Bakgrund: Årligen insjuknar 2000 personer i psykossjukdom i Sverige. Återhämtning följande förstagångsinsjukande i psykos är ett komplext fenomen där personens subjektiva upplevelser är avgörande för återhämtningen. Att ha kunskap om dessa subjektiva upplevelser skapar förutsättningar hos sjuksköterskan att tillgodose en god personcentrerad omvårdnad av denna individgrupp. Syfte: Syftet med denna studie var att beskriva personers upplevelse av återhämtning efter förstagångsinsjuknande i psykos. Metod: Pubmed och Cinahl har använts för att söka artiklar. Totalt tio kvalitativa artiklars resultat har analyserats och granskats enskilt. De enskilda analysernas resultat har sammansatts i ett analysschema där kategorier och subkategorier identifierats.  Resultat: Efter analysen framkom fyra kategorier, Att uppleva ett förlorat jag, Att uppleva stöd, Att uppleva försoning samt Att åter uppleva en ljus framtid, med sammanlagt tio subkategorier som beskrev upplevelser av återhämtning efter förstagångsinsjuknande i psykos. Konklusion: De subjektiva upplevelserna följande återhämtning vid förstagångsinsjuknande i psykos är komplexa och medföljes av diverse känslor och tankar. Denna studies fynd tyder på vikten av sjuksköterskans roll i personens upplevelse där sjuksköterskan måste arbeta utifrån ett personcentrerat förhållningssätt för att kunna tillgodose personens behov av vård och stöd. Vidare forskning bör undersöka hur sjuksköterskan med hjälp av ett personcentrerat förhållningssätt kan främja dessa gynnsamma upplevelser av återhämtning / Background: Annually, 2000 individuals fall ill in a psychotic disorder in Sweden. Recovery following first episode psychosis is a complex phenomenon where the individuals’ subjective experiences are crucial for recovery. To have knowledge about these subjective experiences creates opportunities for the nurse to provide a good person-centered care for this group of individuals. Aim: The aim of this study was to describe individuals’ experiences of recovery following a first episode psychosis Methods: Pubmed and Cinahl has been used to search articles. In total, ten qualitative articles results have been analyzed and reviewed individually. The individually analyses’ results were compiled in an analysis table where categories and subcategories were identified. Results: Following the analysis emerged four categories, To experience a lost self, To experience support, To experience reconciliation and To once again experience a bright future, with a total of ten subcategories which described experiences of recovery following first episode psychosis.  Conclusion: The subjective experiences following recovery from first episode psychosis is complex and is followed by various emotions and thoughts. This study’s findings suggest the importance of the nurse’s role in the individual’s experience where the nurse must work from a person-centered approach to be able to provide the care required for the individual’s recovery. Further research should explore how the nurse, from a person-centered approach, can promote these favorable experiences of recovery

Bakgrund Mer än 2000 personer insjuknar varje år i Sverige i förstagångsinsjuknande i psykos. Insjuknandet kan upplevas som en kris för personen och för dennes närstående samt medföra ett psykiskt, socialt och ekonomiskt lidande. Psykosvården är i behov av stora resurstillgångar från samhället och den drabbade behöver ofta flera stödinsatser från hälso-och sjukvården. Tidigare forskning finns om återhämtning från psykisk ohälsa och från psykossjukdomar. Det finns dock mindre forskning som fokuserar på patienter med förstagångsinsjuknande i psykos och deras upplevelse av återhämtning. Syfte Syftet var att beskriva patienters upplevelse av vad som påverkar återhämtningen efter förstagångsinsjuknande i psykos. Metod Litteraturöversikt med systematisk ansats inkluderat 15 studier med kvalitativ ansats. Litteratursökningar genomfördes i databaserna Cinahl Complete, PsycInfo och PubMed. Dataanalys utfördes genom Thomas och Hardens metod för tematisk analys. Resultat Tre huvudteman framkom i resultatet: Personliga processer bidrar till återhämtning, olika relationer bidrar till återhämtning samt stigma- ett hinder för återhämtning. En individuell förändringsresa genom acceptans, återtagen kontroll och hopp inför framtiden var bidragande faktorer i återhämtningen. Medicinering, stöd från hälso-och sjukvården och närstående samt social tillhörighet bidrog till återhämtningsprocessen. Stigma var hämmande för återhämtningen. Slutsats Återhämtning vid förstagångsinsjuknande i psykos är en komplex och individuell process, som påverkas av både personliga processer samt yttre faktorer. Att uppleva stigma är ett hinder för återhämtning. Specialistsjuksköterskan inom psykiatrisk vård har en central roll i patientens återhämtningsprocess, vilket förutsätter god kompetens och ett personcentrerat förhållningsätt. / Background More than 2000 people fall ill every year in Sweden with a first onset of psychosis. The illness is often experienced as a crisis for the person themselves and their family and can cause psychological, social and financial suffering. Psychiatric care is in need of large resources from the society, and the sufferer often needs several support measures from the health and medical care. Previous research exists on recovery from mental illness and from psychotic illnesses. However, there is less research focusing on first-time psychosis patients and their experience of recovery.  Aim The aim was to describe patients' experiences in what affects recovery after a first episode psychosis Methods Literature review with a systematic approach including 15 studies with a qualitative approach. The literature searches were conducted in the databases Cinahl Complete, PsycInfo and PubMed. Data analysis has been done through Thomas and Harden's methods for the thematic synthesis. Results Three main themes emerged in the results: Personal processes contribute to recovery, different relationships contribute to recovery and stigma - an obstacle to recovery. A individual journey of change through acceptance, regained control and hope for the future were contributing factors in the recovery. Medication, support from health care and relatives and social belonging contributed to recovery. Stigma were inhibiting the recovery. Conclusions Recovery from the first onset of psychosis is a complex and individual process, which is influenced by both personal processes and external factors. Experiencing stigma is a barrier to recovery. The specialist nurse in psychiatric care has a central role in the patient's recovery process, which requires good competence and a person-centred approach.

