Les deux sous-groupes ont présenté une amélioration significative du score total à la PANSS : de 98,5 ± 20,1 à l’inclusion à 67,4 ± 24,0 à la fin de l’étude (diminution moyenne = −31,0 ± 29,0) chez les patients aigus et de 71,5 ± 14,6 à 59,7 ± 18,1 (diminution moyenne = −11,7 ± 15,9) chez les patients non aigus. Cette réponse thérapeutique était associée à une augmentation significative du score total à la PSP de 43,9 ± 15,0 à 62,9 ± 17,1 (amélioration moyenne = 19,0 ± 18,7, p <0,0001) chez les patients aigus, et de 58,1 ± 13,4 à 66,1 ± 15,7 (amélioration moyenne =8,0 ± 14,0, p < 0,0001) chez les patients non aigus. Il existait une amélioration significative du score à la Mini-ICF-APP qui diminuait de 26,8 ± 8,5 à 18,5 ± 9,8 (diminution moyenne = −8,0 ± 10,4, p < 0,0001) chez les patients aigus et de 19,8 ± 7,9 à 15,9 ± 8,8 (diminution moyenne = −4,0 ± 7,5, p < 0,0001) chez les patients non aigus.

L’amélioration symptomatique sous PP à doses flexibles chez des patients aigus ou non-aigus atteints de schizophrénie après échec d’un traitement par antipsychotique oral s’est accompagnée d’une amélioration fonctionnelle cliniquement significative.

Antidepressants are frequently prescribed in patients with psychotic disorders, but little is known about their effects in routine clinical practice. The objective was to investigate the prescribing patterns of antidepressants in relation to the course of depressive symptoms in patients with psychotic disorders.

A cohort of 214 Dutch patients with psychotic disorders received two assessments of somatic and psychiatric health, including a clinician-rated screening for depressive symptoms, as part of annual routine outcome monitoring.

Depressive symptoms were prevalent among 43% (93) of the patients. Antidepressants were prescribed for 40% (86) of the patients and the majority 83% (71) continued this therapy after one year. Multivariable analysis showed that patients with more severe psychopathology had a higher risk to develop depressive symptoms the following year (OR [95% CI]=0.953 [0.912–0.995]). For patients with depressive symptoms at baseline, polypharmacy was a potential risk factor to keep having depressive symptoms (OR [95% CI]=1.593 [1.123–2.261]). Antidepressant use was not an independent predictor in both analyses.

Routine outcome monitoring in patients with psychotic disorders revealed a high prevalence of depressive symptoms. Antidepressants were frequently prescribed and continued in routine clinical practice.

Negative symptoms in patients with schizophrenia are strongly associated to disease burden. Aerobic exercise might be beneficial in treating negative symptoms.

The meta-analysis aims to evaluate the effect of aerobic exercise on negative symptoms in schizophrenia.

The Cochrane Library, Medline, Embase, PsycINFO and CINAHL were searched from their inception until 16 March 2014. Randomised controlled trials (RCT's) comparing aerobic exercise with other psychosocial interventions in schizophrenia were included if negative symptoms were assessed. The methodological quality of the studies was assessed with the Clinical Trial Assessment Measure (CTAM).

Nine studies were included (N= 488). Seven out of nine studies had poor methodological quality as measured with the CTAM. The meta-analysis showed a small non-significant treatment effect in favour of exercise interventions (Hedges’ g = -0.310, CI -0.787 0.168) with a power of 75%. The analysis indicates high heterogeneity (Q(8)=37.163 (P<0.000) I2= 75%). A meta-regression analysis showed that more training sessions were associated with a higher decrease in negative symptoms (Hedges’ g = 0.460 -0.006 0.925 (P=0.053)). This was confirmed in a moderator analysis including studies with >20 sessions (Hedges’ g = 0.640, CI -1.281 0.000, Q(5)=24.214 (P < 0.000) I2=79%).

A large significant effect of exercise was found in five studies comparing exercise to TAU (Hedges’ g=-1.370, CI -2.352 -0.389, Q(4)=29.278 (P< 0.000) I2=86%).

