Rehabilitació neuropsicològica del pacient esquizofrènic, La.

L'objectiu general d'aquesta tesi és valorar la utilitat del tractament de rehabilitació neuropsicològica en pacients esquizofrènics amb dèficits cognitius i predomini de la simptomatologia negativa. El programa utilitzat és l'anomenat Teràpia Integrada de l'Esquizofrènia (IPT, Integriertes Psychologisches Therapieprogramm) dissenyat pel grup de Brenner que disposa d'un manual protocol·litzat a més d'un model teòric susceptible d'estudi empíric. Els efectes de la rehabilitació són analitzats a tres àmbits diferents: funcions cognitives, funcionalisme cerebral mesurat a partir de SPECT i funcionament psicosocial. Per a la realització dels diferents estudis hem aplegat una mostra de 94 pacients diagnosticats d'esquizofrènia amb predomini de la simptomatologia negativa. D'aquests pacients 27 complien els criteris d'inclusió pel que fa a simptomatologia negativa i també el criteri qualitatiu de deterioració cognitiva que queda definit a l'estudi. Aquests pacients han estat sotmesos al tractament de rehabilitació neuropsicològica durant tres mesos. A una mostra de 10 pacients se'ls hi va estudiar amb mètodes de neuroimatge amb SPECT. Un grup de pacients amb predomini dels símptomes negatius però sense dèficit cognitiu han actuat com a control. La part experimental consta de quatre estudis, tres dels quals ja han estat publicats i un està acceptat per publicació. En aquests estudis hem pogut demostrar que els dèficits cognitius s'associen a un pronòstic més perniciós: evolució més cronificada, nivell més baix d'adaptació general, estades més llargues d'hospitalització i una adherència més pobra al tractament farmacològic. Els resultats recolzen que el tractament de rehabilitació neuropsicològica és útil i produeix millories a les funcions prèviament deficitàries. Tal i com estableix el model de Brenner, els canvis a les funcions cognitives elementals (atenció i codificació) estan lligades als canvis a les funcions cognitives més superiors (recuperació i funció executiva). I el que és més important, la millora neuropsicològica està associada a una millora del funcionament psicosocial, concretament un augment de l'autonomia personal i del funcionament psicosocial general. Per altra banda el tractament de rehabilitació neuropsicològica produeix canvis en el flux sanguini cerebral frontal detectable mitjançant estudis d'SPECT realitzats en condicions de neuroactivació. Aquests canvis suposen una reducció de la hipofrontalitat que es deu a la millora del funcionament neuropsicològic.Per tant l'estudi ha pogut confirmar les hipòtesis i es pot concloure que la rehabilitació neuropsicològica és una eina terapèutica que possibilita una millora del funcionament cognitiu, una reducció de l'hipofuncionalisme del flux cerebral frontal, un augment de l'autonomia personal i una millora del funcionament psicosocial als pacients esquizofrènics de pitjor pronòstic

Brain-Derived Neurotrophic Factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor (BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature

Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and critical review

AIM: To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia. METHODS: A systematic, computerised literature search was conducted in the PubMed/Medline and PsychInfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [('cogniti*' and 'remediation' or 'training' or 'enhancement') and ('fMRI' or 'MRI' or 'PET' or 'SPECT') and (schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included. RESULTS: A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimaging studies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless, great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of whole-brain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive, functional and structural improvements tended to be positively correlated

The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

Aim: Genetic variants on metabolic and transport enzymes are good candidates to explain inter-individual differences in response to antipsychotics. The aim of this study is to evaluate and compare the influence of the CYP2D6, CYPC19, CYP1A2 and ABCB1 variants on plasma levels, treatment response and side effects of antipsychotics. Methods: Twenty polymorphisms in selected genes were genotyped in 318 patients diagnosed with schizophrenia, schizoaffective or delusional disorder treated with antipsychotics (clozapine, olanzapine, paliperidone, risperidone, aripiprazole and quetiapine). Plasma drug levels were determined after 6 weeks of treatment. The Positive and Negative Symptoms Scale (PANSS) and UKU scale of side effects were recorded at baseline and after 12 weeks of treatment. The effect of gene variants on plasma drug levels, treatment response and adverse effects were examined by multinomial regression. Results:CYP1A2 was found to be associated with psychic side effects (P = 0.02), with variants predicting higher enzyme activity associated with lower adverse effects, and was the strongest predictor for this adverse effect of all the studied factors. Functional variants in CYP genes were associated with plasma level differences, with higher activity variants associated with lower plasma levels. No association with improvement of the condition, as measured by the PANSS score, was found in this study. Conclusion: The results suggest that increased CYP1A2 activity protects against psychic side effects. Few studies have evaluated the impact of genetic factors on treatment response or side effects, and only in relation to a selection of adverse reactions. These results are a step towards better understanding of the factors behind the different aspects of clinical outcomes, such as various adverse effects

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes

Cognitive reserve assessment scale in health (CRASH): its validity and reliability