INTRODUÇÃO: Transtornos psiquiátricos com sintomas psicóticos trazem prejuízos ocupacionais e sociais significativos aos seus portadores, com aumento da mortalidade e morbidade. Estes transtornos têm sido estudados como alterações do padrão de conectividade funcional nas redes cerebrais do estado de repouso. Entretanto, tais relatos são mais frequentes em pacientes crônicos, com literatura escassa sobre pacientes em primeiro episódio psicótico, principalmente não realizando comparações entre as redes. OBJETIVO: Este foi um estudo exploratório com objetivo de caracterizar a conectividade funcional cerebral das redes do estado de repouso em pacientes de primeiro episódio psicótico através da ressonância nuclear magnética funcional comparando-os a irmãos e a controles de base populacional. MÉTODOS: A amostra foi composta por por 38 pacientes em primeiro episódio psicótico, 13 irmãos e 41 controles de base populacional. Foram coletadas imagens por ressonância magnética funcional e a conectividade funcional foi obtida através do coeficiente de correlação de Pearson da série temporal do sinal BOLD de 264 regiões de interesse. A comparação da conectividade funcional entre os grupos de participantes foi feita pelo método Partial Least Square. Também foi utilizado o método Behavior Partial Least Square para buscar um padrão de conexões alteradas que estivesse associado a gravidade dos sintomas psicóticos, ao tempo de tratamento e a duração da psicose não tratada. A análise estatística contou com 10.000 permutações e um método de reamostragem e foram considerados significativos valores de p<0.05. RESULTADOS: As alterações nas redes, em sua maioria, foram devido à mudança de correlação positiva para correlação negativa nos pacientes em relação aos controles. As redes com maior número de conexões alteradas entre pacientes e controles foram a rede sensóriomotor mão, Default Mode Network (DMN) e rede visual. As conexões estiveram mais alteradas no lobo frontal direito. Não foi encontrada associação entre o padrão de conectividade funcional dos pacientes e a duração de psicose não tratada, o tempo de tratamento farmacológico e a gravidade da psicose. Na comparação entre pacientes e irmãos, foi encontrada uma tendência à significância de um padrão de conexões alteradas. Não foi encontrada diferença significativa entre o grupo de irmãos e o grupo controle. DISCUSSÃO: Pacientes em primeiro episódio psicótico apresentaram maior segregação das redes do estado de repouso comparados a controles de base populacional, corroborando a hipótese etiológica da Esquizofrenia de uma desconectividade funcional do cérebro. A rede sensório-motor mão surpreendentemente foi a rede com maior número de alterações, apontando a necessidade de mais estudos sobre a mesma. Os irmãos não apresentaram um padrão de conexões do repouso diferente dos controles, não corroborando as hipóteses de que tal grupo apresentaria um padrão intermediário entre pacientes e controles. CONCLUSÃO: Os achados apontam para um uma topologia cerebral amplamente prejudicada já no início da psicose, com uma maior segregação entre as redes do estado de repouso em pacientes de primeiro episódio psicótico. / INTRODUCTION: Psychiatric disorders with psychotic symptoms bring significant occupational and social harm to their patients, with increased mortality and morbidity. These disorders have been studies as changes in the functional connectivity patterns in resting state brain networks. However, reports are more frequently made in chronic patients, with a scarce literature from first episode psychosis patients, mostly not making intra-networks comparison. OBJECTIVE: This was an exploratory study that had the objective of characterize the brain functional connectivity of resting networks in first episode psychosis patients through functional magnetic resonance imaging compared to siblings and to population based controls. METHODS: Final sample consisted of 38 first episode psychosis, 13 siblings and 41 population-based controls. Functional magnetic resonance images were collected in first episode psychosis, siblings and population based controls. Functional connectivity was obtained through the Pearson Correlation Coefficient of 264 regions of interest BOLD signal time series´. Comparison of functional connectivity among groups of participants was made using Partial Least Square method. Behavior Partial Least Square was performed to seek for a pattern associated with illness severity, pharmacological treatment time and duration of untreated psychosis. The statistical analysis was conducted with 10,000 permutations and bootstrap considering significant values of p<0.05. RESULTS: Aberrant network connections were mostrly due to changes of positive correlation to negative correlation in patients compared to controle. The majority of altered connections were found in sensory-motor network, DMN and visual network. The areas most affected were right frontal lobe. It was not found a functional connectivity pattern associated with illness severity, treatment time and duration of untreated psychosis. A tendency difference was found in the connectivity pattern between siblings and patients. No different connectivity pattern was found between siblings and controls. DISCUSSION: First episode psychosis presented more segregated resting state networks than controls, reinforcing the disconnectivity etiology hypothesis for schizophrenia. An unexpected result was sensory-motor hand network being the network with more altered connections, pointing to the need of more studies to comprehend it. The sibling group did not differ from the control group, not corroborating the hypotheses that such a group would present an intermediate pattern between patients and controls. CONCLUSION: The findings point to a largely impaired brain topology already at the beginning of the psychosis, with greater segregation between resting state networks in patients with first episode psychosis.