This meta-analysis demonstrated a significant effect of aerobic exercise on negative symptoms in schizophrenia compared to TAU, but no effect compared to any other (active) control condition. The quality of the included studies was low.

Suicide remains the leading cause of premature death in patients with psychotic disorders. The lifetime suicide risk for schizophrenia is approximately 10%.

This study aims to compare the suicide risk over the past decade following recent onset psychosis to findings from the eighties and nineties in the same catchment area and to identify predictors of suicide in the context of the Psychosis Recent Onset Groningen – Survey (PROGR-S).

A medical file search was carried out to determine the current status of all patients admitted between 2000 and 2009. The suicide rate was compared with a study executed in 1973-1988 in the same catchment area. Predictors of suicide were investigated using Cox regression.

The status of 424 of the 614 patients was known in July 2014. Suicide occurred in 2.4% of the patients with psychotic disorders (n=10; mean follow-up 5.6 years); 6 out of 10 suicides took place within two years. Within two decades, the suicide rate dropped from 11% (follow-up 15 years, 8.5% after 5 years) to 2.4%. The Standardized Mortality Rate (SMR) of suicides compared with the general population was 41.6. A higher age was the only significant predictor for suicide. Neuroticism, living situation, disorganized and negative symptoms, and passive coping style showed a trend for significance. A significant reduction in the suicide rate was found for people with psychosis over the past decades.

A considerable drop in suicide rate was found. Given the high SMR, suicide research should have the highest priority.

In schizophrenia the life expectancy is significantly lower compared to the general population. To monitor their functioning over the course of the illness, a protocol for routine outcome monitoring (ROM) has been developed in the Netherlands.

This study investigated the effectiveness of Routine Outcome Monitoring (ROM) in clinical practice. More specifically, we investigated whether ROM outcomes resulted in treatment in accordance with guidelines for schizophrenia.

Out of the ROM database of 2010 (n=1040), a random sample of 100 patients diagnosed with a psychotic disorder was taken. Data from blood tests, a physical examination, interviews, and standardized questionnaires were used. The prevalence of cardiovascular risk factors, psychosocial problems and sexual dysfunctions was calculated. Offered treatment was investigated with the treatment plans of patients.

The sample consisted of 63 males and 37 females. The average age was 44 and the average duration of illness was 17.7 years. High prevalences of cardiovascular risk factors, psychosocial problems and sexual dysfunctions were found. Cardiovascular risk factors remained untreated in 61% of cases, psychosocial problems remained untreated in 85% of cases and sexual dysfunctions were not treated at all in our sample.

High rates of non-treatment were found for cardiovascular risk factors, psychosocial problems and sexual dysfunctions, despite high prevalences as identified with ROM. Thus, ROM outcomes do not result in treatment in accordance with guidelines for the majority of patients. Steps are necessary to bridge the gap between ROM and treatment to ensure this group of severely mentally ill patients receives the best possible treatment.

This study concerned a multicenter double-blind randomized controlled trial in 32 patients with schizophrenia or schizoaffective disorder. All had moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Twenty-four patients participated in the pre- and posttreatment fMRI measurement. Analyses concerned changes in brain activation as measured with functional magnetic resonance imaging (fMRI) during the Tower of London (ToL) task from pre-treatment to post-treatment.

Brain activation increased more in the active group in the right DLPFC and the right medial frontal gyrus as compared to the sham group. Different activation change was also found in the left posterior cingulate, with decreased activation in the active and increased activation in the sham group. The changes in brain activation were accompanied by a significant improvement of negative symptoms in the treatment group (p=0.04).

Our findings suggest that treatment with rTMS over the DLPFC may potentially increase task-related activation in frontal areas and improve negative symptoms in patients with schizophrenia.

Despite important progress, the results of pharmacological treatment of schizophrenia are frequently unsatisfactory. Therefore some patients use natural medicines although it is unclear whether natural medicines are effective and safe. We assessed the evidence for natural medicines with and without antipsychotics in treating symptoms or reducing side effects of antipsychotics in schizophrenia.