Background: the cognitive reserve (CR) concept has not been precisely defined in severe mental disorders and has been estimated using heterogeneous methods. This study aims to investigate and develop the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH), an instrument designed to measure CR in people with severe mental illness; (2) Methods: 100 patients with severe mental illness (non-affective psychoses and affective disorders) and 66 healthy controls were included. The internal consistency and convergent validity of CRASH were assessed. Spearman's correlations coefficients were also performed to examine the relationship between CRASH and neuropsychological tests, psychosocial functioning, and clinical course; (3) Results: the internal consistency was high (Cronbach's alpha coefficient = 0.903). The CRASH global score had a large positive correlation with the Cognitive reserve questionnaire total score (r = 0.838, p < 0.001), demonstrating good convergent validity. The correlation coefficients between the CRASH total scores and clinical, functional, and neuropsychological performance were different between groups. In order to provide clinical interpretation, severity classification based on diagnosis (non-affective psychotic disorders, affective disorders, and healthy controls) have been created; (4) Conclusions: CRASH is the first CR measure developed specifically for patients with severe mental illness, facilitating reliable and valid measurement of this construct. The scale may aid in the stratification of patients and the implementation of personalized interventions

La rehabilitació neuropsicològica del pacient esquizofrènic

[cat] L'objectiu general d'aquesta tesi és valorar la utilitat del tractament de rehabilitació neuropsicològica en pacients esquizofrènics amb dèficits cognitius i predomini de la simptomatologia negativa. El programa utilitzat és l'anomenat Teràpia Integrada de l'Esquizofrènia (IPT, Integriertes Psychologisches Therapieprogramm) dissenyat pel grup de Brenner que disposa d'un manual protocol·litzat a més d'un model teòric susceptible d'estudi empíric. Els efectes de la rehabilitació són analitzats a tres àmbits diferents: funcions cognitives, funcionalisme cerebral mesurat a partir de SPECT i funcionament psicosocial. Per a la realització dels diferents estudis hem aplegat una mostra de 94 pacients diagnosticats d'esquizofrènia amb predomini de la simptomatologia negativa. D'aquests pacients 27 complien els criteris d'inclusió pel que fa a simptomatologia negativa i també el criteri qualitatiu de deterioració cognitiva que queda definit a l'estudi. Aquests pacients han estat sotmesos al tractament de rehabilitació neuropsicològica durant tres mesos. A una mostra de 10 pacients se'ls hi va estudiar amb mètodes de neuroimatge amb SPECT. Un grup de pacients amb predomini dels símptomes negatius però sense dèficit cognitiu han actuat com a control. La part experimental consta de quatre estudis, tres dels quals ja han estat publicats i un està acceptat per publicació. En aquests estudis hem pogut demostrar que els dèficits cognitius s'associen a un pronòstic més perniciós: evolució més cronificada, nivell més baix d'adaptació general, estades més llargues d'hospitalització i una adherència més pobra al tractament farmacològic. Els resultats recolzen que el tractament de rehabilitació neuropsicològica és útil i produeix millories a les funcions prèviament deficitàries. Tal i com estableix el model de Brenner, els canvis a les funcions cognitives elementals (atenció i codificació) estan lligades als canvis a les funcions cognitives més superiors (recuperació i funció executiva). I el que és més important, la millora neuropsicològica està associada a una millora del funcionament psicosocial, concretament un augment de l'autonomia personal i del funcionament psicosocial general. Per altra banda el tractament de rehabilitació neuropsicològica produeix canvis en el flux sanguini cerebral frontal detectable mitjançant estudis d'SPECT realitzats en condicions de neuroactivació. Aquests canvis suposen una reducció de la hipofrontalitat que es deu a la millora del funcionament neuropsicològic. Per tant l'estudi ha pogut confirmar les hipòtesis i es pot concloure que la rehabilitació neuropsicològica és una eina terapèutica que possibilita una millora del funcionament cognitiu, una reducció de l'hipofuncionalisme del flux cerebral frontal, un augment de l'autonomia personal i una millora del funcionament psicosocial als pacients esquizofrènics de pitjor pronòstic

Profile of paliperidone palmitate once-monthly-long-acting in the management of schizophrenia: long-term safety, efficacy and patient acceptability - a review

Background and objectives Short-term studies focused on once-monthly paliperidone palmitate (PP) at doses of 25 mg eq, 50 mg eq, 75 mg eq, 100 mg eq, or 150 mg eq have shown its efficacy and tolerability in the treatment of schizophrenia patients. However, few open-label and long-term studies are available regarding this new pharmacological formulation. Thus, our main aim was to review the scientific evidence on efficacy, safety, tolerability, and preference of PP in these populations. Method Electronic searches were conducted by using PubMed and ISI Web of Knowledge databases. All relevant studies published from 2009 until January 2015 were included without any language restriction if patients met diagnostic criteria for schizophrenia, and adequate information on efficacy, safety, and tolerability of once-monthly PP was available. Results Nineteen studies were identified irrespective of the study design and duration of the follow-up period. Randomized, double-blind, placebo-controlled trials found that schizophrenia patients receiving PP showed a significant improvement in psychotic symptoms and similar adverse events compared to placebo and suggested that all doses of PP were efficacious and well tolerated. Other studies demonstrated noninferiority of PP compared to risperidone long-acting injectable in recently diagnosed schizophrenia patients, chronically ill patients, as well as in acute and nonacute symptomatic schizophrenia patients, and a similar proportion of treatment-emergent adverse events between both groups were also noted. Conclusion Several studies have demonstrated that schizophrenia patients treated with PP show higher rates of improvement of psychotic symptoms compared to placebo, and similar efficacy and tolerability outcomes were noted when comparing PP to risperidone long-acting injectable or oral, paliperidone extended release

Brain-Derived Neurotrophic Factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor (BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature