Rats are social animals that produce high-frequency whistles said to reflect their underlying affective state. Injecting rats with a glutamate agonist (domoic acid) at a sensitive period of brain development, models aspects of schizophrenia. This is known as the neonatal DOM model.

We investigated whether DOM rats display altered social behaviour – as seen in patients with schizophrenia – using their high-frequency whistles as a proxy for the emotional valence of social situations.

We used 19 male Sprague Dawley rats, injected with either a low-dose of domoic acid or saline at postnatal days 8 to 14. The social behaviour of the rats was investigated at four levels:

– anticipation of social interaction;

– dyadic encounter;

– three-chamber test;

– tickling.

Tests were carried out at postnatal days 34 to 40 and 50 to 56. Rat whistles were recorded on all days of testing.

In progress.

The interest in rat whistles as a supplement to traditional behavioural tests has increased. New software allows for detailed qualitative analysis of the whistle subtypes and thus new complexity to their interpretation. This study can help unravel information encoded in the whistles and shed light on the social behaviour of the DOM rat thus investigating it is applicability as a model of schizophrenia.

The authors have not supplied their declaration of competing interest.

Intellectual functioning in schizophrenia has been associated with genetic vulnerability and obstetric complications.

The aim of this study was to assess:

– the incidence of complications during pregnancy, labor and delivery;

– the association of OCs with general intellectual ability in two groups: patients with schizophrenia and their healthy siblings.

Forty-two patients with schizophrenia according to DSM-IV and 43 their healthy siblings were included in the study and examined using MINI and WAIS-R. Their mothers were interviewed to gather data on OCs. The ‘midwife protocol’ of Parnas et al. was used to quantify the presence and entity of OCs.

Asphyxia, mother's serious illness during pregnancy, premature delivery with weight < 2500 g, labor time > 48 h, infarcts in the placenta and eclampsia were statistically more frequent in schizophrenic group. OCs were more common in individuals with a family history. The two investigated groups were different in the following WAIS-R subtests: comprehension (P = 0.018), block design (P = 0.0001), digit symbol (P = 0.001), as well as in performance IQ and total IQ. In the patient group, correlations between OCs indexes and WAIS-R results include all intelligence quotients (verbal, performance, total IQ) and 5 WAIS-R subtests, while in the sibling group: verbal and total IQ and 2 subtests. The correlation between Vocabulary subtest and OCs was the strongest in both groups.

OCs may interact with genetic vulnerability to increase the risk of schizophrenia and have been associated with cognitive deficits in the patient group.

The authors have not supplied their declaration of competing interest.

A number of authors have hypothesized that psychotic patients who consume cannabis constitute a differentiated subgroup of patients that have better cognitive and social skills, necessary to engage in illegal drug consumption, than non-using patients.

Given that the prevalence, and patterns, of cannabis use are culturally driven, we wanted to study first-episode psychosis (FEP) cannabis-using and non-using patients coming from different European countries as part of the EUGEI-STUDY.

We tested the hypothesis of better premorbid social adjustment in cannabis-using FEP patients, by comparing them to FEP non cannabis users and to their respective healthy controls.

A total of 1745 people (746 cases; 999 controls) completed the assessment for premorbid adjustment [Premorbid Adjustment Scale (PAS)] and cannabis use (CEQ-Revised). We first extracted the Premorbid Social Adjustment Factor (PSA) from PAS and then performedlinear mixed models with PSA as dependent variable and cannabis lifetime (Yes/No) and subject status (Cases/Controls) as independent variables. We then considered “Country” as random intercept.

Across all countries, PSA scores were better in patients who had smoked cannabis in their lifetime than patients who had not (P = 0.009). The difference in PSA score between cannabis users and non-users was significantly greater in cases than controls (P = 0.038). The relationship between PSA, cannabis lifetime (Yes/No) and subject status among nations (random intercept) is shown on Fig. 1.

Cannabis-using psychotic patients show better premorbid social adjustment than non-using patients, across 5 European countries.

