Rozprawy doktorskie na temat „Schizophrenia Spectrum Disorders (SSDs)”

Disengagement from mental health services by patients with schizophrenia spectrum disorders is an important issue. Most research in this area has been focused on studying the patients’ demographic and clinical characteristics that may be related to disengagement. However, research on patients’ perspective in regard to their decision of disengagement has been limited. An assessment tool developed based on an in--‐‑depth understanding of patients’ subjective experiences may capture other crucial factors. This may widen our scope of understanding of this phenomenon. Therefore, a mixed research method was employed in this thesis and three independent studies with distinctive research aims were carried out. The first study was a qualitative study which aimed at exploring reasons and factors that patients perceived influential to their decision of disengagement. Six ever--disengaged male patients aged between 18 and 28 with schizophrenia spectrum disorder were interviewed as a purposive sample after a thorough subject identification procedure. A thematic analysis of the data yielded seven themes which grouped into three domains: service (patient--‐‑clinician communication, service orientation, clinic operation); patient (psychological response, perception of illness); and medication (side effects and uncertain efficacy). A 16--‐‑item self--‐‑administered questionnaire, the Patient’s Perception of Psychiatric Service (PPPS) questionnaire, was developed. The construction of PPPS was based entirely on the themes identified from the first qualitative study. This questionnaire measured the subjective perception of the patient about the service and patient--clinician communication. Validation of the PPPS questionnaire was conducted in the second study by recruiting 50 patients with a diagnosis of a schizophrenia spectrum disorder from a psychiatric outpatient clinic. Results demonstrated that the PPPS questionnaire has good internal consistency, test-retest reliability, and convergent validity. The Singh O'ʹBrien Level of Engagement Scale (SOLES), Client Satisfaction Questionnaire (CSQ), and an internalized stigma scale were also translated and validated in this study for use in the third study. The third study explored the relationship between disengagement and the patient’s perception of service, using PPPS, level of engagement (SOLE), satisfaction with service (CSQ), and other factors including clinical characteristics and service utilization. One hundred and fifty patients with schizophrenia spectrum disorder were recruited from two specialized outpatient clinics. In view of local clinical observation, patients who had more than one disengagement episode and each lasted more than two weeks were classified into the severe--‐‑disengagement group. In a forward stepwise regression model, results suggested that PPPS and length of service predict severe disengagement. In this thesis, the use of mixed study methods showed that it was pertinent to incorporate patients’ first person experience into an assessment tool. Measuring patients’ perception of service, by using PPPS, can effectively identify patients with severe disengagement history. PPPS as a patient--‐‑rated self--‐‑administered questionnaire can be used in clinical settings to enhance the understanding of a patient’s appraisal of the service and thus proactive measures can be taken to reduce service disengagement.<br>published_or_final_version<br>Psychiatry<br>Master<br>Master of Philosophy

Les troubles psychotiques sont caractérisés par d’importantes conséquences fonctionnelles avec des preuves émergentes concernant l’altération des fonctions visuelles de bas niveau. Le lien anatomique et fonctionnel entre la rétine et le cortex visuel a notamment permis d’émettre des hypothèses quant à l’association entre les altérations des deux étages visuels. Nous avons investigué les mesures électrophysiologiques visuelles rétiniennes et corticales dans les troubles du spectre de la schizophrénie et dans les situations à risque de psychose dont l’usage régulier de cannabis et les phases précoces de psychose font partie intégrante. Les résultats ont mentionné des altérations portant sur la plupart des cellules rétiniennes et des déficits au regard du cortex visuel primaire, avec un lien potentiel entre les deux types de mesures dans la schizophrénie. L’intérêt des biomarqueurs électrophysiologiques réside également dans le lien décrit avec les symptômes de la psychose, ce qui incite ainsi à les utiliser davantage en pratique clinique à des fins d’améliorations diagnostiques<br>Psychotic disorders are characterized by severe functional consequences, with emerging evidence of impairment in low-level visual functions. Most notably, the anatomical and functional link between the retina and the visual cortex led to hypotheses concerning the association between alterations in both visual stages. We investigated retinal and cortical visual electrophysiological measurements in schizophrenia spectrum disorders and situations at risk of psychosis, of which regular cannabis use and early phases of psychosis are an integral part. The results highlighted alterations in most retinal cells and deficits in the primary visual cortex, with a potential link between both measures in schizophrenia. The relevance of electrophysiological biomarkers also lies in the link described with psychotic symptoms, motivating them to be used more widely in clinical practice to improve diagnosis

Nonostante la comprovata presenza di alterazioni a carico del linguaggio nei disturbi dello spettro schizofrenico (DSS - American Psychiatric Association, 2013), la piena caratterizzazione del fenomeno non è ancora stata raggiunta. L’ipotesi della “schizofrenia come prezzo da pagare per il linguaggio" (Crow, 1997) apre nuove prospettive al problema sotto osservazione e suggerisce la necessità di un approccio volto a integrare gli strumenti attualmente utilizzati per la valutazione clinica delle abilità linguistiche nei DSS. L’obiettivo generale del presente lavoro è l'avanzamento nella comprensione dei disturbi del linguaggio in questa popolazione. A tal fine è stato adottato un approccio interdisciplinare a cavallo tra la neuropsicologia, la psicolinguistica e la linguistica computazione. In particolare, il presente lavoro si concentra: i) sullo studio dell’interazione tra il magazzino semantico e le funzioni esecutive ai compiti di fluenza verbale; ii) sulla produzione e la comprensione della struttura argomentale del verbo e della complessità sintattica; e iii) sulla sensibilità alle violazioni semantiche a carico di diversi ruoli tematici. Quarantatré persone con DSS sono state reclutate presso l’IRCCS Fatebenefratelli di Brescia. I processi di elaborazione linguistica dei partecipanti sono stati studiati attraverso: i) due fluenze verbali analizzate adottando sia punteggi tradizioni, sia algoritmi di Natural Language Processing (NLP); ii) la Northwestern Assessment of Verb Argument Structure (NAVS – Cho-Reyes & Thompson, 2012; Barbieri et al., 2019); iii) uno studio sui movimenti oculari durante un compito di lettura di frasi con violazioni semantiche. Come confronto, lo stesso protocollo sperimentale è stato somministrato a un campione di soggetti sani di controllo appaiati per sesso ed età. Nei compiti di fluenza verbale si sono osservate differenze significative tra i due gruppi relativamente alla dimensione media dei cluster semantici, al numero di switch tra cluster, nonché alle misure di coerenza semantica, mettendo in evidenza il contributo differenziale e non mutualmente esclusivo dell’integrità del magazzino semantico e delle funzioni esecutive alla fluenza verbale. Inoltre, gli algoritmi sperimentali NLP basati sulle misure adottate hanno dimostrato un’elevata prestazione nella classificazione dei soggetti con o senza DSS. Dai risultati della batteria NAVS è stato inoltre possibile identificare una difficoltà specifica dei pazienti rispetto a strutture argomentali complesse, nonché rispetto a frasi aventi un ordine delle parole non canonico, sia in produzione sia in comprensione, compatibili con la Argument Structure Complexiy Hypothesis (ASCH – Thompson, 2003) e con un deficit del movimento sintattico che soggiace alle frasi non canoniche (Chomsky, 1981). Infine, tramite lo studio dei movimenti oculari è stato possibile osservare una diminuita sensibilità alle violazioni sul ruolo tematico di “Agente”, compatibile con la presenza di un “disturbo del Sé” (Henriksen & Noordgard, 2014) nei DSS. In conclusione, i nostri risultati confermano la presenza di deficit specifici a carico delle abilità semantiche e sintattiche osservabili in produzione e in comprensione nei DSS. Inoltre, l’esito dello studio supporta l’applicazione di un approccio multi-disciplinare al problema in oggetto. Il presente studio dimostra come misure di fluenza verbale derivate da un approccio linguistico-computazionale associate a una dettagliata caratterizzazione del linguaggio recettivo e produttivo nei DSS grazie agli strumenti e alle cornici teoriche della psicolinguistica possono contribuire all'avanzamento nella caratterizzazione delle modificazioni del linguaggio nei DSS oltre allo stato dell’arte.<br>Although the presence of language disturbances in people with Schizophrenia Spectrum Disorders (SSD) is well established (American Psychiatric Association, 2013), a full characterization of the phenomenon is still missing. The hypothesis of “schizophrenia as the price we pay for language” (Crow, 1997) opens new perspectives on the problem at stake, and suggests the need for a combined approach aiming at integrating the clinical tools nowadays employed to assess language abilities in SSD. The overall objective of the present work is to advance the understanding of language disturbances in this population by adopting an interdisciplinary approach embracing neuropsychology, psycholinguistics, and computational linguistics. In particular, the present work is focused on: i) the differential contribution of semantic storage and executive functions to verbal fluency; ii) the production and comprehension of verbs argument structure and syntactic complexity, and; iii) the sensitivity to semantics violation on different Thematic Roles. Forty-three persons with SSD were recruited at the IRCCS Fatebenefratelli of Brescia. Participants’ linguistic processes were investigated by means of: i) two verbal fluency tasks for the evaluation of semantic store integrity and executive function performance, both computed manually and derived from Natural Language Processing (NLP) methodologies; ii) the Northwestern Assessment of Verb Argument Structure (NAVS – Cho-Reyes & Thompson, 2012; Barbieri, Brambilla, Thompson, & Luzzatti, 2019); iii) an eye-tracking study on semantic violations. For comparison, the same battery was administered to a sample of healthy control subjects matched by age and gender. In the fluency tasks significant differences in the mean size of semantic clusters, number of switches, as well as measure of coherence were observed between groups, highlighting the differential and non-mutually exclusive contribution of the semantic store integrity and the executive functions to verbal fluency. Moreover, NLP-derived algorithms shown a high-level performance in classifying subjects with and without SSD. A specific difficulty with complex verb argument structure, as well as with non-canonical word order of sentences, both in production and comprehension, was identified in the SSD population. These results are compatible with the Argument Structure Complexity Hypothesis (ASCH – Thompson, 2003) and the presence of an underlying syntactic movement in non-canonical sentences (Chomsky, 1981). Finally, an impaired sensitivity to semantic violations on the “Agent” was observed in the eye-tracking study, compatible with the presence of a “disorder of the self” (Henriksen & Noordgard, 2014) in this population. In summary, our results underline the presence of specific semantic and syntactic impairments in SSD as seen in language production and comprehension. Moreover, our result support the application of a multi-disciplinary approach to the issue at stake. Our study show how the added value of fluency measures derived by a computational linguistic approach paired with a fine-grained characterization of receptive and productive language in SSD by means of the tools and theoretical frameworks derived from psycholinguistics can contribute to further characterize language modifications in SSD beyond the current knowledge.