A systematic review until April 2013. Only RCTs with a Jadad score of 3 or higher, were included.

105 RCTs were identified. Evidence was found for glycine, sarcosine, NAC, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol and vitamin B6 for improving symptoms of schizophrenia when added to antipsychotics. Inconclusive or no evidence was found for omega-3, Dserine, D-alanine, D-cycloserine, B vitamins, vitamin C, dehydroepiandrosteron (DHEA), pregnenolone (PREG), inositol, gamma-hydroxybutyrate (GHB) and des-tyr-gamma-endorphin when added to antipsychotics. Omega-3 without antipsychotics might be beneficial in the prevention of schizophrenia. Only ayurvedic herbs (in one study), no other agents, seemed effective without antipsychotics. Ginkgo and vitamin B6 seemed to be effective in reducing side effects of antipsychotics. All natural agents produced only mild or no side-effects.

High quality research on natural medicines for schizophrenia is scarce. However, there is emerging evidence for improved outcome for glycine, sarcosine, NAC, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol and vitamin B6, all with only mild or no side effects. Most study samples are small, the study periods are generally short, the studies only cover a modest part of the world's population and most results need replication.

Routine Outcome Monitoring (ROM) has become part of the treatment process in mental health care. However, studies have indicated that few clinicians in psychiatry use the outcome of ROM in their daily work. The aim of this study was to explore the degree of ROM use in clinical practice as well as the explanatory factors of this use.

In the Northern Netherlands, a ROM-protocol (ROM-Phamous) for patients with a psychotic disorder has been implemented. To establish the degree of ROM-Phamous use in clinical practice, the ROM results of patients (n = 204) were compared to the treatment goals formulated in their treatment plans. To investigate factors that might influence ROM use, clinicians (n = 32) were asked to fill out a questionnaire about ROM-Phamous.

Care domains that were problematic according to the ROM-Phamous results were mentioned in the treatment plan in 28% of cases on average (range 5–45%). The use of ROM-Phamous in the treatment process varies considerably among clinicians. Most of the clinicians find ROM-Phamous both useful and important for good clinical practice. In contrast, the perceived ease-of-use is low and most clinicians report insufficient time to use ROM-Phamous.

More frequent ROM use should be facilitated in clinicians. This could be achieved by improving the fit with clinical routines and the ease-of-use of ROM systems. It is important for all stakeholders to invest in integrating ROM in clinical practice. Eventually, this might improve the diagnostics and treatment of patients in mental health care.

Little is known about visual hallucinations (VH) in psychosis. We investigated the prevalence and the role of bottom-up and top-down processing in VH. The prevailing view is that VH are probably related to altered top-down processing, rather than to distorted bottom-up processing. Conversely, VH in Parkinson's disease are associated with impaired visual perception and attention, as proposed by the Perception and Attention Deficit (PAD) model. Auditory hallucinations (AH) in psychosis, however, are thought to be related to increased attention.

Our retrospective database study included 1119 patients with non-affective psychosis and 586 controls. The Community Assessment of Psychic Experiences established the VH rate. Scores on visual perception tests [Degraded Facial Affect Recognition (DFAR), Benton Facial Recognition Task] and attention tests [Response Set-shifting Task, Continuous Performance Test-HQ (CPT-HQ)] were compared between 75 VH patients, 706 non-VH patients and 485 non-VH controls.

The lifetime VH rate was 37%. The patient groups performed similarly on cognitive tasks; both groups showed worse perception (DFAR) than controls. Non-VH patients showed worse attention (CPT-HQ) than controls, whereas VH patients did not perform differently.

We did not find significant VH-related impairments in bottom-up processing or direct top-down alterations. However, the results suggest a relatively spared attentional performance in VH patients, whereas face perception and processing speed were equally impaired in both patient groups relative to controls. This would match better with the increased attention hypothesis than with the PAD model. Our finding that VH frequently co-occur with AH may support an increased attention-induced ‘hallucination proneness’.

Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.

A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.

A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.

Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.