The authors have not supplied their declaration of competing interest.

Despite patients with schizophrenia showed the deficits in the fronto-temporal and thalamo-frontal connectivity, the white matter connectivity in patients with schizotypal personality disorder had not been systemically investigated.

This study involved 40 neuroleptic-naïve patients with schizotypal personality disorder (SPD), 60 patients with schizophrenia (SCZ), and 100 healthy controls (HC), and scanned on the 3T MRI scanner. Probablistic tractography was performed using the FATCAT software in AFNI. The target brain regions (bilateral lateral frontal, medial frontal, orbitofrontal, temporal and thalamus) were extracted from the automated segmentation and cortical parcellation. Cross-sectional comparisons in mean fractional anisotropy (FA) performed on the thalamo-lateral frontal, thalamo-medial frontal, thalamo-orbitofrontal, lateral frontal-temporal and orbitofrontal-temporal pathway. We also analyzed the relationship between the white matter pathway and the Positive and Negative Syndrome Scale and GAF.

The diffusion tensor imaging showed that SCZ and SPD had decreased FA in the left thalamo-orbitofrontal pathway. However, SPD showed no alteration in the fronto-temporal pathway, despite SCZ showed decreased FA in the left temporo-orbitofrontal pathway. In SCZ, there were significant correlations between FA value in the left temporo-orbitofrontal pathway and negative symptoms score in PANSS and GAF score. However, SPD showed the trend level relationship between the GAF score and FA value in the left temporo-orbitofrontal pathway.

These results suggest that the deficits in thalamo-frontal connectivity may be a trait marker of schizophrenia spectrum disorder, and the deficits in fronto-temporal connectivity may play a key role towards the vulnerability of psychosis.

The authors have not supplied their declaration of competing interest.

Schizoaffective disorder (SD) is an important cause of morbidity and mortality in hospitalized patients. While SD has been extensively studied in the past, the contemporary data for impact of SD on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 4,66,800 patients were analyzed; 50.90% were female and 49.10% male (P < 0.0001); 61.15% were white, 25.97% black and 12.88% of other race (P < 0.0001). Rate of hospitalization increased from 13,035.05/million to 26,703.21/million from 1998–2011. Overall mortality was 0.50% and mean cost of hospitalization was 20,995.19$. The in-hospital mortality increased from 0.46% to 0.50% (P < 0.0001) and mean cost of hospitalization increased from 11,504.94$ to 31,460.67$. Total spending on SD related admissions increased from $1.2 billion/year to $6.6 billion/year.

While mortality has slightly increased from 1998 to 2011, the cost has significantly increased from $1.2 billion/year to $6.6 billion/year which leads to an estimated $5.4 billion/year additional burden to US health care system. In the era of cost conscious care, preventing SD related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for SD related hospitalization.

The authors have not supplied their declaration of competing interest.

Schizophrenia is an important cause of morbidity and mortality in hospitalized patients. While schizophrenia has been extensively studied in the past, the contemporary data for impact of schizophrenia on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 443,659 patients were analyzed; 38.78% were female and 61.22% were male (P < 0.0001); 48.19% were white, 35.30% black and 16.51% of other race (P < 0.0001). Rate of hospitalization increased from 56,768.47/million to 79,44466/million from 1998–2011. Overall mortality was 0.70% and mean cost of hospitalization was 23,568.47$. The in-hospital mortality decreased from 0.75% to 0.73% (P < 0.0001) and mean cost of hospitalization increased from 12,775.64$ to 36,768.58$. Total spending on schizophrenia related admissions have increased from $1.75 billion/year $6.23 billion/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $1.75 billion/year to $6.23 billion/year which leads to an estimated $4.48 billion/year additional burden to US health care system. In the era of cost conscious care, preventing schizophrenia related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for schizophrenia related hospitalization.

The authors have not supplied their declaration of competing interest.

It is hypothesized that the event-related potentials are generated by different electrophysiological mechanisms, i.e., event-related power increase and enhanced degree of phase-locking over trial. The study aimed to characterize the relative contribution of these mechanisms to the ERP in patients with schizophrenia (SCZ).

One hundred and fifteen chronic stabilized SCZ and 62 healthy controls (HC) recruited to the study of the Italian Network for Research on Psychoses were included. Scalp potentials were recorded during a standard auditory oddball task. Stimulus-locked segments were extracted for all standard trials and correctly hit target trials. Trials contaminated by other artifacts were rejected. For each subject and stimulus type the event-related spectral perturbation (ERSP) and the inter-trial-coherence (ITC) were computed to assess event-related power increase and inter-trial phase-locking. The two groups were compared using Student's t-test followed by Bonferroni correction for multiple comparisons.

SCZ presented a reduced amplitude of both N100 and P3b. For both standard and target stimuli, at Cz and Pz, ERSP was reduced in SCZ in the delta-theta band (from 0 up to 400 ms). The ITC index, at the same channels, was reduced in SCZ in the delta band for standard stimuli (from 0 to 300 ms), and in both delta and theta bands for target stimuli (from 300 to 400 ms).

Our results indicate that alterations of both mechanisms are involved in N100 and P3b amplitude reduction observed in SCZ. Inter-trial phase-locking abnormalities for N100 were limited to the delta band, while for P3b involved delta and theta frequencies.

The authors have not supplied their declaration of competing interest.

There is a scarcity of prospective studies addressing the influence of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on antipsychotic-induced metabolic changes in first-episode schizophrenia (FES) patients.

We aimed at investigating metabolic side effects of second-generation antipsychotics (SGAs) with respect to the MTHFR gene polymorphisms in FES patients.

Polymorphisms in the MTHFR gene (C677T and A1298C) were investigated with respect to changes in body mass index (BMI) and waist circumference (WC) together with serum levels of glucose, lipids, homocysteine, vitamin B12 and folate after 12 weeks of treatment with SGAs in 135 FES patients.

The 677TT genotype was associated with significantly higher BMI, WC and serum levels of triglycerides, as well as significantly lower folate levels at baseline. Additionally, the 677T allele was associated with significantly lower folate levels at baseline. The 677CC homozygotes had significantly higher increase in BMI and serum levels of triglycerides. The 677TT genotype predicted significantly higher increase in homocysteine levels and significantly higher decrease in folate levels. These associations were also significant in the allelic analysis. Only the patients with the 677T allele had significantly lower folate levels and significantly higher homocysteine levels at the follow-up. The 677T allele was also related to significantly lower increase in WC. The 1298CC homozygotes had significantly higher weight gain in the course of treatment with SGAs.

The MTHFR gene polymorphisms might predict antipsychotic-induced weight gain in FES patients. In addition, the MTHFR C677T polymorphism might be also predictive with respect to other metabolic adversities of SGAs.

The authors have not supplied their declaration of competing interest.

Theory of mind (ToM) has repeatedly been shown to be compromised in many patients with schizophrenia (SCZ). It now seems to be quite well-established that patients with profound negative or disorganized symptoms perform poorly on ToM tasks. By contrast, findings in patients with predominant positive symptoms are much more ambiguous.

To investigate the relationship between ToM deficits and different symptoms dimensions in SCZ.

Fifty-eight outpatients with stable SCZ completed the intention-inferencing task (IIT), in which the ability to infer a character's intentions from 28 short comic strip stories is assessed. Symptomatology evaluation comprised the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Clinical Global Impressions Scale Improvement and severity (CGI).

The number of correct answers in the IIT negatively correlated with both the positive (P = 0.015) and negative (P < 0.0001) scales of the PANSS. ToM deficits were correlated with the conceptual disorganization, hallucinations and the suspiciousness/persecution items.

The patients who had more false answers in the IIT also had significantly higher scores at the positive (P = 0.005), negative (P < 0.0001) and general (P < 0.0001) scales of the PANSS. Worse IIT performance correlated with a higher severity index in the CGI. No correlations were found between IIT scores and CDSS scores.