The aim of this thesis was to explore the relationship between anger and aggression, insecure attachment, paranoia and social cognition in psychosis. It is presented as three separate papers: 1) a systematic review examining the relationship between paranoia and aggression in schizophrenia spectrum disorders, 2) an empirical study investigating predictors and mediators of trait anger across the psychosis continuum: the role of insecure attachment, paranoia and social cognition and 3) a critical reflection of the research process. Paper one provides a systematic review of the relationship between paranoia and aggression in schizophrenia spectrum disorders. A comprehensive search of the published literature identified fifteen eligible studies. The quality of the included articles is critically appraised during the synthesis of the findings. Methodological limitations, clinical implications and recommendations for future research are considered. Paper two provides an examination of predictors and mediators of trait anger across the psychosis continuum, considering the role of insecure attachment, paranoia and social cognition. Tests of theory of mind and measures of attachment, hostile attribution bias, paranoia and anger were administered to 174 participants (14 ultra-high risk of psychosis, 20 first-episode psychosis, 20 established psychosis and 120 non-clinical). Multiple regression analysis found attachment avoidance, paranoia and hostile attribution bias were significantly related to trait anger. Mediation analysis revealed paranoia mediated the relationship between attachment avoidance and trait anger. The results are discussed with consideration to previous research and limitations of the study. Clinical implications and recommendations for future research are also offered. Paper three provides a critical reflection of papers one and two, with reference to their design, implementation and interpretation. Personal reflections of the research process as a whole are also provided.

Social cognitive functioning has been shown to be impaired in patients with schizophrenia (SZ), and these impairments are associated with functional outcomes. To better understand these deficits this dissertation investigated the neurocognitive processes associated with several social cognitive tasks. A novel irony comprehension paradigm was developed for use with electroencephalogram (EEG). The N400, a negative event related potential (ERP) that occurs 300-500 ms after the onset of a semantically incongruent word, and the P600, a positive ERP that occurs around 500-800 ms, were used to index irony comprehension. Study 1 revealed that SZ performed worse than healthy controls (HC) across three measures of social cognition – emotion perception, Theory of Mind (ToM), and irony comprehension. Furthermore, negative symptoms of SZ were associated with poor ToM performance. ERP findings showed that HC exhibited hemispheric differences in N400 amplitude in response to ironic sentences, with the left hemisphere showing smaller amplitudes to ironic compared to literal statements, whereas SZ did not show this differentiation. Although HC processed ironic statements differently compared to SZ, the direction of the effect was opposite of what was hypothesized. Study 2 examined the durability of this unanticipated finding in a larger group of HC. The N400 effect from Study 1was not replicated – there were no differences in N400 amplitude for ironic and literal statements. A difference in P600 was found whereby the P600 amplitude for literal was greater than for ironic. Self-reported schizotypal traits were associated with poor ToM performance. Study 3 examined whether computerized cognitive remediation (CCR), which has been shown to improve neurocognition, would generalize to social cognition, and whether these changes could be detected at a neural level using EEG. The CCR program implemented in this study produced no improvement in neurocognition or social cognition. Taken together, these results suggest that several aspects of social cognition are impaired in patients with schizophrenia, on a behavioural and possibly a neural level. Future studies are necessary to determine the most effective framework for CCR to minimize the deficits in interpersonal skills that are linked to both general cognitive abilities and social cognition in those with schizophrenia.<br>Arts, Faculty of<br>Psychology, Department of<br>Graduate

The purpose of this research was to analyze the effectiveness of psychotherapy for individuals diagnosed with schizophrenia spectrum disorders who reside in community residential settings. The present body of literature did not address the utility of psychotherapy treatment for this population. A key area of focus for this research was whether psychotherapy has an impact on psychiatric hospitalization rates for the target population. An additional research question was whether significant differences exist in psychiatric hospitalization rates between males and females for the target population. Data analyses were conducted using archival data from the Blossom Hill Corporation and Sunrise Farm Corporation in the State of Minnesota. Research questions were analyzed with a 2x2 factorial analysis of variance (ANOVA). Results indicated no significant differences in hospitalization rates for individuals in the target population who received psychotherapy (n = 60) compared to those who did not (n = 76). Hospitalization rates also did not differ between gender in psychotherapy treatment response for individuals diagnosed with schizophrenia spectrum disorders in community residential settings. This study has implications for social change because it informs community residential providers in Minnesota serving individuals in the target population about the impact of psychotherapy on reducing psychiatric hospitalizations. Social change is further affected by providing data about how psychotherapy and theory can be used to better treat and understand the target population's mental health stability.

Due to abnormal functioning of the brain’s reward and prediction system patients with schizophrenia spectrum disorders are thought to assign salience to non-relevant objects and events and to form context-inappropriate associations. The brain’s ventral striatum is critical in the formation of associations, and aberrant associations are believed to create delusional content during psychosis. The study wanted to examine the neural response, particularly in the ventral striatum, combined with subjective reports as patients learn associations in an aversive Pavlovian conditioning paradigm. The stimuli were randomized and involved circles of different colors. The conditioned stimuli (CS+) was followed by an unconditioned stimuli (US), consisting of an unpleasant sound, in 50% of events. The unconditioned (CS-) stimuli was followed by a low, not unpleasant sound in 50% of events. The degree of striatal activation was thought to be associated with the severity of patient’s illness. Functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) responses were examined in eleven unmedicated non-institutionalized patients with schizophrenia spectrum disorders and 15 matched healthy controls. No significant within group differences in neural or subjective response to the [CS+ &gt; CS-] contrast were found. No significant associations between severity of illness and degree of striatal activation in response to CS+ or CS- were found. Significant differences in neural activation for the [CS+ &gt; CS-] contrast were found in the ventral striatum, the right inferor frontal gyrus, and the right angular gyrus, with patients exhibiting stronger activation compared to controls. The results and implications are discussed along with suggestions for future research.

This thesis investigated two established neurophysiological biomarkers of schizophrenia: mismatch negativity (MMN) and P3a; purported indices of the deviance detection and orienting response, respectively. In light of recent interest into a shared diathesis model between schizophrenia- and affective-spectrum disorders, this thesis evaluated the utility of MMN/P3a in informing the underlying neurobiology of early stages of schizophrenia- and affective-spectrum disorders. Despite differences in the composition of schizophrenia- and affective-spectrum subgroups, the first two studies showed that MMN/P3a was similarly impaired in the two diagnostic spectrums, with the schizophrenia-spectrum displaying more severe/widespread impairments. The third study utilised a data-driven method and determined three clusters with distinct patterns of MMN/P3a amplitudes among patients with emerging schizophrenia- and affective-spectrum disorders. Critically, about half of the cluster with the greatest neurophysiological impairments consisted of schizophrenia-spectrum patients. The last study explored the stability of MMN/P3a over time and its value in predicting functional outcomes in schizophrenia- and affective-spectrum patients. This study showed that MMN impairments worsen over time, suggestive of ongoing pathophysiological processes. Additionally, greater deficits in MMN amplitudes at baseline were associated with the most severe levels of later disability. In conclusion, this work has been a substantial contribution to the somewhat limited literature on MMN and P3a in early psychotic (and related) disorders. Critically, this thesis supports a re-conceptualisation of the proposed neurophysiological biomarkers of schizophrenia by demonstrating a broader application of MMN and P3a (in early schizophrenia- and affective-spectrum disorders). Accordingly, these studies also provide neurophysiological evidence of a shared diathesis between schizophrenia- and bipolar-spectrum disorders.

Schizophrenie ist eine komplexe Störung, die sich in einer Vielzahl von Symptomen manifestiert. Diese schließen Änderungen in der subjektiven Wahrnehmung von sich als ein Selbst in der Welt ein, die als Selbststörungen bezeichnet werden. Der erste Artikel ist eine theoretische Beurteilung der experimentellen Paradigmen, die zur Messung von Agency verwendet werden. Es setzt sich auch mit dem Verständnis von scheinbar widersprüchlichen empirischen Befunden bezüglich Störungen von Agency in der Schizophrenie auseinander. Der zweite Artikel beschreibt eine Verhaltensstudie, in der 50 Probanden an einem semistrukturiertes Gespräch teilnahmen. Dieses Gespräch wurde mit einem eigens entwickelten Fragebogen zur Selbststörung durchgeführt, welches auf einer phenomänologischen Auffassung der Selbststörung basiert. Das Ziel dieser Studie war, zu untersuchen, ob Selbststörungssymptome, welche bei der Schizophrenie auftreten, ebenfalls in einer nicht-klinischen Population mit erhöhter Schizotypie zu finden sind. Außerdem sollte bestimmt werden, ob der neue Fragebogen Selbststörungssymptome verlässlich misst. In der Tat zeigte die Messung anhand dieses Fragebogens eine hohe Übereinstimmung zwischen verschiedenen Bewertern. In der im dritten Artikel beschriebenen Studie wurde bei 26 Probanden Eyetracking verwendet, um zu untersuchen, ob die bei der Schizophrenie zu beobachtenden Defizite bei willentlichen Sakkaden auch bei Personen mit nicht-klinisch erhöhter Schizotypie auftreten. Der Vergleich zwischen willentlichen und visuell geführten Sakkaden ermöglicht die experimentelle Manipulation des Grades an empfundener Agency über die Augenbewegungen. Es ergab eine starke negative Korrelation zwischen der Reaktionszeit bei visuell geführten Sakkaden und dem Grad der Selbststörung. Mit dieser Studie wird zum ersten Mal ein Zusammenhang zwischen Selbststörungssymptomen und Verhalten in einer Augenbewegungsaufgabe nachgewiesen.<br>Schizophrenia is a complex condition which manifests in a broad variety of symptoms, including alterations in the subjective experience of one as a self within the world, which are termed self disorders. The first paper is a theoretical examination of the experimental paradigms which are used for measuring agency. It also discusses how apparently contradictory empirical findings regarding disorders of agency in schizophrenia can be understood. The second paper refers to a behavioural study of 50 participants using a novel semi-structured interview, based upon a phenomenological conception of self disorder. It addresses whether self disorder symptoms typically found in schizophrenia are also found in a non-clinical high-schizotypy population and whether these symptoms can be measured reliably with this technique. The measurement of self disorders in this format was found to have good inter-rater reliability. The third paper used eye tracking to examine whether the deficits in volitional saccades found in schizophrenia would also be found in 26 non-clinical high-schizotypy subjects. Comparing volitional to visually-guided saccade allows experimental manipulation of the degree of agency over the eye movement that a subject experiences. A strong negative correlation between visually guided saccade latency and self disorder score was found. This is the first time that a link from self disorder symptoms to performance in eye movement tasks has been made.