Introdução: Os receptores ionotrópicos do glutamato, como o N-metil-D-Aspartato (NMDA), estão envolvidos em desordens psiquiátricas. NMDARs são complexos heteroméricos que incorporam tres diferentes subunidades: NR1, NR2 e NR3. Objetivos: quantificar os níveis plasmáticos das subunidades NR1 e NR2 NMDAR em pacientes em primeiro episódio psicótico (PEP), em comparação com os irmãos e controles saudáveis. Métodos: Este é um estudo transversal de PEP na região de Ribeirão Preto, Brasil, sendo o grupo controle composto por indivíduos saudáveis, pareados por idade, sexo e mesma área de abrangência dos casos. Foram coletados 5 mL de amostra de sangue próxima a data de diagnóstico de PEP. A quantificação plasmática das subunidades NR1 e NR2 foi realizada por ELISA. Os dados foram analisados por ANOVA (significante se p<0,05) e curva ROC. Resultados: Foram incluídos 166 pacientes em PEP (idade: x = 30,34 ± 12,2 anos; 64% homens), destes 84 com diagnóstico de psicose não afetiva, 51 com transtorno bipolar e 31 com transtorno depressivo. Foram tambem incluídos 76 irmãos e 166 controles saudáveis. Os níveis plasmáticos das subunidades NR1 e NR2 foram significativamente menores em pacientes com transtornos psicóticos (NR1: x = 71,0 ± 100,3 pg/mL, NR2: x = 2,5 ± 2 ng/ml), transtorno bipolar (NR1: x = 185,7 ± 319,5 pg/ml; NR2: x = 2,1 ± 2,2 ng/ml), transtorno depressivo (NR1: x = 83,2 ±185,0 pg/ml; NR2: x = 2,1± 2,1 ng/ml) em comparação com os irmãos (NR1: x = 140,6 ± 193,8 pg/ml; NR2: = 6,2 ± 1,5 ng/ml) e voluntários saudáveis (NR1: x = 146,7 ± 361,1 pg/ml; NR2: x = 4,8 ± 2,2 ng/ml) [NR1 e NR2, p < 0,001]. Indivíduos com valores plasmáticos de NR2 inferiores a 3,648 ng/mL apresentam um risco 14,72 vezes maior de estar doente (PEP) de quem não possui o NR2 abaixo deste valor. Conclusões: Este é o primeiro estudo relatando a quantificação e a redução das concentrações plasmaticas das subunidades NR1 e NR2 em transtornos psiquiátricos graves quando comparados aos irmãos e controles, podendo a subunidade NR2 ser um candidato a biomarcador plasmático em pacientes com PEP. / Background: Ionotropic glutamate receptors, such as N-Methyl-D-Aspartate (NMDA), are involved in pathophysiology of several psychiatric disorders. NMDARs are described as heteromeric complexes incorporating distincts subunits within a repertoire of three types: NR1, NR2 and NR3. Aim: to quantify the NR1 and NR2 subunits NMDAR plasma levels in patients with first episode psychosis (FEP), compared with siblings and healthy controls. Methods: This is a cross-sectional study of FEP conducted in Ribeirão Preto, Brazil. The control group were composed by healthy subjects matched for age, sex and same coverage area of cases. 5 ml of blood sample were collected next to the date of FEP diagnosis. NR1 and NR2 subunits plasmatic quantification was performed by ELISA. Data were analyzed by ANOVA (significant at p < 0.05) and ROC curve. Results: FEP sample comprised 166 patients (age: x = 30.34 ± 12.2 years; 64% men), of these 84 with a diagnosis of psychotic disorder, 51 with bipolar disorder and 31 with depressive disorder. It was also included 76 siblings and 166 healthy controls. NR1 and NR2 subunits plasma levels were significantly lower in patients with psychotic disorders (NR1: x = 71.0 ± 100.3 pg / ml, NR2: x = 2.5 ± 2 ng/ml), bipolar disorder (NR1: x = 185.7 ± 319.5 pg/mL; NR2: x = 2.1 ± 2.2 ng/ml), depressive disorders (NR1: x = 83.2 ± 185.0 pg/mL; NR2: x = 2.1 ± 2.1 ng/ml) compared with siblings (NR1: x = 140.6 ± 193.8 pg/mL; NR2: x = 6.2 ± 1.5 ng/ml) and healthy volunteers (NR1: x = 146.7 ± 361.1 pg / mL; NR2: x = 4.8 ± 2.2 ng/ml) [NR1 and NR2, p < 0.001]. Interestingly, individuals with NR2 plasma values less than 3.648 ng/ml present 14.72 times a higher risk to be in FEP than other patients. Conclusions: This is the first study reporting the measurement and reduction of NR1 and NR2 subunits plasma concentrations in severe psychiatric disorders when compared to siblings and controls. And highlighting that NR2 subunit can be a candidate for plasma biomarker in patients with FEP.

Orientador: Prof. Dr. João Ricardo Sato / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2016. / Diversos estudos reportaram alterações cerebrais ao longo do curso da esquizofrenia. Até mesmo nos estágios incipientes, como no Primeiro Episódio Psicótico (PEP). Métodos de aprendizagem de máquina podem ser utilizados para análise multivariada de dados de neuroimagem, porém a grande maioria dos estudos os emprega principalmente para previsões entre grupos, como discriminar pacientes com esquizofrenia de controles saudáveis. No presente estudo, foi aplicado o método maximum entropy linear discriminant analysis (MLDA) com o objetivo de buscar um melhor entendimento dos estágios da esquizofrenia. Foram analisados dados neuro-volumétricos provenientes de imagens de ressonância magnética de 143 pacientes crônicos com esquizofrenia, 32 pacientes PEP e 82 controles saudáveis. O método projeta as características multivariadas de um sujeito em um sub-espaço discriminante univariado, provendo um "escore de esquizofrenia". Inicialmente, a performance do MLDA na tarefa de discriminação entre pacientes com esquizofrenia de controles foi avaliada e foram identificados as regiões cerebrais que mais contribuíram para a classificação. Por fim, foram utilizados os escores provenientes do MLDA para realizar uma comparação entre os padrões volumétricos de pacientes PEP e pacientes com esquizofrenia e controles saudáveis. A classificação atingiu uma acurácia balanceada de 72.96%. O grupo PEP apresentou uma distribuição de escores mais similar aos pacientes com esquizofrenia em comparação aos controles saudáveis. Após repetição das análises excluindo as regiões afetadas por medicação anti-psicótica, a acurácia permaneceu aproximadamente a mesma (73.66%), porém os escores do PEP se tornaram mais similares ao grupo controle. Os resultados do presente estudo sugerem que as primeiras estruturas alteradas no PEP podem ser as regiões afetadas por anti-psicóticos. Entre as estruturas mais discriminantes na classificação se encontravam, principalmente, estruturas relacionadas ao sistema límbico e a circuiteria envolvida em comportamentos orientados a objetivos. Em conclusão, nossos resultados sugerem a importância de considerar os efeitos dos anti-psicóticos, a fim de entender os substratos neurais envolvidos na esquizofrenia. / Several studies reported brain changes along the course of the schizophrenia. Even in the early stages, such as first episode psychosis (FEP). Machine learning methods can be applied for multivariate analysis of neuroimaging data, however, they have been employed in most of the studies with main concern in group prediction, such as discriminating schizophrenic patients from healthy controls. In the present study we applied the maximum entropy linear discriminant analysis (MLDA) aiming to a better comprehension of the schizophrenia stages. We analysed brain structures volumetric data from MRI images of 143 patients with chronic schizophrenia, 32 FEP patients and 82 healthy controls. The method projects the multivariate characteristics of a subject onto a univariate discriminant subspace, providing a "schizophrenia score". First, the performance of MLDA in the discrimination task between schizophrenia patients from controls was evaluated and we identified the brain regions that most contribuited to the classification. Finally, we utilized the scores provided by MLDA to make a comparison among the volumetric patterns of FEP patients and schizophrenic patients and healthy controls. The classification achieved a balanced accuracy of 72.96%. We found that the FEP group had a score distribution more similar to patients with schizophrenia in comparison with healthy subjects. After the exclusion of regions affected by antipsychotic medication and repeating MLDA analysis, the accuracy remained approximately the same (73.66%), but the FEP scores became more similar to control group. Our results suggest that the first structures altered in FEP might be the regions affected by antipsychotics. Structures related to the limbic system and the circuitry involved in goal-directed behaviours were the most discriminant regions in the classification. In conclusion, our results suggest the importance of taking into account the brain structural effects of antipsychotic drugs in order to understand the neural substrates involved in schizophrenia.

Introdução: Os receptores ionotrópicos do glutamato, como o N-metil-D-Aspartato (NMDA), estão envolvidos em desordens psiquiátricas. NMDARs são complexos heteroméricos que incorporam tres diferentes subunidades: NR1, NR2 e NR3. Objetivos: quantificar os níveis plasmáticos das subunidades NR1 e NR2 NMDAR em pacientes em primeiro episódio psicótico (PEP), em comparação com os irmãos e controles saudáveis. Métodos: Este é um estudo transversal de PEP na região de Ribeirão Preto, Brasil, sendo o grupo controle composto por indivíduos saudáveis, pareados por idade, sexo e mesma área de abrangência dos casos. Foram coletados 5 mL de amostra de sangue próxima a data de diagnóstico de PEP. A quantificação plasmática das subunidades NR1 e NR2 foi realizada por ELISA. Os dados foram analisados por ANOVA (significante se p<0,05) e curva ROC. Resultados: Foram incluídos 166 pacientes em PEP (idade: x = 30,34 ± 12,2 anos; 64% homens), destes 84 com diagnóstico de psicose não afetiva, 51 com transtorno bipolar e 31 com transtorno depressivo. Foram tambem incluídos 76 irmãos e 166 controles saudáveis. Os níveis plasmáticos das subunidades NR1 e NR2 foram significativamente menores em pacientes com transtornos psicóticos (NR1: x = 71,0 ± 100,3 pg/mL, NR2: x = 2,5 ± 2 ng/ml), transtorno bipolar (NR1: x = 185,7 ± 319,5 pg/ml; NR2: x = 2,1 ± 2,2 ng/ml), transtorno depressivo (NR1: x = 83,2 ±185,0 pg/ml; NR2: x = 2,1± 2,1 ng/ml) em comparação com os irmãos (NR1: x = 140,6 ± 193,8 pg/ml; NR2: = 6,2 ± 1,5 ng/ml) e voluntários saudáveis (NR1: x = 146,7 ± 361,1 pg/ml; NR2: x = 4,8 ± 2,2 ng/ml) [NR1 e NR2, p < 0,001]. Indivíduos com valores plasmáticos de NR2 inferiores a 3,648 ng/mL apresentam um risco 14,72 vezes maior de estar doente (PEP) de quem não possui o NR2 abaixo deste valor. Conclusões: Este é o primeiro estudo relatando a quantificação e a redução das concentrações plasmaticas das subunidades NR1 e NR2 em transtornos psiquiátricos graves quando comparados aos irmãos e controles, podendo a subunidade NR2 ser um candidato a biomarcador plasmático em pacientes com PEP. / Background: Ionotropic glutamate receptors, such as N-Methyl-D-Aspartate (NMDA), are involved in pathophysiology of several psychiatric disorders. NMDARs are described as heteromeric complexes incorporating distincts subunits within a repertoire of three types: NR1, NR2 and NR3. Aim: to quantify the NR1 and NR2 subunits NMDAR plasma levels in patients with first episode psychosis (FEP), compared with siblings and healthy controls. Methods: This is a cross-sectional study of FEP conducted in Ribeirão Preto, Brazil. The control group were composed by healthy subjects matched for age, sex and same coverage area of cases. 5 ml of blood sample were collected next to the date of FEP diagnosis. NR1 and NR2 subunits plasmatic quantification was performed by ELISA. Data were analyzed by ANOVA (significant at p < 0.05) and ROC curve. Results: FEP sample comprised 166 patients (age: x = 30.34 ± 12.2 years; 64% men), of these 84 with a diagnosis of psychotic disorder, 51 with bipolar disorder and 31 with depressive disorder. It was also included 76 siblings and 166 healthy controls. NR1 and NR2 subunits plasma levels were significantly lower in patients with psychotic disorders (NR1: x = 71.0 ± 100.3 pg / ml, NR2: x = 2.5 ± 2 ng/ml), bipolar disorder (NR1: x = 185.7 ± 319.5 pg/mL; NR2: x = 2.1 ± 2.2 ng/ml), depressive disorders (NR1: x = 83.2 ± 185.0 pg/mL; NR2: x = 2.1 ± 2.1 ng/ml) compared with siblings (NR1: x = 140.6 ± 193.8 pg/mL; NR2: x = 6.2 ± 1.5 ng/ml) and healthy volunteers (NR1: x = 146.7 ± 361.1 pg / mL; NR2: x = 4.8 ± 2.2 ng/ml) [NR1 and NR2, p < 0.001]. Interestingly, individuals with NR2 plasma values less than 3.648 ng/ml present 14.72 times a higher risk to be in FEP than other patients. Conclusions: This is the first study reporting the measurement and reduction of NR1 and NR2 subunits plasma concentrations in severe psychiatric disorders when compared to siblings and controls. And highlighting that NR2 subunit can be a candidate for plasma biomarker in patients with FEP.

Objectifs: Les études quantitatives ont documenté l’ampleur des problèmes d’observance en début de psychose et les conséquences cliniques qui en découlent. La compréhension du phénomène demeure toutefois limitée. Notre étude propose d’explorer, à partir de trois perspectives (celles des patients, des proches et des cliniciens), les raisons pour lesquelles les patients en début de psychose acceptent ou refusent les traitements. Méthode: La collecte des données s’est faite à l’aide d’entrevues individuelles semi-structurées auprès de 18 patients d’une clinique spécialisée en psychose débutante classifiés comme étant observants, ambivalents ou non observants, et auprès de 13 de leurs proches, ainsi qu’à l’aide d’un focus group réunissant 8 cliniciens de la clinique. Résultats: L’observance semble s’inscrire dans un processus marqué par une certaine ambivalence pour la plupart des sujets. Cette ambivalence est modulée par: des enjeux identitaires, des enjeux relationnels, la compréhension du diagnostic et la signification du traitement. Conclusion: L’ambivalence et l’inobservance seraient des étapes normales du processus au cours duquel le patient lutte pour reconstruire son identité. La présence d’un lien de confiance permet la résolution progressive de l’ambivalence, facilitant ainsi le processus de réappropriation du traitement par le patient. / Objective: Quantitative studies have documented the extent of compliance issues in early psychosis and the ensuing clinical consequences. However, an in-depth understanding of this phenomenon remains limited. Drawing upon the perspectives of a sample of patients, their families, and clinicians, this study explores why patients suffering from early-stage psychosis accept or refuse treatment. Method: Data collection was conducted using semi-structured individual interviews with 18 patients from a clinic specializing in early psychosis who were identified as compliant, ambivalent or non-compliant. In addition, interviews were conducted with 13 of their family members, as well as a focus group composed of 8 clinicians working at the clinic. Results: For the majority of patients, compliance appeared to evolve according to a process characterized by varying degrees of ambivalence. In particular, identity issues, relational issues, the understanding of the diagnosis, and the meaning of treatment were key to understanding patients’ sense of ambivalence. Conclusion: Ambivalence and non-compliance can be seen as normal stages of a process whereby the patient struggles to rebuild his or her sense of self and constructs their ongoing identity. A relationship of trust may facilitate a gradual resolution of the ambivalence, promoting a patient’s sense of ownership and empowerment in the context of treatment.

O reconhecimento de expressões faciais de emoções (REFE) possui valor adaptativo, sendo importante para o funcionamento social e o relacionamento interpessoal. Evidências apontaram que alterações no REFE podem estar associadas a transtornos psiquiátricos como a depressão maior (incluindo o subtipo psicótico) e ao estresse precoce. Associações também foram verificadas entre a vivência de estresse precoce e o desenvolvimento da depressão na vida adulta. Considerando esses aspectos, além da escassez de pesquisas na área envolvendo o subtipo psicótico da depressão, este estudo se justifica pela pertinência de averiguar se a interação entre a depressão psicótica e o estresse precoce altera o REFE. Assim, objetivou-se investigar a possível influência do episódio depressivo psicótico e da história de estresse precoce, considerados individualmente e em interação, sobre a acurácia e vieses no REFE. Adicionalmente, foi investigada a existência de associações entre a gravidade geral do estresse precoce e a acurácia específica no REFE. Participaram do estudo 49 pacientes com diagnóstico de primeiro episódio depressivo maior com características psicóticas e 49 controles saudáveis, emparelhados e subgrupados de acordo com o sexo e a história de estresse precoce. Todos os participantes passaram por uma bateria de avaliações, incluindo uma entrevista diagnóstica padronizada, escalas de avaliação da gravidade de sintomas psiquiátricos e funcionamento global, além de questionários sobre aspectos sociodemográficos, histórico clínico, uso de drogas e medicamentos e história de estresse precoce. Por fim, os participantes foram submetidos à Degraded Facial Affect Recognition Task (DFAR), uma tarefa comportamental de escolha forçada no REFE, composta por fotografias degradadas (i.e., com contraste visual reduzido em 30%) de expressões faciais de neutralidade, alegria, medo e raiva, às quais foram atribuídos rótulos emocionais correspondentes. Os dados foram analisados por meio de estatística descritiva e inferencial, utilizando os testes qui-quadrado ou exato de Fisher, U de Mann-Whitney, ANOVA de três vias com post hoc Bonferroni e Correlação de Spearman. Os principais resultados apontaram que a vivência de estresse precoce foi associada a uma maior acurácia no REFE de alegria nos controles e menor acurácia nos pacientes. O REFE de alegria também foi correlacionado com a gravidade geral do estresse precoce, tendo apresentado uma correlação positiva nos controles e negativa nos pacientes. Alterações no REFE de medo também foram associadas à interação entre depressão psicótica e estresse precoce, mas somente nas mulheres. Aquelas com diagnóstico de depressão psicótica e história de estresse precoce tiveram pior acurácia em comparação com mulheres depressivas psicóticas sem história de estresse precoce e com mulheres saudáveis com história de estresse precoce. Em conclusão, os resultados confirmaram que alterações no REFE foram associadas com a interação entre a depressão psicótica e o estresse precoce. Isso chama a atenção para a importância de se considerar a influência do estresse precoce em interação com outros transtornos psiquiátricos na investigação do reconhecimento emocional. / Facial emotion recognition (FER) has an adaptive value, being important for social functioning and interpersonal relationship. Evidence has indicated that FER alterations may be associated with psychiatric disorders such as major depression (including its psychotic subtype) and with early-life stress. Associations were also found between the experience of early-life stress and the development of depression in adult life. Considering these aspects, as well as the lack of research in this field involving the psychotic subtype of depression, this study is justified by the pertinence of investigating whether the interaction between psychotic depression and early-life stress alters FER. Thus, the objective was to investigate a possible influence of psychotic depressive episode and early-life stress history, considered individually and in interaction, on FER accuracy and bias. In addition, it was investigated the existence of associations between early-life stress general severity and specific FER accuracy. The study included 49 patients with diagnosis of first major depressive episode with psychotic features and 49 healthy controls, matched and subgrouped according to sex and earlylife stress history. All participants underwent a battery of assessments, including a standardized diagnostic interview, assessment scales on severity of psychiatric symptoms and global functioning, as well as questionnaires on sociodemographic aspects, clinical history, drug and medication use and early-life stress history. Finally, participants were submitted to the Degraded Facial Affect Recognition Task (DFAR), a FER forced-choice behavioral task, composed of degraded photographs (i.e., with visual contrast reduced by 30%) portraying facial expressions of neutrality, joy, fear and anger, to which a corresponding emotional label were assigned. Data were analyzed through descriptive and inferential statistics, using chi-square test or Fisher\'s exact test, Mann-Whitney U test, three-way ANOVA with Bonferroni post hoc test, and Spearman\'s correlation test. The main results pointed out that early-life stress experience was associated with greater accuracy in FER of joy in controls and lower accuracy in patients. FER of joy was also correlated with early-life stress general severity, presenting a positive correlation in controls and a negative correlation in patients. Alterations in FER of fear were also associated with the interaction between psychotic depression and early-life stress, but only for women. Those with psychotic depression diagnosis and early-life stress history had worse accuracy compared both to depressed psychotic women with no early-life stress history and to healthy women with early-life stress history. In conclusion, results confirmed that FER alterations were associated with the interaction between psychotic depression and early-life stress. This draws attention to the importance of considering the influence of early-life stress on interaction with other psychiatric disorders in the investigation of emotional recognition.