Our results confirm the relationship between ToM deficits and negative symtomps and suggest that ToM may also be correlated to specific positive symptoms.

The authors have not supplied their declaration of competing interest.

Intervention in the early-stages of psychosis may be able to shape the clinical course; critical period (CP) is best represented by the first 5 years from first admission (FA).

To investigate the effectiveness of pharmacological intervention within and beyond the CP.

(1) To compare hospitalization rates of patients stabilized on treatment with LAIs and CLZ. (2) To determine whether treatment with LAIs and CLZ within CP can influence hospitalization rates.

Data were retrospectively collected from patients diagnosed with non-affective psychoses with FA between 2000 and 2014; 200 patients were then divided into three groups, according to stabilized treatment regimen during the final year of observation: treatment as usual (TAU), CLZ, LAIs. hospitalization duration (HSPD) and frequency (HSP) were calculated for each group.

Despite a major severity before assignment to either CLZ or LAIs treatment, HSPD and HSP in both groups shifted below those observed for the TAU arm. Patients who began treatment with LAIs within the CP showed a highly significant decrease of both HSPD and HSP (respectively 17.4 ± 18 vs. 2.6 ± 8.2; Z = −2.856; P < 0.005 and 1.1 ± 0.8 vs. 0.2 ± 0.5; Z = −3.115; P < 0.005). No significant changes in hospitalization rates were observed for subjects who began treatment with LAIs after the CP.

Our study confirms that treatment with either CLZ or LAIs significantly impacts the course of psychotic disorders. The data seem to suggest that LAIs and CLZ should be considered more effective than conventional oral antipsychotics in the early-stages of psychotic illness. The difference among treatments tends to wane beyond the CP, especially for LAIs.

The authors have not supplied their declaration of competing interest.

Lurasidone has demonstrated low propensity for metabolic disturbance in adult patients with schizophrenia in short-term studies.

To evaluate metabolic syndrome occurrence during long-term lurasidone treatment in patients with schizophrenia.

To compare metabolic syndrome rates with lurasidone versus other antipsychotic agents.

Metabolic syndrome rates (as defined by the US National Cholesterol Education Program-Adult Treatment Panel III) were evaluated in adult patients with schizophrenia treated with lurasidone in 2 long-term, active-controlled studies (quetiapine XR or risperidone). In the quetiapine XR-controlled study, patients completing a 6-week, double-blind, placebo-controlled, fixed-dose trial of lurasidone (74 mg/d or 148 mg/d) or quetiapine XR (600 mg/d) continued on double-blind, flexibly dosed lurasidone (37–148 mg/d) or quetiapine XR (200–800 mg/d) for up to 12 months. In the risperidone-controlled study, patients received double-blind, flexibly dosed lurasidone (37–111 mg/d) or risperidone (2–6 mg/d) for up to 12 months.

Among patients without metabolic syndrome at baseline in the quetiapine XR-controlled study, 2.4% (2/84) of lurasidone-treated patients and 7.4% (2/27) of quetiapine XR-treated patients developed metabolic syndrome at month 12 (P = NS). Of patients without metabolic syndrome at baseline in the risperidone-controlled study, 10.3% (12/117) and 23.2% (16/69) of lurasidone- and risperidone-treated patients, respectively, developed metabolic syndrome at month 12 (P = 0.02).

Long-term treatment with lurasidone was associated with lower rates of metabolic syndrome in patients with schizophrenia compared to treatment with quetiapine XR or risperidone.

Sunovion Pharmaceuticals Inc.

NCT00789698, NCT00641745.

The authors have not supplied their declaration of competing interest.

It has been shown that patients with schizophrenia are super-sensitive towards dopamine-releasing agents such as amphetamine. Here, we studied the effects of amphetamine sensitization on amphetamine-induced dopamine release in healthy subjects.

To measure d-amphetamine-induced dopamine release as measured with the D2,3 agonist radioligand [11C]-(+)-PHNO-PET via change in non-displacable binding potential (BPND) and behavioral measures of d-amphetamine effects with drug effects questionnaire (DEQ) and subjective states questionnaire (SSQ).