Abstract Both genetic and biological and psychosocial environmental risk factors contribute to the aetiology of schizophrenia spectrum disorders. Among the much studied environmental risk indicators are parental Communication Deviance (CD) and the winter or spring birth of a child. Genetic and environmental risk factors do not function in isolation from each other, but gene-environment interactions play a major role in the aetiology of psychotic disorders. The aim of this doctoral thesis is to investigate the role of parental CD as a risk factor (together with other risk indicators) for thought disorders and schizophrenia spectrum disorders in an adoptive child. A systematised review was performed concerning the association between parental Communication Deviance and schizophrenia spectrum and thought disorders in offspring. A meta-analysis could only be performed for the association of parental CD with schizophrenia spectrum disorders in offspring. A large overall effect size was found (0.79, 95%CI 0.21–1.37). The studies included in the systematised review suggest that frequent parental CD and thought disorders in the offspring are connected with each other. The two original studies are based on the data derived from the total sample of the Finnish Adoptive Family Study (n=382). First, the association between parental Communication Deviance scored from individual and family Rorschach protocols and the characteristics of the adoptive child and the parents themselves was investigated. The variability of CD in the adoptive parents in individual and family Rorschach situations was most closely associated with the characteristics of the parents themselves. The association of an adoptive child’s thought and schizophrenia spectrum disorders with the child’s genetic risk for schizophrenia spectrum disorders, winter or spring birth, and parental Communication Deviance, and their interactions was also explored. The adoptive child’s thought disorders were associated only with parental CD. None of the risk indicators or their interactions predicted the adoptee’s schizophrenia spectrum diagnosis. In conclusion, the results indicate that the amount of Communication Deviance is a stable trait of an individual. It may be considered as a risk indicator for schizophrenia spectrum disorders in offspring and, with a lower level of confidence, also for thought disorders in offspring<br>Tiivistelmä Skitsofreniaspektrin sairauksien varsinaisia syytekijöitä ei tunneta, mutta niillä on lukuisia sekä perimään että biologiseen ja psykososiaaliseen ympäristöön liittyviä riskitekijöitä. Nykytietämyksen mukaan riskitekijät eivät vaikuta sairauden syntyyn itsenäisesti, vaan perimän ja ympäristön vuorovaikutuksella on merkittävä osuus. Paljon tutkittuja ympäristöön liittyviä riskitekijöitä ovat lapsen talvi- tai kevätsyntymä ja vanhempien hajanainen kommunikaatio. Tässä väitöskirjassa tutkitaan vanhempien hajanaista kommunikaatiota adoptiolapsen ajatushäiriöiden ja skitsofreniaspektrin sairauksien riskitekijänä. Vanhempien hajanaisen kommunikaation ja lapsen skitsofreniaspektrin sairauksien ja ajatushäiriöiden yhteydestä laadittiin systemaattinen katsaus. Meta-analyysi voitiin tehdä vain skitsofreniaspektrin sairauksiin liittyen. Vanhempien hajanaisen kommunikaation ja lapsen skitsofreniaspektrin sairauksien välisellä yhteydellä havaittiin olevan suuri efektikoko (0,79, 95 % luottamusväli 0,21–1,37). Katsaukseen sisällytetyt tutkimukset viittaavat siihen, että vanhempien hajanaisella kommunikaatiolla ja lapsen ajatushäiriöillä on myös yhteys. Väitöskirjan alkuperäistutkimukset perustuvat Suomalaisen adoptiolapsiperhetutkimuksen aineistoon (n= 382). Aluksi tutkittiin vanhempien yksilö- ja perhe-Rorschach-tilanteissa mitatun hajanaisen kommunikaation määrän ja lapsen ja vanhempien ominaisuuksien välistä yhteyttä. Hajanaisen kommunikaation määrän vaihtelu selittyi pääosin vanhempien ominaisuuksilla. Seuraavaksi tutkittiin adoptiolapsen ajatushäiriöiden ja skitsofreniaspektrin sairauksien yhteyttä lapsen skitsofreniaspektrin sairauksille altistavan perimän, talvi- tai kevätsyntymän ja vanhempien hajanaisen kommunikaation kanssa. Huomioon otettiin myös riskitekijöiden yhteisvaikutukset. Mikään riskitekijä tai niiden yhteisvaikutus ei ollut yhteydessä lapsen skitsofreniaspektrin sairauteen. Lapsen ajatushäiriöt olivat yhteydessä ainoastaan vanhempien hajanaiseen kommunikaatioon. Tutkimuksen tulokset osoittavat, että vanhempien hajanainen kommunikaatio on kohtalaisen muuttumaton piirre, joka on lapsen skitsofreniaspektrin sairauksien riskitekijä. Tulokset viittaavat myös siihen, että vanhempien hajanainen kommunikaatio voi olla lapsen ajatushäiriöiden riskitekijä

<p> Mild traumatic brain injury (mTBI) and schizophrenia spectrum disorders (SSD) are conditions characterized by frontal lobe deficits. Past research has shown increased violent and aggressive behavior in both conditions; however, few studies have examined the mechanisms driving this relationship, particularly in non-athlete or non-veteran populations. The current study examined the neurodegenerative effects of repeated mTBI over time on cognitive flexibility and stability deficits in a homeless population. Additionally, we investigated the mediating effects of these deficits on the impact of both repeated lifetime mTBI and presence of an SSD on violent crime. Consistent with expectations, the number of lifetime mTBIs positively predicted violence levels across multiple measures of violent crime, however cognitive flexibility and stability deficits did not mediate this relationship. Furthermore, comorbidity of mTBI and SSD increased the frequency of violent crimes greater than either condition alone. Implications for risk assessment, intervention strategies and violence reduction are discussed.</p><p>

Abnormality of dopamine D2 receptor (D2R) function, often observed as D2R supersensitivity (D2RSS), is a commonality of schizophrenia and related psychiatric disorders in humans. Moreover, virtually all psychotherapeutic agents for schizophrenia target D2R in brain. Permanent D2RSS as a feature of a new animal model of schizophrenia was first reported in 1991, and then behaviorally and biochemically characterized over the next 15–20 years. In this model of schizophrenia characterized by production of D2RSS in ontogeny, there are demonstrated alterations of signaling processes, as well as functional links between the biologic template of the animal model and ability of pharmacotherapeutics to modulate or reverse biologic and behavioral modalities toward normality. Another such animal model, featuring knockout of trace amine-associated receptor 1 (TAAR1), demonstrates D2RSS with an increase in the proportion of D2R in the high-affinity state. Currently, TAAR1 agonists are being explored as a therapeutic option for schizophrenia. There is likewise an overlay of D2RSS with substance use disorder. The aspect of adenosine A2A-D2heteroreceptor complexes in substance use disorder is highlighted, and the association of adenosine A2Areceptor antagonists in discriminative and rewarding effects of psychostimulants is outlined. In summary, these new animal models of schizophrenia have face, construct, and predictive validity, and distinct advantages over earlier models. While the review summarizes elements of D2RSS in schizophrenia per se, and its interplay with substance use disorder, a major focus is on presumed new molecular targets attending D2RSS in schizophrenia and related clinical entities.

Semantic clustering has been used as a measure of learning strategies in a number of clinical populations and has been found to be deficient in individuals with Schizophrenia, but less attention has been paid to the dynamic use of this strategy over the course of fixed-order learning trials. In the current study, we examined this pattern of clustering use over trials in a sample of individuals with Schizophrenia, and explored whether the addition of this dynamic information would help us to better predict specific executive deficits. Results suggested that a decrease in semantic clustering across trials was associated with some executive deficits in the predicted manner. Nonetheless, the overall semantic clustering index generally proved more effective for the purposes, suggesting that in this population, the addition of dynamic information in strategy use is not likely to add considerably to clinical prediction and understanding.

Despite the relevance of formal thought disorder (TD) in psychosis very little is known about its social and environmental predictors and about the role of both cognitive and affective processes in these experiences. Such knowledge is important because it can inform the development of targeted therapeutic strategies to address TD. In Chapter 2 a narrative review of the field of TD is presented. Of note is the consistency of the evidence supporting the role of internal source monitoring, ‘theory-of-mind’ and negative affect in TD and the limited literature on the environmental factors associated with these experiences. The review is concluded with a diagram of a tentative cognitive-developmental model summarising some of the core research findings. Chapter 3 covers the findings of an investigation on the role of both internal source monitoring and negative affect in TD. The study tested the hypothesis that the relationship between negative affect and worsening of TD is mediated by the temporary worsening of the ability to monitor self-generated cognitions in 80 patients diagnosed with schizophrenia-spectrum disorder and 30 comparisons. The results of the study partially supported this hypothesis. In Chapter 4, the role of inner speech and self-concept in TD is explored. The hypothesis was that different dimensions of TD would be differentially associated with these two variables. The analyses revealed that poverty of speech was strongly associated with less reported inner speech in patients. In contrast, poor clarity of self-concept was significantly associated with speech disorganisation. In Chapter 5, the specific role of social isolation in TD was tested using the same sample. The analyses revealed that social isolation was robustly associated with TD, and more importantly, that the association remained significant even when comorbid psychotic symptoms (hallucinations and delusions) were controlled for statistically. In Chapter 6 a systematic review of the field of communication deviance (CD) is presented. The review covers not just case-control studies but also adoption studies that have supported the association between parental CD and offspring’s TD. Some of the core questions and methodological issues that have been raised in the field are explored and it is argued that CD is an important environmental risk factor for TD. Some plausible developmental pathways that could potentially explain the relationship between parental CD and offspring’s TD are also discussed. Chapter 7 covers a meta-analysis of the studies published between 1959 and 2012 that have tested CD in parents of psychotic offspring and controls. The analysis revealed a significant, robust and stable pooled effect-size when the data was analysed taking into consideration the different methodological features. A sub-analysis revealed that CD was significantly more prevalent in mothers. Unfortunately, there was not enough data to test a specific association between parental CD and offspring’s TD. Chapter 8 presents a study where the association between CD measured in the speech of 287 primiparous mothers and maternal sensitivity was tested prospectively. The analyses revealed robust and significant associations between maternal CD (at 32 weeks into pregnancy) and maternal sensitivity in the context of infant’s distress during a lab-based play protocol (at 29 weeks after birth). A plausible developmental pathway linking CD and maternal sensitivity to specific cognitive mechanisms in the offspring is presented. Finally, in Chapter 9, an integration of both social predictors and psychological mechanisms of TD is presented with the aim to promote potential avenues for future research.