La esquizofrenia está considerada un síndrome clínico heterogéneo con una etiopatogenia de origen multifactorial, en el que se incluyen factores ambientales, caracteriales y genéticos. A pesar de que más del 50% de la variabilidad de la enfermedad se puede deber a uno o varios factores genéticos, sólo un número limitado de variantes de riesgo genético y con un efecto muy débil han podido ser identificados. Muchos de ellos no han podido reproducirse tanto por la diversidad de las muestras y poblaciones estudiadas como por su asociación a diversas enfermedades mentales. Parte de esta heterogeneidad ha intentado ser solventada mediante el uso de endofenotipos o fenotipos intermedios y marcadores biológicos, usados como marcadores de vulnerabilidad genética. El gen de la Catecol-O-Metil Transferasa (COMT), que codifica un enzima catabolizador de dopamina en el córtex prefrontal ha sido estudiado como uno de los genes candidatos más prometedores en el estudio de la etiopatogenia de la esquizofrenia, especialmente el polimorfismo rs4680 (COMT Val158Met). La posibilidad de asociar alteraciones en la regulación dopaminérgica prefrontal se encontraría refrendada por la hipótesis dopaminérgica revisada, según la cual, en la esquizofrenia existiría un desequilibrio dopaminérgico, con un incremento en la función dopaminérgica subcortical D2 y un déficit de estimulación D1 cortical. El polimorfismo COMT Val158Met no ha podido confirmar su asociación con esquizofrenia, existiendo en todo caso un riesgo muy débil asociado al alelo hiperfuncionante Val158. El estudio de endofenotipos y marcadores biológicos ha sugerido la asociación del polimorfismo con alteraciones cognitivas, neurofisiológicas, neuroanatómicas y a fenotipos clínicos como agresividad, suicidio, síntomas psicóticos, edad de inicio y respuesta clínica, encontrándose resultados heterogéneos, así como la existencia de una modulación del riesgo de asociación por el consumo de cannabis. Gran parte de la heterogeneidad puede explicarse por problemas metodológicos, relacionados con la validez y representatividad de las muestras, que podrían solventarse con la recogida sistemática de variables en muestras epidemiológicas en fases iniciales de la enfermedad. Partiendo de la hipótesis de la existencia de una alteración dopaminérgica prefrontal en la esquizofenia, el alelo Val158 del gen COMT estaría asociado a una expresión de síntomas psicóticos más graves, especialmente los negativos y a factores de mal pronóstico. Igualmente el consumo de cannabis podría modular este riesgo, incrementando el riesgo o contrarrestando los factores protectores. El objetivo principal fue estudiar la asociación de la presentación clínica y evolución a las seis semanas de tratamiento antipsicótico de pacientes con un primer episodio de psicosis y las variantes del polimorfismo COMT Val158Met así como su interacción con el consumo de cánnabis premórbido. Los objetivos secundarios fueron estudiar la incidencia de esquizofrenia y validar la representatividad de la muestra, analizar la relación entre el polimorfismo Val158Met y sintomatología clínica, edad de inicio, respuesta al tratamiento y estimar la presencia de interacciones gen-ambiente con el consumo de cánnabis premórbido. Para ello, se reclutaron 174 pacientes consecutivos con un primer episodio de psicosis de esquizofrenia, trastorno esquizofreniforme, trastorno esquizoafectivo, trastorno psicótico breve o trastorno psicótico no especificado, incluidos dentro del programa PAFIP, diseñado para la detección y tratamiento de los casos incidentes en la comunidad de Cantabria de Febrero 2001 a Febrero 2005. Los pacientes fueron evaluados con una entrevista semiestructurada, las escalas SANS, SAPS, HDRS, CDS, YMRS y la entrevista SCID-I. Fueron seguidos durante las primeras seis semanas de tratamiento antipsicótico de asignación aleatoria (olanzapina, risperidona o haloperidol). El genotipo del polimorfismo rs4680 se determinó en muestras de sangre venosa. Un primer estudio mostró una incidencia tratada de 1.38/10000 y la asociación de esta incidencia a factores de riesgo como edad menor de 25 años, sexo masculino, estado marital soltero, desempleo nivel educativo primario, ambiente urbano y consumo de cannabis. Un segundo estudio encontró una asociación del alelo Val158 con sintomatología negativa al inicio y edad de inicio temprana, diagnóstico de esquizofrenia y duración de psicosis sin tratar prolongada en mujeres. En un tercer estudio se mostró la asociación del consumo de cánnabis premórbido con edad de inicio más temprana y una interacción entre consumo de cannabis y el genotipo, de modo que el consumo de cannabis contrarresta el efecto protector del alelo 158 Met. Finalmente, en un cuarto estudio se confirmó la persistencia de la asociación del genotipo Val158Met con mayor sintomatología negativa tras seis semanas de tratamiento, no encontrando diferencias en cuanto a la respuesta clínica. Los resultados muestran que el polimorfismo COMT Val158Met pueden estar asociados a una edad de inicio más temprana y una mayor gravedad de síntomas negativos. Del mismo modo, el consumo de cánnabis premórbido se asocia a una menor edad de inicio y se encuentra un patrón de interacción con el polimorfismo, eliminando los efectos protectores del alelo Met158. Los hallazgos sugieren la importancia del polimorfismo COMT Val158Met y del consumo de cannabis en la etiopatogenia de la esquizofrenia, que podría explicarse por la disminución de trasmisión dopaminérgica prefrontal. / The schizophrenia is considered a heterogeneous syndrome which has multifactorial causes, including environmental, characterial and genetic factors. Despite the fact that 50% of the variability of the illness is explained by genetic factors, only a limited number of genetic variants have been identified as weak risk factors. Most of them have not been replicated because of the heterogeneity of the studied samples and the association with other mental illnesses. This variability has been tried to be solved by the use of endophenotypes and biological markers, as indicators of genetic vulnerability. Catechol-O-Methyltransferase gene, that codifies a dopamine degradation enzyme active in prefrontal cortex, has been studied as one of the most promising candidates in the etiopathogenesis of schizophrenia, particularly the rs4860 polymorphism (Val158Met). The possible association with an altered prefrontal dopaminergic transmission would be supported by the revised dopaminergic theory. Following this theory, there is a dopaminergic disequilibrium in schizophrenia, with an increase in subcortical D2 dopaminergic transmission and a deficit in D1 cortical stimulation. COMT Val158Met polymorphism has not consistently associated with schizophrenia. The study of endophenotypes and biological markers has suggested associations with cognitive deficits, neurophysiologic