To study d-amphetamine-induced sensitization in healthy subjects on a behavioral and neurochemical level with [11C]-(+)-PHNO-PET in order to gain more knowledge on sensitization-induced changes in the dopaminergic system.

Twelve stimulant-naïve healthy male subjects underwent three 90-min [11C]-(+)-PHNO-PET-scans and four oral administrations of d-amphetamine. After a naïve baseline scan, subjects underwent a PET scan with previous ingestion of 0.4 mg/kg bodyweight of d-amphetamine 90–120 minutes before scanning. Subsequently, subjects were sensitized to d-amphetamine with the same dose on two separate days. Thereafter, they underwent another PET scan with previous d-amphetamine ingestion. DEQ and SSQ were administered before, 60 min, 90–120 min, and 210 min after amphetamine ingestion.

We found significant sensitization effects on a behavioral level and on a neurochemical level after four administrations of amphetamine. Items of the SSQ, which showed significant sensitization effects were “outgoing”, “energetic”, “lively”, “alert” and “focused”.

We were able to induce significant behavioral and neurochemical sensitization in healthy humans, which were measured with [11C]-(+)-PHNO-PET for the first time. This sensitization model will be useful for studying the neurobiology of schizophrenia.

The authors have not supplied their declaration of competing interest.

Clozapine is the only drug approved for resistant schizophrenia, but remains underused because of its side effects. Sedation is common, but its management is unclear.

To analyze factors associated with clozapine-induced sedation and the efficacy of common treatment strategies.

To determine clozapine-induced sedation factors and possible therapeutic strategies.

Using two years’ electronic records of a community cohort of resistant schizophrenia spectrum disorder cases on clozapine, we performed three analyses: a cross-sectional analysis of which factors were associated with number of hours slept (objective proxy of sedation), and two prospective analyses: which factors were associated with changes in hours slept, and the efficacy of the main pharmacological strategies for improving sedation.

One hundred and thirty-three patients were included; 64.7% slept at least 9 hours/daily. Among monotherapy patients (n = 30), only norclozapine levels (r = .367, P = .033) correlated with sleeping hours. Multiple regression analyses confirmed the findings (r = .865, P < .00001). Using the cohort prospectively assessed (n = 107), 42 patients decreased the number of hours slept between two consecutive appointments. Decreasing clozapine (40%) or augmenting with aripiprazole (36%) were the most common factors. In the efficacy analysis, these two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects, respectively. The majority (81.8% and 73.9%) did not report differences in the hours slept.

Sedationis common and involves pharmacological and non-pharmacological factors. The only correlation was a weak correlation between norclozapine plasma levels and total sleeping hours. Reducing clozapine and aripiprazole augmentation were the most successful strategies to ameliorate sedation, although both strategies were effective only in a limited numbers of subjects.

The authors have not supplied their declaration of competing interest.

Schizophreniform disorder (SD) is an important cause of morbidity and mortality in hospitalized patients. While SD has been extensively studied in the past, the contemporary data for impact of SD on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 8645 patients were analyzed; 36.21% were female and 63.79% were male (P < 0.0001); 49.04% were white, 39.06% black and 19.9% of other race (P < 0.0001). Rate of hospitalization decreased from 599.22/million to 394.47/million from 1998–2011. Overall mortality was 0.23% and mean cost of hospitalization was 17930.23. The in-hospital mortality reduced from 0.21% to 0.15% (P < 0.0001) and mean cost of hospitalization increased from 9662.88$ to 27,749.68$ from 1998–2011. Total spending on SD related admissions have increased from $47.59 million/year to $853.83 million/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $47.59 million/year to $853.83 million/year, which leads to an estimated $806.24 million/year additional burden to US health care system from 1998 to 2011. In the era of cost conscious care, preventing SD related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for SD related hospitalization.

The authors have not supplied their declaration of competing interest.

Cognitive impairments clearly impact the daily functioning of patients with psychosis.