Olfactory identification deficits have received recent attention as a potentially useful endophenotype for schizophrenia. Examination of this deficit in individuals with schizotypal personality features (SPF) offers an alternative approach to multiple confounds present when examining individuals with schizophrenia. The aim of the current study was to compare the relative sensitivity of performance on measures of olfaction identification and sustained attention to the presence of SPF. Twenty-six undergraduates were defined as having SPF based on scoring in the top 10% of the Abbreviated Schizotypal Personality Questionnaire (SPQ-B; mean age 19.6, SD = 1.1; 62% female). These individuals were compared to twenty-six controls (scoring lower than half a standard deviation above the mean; mean age 19.8, SD = 1.6; 62% female). All participants were administered the Schizotypal Personality Disorder (SPD) section of the Structured Clinical Interview for DSM IV Axis II Personality Disorders (SCID-II). In addition, participants were administered the Brief Smell Identification Test (B-SIT) and a six-minute degraded-stimuli Continuous Performance Test (CPT). Group differences in performance indices of the CPT did not approach statistical significance. Similarly, there were no statistically significant group differences for males or females in performance on the B-SIT. Correlational analyses examined cognitive performance with a dimension score derived by summing quantitative ratings from the SPD items on the SCID-II. The SPD dimension score showed a statistically significant positive correlation with several performance indices of the CPT, including omission errors (rs(52) = .51, p < .001) and commission errors (rs(52) = .38, p < .005). In contrast, the B-SIT scores were not correlated with the SPD dimension score for males or females. Contrary to our hypothesis, results from the current study suggest that olfactory identification deficits may not represent a robust endophenotype consistently found in samples with schizotypal personality features. With regard to sustained attention, our differential findings suggest that schizotypal traits may be more adequately assessed through an interview by trained clinicians who use clinical judgment to determine the presence of phenotypic aspects of SPD (e.g., SCID-II), rather than relying on self-report measures (e.g., SPQ-B). Implications as well as limitations and future directions of these findings are discussed.<br>M.S.<br>Department of Psychology<br>Sciences<br>Psychology PhD

Thesis advisor: Judith Shindul-Rothschild<br>Clinical Characteristics Of People In Randomized Clinical Trials Of First Episode Schizophrenia Spectrum Disorders: Attrition Versus Non-Attrition Groups Submitted by Joanne D. Wojcik PhD, RN Dissertation Advisor Judith Shindul-Rothschild, PhD, RN Abstract Background: Early identification of psychosis and intensive treatment has been the focus of the treatment of people with a first episode (FE) schizophrenia spectrum disorder (SSD). Attrition rates in studies of people in the first episode are high, which makes it difficult to understand the meaning of the study outcomes. High attrition rates affect the validity of a study by decreasing its power and the study's ability to detect differences between treatment groups. Additionally, the people who leave a study may be different from those who stay in demographic, illness and treatment characteristics. Method: This study is a secondary analysis of a group of FE SSD participants enrolled in one of three separate double-blind, randomized, drug trials. The variables were first analyzed across the three drug study data sets to determine if the patient populations are comparable across the three studies to allow for the merging of the data. Exploratory and descriptive statistics of study participants were conducted in a comparison of the three studies, for the merged group, and for the attrition and non-attrition groups. Effect sizes (Cohen's d) were calculated for each variable in the individual studies and in the merged dataset for the magnitude of difference between the attrition and non-attrition groups. Results: The three studies were merged after analysis found no consistent difference in demographic and illness characteristics between the three studies. There was no significant difference between the attrition and non-attrition groups in the merged data in demographic and illness characteristics. Treatment characteristics consistently found lack of efficacy and patient withdrawal of consent to be the two most frequent reasons for attrition from the studies. In addition, participants receiving a typical agent were less likely to complete the study. Effect size calculations found attrition group to more likely be Caucasian, with a lower median income. The attrition group had more years of education, but was not in school in the year previous to hospitalization. Conclusion: Historically, attrition is a major problem in clinical trials of people in a first episode of schizophrenia spectrum disorders. People receiving typical antipsychotic medication are more likely to leave a study. Most common reasons for attrition include lack of efficacy and withdrawal of consent<br>Thesis (PhD) — Boston College, 2009<br>Submitted to: Boston College. Connell School of Nursing<br>Discipline: Nursing

Background: Impairments in executive functioning and autobiographical memory (AM) are common in people with schizophrenia spectrum disorders (SSD). There is a need for greater understanding of how neurocognitive factors such as these relate to recovery. This is important because improving treatments requires better understanding of the psychological process involved in recovery from SSD. Aims: We aimed to determine the feasibility of assessing AM and metacognitive functioning in the acute phase of psychosis during inpatient admission. Relationships between neuropsychiatric measures and autobiographical memory were explored with a view to refining the use of this assessment battery with participants who are acutely psychotic. Methods: Twelve people diagnosed with a schizophrenia spectrum disorder were recruited from adult inpatient psychiatric wards shortly after admission. They completed the Autobiographical Memory Interview, Indiana Psychiatric Illness Interview, Hayling Sentence Completion Task, BMIPB Story Recall Task and the Positive and Negative Syndrome Scale (PANSS) interview in baseline assessment. Four participants were re-tested prior to discharge and rated their own recovery using the Questionnaire on the Process of Recovery. Ward clinicians also rated recovery in terms of symptom remission for eleven of the participants. Results: A moderate correlation between metacognition and semantic AM (r=.716) was identified at baseline. Correlations of moderate strength were identified between clinician ratings of recovery and metacognition (r=-.725) and PANSS (r=.877) scores at baseline assessment. Conclusions: The study faced difficulties recruiting sufficient numbers of eligible participants at baseline and retaining them to allow for follow up assessment. Hence, the results are preliminary but the data do suggest possible neuropsychological correlates of recovery from acute psychosis. If the recruitment and retention issues could be addressed, this paradigm could be applied to a larger sample to test the findings of this pilot study.

Background and objectives: Whilst Active and Receptive Music Therapy techniques have been widely researched and are employed within a range of contexts and with diverse client populations, this study reports on their specific qualitative musical and verbal affordances in major depressive disorder and schizophrenia-spectrum psychotic disorders. The study also describes and compares the respective and joint contributions of the music therapy techniques in giving rise to the affordances as well as reporting on the similarities and differences within and between diagnostic groups. This is the first study of its kind within the South African context. Methods: A qualitative research approach using a case study design, sampled purposefully twenty patients of the above mentioned diagnostic groups for participation in this study comprising a course of eight twice weekly music therapy sessions. The primary data sources were transcribed video recordings of therapy sessions and an individual in-depth semi-structured interview after the course of therapy. Clinical session notes served as a corroborative data source. In-depth content and thematic analysis explored and compared qualitative affordances during music therapy comprising active and Receptive Music Therapy techniques. The qualitative affordances under investigation were i) musical qualities, and ii) verbal expressions. Emerging from these affordances were the respective and combined affordances of the music therapy techniques as well as the similarities and differences between the diagnostic groups. Findings: Thirteen themes emerged from the analysis of clients' verbatim verbal responses to both active music making and Receptive Music Therapy techniques. These themes are: i) not to feel; ii) to do or not to do; iii) grappling with the desired future; iv) hurt and fear of undesirable outcomes; v) sadness, brokenness and futility; vi) anger, trust and vulnerability; vii) desire for connection with and affection of others; viii) barricaded from being present, now; ix) tensing and un-tensing; x) personal relating to one’s musical expression; xi) reflections on the music and music making in therapy; xii) resilience and courage and xiii) invigoration and liberation. The Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and x) resolution and arrival. The emerging themes express the extent of musical and verbal expression of all clients representing both diagnostic groups. Most saliently among clients with depression the affordances were the themes on accessing creativity, accessing and articulating internal feelings, experiencing resilient parts of self, reflecting on and integrating symbolic material, motivation to act and extending musical and verbal expression during social interaction. Among clients suffering from schizophrenia spectrum disorder, the most striking affordances were experiences of regularity and flow within disorganization, orientation to ‘here and now’ experiences through active music making and working with symbolic material expressed on a continuum of concrete to abstract. Clients from both diagnostic groups experienced a reduction in unwanted symptoms as expressed through increased energy levels, experiences of pleasure in music making and spontaneous musical and verbal self-expression. Conclusion: This study revealed qualitative affordances of specific music therapy techniques expressed through verbal content and musical qualities. These showed responses within a therapeutic relationship that express inter- and intra-personal connection, give voice to what is not always verbally accessible and facilitate multi-sensory, creative experiences, increased motivation, emotional expression, and the reclamation of energy, spontaneity and resilience.<br>Thesis (PhD)--University of Pretoria, 2017.<br>Psychiatry<br>PhD<br>Unrestricted