and neuroanatomic markers and with clinical phenotypes, such as aggressiveness, suicide, psychotic symptoms, age of onset and clinical response. It also has been reported an interaction with cannabis in the modulation of the risk of psychosis. This heterogeneity could be explained by methodological biases, related to the validity and representativeness of the studied samples and may be solved with the systematic study of epidemiological samples of patients in the initial phases of psychosis. Following the hypothesis of the existence of an altered prefrontal dopaminergic transmission, the Val158 allele in the COMT gene would be associated with more severe psychotic symptoms, particularly negative symptoms and with poor prognostic factors. Likewise, the premorbid use of cannabis could modulate this risk, increasing the risk or counteract the protective factors. The main objective was to study the association between the clinical onset and evolution in the first 6 weeks of treatment and the COMT Val158Met polymorphism as well as the interaction with premorbid cannabis use. The secondary objectives were to study the incidence of schizophrenia and validate the representativeness of the sample, to analyse the relation between the Val158Met polymorphism and clinical symptoms, age of onset, clinical response to treatment and to estimate the presence of gen-environment interactions with the premorbid cannabis use. 174 consecutive first episode psychosis patients with a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder or psychosis non-otherwise specified were included in the PAFIP program. The program was designed for the detection and treatment of all cases in the region of Cantabria, form February 2001 to February 2005. The patients were assessed with a semi-structured interview, SANS, SAPS, HDRS, CDS, YMRS scales and the SCID-I interview. They were followed up to 6 weeks and treated with a randomly assigned antipsychotic (olanzapine, risperidone or haloperidol). Rs4680 polymorphism was assessed in peripheric blood samples. A first study showed a treated incidence of 1.38/10000 and the association with several risk factors such as age under 25 years, male gender, single marital status, unemployment, primary educational level, urban environment and cannabis use. A second study found an association between the Val158 allele and negative symptoms severity at onset, early age of onset, schizophrenia diagnosis and longer duration of untreated psychosis in females. A third study showed an association between premorbid cannabis use and early age of onset and an interaction between cannabis use and genotype, indicating that the cannabis use counter act the protective effect of the Met158Met allele in age of onset. Finally, in a fourth study the association between the Val158 allele and negative symptoms was confirmed after 6 weeks of treatment, although no relation was found with clinical response. The results showed that the COMT Val158Met polymorphism could be associated with an earlier age of onset and a higher severity of negative symptoms. Likewise, the premorbid use of cannabis was associated with an earlier age of onset and there was found a gene-environmental interaction, deleting the protective effect of the Met158 Allele. These findings suggest the importance of COMT Val158Met polymorphism and premorbid cannabis use in the etiopathogenesis of the schizophrenia that could be explained by a decrease in the prefrontal dopaminergic transmission.

Introducció: Són molts els estudis que, en els darrers quinze anys, han demostrat l'efectivitat delsprogrames d'intervenció precoç en la esquizofrènia i el seu impacte sobre el pronòstic de lamalaltia. De fet, la intervenció preventiva a la fase prodròmica i posterior al primer episodi haesdevingut una de les línies principals de recerca i d'aplicació clínica per l'abordatge de laesquizofrènia.Objectiu: Avaluar l'impacte d'una intervenció psicoterapèutica durant la fase inicial de laesquizofrènia sobre la millora clínica i les recaigudes d'un grup que va rebre una intervencióprecoç (PIPE) en comparació amb un grup control (GC) que va rebre controls psiquiàtrics rutinaris.Mètode: Es va realitzar un assaig clínic controlat a simple cec per tal de comparar un grup que vaser tractat amb un programa de controls rutinaris (CG) amb un grup que va participar en elprograma PIPE. Es van aleatoritzar 34 pacients que estaven a la fase inicial de l'esquizofrènia aambdós grups: GC (n=13) i GC+PIPE (n=21). El programa PIPE va estar conformat per teràpiaindividual i familiar cognitivo-motivacional, tenint una duració de 18 mesos (entre 34-36sessions). Les avaluacions clíniques es van portar a terme a la valoració basal, als 3,6,9,12 i 18mesos per avaluadors externs, a més del seguiment als 6 mesos d'haver finalitzat la intervenció. Esva avaluar als pacients mitjançant l'escala PANSS (versió espanyola de l'Escala dels síndromespositiu i negatiu; Cuesta i Peralta, 1994) , l'escala BPRS (Brief Psychiatry Rating Scale; Overall iGorham, 1962), l'escala CGI (Clinical Global Impressions; National Institute of Mental Health,1976) i l'EEAG (Escala d' Avaluació de l'Activitat Global; American PsychiatricAssociation,1995). A més, es van recollir els índexs de recaigudes globals i específiques en númerode hospitalitzacions, estades a l'hospital de dia, visites a urgències, visites no programades,agudització simptomàtica i els increments de medicació.Resultats principals: S'observen diferencies estadísticament significatives entre els dos grupsesmentats ja als tres mesos d'intervenció respecte a l'avaluació basal (p=0,000) que es mantenenestables fins al seguiment als 6 mesos (p=0,000) a l'avaluació amb l'escala BPRS. Respecte al'avaluació del síndrome positiu, negatiu i de psicopatologia general puntuat amb la PANSSs'observen també diferències notables als sis mesos que es mantenen fins al final de la intervencióals 18 mesos (PANSS-P, p=0,02;PANSS-N, p=0,004;PANSS-PG, p=0,000). D'acord amb aquestsresultats es presenten diferències estadísticament significatives a les puntuacions de les escales CGIi EEAG amb resultats notables ja als sis mesos (CGI, p=0,000; EEAG, p=0,001) i que es mantenenfins al seguiment (CGI, p=0,000; EEAG, p=0,000). Respecte a les recaigudes s'observendiferències estadísticament significatives entre els grups als 18 i als 6 mesos de seguiment ennúmero d'hospitalitzacions (p=0,000), en estades a l'hospital de dia (p=0,000), visites al serveid'urgències (p=0,048) i en augments de medicació (p=0,002). Resultats semblants s'observen a lesmesures de recaigudes globals en la comparació entre grups tant al final de la intervenció comdurant el seguiment als 6 mesos (p=0,018; p=0,048 respectivament).Conclusió principal: El programa d'intervenció precoç PIPE té un impacte alt sobre la milloraclínica i les recaigudes als 18 mesos d'intervenció que es manté durant el període de seguiment als6 mesos.