To assess cross-sectionally whether there are differences in the cognitive domains assessed with the CAI, for considering the real-world functioning of a sample of patients with psychosis.

The sample consisted of 76 patients with a DSM-IV psychotic disorder. Patients were assessed with the cognitive assessment interview (CAI), which is an interview-based measure of cognitive functioning that is intermediate between cognitive functioning and daily functioning, and three subscales of the specific levels of functioning (SLOF), an informant-rated measure of functioning. The CAI was used to assess the patient and an informant, and these scores were integrated into a rater composite score. We divided the sample by a median-split procedure for each of the three functional domains, and then applied ANOVAs to compare the two groups (impaired/not impaired) in the six cognitive domains of the CAI: working memory, attention, verbal memory, problem solving, processing speed, and social cognition.

We found significant differences between the impaired vs. non-impaired groups in most of the cognitive domains assessed with the CAI (Fig. 1).

Interview-based assessment of cognition with the CAI allows for the prediction of everyday functioning in patients with psychosis. Impairment in almost all CAI cognitive domains, except for social cognition, was associated with poorer psychosocial functioning.

The authors have not supplied their declaration of competing interest.

Schizophrenia is a severe mental disorder, with complex symptoms involving psychosis, negative symptoms and cognitive impairment. The Trail Making Test (TMT) has been widely used to assess attention and executive function. Functional transcranial Doppler sonography (fTCD) of basal cerebral arteries allows monitoring of aberrant cerebral hemodynamics during cognitive tasks in this patient group.

We assessed cerebral hemodynamics in the middle cerebral arteries (MCA) using fTCD while patients with schizophrenia and healthy subjects performed the TMT and a control task.

Fifteen patients with chronic schizophrenia and 15 healthy controls performed the TMT-A and -B during fTCD measurements of the MCA. Dependent measures were performance, mean cerebral blood flow velocity (MFV) and the lateralization.

Patients demonstrated an overall decreased speed of solution (P = 0.002), and there was no significant effect of age. They showed a significantly increased flow pattern for the TMT-B (P = 0.005). There were no lateralization differences between diagnostic groups.

There was a performance deficit in patients with schizophrenia for both TMT-A and -B that fits well with results of existing literature. The aberrant hemodynamic response supports the idea that cognitive performance elicits an aberrant cerebral hemodynamic correlate. It adds to the notion that fTCD is a valuable tool to correlate psychological paradigms with brain perfusion in patients with schizophrenia.

The authors have not supplied their declaration of competing interest.

Previous studies have demonstrated that family history is associated with earlier age at onset, severity of positive and negative symptoms, and the duration of untreated illness. Hereditary factors may contribute a vulnerability for antisocial and/or violent behaviour per se, and for other stable characteristics such as aggressive behaviour.

To analyze the impact of family history of schizophrenia and aggressive behavior among members of family on severity of disease and aggressive behavior of patients.

The study population consisted of 120 male schizophrenic patients classified into non-aggressive (n = 60) and aggressive (n = 60) groups, based on indication for admission in hospital (aggression/anything else but aggression). For severity of disease, we assessed psychopathology using the Positive and Negative Syndrome Scale (PANSS), the number of hospitalizations and the total equivalent dose of therapy (collected from medical record). The presence of a family history and aggression in family was assessed using a semi-structured interview of patients and, when available, family members.

Twenty-seven (22.5%) participants were determined to have at least one family member with schizophrenia or another psychotic disorder, with no difference between aggressive (10%) and non-aggressive (12.5%) group. There was no significant interaction between family history and severity of disease (PANSS, number of hospitalizations, total equivalent dose of therapy). Aggressive behaviour in first-degree family member had no influence on aggressive behaviour of patients with schizophrenia.

Family history of schizophrenia does not affect the severity of disease nor aggressive behaviour.

The authors have not supplied their declaration of competing interest.