BACKGROUND: schizophrenic and bipolar disorders are complex and disabling psychiatric diseases whose classical nosography and classification are still under challenging debate aiming to overcome the traditional “Kraepelinian Dichotomy”. For the past hundred years most clinical work and research in psychiatry has proceeded under the assumption that schizophrenia and bipolar disorderaredistinctentities with separate underlying disease processes and treatments. In more recent years there has been increasing evidence for phenomenological, biological and genetic overlap between the two disorders (Potash and Bienvenu 2009). Nowadays, the categorical approach to psychiatric nosography is in contrast with the recent neurobiological, neuropsychological and genetic findings in affective and schizophrenic disorders. Further, symptoms and signs constituting bipolar and schizophrenic disorders are continuously, not dichotomously, distributed; there may be no point of “real cleavage” (Phelps et al. 2008). This recognition has led some clinicians and researchers to call for a diagnostic model that, moving to a “dimensional perspective”, formally recognizes a continuous spectrum from schizophrenic to bipolar (and recurrent depressive) disorders. Kelsoe argued that the existing data coming from various fields of research in bipolar and schizophrenic disorders may best fit a model in which different set of genes predispose to overlapping phenotypes in a continuum. Given the apparent overlap of regions of the genome implicated in bipolar disorder with those for schizophrenia (Kelsoe 1999; Berrettini 2000), the data suggest the possibility that a common polygenic background predisposes to both bipolar disorder and schizophrenia, according to the so-called “multiple threshold model” (Kelsoe 2003). As highlighted by Craddock and Owen, the recent findings are compatible with a model of functional psychosis in which susceptibility to a spectrum of clinical phenotypes is under the influence of overlapping sets of genes, which, together with environmental and epigenetic factors, determine an individual’s expression of illness (Craddock and Owen 2005). A lot of interest is focusing on brain structural abnormalities in patients suffering from schizophrenia and bipolar disorder. A huge amount of neuroimaging studies has been published so far, however the literature is heterogeneous and there is still some degree of uncertainty concerning what key regions are involved in the pathogenesis of such disorders. Schizophrenia and Bipolar Disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. To date there is no consensus about whether, and to what extent, gray matter loss in Schizophrenia is mirrored in Bipolar Disorder and what is the effect of medication or other confounding factors. Studies in family members of patients, who share the risk of the disease but not the confounding factors, may help elucidate whether abnormalities in brain structures are shared by both illnesses. AIM OF THE STUDY: to investigate hippocampal gray matter volume differences in a group of patients with bipolar-schizophrenic spectrum disorders, a group of their unaffected first-degree relatives, and a group of healthy control subjects. METHODS: a total of 104 subjects - 36 schizophrenic or schizoaffective (SZ), 27 bipolar (BP), 2 major depression, 8 unaffected relatives (UR), and 31 healthy controls (HC) - underwent 1,5 T MRI scanning, with volumetric T1 3D acquisition protocol, at the Neuroradiology Unit of Conegliano Hospital. We calculate bilateral hippocampal gray matter volume (HV) and total cerebral volume (TCV) in a sample of 31 SZ, 27 BP, 8 UR and 26 HC, with a stereological method using ANALYZE 10.0 software. RESULTS: we found statistically significant reductions in bilateral HV in the BP-SZ patients compared to HC; the direct comparison between patient groups identified statistically significant reduction in the right HV of SZ, but no significant differences for left HV or TCV (however statistical significance was lost after normalization); statistically significant reduction in the left HV and a trend towards statistical significance for right HV in the UR compared to HC (a trend towards statistically significant reduction in bilateral HV persisted after normalization). CONCLUSION: it might be speculated that the alterations of the gray matter volume in the hippocampus highlighted in our study could be interpreted as a possible structural “biological marker” in the schizophrenic-bipolar spectrum.<br>INTRODUZIONE: schizofrenia e disturbo bipolare sono malattie psichiatriche complesse e invalidanti, il cui inquadramento nosografico è oggetto di continuo dibattito nel superamento della classica “dicotomia Kraepeliniana” tra Dementia Praecox e Malattia Maniaco-Depressiva. Negli ultimi cento anni, buona parte della pratica clinica e della ricerca in psichiatria sono state basate sull’assunto che schizofrenia e disturbo bipolare fossero entità categorialmente distinte, separate da distinti meccanismi patologici e trattamenti. In anni più recenti invece, si sono accumulate numerose evidenze a supporto di una parziale sovrapposizione fenomenologica, biologica e genetica tra questi disturbi (Potash e Bienvenu 2009). Attualmente, l’approccio nosografico “categoriale” nei disturbi affettivi e schizofrenici è in contrasto con le più recenti scoperte in ambito neurobiologico, neuropsicologico e genetico. Inoltre è stato evidenziato come, nemmeno dal punto di vista clinico vi sia un reale punto di “separazione” tra i due disturbi, che presentano segni e sintomi comuni e sovrapponibili (Phelps et al. 2008). Tale consapevolezza ha portato clinici e ricercatori a orientarsi verso un modello diagnostico che, spostandosi in una prospettiva “dimensionale”, formalmente riconosce l’esistenza di uno spettro tra disturbi schizofrenici e bipolari. Kelsoe afferma che i dati provenienti dai vari filoni di ricerca nei disturbi bipolari e schizofrenici potrebbero essere meglio spiegati da un modello in cui differenti set di geni predispongono a fenotipi clinici che si sovrappongono in un continuum. Data la documentata sovrapposizione fra regioni genomiche implicate nel disturbo bipolare con quelle della schizofrenia (Kelsoe 1999; Berrettini 2000), le evidenze suggeriscono la possibilità che un substrato poligenico comune possa conferire una predisposizione a entrambi i disturbi, secondo il cosiddetto modello delle “soglie multiple” (Kelsoe 2003). Come sottolineato da Craddock e Owen, le più recenti scoperte in tale ambito sono compatibili con un modello di psicosi funzionale, nel quale la suscettibilità ad uno spettro di fenotipi clinici è sotto l’influenza di un set di geni condivisi, che, insieme a fattori ambientali ed epigenetici, determina l’espressione di malattia in ciascun individuo (Craddock e Owen 2005). Notevole interesse si sta inoltre focalizzando sulle alterazioni strutturali cerebrali in pazienti affetti da schizofrenia e disturbo bipolare. Nonostante l’ingente mole di studi di neuroimaging finora pubblicati, la letteratura sull’argomento è molto eterogenea ed esiste ancora notevole incertezza su quali siano le specifiche regioni cerebrali coinvolte nella patogenesi di tali disturbi. Schizofrenia e Disturbo Bipolare condividono una serie di sintomi e fattori di rischio, ma non è ancora stato chiarito se questi disturbi siano caratterizzati da comuni modificazioni morfometriche cerebrali e se tali alterazioni riflettano l’impatto di geni comuni di suscettibilità sulla morfologia del cervello. Ad oggi, non è stato definitivamente chiarito se, e fino a che punto, la documentata perdita di sostanza grigia nella Schizofrenia si rifletta anche nel Disturbo Bipolare e su quali siano gli effetti della farmacoterapia o di altri fattori di confondimento. Gli studi sui membri non affetti di pazienti schizofrenici e bipolari, che condividono la predisposizione genetica ai disturbi, ma non i fattori di confondimento, posso rivelarsi utili nel verificare se le varie anomalie cerebrali siano condivise nelle due patologie. SCOPO DELLO STUDIO: analizzare eventuali differenze volumetriche nella sostanza grigia ippocampale in un gruppo di pazienti dello spettro bipolare-schizofrenico, un gruppo di familiari di primo grado non affetti e un gruppo di soggetti sani di controllo. MATERIALI E METODI: un totale di 104 sogetti - 36 pazienti con disturbo schizofrenico o schizoaffettivo (SZ), 27 pazienti con disturbo bipolare (BP), 2 pazienti affetti da depressione maggiore ricorrente, 8 familiari di primo grado non affetti (UR) e 31 controlli sani (HC) sono stati sottoposti ad una procedura di Risonanza Magnetica cerebrale ad 1,5 Tesla, secondo un protocollo di acquisizione di sequenze T1 3D volumetriche, presso l’Unità Operativa di Neuroradiologia del Presidio Ospedaliero di Conegliano. Mediante l’utilizzo del Software ANALYZE 10.0, sono stati calcolati, con un metodo stereologico, i volumi bilaterali della sostanza grigia ippocampale (HV) ed il volume cerebrale totale (TCV) in un campione di 31 SZ, 27 BP, 8 UR e 26 HC. RISULTATI: sono state riscontrate riduzioni volumetriche statisticamente significative della sostanza grigia di ippocampo destro e sinistro tra i gruppi di pazienti dello spettro bipolare-schizofrenico rispetto ai controlli; nel confronto diretto tra il gruppo di pazienti schizofrenici e quello dei bipolari è stata identificata una riduzione statisticamente significativa del volume della sostanza grigia dell’ippocampo destro (tale significatività non persiste in seguito a normalizzazione) e nessuna significativa differenza nei volumi della sostanza grigia dell’ippocampo sinistro o nel volume cerebrale totale; nel confronto tra il gruppo di familiari di primo grado non affetti rispetto al gruppo di soggetti sani di controllo è stata evidenziata una significativa riduzione volumetrica della sostanza grigia dell’ippocampo sinistro e un trend verso la significatività statistica per l’ippocampo destro (tali riduzioni volumetriche della grigia ippocampale mantenevano bilateralmente tale trend verso la significatività statistica anche dopo la normalizzazione). CONCLUSIONE: la alterazione volumetrica della sostanza grigia ippocampale evidenziata nel nostro studio potrebbe essere interpretata come un possibile “marker biologico” strutturale nei disturbi dello spettro schizofrenico-bipolare.

Background: Various studies have shown that people with serious mental illness have an increased risk for metabolic syndrome with prevalence ranging from 28.7% to 60%. Given the amount of evidence suggesting a link between clozapine and metabolic syndrome, several guidelines have recommended regular clinical monitoring of metabolic syndrome in patients on clozapine. Aim: To determine the screening, prevalence and associated risk factors of metabolic disorders in forensic patients with schizophrenia spectrum disorders who are on clozapine (study group) compared to patients on haloperidol (control group). Methods: It is a retrospective, folder review of forensic male adult patients at Valkenberg Hospital, Observatory Cape Town. Results: There were 45 patients in the study group and 23 patients in the control group. Eight patients (17.8%) in the study group (Clozapine) met criteria for metabolic syndrome according to the NCEP-ATP III criteria and none of the patients in the control group (Haloperidol) did (χ 2 (1) = 4.441, p = .035 V = .257). Patients who had a diagnosis of schizoaffective disorder were also on mood stabilisers in addition to clozapine. Again, while none of the patients on Haloperidol met the criteria for Metabolic syndrome, 6 (24%) of the 25 patients on concurrent Clozapine and sodium valproate did, (χ 2 (1) = 6.051, p = .023 V = .359). In terms of metabolic disorders, a significantly higher proportion of patients in the study group has hypertension and hyperlipidaemia (p = .003 and p = .021 respectively). Less than 25% of all patients were fully screened for metabolic syndrome. There was a very low rate of screening of blood tests: fasting glucose, total cholesterol, trigylcerides, High Density Lipoprotein(HDL) or Low-Density Lipoprotein (LDL). Conclusion: The prevalence of metabolic syndrome was higher in the clozapine group than haloperidol group, which is unsurprising since clozapine is usually associated with a higher risk of metabolic syndrome. However, the prevalence on metabolic syndrome in this study sample was relatively low compared to other studies. This could be due to the low rate of screening of each criteria of metabolic syndrome. Screening for metabolic syndrome should be regularly performed by health professionals in patients with serious mental illness. Further studies are needed to investigate the risk of metabolic syndrome for patients who are on a combination of clozapine and mood stabilisers.

