Cognitive behavioural therapy for help-seeking adolescents and young adults with at-risk-mental state: Effects on subclinical positive symptoms.

AIM: Cognitive behavioural therapy (CBT) is effective for at-risk-mental state (ARMS) in reducing/delaying transition to psychosis. However, previous systematic reviews pointed out the small number of trials as a limitation and suggested that additional outcomes should be evaluated, not only prevention of first psychosis episode. No study assessed the CBT effects on subclinical psychotic symptoms. The present study investigated the effects of CBT on the transition risk (primary outcome), and on overall remission from ARMS and severity of subclinical symptoms, that is, unusual content of thought, non-bizarre ideas, perceptual abnormalities, disorganized speech (secondary outcome). METHODS: CBT consisted of 30 individual weekly sessions over 7 months. Fifty-eight participants with ARMS detected by the Comprehensive Assessment of At-Risk-Mental States were randomized to CBT or control condition. RESULTS: Respectively in the CBT and control groups, 1 (3.40%) and 5 (26.31%) participants at post-treatment and 3 (10.30%) and 8 (42.10%) at follow-up made transition with a difference between the two groups, despite at borderline significance. At post-treatment and follow-up, respectively, the number of participants recovered from ARMS was significantly higher in CBT (76.92% and 61.53%) than in control (10.52% and 15.80%). Participants in the control group reported lower reductions on all the subclinical symptoms over time as compared with those in CBT. CONCLUSIONS: This is the first study assessing CBT on subclinical positive symptoms in ARMS. CBT seems to be a tailored approach able to produce short- and long-term benefits on this outcome.

Terapia cognitivo-comportamentale per giovani ad alto rischio di un primo episodio di psicosi: un trial randomizzato controllato.

Scopo. Nell'ultimo ventennio l'interesse di ricercatori e clinici nella prevenzione di disturbi psicotici è cresciuto notevolmente. Gli studi internazionali su strategie a favore di giovani "ad alto rischio di un primo episodio di psicosi" sono ancora in numero ridotto, mentre in Italia risultano del tutto assenti. Oltre a manifestare sintomi psicotici sotto-soglia, questa popolazione di frequente riporta un compromesso funzionamento. La terapia cognitivo-comportamentale (TCC) è la strategia di prima linea, ma si rileva in letteratura l'importanza di studi su ulteriori misure di esito, quali il funzionamento. Il presente studio ha valutato se un protocollo di TCC modulare riducesse il rischio di un primo episodio psicotico in un gruppo di giovani ad alto rischio a post-trattamento e follow-up rispettivamente di 6 e 14 mesi a confronto con trattamento di supporto psicologico di routine ( treatment as usual). Metodi. Cinquantotto partecipanti (età media=25,51, 67,20% maschi) che soddisfacevano criteri per stati mentali a rischio alla Comprehensive Assessment of At-Risk-Mental States sono stati randomizzati a TCC o treatment as usual. Il protocollo di TCC ha incluso 30 sedute settimanali. Risultati. Nel gruppo TCC, il numero di giovani che ha sviluppato un primo episodio psicotico a follow-up è stato inferiore (n=4, 10,30%) a quello del gruppo di controllo (n=8, 27,60%), sebbene tale differenza sia risultata di significatività marginale [Log rank test χ2(1)= 3,66, p=0,05]. I giovani con funzionamento baseline più alto hanno ottenuto maggiori benefici al di là del tipo di percorso. Conclusioni. Anche nel contesto italiano, la TCC sembra efficace e promettente nel prevenire un primo episodio psicotico in giovani con stato mentale a rischio.

Brain Network Underlying the Improvement of Social Functioning in Schizophrenic Patients After One-year Treatment with Social Skills Training.

