Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses.

BACKGROUND: 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. Method 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. RESULTS: 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). CONCLUSIONS: 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.

Longitudinal study of neurological soft signs in first-episode early-onset psychosis.

BACKGROUND: In recent decades, the assessment of neurological soft signs (NSS) in patients with psychosis has become a subject of special interest. The study of the progression of NSS during adolescence will provide valuable information about the role of NSS as endophenotypes or biomarkers and about brain development at a stage in which brain maturation has not yet been completed. METHODS: Neurological soft signs were assessed in a sample of 110 first episodes of early-onset psychosis (EOP) and 98 healthy children and adolescents at two different times in a 2-year follow-up period. RESULTS: Patients with EOP showed more NSS than controls both at baseline (p < .001) and the 2-year follow-up (p < .001). No differences were found in the number of signs among the different diagnostic subgroups (schizophrenia, bipolar disorder, and other psychoses). When we examined the changes in NSS over the follow-up, the reduction of NSS in the patients was greater than the controls for 'Motor coordination' (p = .032), 'Others' (p < .001), and 'Total score' (p < .001) of the NES. CONCLUSION: Despite the greater reduction of NSS in patients than in controls along the follow-up, patients still have more neurological signs than healthy controls; therefore, these signs may be considered a trait marker. NSS do not seem to be specific to schizophrenia as they are present in different EOPs.

Insight correlates in child- and adolescent-onset first episodes of psychosis: results from the CAFEPS study.

BACKGROUND: The correlates of insight in early-onset psychosis have received little previous attention. METHOD: 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. RESULTS: 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 rho=0.21, p=0.039), its consequences (Spearman's rho=0.28, p=0.006) and the need for treatment (Spearman's rho=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. CONCLUSIONS: 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.

Neuropsychological functioning in adolescents with first episode psychosis: a two-year follow-up study.

Cognitive deficits are a core feature of psychotic disorders. Both in adult and adolescent populations, studies have shown that patients with psychosis have poorer cognitive functioning than controls. The cognitive domains that seem to be affected are mainly attention, working memory, learning and memory, and executive function. However, with regard to the trajectory of cognitive function throughout the illness, there is still a dearth of prospective data in patients who develop psychosis during adolescence. In this article, neuropsychological functioning was assessed in a sample of 24 first episodes of early onset psychosis (EOP) and 29 healthy adolescents at baseline and after a two-year follow-up. Patients with EOP showed lower scores than controls in overall cognitive functioning and in all specific domains assessed (attention, working memory, executive function, and learning and memory) both at baseline and the two-year follow-up. When changes in cognitive functioning over two years were assessed, patients and controls showed significant improvement in almost all cognitive domains. However, this improvement disappeared in the patient group after controlling for improvement in symptomatology. Our findings support a neurodevelopmental pathological process in this sample of adolescents with psychosis.

Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence.

PURPOSE: The aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in outpatients with schizophrenia as compared to oral administration of the same antipsychotic. METHODS: Forty-six previously violent patients with schizophrenia were randomised to receive treatment with oral or depot zuclopenthixol for 1 year. Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence. An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month. RESULTS: Violence during the follow-up year was inversely proportional to treatment adherence, better compliance, and greater reduction of positive symptoms. Lower frequency of violent acts was observed in the depot group. The level of insight at baseline was not significantly associated with violence recidivism. Regardless of route of administration, treatment non-adherence was the best predictor of violence. CONCLUSIONS: Some patients with schizophrenia and prior violent behaviour may benefit from the depot formulation of antipsychotic medication.