Recording and analysis of event-related potentials is safe and harmless method of evaluation of cognition and is suitable to follow the changes of cognitive processes induced by psychoactive drugs or other therapeutic procedures. The main aim of the work was to evaluate the influence of atypical antipsychotics risperidone and quetiapine and such nonpharmacological methods as electroconvulsive therapy and metaglossotherapy on the changes of information processing in the auditory system using event-related potential P300 recording and analysis method. Auditory P300 potential was elicited applying “odd-ball” paradigm and recorded at 3 electrode sites (Fz, Cz, Pz). 4 parameters of P300 potential were measured: N2 latency, P300 latency, P300 amplitude and recognition time of target stimulus. Total number of 85 patients with schizophrenia spectrum disorders and mood disorders were studied. Results of this work showed that the parameters of P300 potential are sensitive indicators of abnormalities of information processing in auditory system in the case of schizophrenia spectrum disorders. More considerable positive influence on the event-related potential P300 had atypical antipsychotic quetiapine and that nonpharmacological methods of treatment of psychiatric disorders are as effective as drug therapy with atypical antipsychotics in remediation of cognitive functions.<br>Kognityvieji sukeltieji potencialai arba su įvykiu susiję potencialai (SĮSP) leidžia įvertinti kai kurias kognityviąsias funkcijas. Jie nuo pat sukūrimo pradžios yra sėkmingai taikomi ir psichikos sutrikimų tyrimuose. SĮSP neinvaziškumas, objektyvumas, saugumas leidžia juos taikyti kognityviųjų funkcijų pokyčių, sukeltų medikamentinio gydymo ar kitos nemedikamentinės terapinės procedūros, įvertinimui. Pagrindinis darbo tikslas buvo įvertinti informacijos apdorojimo klausos sistemoje kitimą atipinių antipsichotikų risperidono ir kvetiapino poveikyje ir nemedikamentinių terapijos metodų - elektros impulsų terapijos bei metaglosoterapijos - poveikyje taikant su įvykiu susijusio potencialo P300 skaitmeninio registravimo ir kiekybinės analizės metodus. Klausos sukeltas P300 potencialas buvo registruojamas taikant „atsitiktinio įvykio“ principą trimis elektrodais (Fz, Cz ir Pz). Buvo matuojami 4 sukeltojo potencialo P300 parametrai: N2 latencija, P300 latencija, P300 amplitudė ir reikšmingo dirgiklio atpažinimo laikas. Darbo rezultatai parodė, kad SĮSP parametrai yra jautrūs informacijos apdorojimo klausos sistemoje procesų pažeidimo šizofrenijos spektro sutrikimų atveju rodikliai. Didesnę teigiamą įtaką klausos sukeltajam potencialui P300 turėjo atipinis antipsichotikas kvetiapinas. Nemedikamentiniai psichikos sutrikimų gydymo metodai nenusileidžia efektyvumu gerinant pacientų kognityviąsias funkcijas medikamentinei terapijai atipiniais antipsichotikais.

Kognityvieji sukeltieji potencialai arba su įvykiu susiję potencialai (SĮSP) leidžia įvertinti kai kurias kognityviąsias funkcijas. Jie nuo pat sukūrimo pradžios yra sėkmingai taikomi ir psichikos sutrikimų tyrimuose. SĮSP neinvaziškumas, objektyvumas, saugumas leidžia juos taikyti kognityviųjų funkcijų pokyčių, sukeltų medikamentinio gydymo ar kitos nemedikamentinės terapinės procedūros, įvertinimui. Pagrindinis darbo tikslas buvo įvertinti informacijos apdorojimo klausos sistemoje kitimą atipinių antipsichotikų risperidono ir kvetiapino poveikyje ir nemedikamentinių terapijos metodų - elektros impulsų terapijos bei metaglosoterapijos - poveikyje taikant su įvykiu susijusio potencialo P300 skaitmeninio registravimo ir kiekybinės analizės metodus. Klausos sukeltas P300 potencialas buvo registruojamas taikant „atsitiktinio įvykio“ principą trimis elektrodais (Fz, Cz ir Pz). Buvo matuojami 4 sukeltojo potencialo P300 parametrai: N2 latencija, P300 latencija, P300 amplitudė ir reikšmingo dirgiklio atpažinimo laikas. Darbo rezultatai parodė, kad SĮSP parametrai yra jautrūs informacijos apdorojimo klausos sistemoje procesų pažeidimo šizofrenijos spektro sutrikimų atveju rodikliai. Didesnę teigiamą įtaką klausos sukeltajam potencialui P300 turėjo atipinis antipsichotikas kvetiapinas. Nemedikamentiniai psichikos sutrikimų gydymo metodai nenusileidžia efektyvumu gerinant pacientų kognityviąsias funkcijas medikamentinei terapijai atipiniais antipsichotikais.<br>Recording and analysis of event-related potentials is safe and harmless method of evaluation of cognition and is suitable to follow the changes of cognitive processes induced by psychoactive drugs or other therapeutic procedures. The main aim of the work was to evaluate the influence of atypical antipsychotics risperidone and quetiapine and such nonpharmacological methods as electroconvulsive therapy and metaglossotherapy on the changes of information processing in the auditory system using event-related potential P300 recording and analysis method. Auditory P300 potential was elicited applying “odd-ball” paradigm and recorded at 3 electrode sites (Fz, Cz, Pz). 4 parameters of P300 potential were measured: N2 latency, P300 latency, P300 amplitude and recognition time of target stimulus. Total number of 85 patients with schizophrenia spectrum disorders and mood disorders were studied. Results of this work showed that the parameters of P300 potential are sensitive indicators of abnormalities of information processing in auditory system in the case of schizophrenia spectrum disorders. More considerable positive influence on the event-related potential P300 had atypical antipsychotic quetiapine and that nonpharmacological methods of treatment of psychiatric disorders are as effective as drug therapy with atypical antipsychotics in remediation of cognitive functions.

O presente estudo investigou a prevalência e a validade de construto das experiências psicóticas (EPs) na gestação e os fatores de risco associados em uma amostra comunitária do município de São Paulo. Foram investigados fatores de risco sociodemográficos, ambientais, transtornos psiquiátricos no presente e ao longo da vida, violência doméstica, capacidade intelectual e histórico familiar de transtornos psiquiátricos. Foram também avaliados desfechos da gestação e do parto. Trata-se de um estudo prospectivo, com início no 3º trimestre de gestação. As entrevistas de avaliação foram realizadas por psicólogos treinados. Para a avaliação das EPs, foi utilizado o instrumento de entrevista diagnóstica padronizada breve - Mini International Neuropsyquiatric Interview (M.I.N.I), validado para a realidade brasileira. Para os fatores de risco sociodemográficos, foram aplicados: questionário socioeconômico (QSE), densidade demográfica (DM) e utilizado o critério de classificação econômica do Brasil CCEB, pela Associação Brasileira de Empresas de Pesquisa (ABEP) e World Health Organization - WHO para violência doméstica. Foi realizada a avaliação da capacidade intelectual através da Escala de Inteligência Wechsler para adultos, terceira versão (WAISS-III) e investigado o histórico familiar para transtornos mentais através do The Family History Screen (FHS). Os resultados apontaram uma prevalência de 19,22% das EPs na gestação e compartilhando os fatores de risco presentes na esquizofrenia, como: urbanicidade, gestantes jovens, o uso de drogas e álcool, desvantagem socioeconômica, baixo nível de escolaridade, exposição à situações de violência, a presença dos transtornos psiquiátricos como depressão e ansiedade, e histórico familiar para qualquer condição psiquiátrica. Este estudo, realizado em uma região urbana da cidade de São Paulo, com altos índices de vulnerabilidade social, indica que a prevalência de EPs em gestantes é alta, afetando cerca de 1 em 6 mulheres. A presença de EPs associa-se fortemente com psicopatologia geral e com amplos fatores de risco. Neste sentido, a presença de EPs pode se constituir em um importante indicador de risco a ser avaliado em ambientes clínicos durante a gestação. Estudos futuros que possam investigar a sua utilidade para indicação de intervenções são necessários, assim como estudos que investiguem o curso de EPs apos o período gestacional e a sua associação com desfechos de saúde nas mulheres e em seus filhos<br>This research investigated the prevalence and construct validity of psychotic experiences (PEs) during pregnancy and the risk factors in a community sample in the city of São Paulo. Sociodemographic and environmental risk factors, psychiatric disorders, domestic violence, intellectual capacity and family history of psychiatric disorders in the present and throughout life were the investigated elements. Pregnancy and delivery outcomes were also evaluated. This is a prospective research, starting in the 3rd trimester of pregnancy. The evaluation interviews were conducted by trained psychologists. For the evaluation of PEs, the brief standardized diagnostic interview tool was used - Mini International Neuropsyquiatric Interview (M.I.N.I), validated for the Brazilian reality. For the sociodemographic risk factors, both socioeconomic questionnaire (SEQ) and population density (PD) were applied and the criterion of economic classification in Brazil (CECB) was used by the Brazilian Association of Research Companies (BARC) and World Health Organization - WHO for domestic violence. The intellectual capacity evaluation was carried out, using the Wechsler Intelligence Scale for Adults, third version (Waiss-III), and the family history of mental disorders was investigated through The Family History Screen (FHS). The results indicated a prevalence of 19.22% of PEs during pregnancy and sharing the risk factors present in schizophrenia, such as urbanicity, young pregnant women, use of drugs and alcohol, socioeconomically disadvantaged, low educational level, exposure to situations of violence, the presence of psychiatric disorders such as depression and anxiety, and family history of any psychiatric condition. This research, conducted in an urban area of the city of São Paulo, with high social vulnerability, indicates that the prevalence of PEs in pregnant women is high, affecting about 1 in 6 of them. The presence of PEs is strongly associated with general psychopathology and broad risk factors. In this sense, the presence of PEs may constitute an important risk factor to be evaluated in clinical environments during pregnancy. Future researches intending to look into its usefulness for indication of interventions are needed, as well as studies to search into the course of PEs after pregnancy and its association with health outcomes for women and their children