PURPOSE: To assess changes in social and neuro-cognition and regional cerebral blood flow (rCBF) in schizophrenic patients with psychotic syndrome treated with Social Skill Training (SST). METHODS: 17 patients underwent two high resolution rCBF SPECT at rest before and after a one-year treatment with SST. Patients were assessed using a neuropsychological evaluation (W.A.I.S.-R, T.M.T, Verbal Fluency, W.C.S.T.). SPM8 was used to investigate rCBF changes from the pre- to the post-SST condition and the relationship between rCBF and clinical scores used as covariates of interest. RESULTS: All patients presented with an improvement in social perception, ability to deal with abstract social conventions, rules and judgments about people (Comprehension and Picture Completion sub-tests) and some neuro-cognitive functions sustaining the process of socially relevant information. The main effect of SST was to produce rCBF increases in precuneus, PCC, superior parietal lobules, PMC, pre-SMA, precentral gyrus, dmPFC, dlPFC, vmPFC, OFC (p<0.0001 uncorrected). The SPM analysis showed that Comprehension was supported by PMC, dmPFC, OFC and vmPFC, while the Picture Completion was supported by PMC and dmPFC (p<0.0001). CONCLUSION: SST in schizophrenic patients improves resting neural activity in cortical areas of the amigdala-based and non-amygdala networks of social brain, including dmPFC and vmPFC, and dlPFC, which are known to be part of default mode and task-positive networks and to be implicated in schizophrenia.

Does a subclinical cardiotoxic effect of clozapine exist? Results from a follow-up pilot study.

AIM: The aim of the present study was to investigate by serial echocardiography and dosage of NT-pro-BNP, whether, in previously healthy subjects, long term therapy with clozapine may lead to subclinical cardiac toxicity. METHODS AND RESULTS: 38 patients (24 males, 14 females, mean age 38.4 years) suffering from a severe personality disorder were enrolled. At inclusion duration of clozapine treatment averaged 66 months at a mean daily dose of 296 mg. Clinical evaluation, NT-pro-BNP dosage and echocardiography were performed at baseline, 3 and 12 months. At first visit 15 patients showed depression of left ventricular function (12 had LVEF between 50 and 55%, 2 < 50% and < 30%). Biventricular dysfunction was observed in 10. NT-pro-BNP showed a significant inverse relation with LVEF (r2= -0.4619, p < 0.0001). At 1 year the whole group did not show significant changes in clinical, ECG and echocardiographic measurement, however a LVEF decrease > 5% was found in 33% of patients with baseline normal LVEF while LVEF remained below 55% in 70% of group B patients. LVEF and NT-pro-BNP values were still significantly different in the two groups at the term of follow-up. CONCLUSIONS: subclinical heart dysfunction, frequently biventricular, occurs in 1/3 of young, previously healthy, clozapine treated patients. NT-pro-BNP values relate inversely with LVEF. At 1 year follow -up a LVEF decrease >5% occurred in 1/3 of patients with baseline normal left ventricular function.

Usefulness of NT-pro-BNP and echocardiography in the diagnosis of subclinical clozapine-related cardiotoxicity.

BACKGROUND: Available information regarding clozapine-related cardiomyopathy is limited to reports of severe left ventricular dysfunction not rarely with fatal clinical evolution. A subclinical cardiotoxic effect might be diagnosed using echocardiography and N-terminal pro-B-type natriuretic peptide assay. METHODS: Thirty-eight patients with psychotic disorder in chronic therapy with clozapine (24 male and 14 female subjects; mean age, 38.4 years) were enrolled. Left ventricular ejection fraction (LVEF) was measured by area-length method (average of 5 measurements). RESULTS: Twelve patients showed a mild depression of left ventricular function (LVEF between 50% and 55%), 2 LVEF less than 50% and 1 less than 30%. The area under the receiver operating characteristic curve for N-terminal pro-B-type natriuretic peptide as a predictor of left ventricular dysfunction was 0.87. CONCLUSIONS: A subclinical left ventricular dysfunction was found in 3 of 38 patients, whereas a mild impairment of the left ventricular systolic function occurred in 1 of 3 of young, previously healthy, clozapine-treated patients A prospective study in clozapine-naive patients may be useful to better understand cardiotoxic effects of clozapine.