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Background The high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. Method Three hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. Results Strong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. Conclusions Findings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.

Aims Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis. Methods Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up. Results The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506). Conclusions Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

Background: Child maltreatment has been associated with a wide range of mental disorders in adulthood. Whether child maltreatment is specifically associated with psychosis risk in individuals at ultra-high risk (UHR) for psychosis, or leads to a general vulnerability for overall psychopathology in the UHR stage remains unclear. The present study examines the association between child maltreatment and transition to psychosis and other mental disorders. Methods: The sample consisted of 259 UHR individuals from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Participants were followed-up for 2 years to assess clinical outcome. Clinical outcome was assessed at 6 months, 12 months, and 24 months after baseline. Child maltreatment before the age of 17 years was assessed at baseline. Results: Our findings show that a history of emotional abuse was associated with an increased risk for transition to psychosis (OR = 3.78, 95% CI = 1.17 to 12.39, P = -027). Apart from psychosis, a history of physical abuse was associated with depressive disorder (OR = 4.92, 95% CI = 2.12 to 11.39, P = .001), post-traumatic stress disorder (OR = 2.06, 95% CI = 1.10 to 3.86, P = .023), panic disorder (OR = 2.00, 95% CI = 1.00 to 3.99, P = .048) and social phobia (OR = 2.47, 95% CI = 1.18 to 5.16, P = .016) at follow-up. Conclusion: Our findings suggest that in the UHR stage child maltreatment is a pluripotent risk factor for developing psychosis, depressive disorder, post-traumatic stress disorder (PTSD), panic disorder, and social phobia in adulthood.

Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.

In this paper we report the clinical utility of the diagnostic guidelines for ICD-11 mental, behavioural and neurodevelopmental disorders as assessed by 339 clinicians in 1,806 patients in 28 mental health settings in 13 countries. Clinician raters applied the guidelines for schizophrenia and other primary psychotic disorders, mood disorders (depressive and bipolar disorders), anxiety and fear-related disorders, and disorders specifically associated with stress. Clinician ratings of the clinical utility of the proposed ICD-11 diagnostic guidelines were very positive overall. The guidelines were perceived as easy to use, corresponding accurately to patients’ presentations (i.e., goodness of fit), clear and understandable, providing an appropriate level of detail, taking about the same or less time than clinicians’ usual practice, and providing useful guidance about distinguishing disorder from normality and from other disorders. Clinicians evaluated the guidelines as less useful for treatment selection and assessing prognosis than for communicating with other health professionals, though the former ratings were still positive overall. Field studies that assess perceived clinical utility of the proposed ICD-11 diagnostic guidelines among their intended users have very important implications. Classification is the interface between health encounters and health information; if clinicians do not find that a new diagnostic system provides clinically useful information, they are unlikely to apply it consistently and faithfully. This would have a major impact on the validity of aggregated health encounter data used for health policy and decision making. Overall, the results of this study provide considerable reason to be optimistic about the perceived clinical utility of the ICD-11 among global clinicians.

La presente tesis doctoral se ha desarrollado dentro del marco del nuevo paradigma de la detección e intervención temprana de los trastornos psicóticos. En la primera parte de la tesis se presentan y desarrollan los principales conceptos teóricos y metodológicos, así como la justificación y el estado de la cuestión del paradigma de detección e intervención temprana en psicosis. En esta primera parte se incluyen tres artículos teóricos que han sido recientemente publicados en revistas científicas. El primer artículo presenta una revisión y actualización sobre la investigación del Trastorno Esquizotípico de la Personalidad en la adolescencia, destacando su relevancia en la detección e intervención temprana de los trastornos psicóticos. En el segundo artículo se presenta una revisión de los principales programas de detección e intervención temprana en psicosis que se han desarrollado en diferentes países, lo cual, nos ayuda a tener una visión general de los enfoques psicoterapéuticos actuales en psicosis incipiente. El tercer artículo tiene la finalidad de presentar y describir el tratamiento integrado y adaptado a las necesidades del Programa de Psicosis Incipiente-Sant Pere Claver (PPI-SPC) que se está llevando a cabo actualmente en Barcelona, dentro del cual se desarrolló el trabajo empírico de la presente tesis. La segunda parte de la tesis está constituida por cuatro estudios empíricos que se llevaron a cabo con familiares y pacientes en riesgo a desarrollar psicosis, identificados como Estados Mentales de Alto Riesgo (EMAR) y pacientes que habían presentado un Primer Episodio de Psicosis (PEP). Todos los pacientes recibían tratamiento y formaban parte del PPI-SCP. El Estudio 1 presenta una descripción general y comparación de las principales características clínicas y psicosociales de los dos grupos de pacientes, con la finalidad de caracterizar las similitudes y diferencias entre los pacientes EMAR y PEP. El Estudio 2 analiza la relación entre la calidad de vida subjetiva, la severidad clínica y el deterioro funcional de los pacientes EMAR. En el Estudio 3 se describe y caracteriza el perfil de emoción expresada, las atribuciones de la enfermedad y el estado emocional de los familiares de pacientes EMAR y PEP. Además, se investigan las diferentes asociaciones entre estos factores familiares y se comparan los resultados de ambos grupos para comprobar si existen diferencias entre la fase de riesgo y los inicios de la psicosis. El Estudio 4 tiene la finalidad de comprobar por una parte, si el ambiente familiar tiene un impacto en el estatus clínico y funcional de los pacientes EMAR y PEP, y, por otra parte, si las atribuciones de los familiares sobre el trastorno tienen un papel mediador en la asociación entre la emoción expresada y el estatus clínico/funcional de los pacientes. En términos generales, la presente tesis aporta resultados de suma relevancia clínica e investigadora que pueden ser de gran utilidad para mejorar las estrategias de tratamiento tanto en los pacientes como en sus familiares y asistir al diseño de políticas sanitarias. Además, los resultados son comparables con los principales hallazgos de los diversos programas y estudios de psicosis temprana en diferentes países del mundo. Los resultados de esta tesis justifican la importancia de la detección precoz y hacen evidente la necesidad de mejorar el tratamiento sobretodo en las fases de riesgo, ya que los pacientes EMAR presentan una gravedad clínica y un deterioro funcional considerables. Por otro lado, los resultados demuestran que, incluso en las fases iniciales del trastorno psicótico, el ambiente familiar es crucial, ya que la expresión de afecto negativo como el criticismo y las atribuciones de culpa hacia al paciente, tienen un efecto en los síntomas y el funcionamiento de los pacientes EMAR y PEP., The present thesis has been developed within the framework of the new paradigm of early detection and intervention in psychosis. In the first part of the thesis the main theoretical and methodological constructs, as well as the rational and state of the art of the early detection and intervention in psychosis paradigm are developed. In this first part three theoretical articles that have been recently published on scientific journals are included. The first article presents an overview and update of current research about Schizotypal Personality Disorder in adolescence, emphasizing on its relevance for early detection and intervention of schizophrenia spectrum disorders. The second article presents, the basic concepts, rationale and state of the art of the early detection and intervention paradigm, and it also presents a review of main detection and intervention programs in early psychosis developed worldwide, which brings us an overview of the current psychotherapeutic approaches in early psychosis. The third article, aims to present and describe the integrated need-adapted treatment approach of the SPC-EPP currently being developed in Barcelona, in which the empirical work of this thesis was conducted. The second part of the thesis contains four empirical studies conducted with relatives and patients identified as At-Risk Mental State (ARMS) and First-Episode Psychosis who receive treatment and belong to the SPC-EPP. Study 1 presents an overall description of clinical and psychosocial features of ARMS and FEP groups. Furthermore, both groups were compared in order to characterize commonalities and differences between the at-risk and onset of disorder stages. Study 2 focused on analyzing how subjective quality of life was associated with symptom severity and functional impairment in ARMS patients. Study 3 and Study 4 are focused on the study of family factors that have been demonstrated to be related with the course and outcome of psychotic disorders. Thus, Study 3 characterizes the profile of relatives’ Expressed Emotion (EE), illness attributions and emotional states in early stages of psychosis on the one hand, and examines how these family factors are associated and how they differ between ARMS and FEP groups, on the other hand. Study 4 aims to examine if family environment, through the relatives’ EE has an effect on clinical and functional status of early psychosis patients, as well as to examine the possible mediating role of relatives’ attributions in the association between EE and illness severity. Overall, this thesis provides highly relevant clinical and research results that can be useful to improve treatment strategies in patients and their families and assist to the design of health policies. Furthermore, findings are consistent and comparable with several programs and studies in early psychosis at different countries. On the one hand, findings justify the importance of early detection and highlight the need of improve treatment, especially in at-risk stages of psychosis, given that patients at this stage show considerable clinical severity and functional impairment. On the other hand, findings demonstrate that even in the early stages of psychotic disorder the family environment is crucial, since relatives’ negative affect in form of criticism and Emotional Over-Involvement (EOI), along with relatives’ attributions of blame toward the patient, have an effect on symptoms and functioning of both ARMS and FEP patients. Therefore, family intervention should be a priority target of early psychosis programs, in order to inform relatives about the nature and course of psychosis, to help them to better cope and adequately address the challenges of the disorder over time, as well as to reduce negative appraisals, distress and, therefore, to prevent the entrenchment of high-EE attitudes over time.

El pronòstic de la psicosi pot canviar en gran mesura en funció de si és tractada precoçment o no: les psicosis tractades tardanament presenten major resistència als fàrmacs i aparició d'anormalitats cerebrals més pronunciades. Per això, aquesta malaltia considerada fins fa poc de molt mal pronòstic, albira un indici d'esperança: si es detecten els casos psicòtics i les primeres crisis ràpidament, l'evolució de la malaltia pot ser millor. Investigadors de la UAB han estudiat l'estat de la qüestió en la detecció i el tractament de la psicosi i presenten les justificacions per advocar per una detecció i intervenció primerenques de la malaltia. El pronóstico de la psicosis puede cambiar en gran medida en función de si es tratada precozmente o no: las psicosis tratadas tardíamente presentan mayor resistencia a los fármacos y aparición de anormalidades cerebrales más pronunciadas. Por ello, esta enfermedad considerada hasta hace poco de muy mal pronóstico, vislumbra un atisbo de esperanza: si se detectan los casos psicóticos y las primeras crisis rápidamente, la evolución de la enfermedad puede ser mejor. Investigadores de la UAB han estudiado el estado de la cuestión en la detección y tratamiento de la psicosis y presentan las justificaciones por abogar por una temprana detección e intervención.