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população geral e estão associados a grande morbidade e disfuncionalidade. Apesar disso, as bases fisiopatológicas destes transtornos ainda estão em investigação. Estudos neuropatológicos post-mortem e de neuroimagem in vivo sugerem haver comprometimento da microestrutura de substância branca (SB) cerebral nestas condições clínicas, associado a alterações da conectividade cerebral. No entanto, nenhuma investigação prévia de neuroimagem avaliou especificamente se tais anormalidades microestruturais podem ser dependentes do estado clínico do paciente, i.e., se tais alterações podem variar de acordo com a fase da doença. Outra linha de investigação biológica em psicoses aponta para alterações na atividade da fosfolipase A2 (PLA2), uma enzima essencial a diversas funções na homeostase cerebral, incluindo manutenção de membrana celular, mielinização e atividade inflamatória. Estudos prévios sugerem haver relação entre alterações na atividade desta enzima e as fases da esquizofrenia. Entretanto, não há estudos translacionais que tenham avaliado como tais alterações se relacionam com anormalidades microestruturais de SB em pacientes psicóticos. OBJETIVOS: Investigar a hipótese de que alterações de microestrutura de SB presentes em pacientes em fase aguda do primeiro episódio psicótico (PEP) sejam potencialmente reversíveis após estabilização clínica; investigar também possíveis alterações estado-dependentes da atividade de PLA2 no PEP; e examinar interações entre manifestações clínicas, microestrutura de SB cerebral e atividade de PLA2 na fisiopatologia do PEP. METODOLOGIA: Pacientes em PEP não afetivo foram avaliados em dois períodos no tempo: durante a fase aguda da doença (T0); após remissão estável de sintomas (T1). Um grupo controle de voluntários saudáveis (CS) também foi avaliado longitudinalmente. Para investigar alterações de microestrutura de SB estado-dependentes, análises voxel-a-voxel de mapas cerebrais de índices de anisotropia (fractional anisotropy, FA) e difusividade (trace, TR) foram conduzidas, assim como o cálculo de correlações entre tais índices de DTI, variáveis clínicas e atividade de PLA2. A atividade dos três principais subgrupos de PLA2 em plaquetas foi estimada através de um método radioenzimático. RESULTADOS: 25 pacientes PEP e 51 CS foram avaliados em T0, com coleta de dados clínico-demográficos, ressonância magnética (RM) e amostra de sangue. Destes, 21 PEP e 36 CS realizaram a segunda aquisição de RM. No baseline (T0), os pacientes PEP apresentaram redução difusa de FA (p < 0,05, FDR), afetando principalmente SB fronto-límbica e fascículos associativos, projetivos e comissurais. As análises longitudinais demonstraram que a remissão clínica se associou a aumentos de FA em tratos de SB acometidos em T0 (p < 0,001, não corrigido), além de robustas correlações inversas entre aumentos de FA e redução sintomas ao longo do tempo (p < 0,05, FDR). As análises de PLA2 não demostraram efeitos estado-dependentes ou correlações consistentes com os índices de DTI. CONCLUSÃO: Alterações da microestrutura de SB afetando tratos cerebrais essenciais para a integração de informação perceptual, cognição e emoções são detectáveis logo após o início do PEP e podem ser parcialmente revertidas em relação direta com a remissão de sintomas psicóticos agudos. Nossos achados reforçam a visão de que anormalidades de SB de tratos cerebrais são um componente neurobiológico central nos transtornos psicóticos agudos, e que a recuperação de tal patologia de SB pode levar à melhora clínica. Por outro lado, a atividade de PLA2 não parece ter associação direta com o estado de doença ou moderar as alterações microestruturais dinâmicas de SB aqui observadas. Estudos com amostras maiores e com um maior número de avaliações ao longo do tempo são necessários para confirmar e ampliar os resultados aqui apresentados<br>INTRODUCTION: Psychotic disorders are frequent conditions in the general population and are associated to severe morbidity and functional impairment. Notwithstanding, the pathophysiological basis of such disorders is still under investigation. Post-mortem neuropathologic investigations and in vivo neuroimaging studies have pointed to the occurrence of abnormalities in the microstructure of brain white matter (WM) in such clinical conditions, which are associated to changes in brain connectivity. However, no previous neuroimaging investigation has specifically examined whether such microstructural abnormalities would be state-dependent, i.e., whether such changes could relate to the illness phase. Another field of biological investigation in psychosis points to changes in the activity of phospholipase A2 enzyme (PLA2), which is essential to several functions implicated in brain homeostasis, such as the maintenance of cellular membrane, myelination and inflammatory activity. Previous studies suggest the existence of a relationship between changes on PLA2 activity and schizophrenia phase. Nonetheless, no translational study to date has examined the potential interplay between PLA2 activity and WM microstructural abnormalities in psychotic patients. OBJECTIVES: To investigate the hypothesis that WM microstructural changes observed in patients during the acute first-episode psychosis (FEP) are potentially reversible following clinical remission; to investigate possible state-dependent changes in PLA2 activity in FEP; and to examine interactions between clinical manifestations, brain WM microstructure and PLA2 activity in the pathophysiology of FEP. METODOLOGY: Patients with non-affective FEP were evaluated in two time points: during the acute phase (T0) and following sustained remission (T1). A control group of healthy volunteers (HC) was also longitudinally studied. In order to investigate state-dependent WM microstructure changes, voxelwise analyses of brain maps of anisotropy (fractional anisotropy, FA) and diffusivity (trace, TR) indexes were conducted, as well as correlations between such DTI metrics, clinical variables and PLA2 activity. The activity of the three main PLA2 subgroups was assessed in platelets using a radioenzymatic method. RESULTS: 25 FEP and 51 HC were evaluated at T0 (clinical and demographic data, MRI scanning, and blood collection). Out of these, 21 FEP and 36 HC also underwent a second MRI acquisition. At baseline (T0), FEP patients presented widespread reduction of FA (p < 0.05, FDR), affecting mainly fronto-limbic WM and associative, projective and commissural fasciculi. Longitudinal analyses showed that clinical remission was associated with FA increase in WM tracts that were affected at T0 (p < 0.001, uncorrected), besides robust inverse correlations between FA increase and symptoms reduction over time (p < 0.05, FDR). PLA2 analyses failed to show state-dependent effects or consistent correlations to DTI indexes. CONCLUSION: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities are a key neurobiological feature of acute psychotic disorders, and that recovery from such WM pathology can lead to amelioration of symptoms. In the other hand, it seems that PLA2 activity has no direct relationship to the disease state or modulatory effects on the dynamic WM changes observed herein. Studies with larger samples and with more time points evaluations are necessary to confirm and expand the findings reported herein

La schizophrénie précoce (SP) est une forme rare, sévère et neurodéveloppementale de schizophrénie débutant avant l’âge de 18 ans. Afin de mieux comprendre les bases génétiques complexes de ce trouble nous avons développé un projet pilote avec pour objectif principal de caractériser sur le plan clinique et génétique les patients atteints de SP. Compte tenu du chevauchement clinique et génétique de la SP avec les autres troubles neurodéveloppementaux, dont le Trouble du Spectre de l’Autisme (TSA) et le Trouble Déficit de l’Attention Hyperactivité (TDAH), nous avons porté une attention particulière aux gènes impliqués dans le neurodéveloppement.Il s'agit d'une étude multicentrique conduite d’avril 2014 à mai 2023. Les critères d'inclusion sont: âge de 7 à 22 ans, un diagnostic de SP (K-SADS-PL DSM-5) avec des symptômes autistiques prémorbides (ADI-R 0-5 ans) et un QI&gt; 40; les parents et les frères et sœurs sont inclus. L’exploration du profil clinique a été effectuée à l’aide d’outils standardisés (KSADS-PL, PANSS) et a compris des évaluations neurocognitives (WISC-V/WAIS-IV). L’exploration génétique (approche hiérarchisée) a compris une recherche de l’X-Fragile, la réalisation d’un CGH-array puis, en cas de négativité des examens précédents, la réalisation d’un séquençage de l’ADN (exome) en trio. Nous avons procédé à la priorisation des gènes en combinant de multiples outils bio-informatiques.20 sujets ont été inclus: 15 Garçons et 5 filles. L’âge moyen de début du trouble était de 8,90 ans (+/-2,30). Les comorbidités psychiatriques étaient le TDAH (15/20 patients), les troubles anxieux (14/20) et le TSA (13/20). Le QI moyen était de 70,26 (+/-18,09). Un retard de langage et une rupture scolaire étaient notés chez 18/20 patients. L’affection somatique principale était l’asthme (15/20 patients). Sur le plan génétique, nous rapportons chez une patiente (ségrégation familiale) une duplication 10q26.3 (324 Kb) comprenant une partie du gène INPP5A. Nous avons montré que son homologue de la drosophile 5PtaseI est spécifiquement exprimée dans le système nerveux central. Enfin, grâce aux séquençages de l’ADN (9 exomes en trio ; mère, père, enfant soit 27 sujets) et aux outils bio-informatiques, nous avons identifié la présence de variants dans les gènes appartenant aux voies de signalisation Wnt, cadhérine et cholécystokinine.Ainsi, nous avons mis en évidence chez nos patients atteints de SP une grande hétérogénéité clinique avec des comorbidités psychiatriques et des atteintes neurodéveloppementales systématiquement associées. INPP5A est un gène exprimé dans le cerveau (humain, souris et drosophile), très conservé entre espèces et qui code une InsP3 5-phosphatase dont les produits d’hydrolyse mobilisent le calcium intracellulaire, essentiel pour la morphogenèse des épines dendritiques dans les neurones. L’altération de ce processus, par dysrégulation de la voie de signalisation InsP3/Ca2+, est retrouvée à la fois dans la schizophrénie et le TSA, renforçant le lien entre ces troubles. De plus, nous avons effectué la première description de l’implication potentielle de voies de signalisation Wnt, Cadhérine et Cholécystokinine dans la SP. L’implication de ces différentes voies de signalisation décrite de manière variable dans d’autres troubles neurodéveloppementaux et/ou psychiatriques souligne l’hétérogénéité génétique de ce trouble. Élucider les mécanismes moléculaires de la SP et ouvrir la voie à une intervention thérapeutique spécifique nécessitera d’effectuer systématiquement et à grande échelle : 1) le diagnostic syndromique précis de SP avec un âge exact de début de la maladie et le phénotype neurodéveloppemental associé ; 2) une évaluation génétique hiérarchisée allant jusqu’au séquençage du génome et 3) le partage des données à l’échelle internationale avec la constitution de bases de données spécifiques, comparables, génétiques et moléculaires corrélées aux phénotypes de précision des différentes formes de SP<br>Early-onset schizophrenia (EOS) is a rare, severe and neurodevelopmental form of schizophrenia beginning before the age of 18. In order to better understand the complex genetic basis of this disorder, we have developed a pilot project with the main objective of clinically and genetically characterize EOS patients presenting additional neurodevelopmental disabilities. Given the clinical and genetic overlap of EOS with other neurodevelopmental disorders, including Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), we paid particular attention to the genes involved in neurodevelopment.This is a multi-center study carried out from April 2014 to May 2023 in a paediatric population. Inclusion criteria are: age 7-22 years, a diagnosis of EOS (K-SADS-PL DSM-5) with premorbid autistic symptoms (ADI-R 0-5 years) and IQ &gt; 40; parents and siblings are included. Clinical profile explorations are performed using standardized tools (KSADS-PL and PANSS) and included neurocognitive assessments (WISC-V/WAIS-IV), the search for psychiatric co-morbidities, neurodevelopmental disorders and associated extracerebral somatic pathologies. The exploration of the genetic profile consists in identifying genetic mutations by a hierarchical approach searching for Fragile-X Syndrome (PCR), CGH-array and, in case of negativity of the previous examinations, DNA sequencing (exome) in trio (mother, father, child). Finally; we proceed to the prioritization of genes by combining multiple bioinformatics tools.20 subjects were included: 15 boys and 5 girls. The mean age of onset of the disorder was 8.90 years (+/-2.30). Psychiatric comorbidities (DSM-5) were ADHD (15/20 patients), anxiety disorders (14/20) and ASD (13/20). The mean IQ was 70.26 (+/-18.09). Language delay and school disruption were noticed in 18/20 patients. The main associated somatic condition was asthma (15/20 patients). Genetically, we report a 10q26.3 324 kb microduplication in one patient (with familial segregation), encompassing part of the INPP5A gene. We have shown that its homologue 5PtaseI is specifically expressed in the Drosophila central nervous system. Furthermore, we have identified, through DNA sequencing of 9 exomes of patients in trio (27 subjects with mother, father and child) and bioinformatics tools, the presence of variants in genes belonging to the Wnt, cadherin and cholecystokinin signaling pathways.In our EOS patients, we have shown a large clinical heterogeneity with psychiatric co-morbidities and neurodevelopmental disorders systematically associated. INPP5A is expressed in the brain (human, mouse and Drosophila), is highly conserved between species and encodes a InsP3 5-phosphatase whose hydrolysis products mobilize intracellular calcium, essential for the morphogenesis of dendritic spines in neurons. The alteration of this process, by the InsP3/Ca2+ signaling pathway, is found in both schizophrenia and ASD, strengthening the link between these disorders. In addition, we have made the first description of the potential involvement of the Wnt, Cadherin and Cholecystokinin signaling pathways in EOS. The already described involvement of these different pathways in other neurodevelopmental and/or psychiatric disorders underlines the genetic heterogeneity of this disorder. Therefore, elucidating the molecular mechanisms of EOS and paving the way for specific therapeutic interventions will require systematic and large-scale: 1) definition of the precise syndromic diagnosis of EOS with an exact age of onset and determination of the premorbid neurodevelopmental phenotype, psychiatric comorbidities and associated extracerebral somatic pathologies; 2) genetic evaluation using a hierarchical approach up to whole genome sequencing; 3) data sharing between teams on an international scale with the constitution of specific, comparable, genetic, and molecular databases correlated to the precise phenotypes of the different forms of EOS