<(p> / Introducción: Son muchos los estudios que en los últimos quince años han demostrado laefectividad de los programas des intervención precoz en la esquizofrenia y su impacto sobre elpronóstico de la enfermedad. De hecho, la intervención preventiva en la fase prodrómica yposterior al primer episodio se ha convertido en una de las líneas principales de investigación y deaplicación clínica para el abordaje de la esquizofrenia.Objetivo: Evaluar el impacto de una intervención psicoterapéutica durante la fase inicial de laesquizofrenia sobre la mejoría clínica y las recaídas de un grupo que recibió una intervenciónprecoz (PIPE) en comparación con un grupo control (GC) que recibió controles psiquiátricosrutinarios.Método: Se realizó un ensayo clínico controlado a simple ciego para comparar un programa decontroles rutinarios (CG) con el programa PIPE. Se aleatorizaron 34 pacientes que estaban en lafase inicial de la esquizofrenia a ambos grupos: GC (n=13) y GC+PIPE (n=21). El programa PIPEestuvo conformado por terapia individual y familiar cognitivo-motivacional, teniendo una duraciónde 18 meses (entre 34-36 sesiones). Las evaluaciones clínicas se llevaron a cabo en la valoraciónbasal, a los 3,6,9,12 y 18 meses por evaluadores externos, además del seguimiento a los 6 meses.Se evaluó a los pacientes mediante la escala PANSS (versión española de la Escala de lossíndromes positivo y negativo; Cuesta y Peralta, 1994), la escala BPRS (Brief Psychiatry RatingScale; Overall y Gorham, 1962), la escala CGI (Clinical Global Impressions ; National Institute ofMental Health, 1976) y la EEAG (Escala de Evaluación de la Actividad Global; AmericanPsychiatric Association,1995). Además, se recogieron los índices de recaídas globales y específicasen número de hospitalizaciones, estancias en hospital de día, visitas a urgencias, visitas noprogramadas, agudización sintomática e incrementos de medicación.Resultados principales: Se observan diferencias estadísticamente significativas entre los gruposmencionados ya a los tres meses de intervención respecto a la evaluación basal (p=0,000) que semantienen estables hasta el seguimiento a los 6 meses (p=0,000) en la evaluación con la escalaBPRS. Respecto a la evaluación del síndrome positivo, negativo y de psicopatología generalpuntuado con la PANSS se observan también diferencias notables a los seis meses que semantienen hasta el final de la intervención a los 18 meses (PANSS-P, p=0,02;PANSS-N,p=0,004;PANSS-PG, p=0,000). En acorde con estos resultados se presentan diferenciasestadísticamente significativas en las puntuaciones de las escalas CGI y EEAG con resultadosnotables ya a los seis meses (CGI, p=0,000; EEAG, p=0,001) y que se mantienen hasta elseguimiento a los 6 meses (CGI, p=0,000; EEAG, p=0,000). Respecto a las recaídas se observandiferencias estadísticamente significativas entre los grupos a los 18 meses y los 6 meses deseguimiento en número de hospitalizaciones (p=0,000), en estancias en hospital de día (p=0,000),en visitas al servicio de urgencias (p=0,048) y en aumentos de medicación (p=0,002). Resultadossimilares se observan en las recaídas globales en la comparación entre grupos tanto al final de laintervención como en el seguimiento a los 6 meses (p=0,018; p=0,048 respectivamente).Conclusión principal: El programa de intervención precoz PIPE tiene un impacto alto sobre lamejoría clínica y las recaídas a los 18 meses de intervención que se mantiene durante el periodo deseguimiento a los 6 meses. / Introduction: Many studies have shown the effectiveness of early intervention programs forschizophrenia and its impact on illness outcome. In fact, the preventive intervention in theprodromical period and after the first episode of psychosis has become the main way for theresearch and clinical procedures for schizophrenia treatments.Objective: The aim of the current study is to assess the improvement and relapse rates of patientswith a diagnosis of schizophrenia (initial phase), which were taking part in a specific Cognitive-Motivational Therapy program (PIPE) in comparison with patients who received the usualpsychiatric treatment (Routine Care, RC).Method: A randomized, controlled, single-blind clinical trial was carried out. A total of 34 patientsand families who were in the initial phase of schizophrenia were allocated either to theexperimental intervention program plus routine care (PIPE, n=21) or to routine care alone (RC,n=13). PIPE consisted of an individual and a family Cognitive-Motivational Therapy, with 18months of length (between 34-36 therapy sessions). Clinical assessments were carried out byexternal raters at baseline, at 3,6,9,12 and 18 months, and the follow-up after 6 months. Patientswere assessed by the PANSS (spanish version of Positive and Negative Syndrome ofSchizophrenia, Cuesta & Peralta, 1994), the BPRS scale (Brief Psychiatry Rating Scale; Overall &Gorham, 1962), the CGI scale (Clinical Global Impressions; National Institute of Mental Health,1976) and the EEAG (Escala de Evaluación de la Actividad Global; American PsychiatricAssociation,1995). On the other hand, global and specific relapses rates were collected attending tothe number of admissions in acute care, admissions in day hospital, emergencies, non programmedvisits and deterioration of symptoms that require intervention by professionals (increase in / changeof medication or non-scheduled visits).Main results: Significantly clinical effects were observed in patients treated within PIPE program(pre-treatment vs. post-treatment at p=0,000) on the BPRS, already after three months. That resultsremain stable to the follow-up after 6 months (p=0,000). In reference to the evaluation for thepositive, negative syndrome and general psychopathology scored with the PANSS were alsoobserved remarkable differences from the 6th month of the intervention to the 18th month(PANSS-P, p=0,02;PANSS-N, p=0,004;PANSS-PG, p=0,000). According to those results,significant statistical differences were observed in CGI and EEAG scores. Those differences wereobserved already after six months (CGI, p=0,000; EEAG, p=0,001) with respect to the baselineassessment and remained stable to the follow-up after 6 months (CGI, p=0,000; EEAG, p=0,000).Statistical significant differences were found between groups with respect to relapses after 18 and 6months follow-up in admissions in the acute care unit (p=0,000), admissions at day hospital(p=0,000), emergencies (p=0,048) and pharmacological treatment increase (p=0,002). Analogueresults were observed in global relapses between groups at the end of the intervention and thefollow-up after 6 months (p=0,018; p=0,048 respectively).Main conclusion: The results show a positive impact of the PIPE intervention program on theimprovement of symptoms and the relapses in patients who are in the initial phase ofschizophrenia.