Cardiovascular side effects of antipsychotics are been studied both in typical and atypical antipsychotics but, in particular, with clozapine few systematic studies of these effects have been performed. In this study, we reviewed electrocardiographic (ECG) data from patients treated with clozapine.

Observational, retrospective study in our Clozapine Day Clinic from 2000 to 2008. We recluted 197 patients (70% men) with mean age 31,75 ± 9,0 years who began treatment with clozapine. All of them had an electrocardiogram taken before starting treatment and after 18 weeks of follow-up. None suffered from heart diseases. QTc was evaluated by Bazett formula (QT/ (R-R’)1/2). Treatment prescribed was taken down and drug serum levels were detected. Statistical analysis was executed by SPSS 17.0.

There was significant correlation between doses prescribed and levels of clozapine and norclozapine (r=.304, p=.023; r=.354 p=.007), between levels of clozapine, norclozapine and QTc enlargement (r=.348, p=.008; r=.268 p=.046) and between levels of clozapine, norclozapine and heart rate (r=.390, p=.003; r=.326 p=.014). There were no differences between QTc and treatment with clozapine or other antipsychotic (p=0.902), between sex or if polypharmacy existed. ECG alterations were a case of supraventricular extrasystoles, another of Wolf-Parkinson -White Syndrome and other inespecific alterations like repolarizations or left hypertrophy.

We did not find either major incidence on cardiological effects or significative QTc enlargement during treatment with clozapine in contrast to other antipsychotic previously prescribed. Therefore clozapine may be in the same cardiologic safety rank than other antipsychotics.

Brain volume abnormalities and oxidative cell damage have been reported to be pathological characteristics of schizophrenia patients. This study aims to assess a potential relationship between these two characteristics in child and adolescent patients with first-episode psychosis.

26 child and adolescent patients with first-episode early-onset schizophrenia, and 78 age- and gender-matched healthy controls were assessed. Magnetic resonance imaging (MRI) scans were used for volumetric measurements of five cerebral regions: gray matter of the frontal, parietal, and temporal lobes, sulcal cerebrospinal fluid (CSF), and lateral ventricles. Oxidative cell damage was traced by means of a systemic increase in lipid hydroperoxides (LOOH).

Lateral ventricle volumes were significantly higher in schizophrenia patients than in controls. In schizophrenia patients, a significant positive relationship was found between oxidative cell damage (LOOH levels) and the abnormal enlargement of the lateral ventricles, after controlling for total intracranial volume, age, gender, daily smoking status, intelligence quotient (IQ), psychopathology, and time since onset of psychotic symptoms. No association was found between brain volumes and oxidative cell damage in control subjects.

Our results suggest that, in patients with first-episode early-onset schizophrenia, enlargement of the lateral ventricles is associated with chronic oxidative cell damage.

Previous studies have reported progressive brain changes and cognitive deficits in early-onset psychosis (EOP). Little is known on the relationship between longitudinal changes in brain structure and neurocognition.

Naturalistic 5-year prospective study comparing frontal gray matter (GM) volume and executive functions in adolescents with a first episode of EOP and a sample of healthy controls at baseline, 2-year and 5-year follow-up.

Thirty-six patients (age at baseline 15.8 ±.7, 66.6% male) and 34 controls (15.4±1.4, 55.9% male) comprised the study sample. Both patients and controls presented with frontal GM loss during the first five years of follow-up. During the first two years, patients presented with significantly greater GM loss than controls in the left (F=9.642, p=0.003) and right frontal lobe (F=7.585, p=0.008), with no significant differences between year 2 and 5. Patients with EOP performed significantly worse in executive tasks than controls in all visits. During the first two years of follow-up, controls, but not patients, presented with a significant improvement in executive functioning (F=7.523, p=0.009), with similar evolution of cognitive functioning between years 2 and 5 in both groups (F=0.908, p=0.346). Changes in frontal GM volume and executive functioning were not significantly correlated within the entire follow-up period.

Over the first two years of illness, patients with EOP show greater frontal GM loss and less improvement in executive functions than expected. This could be a critical period for the development of deficits in EOP, in which more intensive interventions would be warranted.

To develop a Support Vector Machine (SVM) algorithm as a predictive tool for diagnostic outcome in patients with FE-EOP, based on clinical and biomedical data at the emergence of the illness.

Two-year, prospective longitudinal study, where 81 patients (9-17 years of age) with a FE-EOP and stable diagnosis at follow-up and 41 age and sex-matched healthy controls (HC) were included. Structured diagnostic interviews, clinical and cognitive scales, a MRI scan and biochemical tests were conducted at baseline. Three SVM classification algorithms were developed (SSD vs HC group, non-SSD vs HC group, and SSD vs non-SSD group). Jackknifing was used to validate the algorithms and to calculate performance estimates. Enhanced-Recursive Feature Elimination was performed in order to gain information about the predictive weight for diagnosis of each variable.

The SSD-versus-non-SSD classifier achieved an overall accuracy of 83.1%, sensitivity of 86.6% and specificity of 77.8%. The variables during a FE-EOP with higher predictive value for a diagnosis of SSD were clinical variables such as negative symptoms preceding or during the psychotic onset, poor insight and duration of illness until first psychiatric contact. Biochemical, neuroimaging, and cognitive variables at baseline did not provide any additional predictive value.

SVM may serve as a predictive tool for early diagnosis of SSD during a FE-EOP. The most discriminative variables during a FE-EOP for a future diagnosis of SSD are clinical variables.

Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years.

The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis.

At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively).

Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders.

Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls.

EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405).

Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

The correlates of insight in early-onset psychosis have received little previous attention.

We studied clinical correlates of insight in a sample of 110 adolescent recent-onset psychosis patients (mean age 15.53 years; psychotic symptoms present for <6 months). Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) at baseline, 6 months and 12 months follow-up.

Insight improved over the early phases of the illness, in parallel with psychopathological improvement. Poor insight at baseline and 6 months correlated with poor functioning at 6 and 12 months respectively. Schizophrenia patients had poorer insight than patients with bipolar disorder at 6 and 12 months but not at baseline. Logistic and linear regressions were used to predict 12-month diagnoses and functioning based on insight measurements. Baseline awareness of illness was a significant predictor for diagnosis [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.05–1.97]. Treatment compliance at 6 months did not correlate with baseline SUMD subscores, but correlated with insight into having a disorder (Spearman's ρ=0.21, p=0.039), its consequences (Spearman's ρ=0.28, p=0.006) and the need for treatment (Spearman's ρ=0.26, p=0.012) at 6 months. The ‘attribution of symptoms’ dimension of insight is poorly correlated with other insight dimensions and with other clinical variables.

Poor insight correlates with symptom severity and global functioning but also has some trait value for schizophrenia, which is apparent once acute psychotic symptomatology is not prominent. A multi-dimensional approach to the assessment of insight is necessary, as different dimensions are influenced by different factors.