Professional Doctorate - Doctor of Clinical Psychology (DCP)<br>Scope: Negative symptoms represent a fundamental component of schizophrenia. Furthermore, as noted in the DSM-IV (American Psychiatric Association, 2000), poor social functioning has been classified as a diagnostic criterion for the disorder. The relationship between both factors has been highlighted in the literature, with negative symptoms being identified as predictors of social functioning. Consequently, considerable research has been devoted to identifying the factors that contribute to negative symptoms. While impairments in neuropsychological functioning have been shown to be contributory factors, research has also demonstrated that a range of psychological variables has provided further clarity regarding negative symptomatology. Purpose: The broad aim of the current research was to gain a greater understanding of the processes that contribute to negative symptoms and social functioning in schizophrenia and schizophrenia spectrum disorders. More specifically, a theoretical model was proposed which predicted that self-efficacy would mediate the relationship between internalized stigma and both negative symptoms and social functioning. Methodology: Sixty participants, who had been diagnosed with schizophrenia or a schizophrenia spectrum disorder and admitted to acute mental health facilities in the Hunter Region of New South Wales, Australia, were recruited for the current research. A broad range of assessment tasks were utilized, with all tasks being completed in approximately 60 – 90 minutes. In relation to self-efficacy, the Self-Efficacy Questionnaire (SEQ) was designed to evaluate the participants’ expectancies about their performance on the Faux Pas Test. Results: Initial results indicated that internalized stigma was strongly correlated with negative symptoms, social functioning and self-efficacy. Furthermore, self-efficacy was also found to be strongly associated with negative symptoms and moderately related to social functioning. Additional analyses that utilized a bootstrapping procedure and accompanying SPSS macro for small sample sizes did not support the mediational model. In other words, support was not obtained for the mediating role of self-efficacy in relation to the association between internalized stigma and both negative symptoms and social functioning. Conclusions and Clinical Implications: While support was not found for the proposed theoretical model outlined in the current research, a greater understanding was gained concerning the relationship between internalized stigma, self-efficacy and both negative symptoms and social functioning in schizophrenia and schizophrenia spectrum disorders. In brief, the findings of the study highlighted the clinical relevance of research into internalized stigma and the psychological construct of self-efficacy. Furthermore, the research findings have important implications for intervention development and implementation during times of acute admission. Specific theoretical and clinical implications of the findings, together with recommendations for future research, are outlined.

During the last ten years the prevalence of autism and Autism Spectrum Disorder (ASD) have increased greatly. In the 60s the most reported rate was 0.5/1.000, while currently the prevalence of ASD in adults is approximately 1/100. Such rapid and significant increase in prevalence estimates raises a number of questions as to the origins of this increase. A recurring issue is the overlap and boundaries between Intellectual Developmental Disorder (lDD), coexisting ASD and Schizophrenia Spectrum Disorders (SSD). In clinical practice many People with IDD (PwIDD) have both pervasive autistic traits and a concurrent diagnoses of SSD, and many with ASD have coexisting IDD and receive a diagnosis of SSD. Furthermore people with SSD may often have a mild lDD, or borderline intellectual functioning, or other cognitive problems prior the onset of psychotic disorder. Co-occurrence of other psychiatric disorders is also frequent in the three groups, particularly in those with IDD and ASD. Differential diagnosis between SDD, lDD, and ASD (and may or may not have been clinically identified) is often challenging especially for the psychiatrist without specific training. The aim of the research project is to identify some clinical characteristics that relate most with each of the three specific conditions and their combination, which might contribute in turn to the development of better criteria of differential diagnosis and psychiatric comorbidity.

Alterations in self-experience is a relatively omitted topic in czech literature. For that reason, the following diploma thesis deals with this issue, in relation to unipolar depression and schizophrenia spectrum disorders. The thesis is divided into two parts - theoretical and practical part of the research. Each chapter of the theoretical part summarizes the crucial information about schizophrenia and other disorders from schizophrenia spectrum that later appears in the research sample - as well as depression. The chapter describes symptomatology, diagnostics, epidemiology, etiopathogenesis and the treatment of the abovementioned disorders. Hereafter, the subject of alterations in self-experience is introduced and the two main phenomenologically oriented approaches to this phenomena. After that, the concrete manifestations of alterations in self-experience in schizophrenic disorders and depression are outlined. The concluding chapter of the theoretical part provides a brief account of the most famous methods in the research that focuses on alterations in self-experience. The research part of the thesis includes two sections. The first one aims to compare the changes in the experience of self in schizophrenic disorders and depression. For this purpose, the newly developed Self-disturbances Scale....

Résumé en français Objectifs : Ce mémoire propose d’explorer l’assiduité aux interventions psychosociales chez les personnes atteintes de troubles psychotiques en répondant à trois questions : 1- Quels sont les facteurs influençant l’assiduité aux interventions psychosociales pour une clientèle atteinte de troubles psychotiques? 2- Sont-ils comparables aux facteurs influençant l’observance à la médication? 3- Quel est le taux d’abandon des interventions psychosociales et quels sont les facteurs qui font varier ce taux? Méthodes : Cette étude a permis de faire la synthèse des facteurs influençant l’observance à la médication à partir des revues systématiques publiées sur le sujet, et d’établir les facteurs influençant l’assiduité aux interventions psychosociales à partir des raisons d’abandon citées dans les essais cliniques randomisés publiés. Une méta-analyse a permis de combiner les essais cliniques rapportant les abandons et ainsi d’en établir un taux. Résultats : Nous avons répertorié 92 essais cliniques randomisés sur les interventions psychosociales avec les personnes atteintes de troubles psychotiques. De ce nombre, 43 ont permis de répertorier les raisons d’abandon. Les raisons d’abandon s’avèrent principalement liées à la maladie et liées à l’accessibilité, la continuité et la qualité des soins et services. Un taux d’abandon de 13% a été obtenu à partir de l’agrégation de 74 études dans la méta-analyse. Des facteurs faisant varier ce taux ont été identifiés. Conclusion : Plusieurs facteurs (personnels, lié aux traitements, sociaux) influençant l’assiduité aux interventions psychosociales chez les personnes atteintes de troubles psychotiques ont été identifiés. De plus, le faible taux d’abandon obtenu démontre bien la faisabilité clinique de ce type d’intervention. S’ajoutant à l’efficacité déjà bien démontrée de certaines modalités d’intervention psychosociales, le taux d’assiduité à ces mêmes modalités constitue un argument supplémentaire pour en assurer la disponibilité aux personnes atteintes d’un trouble psychotique.<br>Abstract Aims : This report suggest investigating the compliance in the psychosocial treatment among persons with schizophrenia spectrum disorder by answering three questions : 1- What are factors influencing compliance in the psychosocial treatment among persons with schizophrenia spectrum disorder? 2- Are they comparable to factors influencing compliance with pharmacological treatment? 3- What is the dropout rate of the psychosocial treatment and which are the factors which make vary this rate? Methods : A systematic review allowed to make the synthesis of factors influencing the compliance in the medication from the systematic reviews published on the subject and to establish factors influencing the compliance in the psychosocial treatment from the reasons of drop-out specified in the published randomized clinical trials. A meta-analysis allowed to combine clinical trials reporting drop-out and so to establish a rate. Results : We listed 92 clinical trials randomized on the psychosocial treatment among persons suffering from schizophrenia spectrum disorder , of this number 43 allowed to list the reasons of drop-out. The reasons of drop-out turn out mainly related to the disease and related to the accessibility, the continuity and the quality of the care and the services. A 13 % dropout rate was obtained from the aggregation of 74 studies in the meta-analysis. Factors making vary this rate were identified. Conclusions: Several factors which influence the compliance in the psychosocial treatment among persons suffering from schizophrenia spectrum disorders are identified. Furthermore, the low drop-out rate calculated demonstrates well the clinical feasibility of this type of treatment. Being added to the efficiency already well demonstrated by certain psychosocial modalities of treatnebt, the compliance rate in these same modalities establishes an additional argument to assure the availability among persons suffering from schizophrenia spectrum disorders.