Dysregulation of the apoptotic process is associated with the etiopathogenesis of schizophrenia, which is observed at the brain and peripheral blood levels. A significant negative correlation between the duration of the disease and serum sFasL concentration was demonstrated by other authors. It was shown that an increased rate of apoptosis is more pronounced in neuroleptic-free patients with the first-episode of schizophrenia than in patients with chronic disease.

Search for a predictor of good response to antipsychotic treatment based on the analysis of the sFasL plasma level and its relationship with clinical symptoms.

Fifty-three patients with chronic schizophrenia and 46 healthy individuals were enrolled in the study. The concentration of sFasL was measured by ELISA. Clinical assessments (PANSS, SANS, SAPS) and blood analyses were conducted three times: during the active phase of disease (at admission), after 4 weeks of pharmacotherapy, and after reaching remission.

In the schizophrenia group, non-altered levels of sFasL (P = 0.1; U Mann-Whitney test), compared to the control, were detected at admission. The initial level of sFasL correlated negatively (r = −0.33; P = 0.04; Spearman's rank) with blood leukocyte count. Despite clinical improvement, no significant changes in the level of sFasL were observed. However, the sFasL level correlated negatively with the PANSS general psychopathology reduction after 4 weeks of pharmacotherapy (r = −0.7; P = 0.04) and after remission (r = −0.39; P = 0.026).

The results indicate a possible role of sFasL in apoptosis of blood leukocytes and suggest that the reduction of sFasL level can predict level of PANSS general psychopathology after antipsychotic treatment in schizophrenia.

The authors have not supplied their declaration of competing interest.

Basic symptoms are subjective complaints that present at the early states in psychotic disorders and persist in the long-term. They can be studied using hetero applied clinical instruments or self-administered questionnaires. Basic symptoms can be useful as screening tools in at risk populations.

To determine if basic symptoms (subjective cognitive deficits) are associated with the objectively measured cognitive deficit after controlling for functioning and symptomatology.

One observational, transversal, psychopathological and neuropsychological study was performed on a schizophrenia outpatients sample (n = 78). Correlations were measured by using Spearman's Rho coefficient. Basic symptoms were registered by using the Frankfurt Complaints Questionnaire (FCQ-3); cognitive status was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); clinical status was assessed by PANSS and Clinical Global Impression (CGI); functional status was measured with Global Assessment of Functioning (GAF).

All the dimensions were related to subjective complaints: cognitive functioning (r = −.38; P < .001); positive symptoms (r = .54; P < .001); negative symptoms (r = .26; P < .02); general symptoms (r = .41; P < .001); CGI (r = .57; P < .001); GAF (r = −.45; P < .001). The association between subjective and objective cognitive deficit remains significative after controlling for the clinical and functional variables, except when controlling for CGI.

The evaluation of basic symptoms with FCQ-3 is related with an objective cognitive deficit and could be useful as a screening tool.

The authors have not supplied their declaration of competing interest.

In a recent 26-week placebo-controlled, crossover trial (n = 52) we found significant positive effects on verbal and visual memory, and negative symptoms in clozapine-treated patients with refractory schizophrenia.

In this 1-year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.

To evaluate the persistence of improvements in cognitive functioning and symptoms of memantine add-on therapy to clozapine in schizophrenia.

Completers of the first trial who experienced a beneficial effect of memantine after 12 weeks continued memantine for one year. Primary endpoints were change from baseline to 26 weeks treatment and 26 weeks to 52 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Secondary endpoints were change on the Health of the Nation Outcome Scales (HoNOS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).

Of 32 completers who experienced a beneficial effect of memantine 23 patients continued memantine for one year. Memory improvement was sustained, verbal recognition memory improved even further between t = 26 weeks and t = 52 weeks. Continued treatment with memantine add-on to clozapine was associated with significantly improved PANSS positive, negative and overall score, CGI-S and HoNOS scores.

In the extension phase the positive effect of memantine add-on therapy on verbal memory sustained and positive, negative and overall symptoms of schizophrenia, clinical global status and psychosocial functioning significantly improved. Memantine was well tolerated without serious adverse effects.

The authors have not supplied their declaration of competing interest.