There has been concern about the impact of cannabis use on the onset, course and relapse of psychosis. Evidence from retrospective and a small number of prospective studies has suggested that cannabis use may precipitate a latent psychosis, exacerbate psychotic symptoms and increase the likelihood of psychotic relapse. The purpose of the current study was to examine the influence of cannabis use on psychotic symptom exacerbation and relapse within the stress vulnerability-coping model of psychosis. Two studies were conducted. The influence of cannabis use on the onset and course of psychosis was retrospectively examined in the first study. The second study prospectively examined the influence of cannabis use on psychotic symptom exacerbation and relapse over a 6-month period. The influence of the severity of psychotic symptoms on a relapse in cannabis use was also explored. Eighty-four participants were assessed at admission, 81 of whom were followed up for a 6-month period. Measures consisted of structured diagnostic interviews and self-report measures of stress, medication compliance, family functioning, premorbid adjustment, quality of life, substance use and psychotic symptoms. The onset of cannabis use clearly preceded the onset of psychosis. Cannabis use was predictive of the severity of psychotic and general psychopathology symptoms at admission. Both the frequency and quantity of cannabis use was predictive of time to psychotic relapse over the 6-month follow up period. Psychotic symptom severity was predictive of a substantial increase in the quantity but not the frequency of cannabis use. Cannabis use was related to the onset, course and relapse of psychosis.

Population-based evidence suggests that the prevalence of psychotic symptoms varies with ethnicity. However, the validity of these self-reported experiences, both as measures of psychotic symptoms per se and as measures of ethnic variation in risk for reporting these symptoms, is questionable. Cultural background and social position may affect the experience and expression of symptoms, which may in turn affect their measurement in survey research. This thesis explores these issues by assessing the psychometric properties of psychosis screening instruments as measures of ethnic differences in psychosis risk in two contexts, Great Britain and the United States. Following this, differences in risk for reporting psychotic symptoms were examined in the context of the varying social and economic conditions to which different ethnic groups and migrant generations are exposed. This was accomplished in the following way: Firstly, the prevalence of self-reported psychotic symptoms was examined across ethnic and generational groups in two large samples of British and American populations; Secondly, the construct validity of the instruments was assessed by means of exploratory and confirmatory factor analyses of response to their symptom indicators. The concurrent validity of the symptoms with measures of self-perceived cognitive and social dysfunction was then examined in a structural equation modeling framework; Thirdly, the cross-ethnic and cross-generational validity of response to these screening instruments was assessed in a multiple-group confirmatory factor analysis framework in which in which the psychometric characteristics of the instruments were compared; And finally, ethnic and generational differences in risk for reporting psychotic symptoms were examined in the context of differential exposure to racial discrimination. Both instruments had construct validity in their measurement of psychotic symptoms, with the exception of one item in the British instrument, as well as concurrent validity with measures of self-perceived cognitive or social dysfunction. The British instrument performed adequately in the measurement of psychotic symptoms across ethnic groups, but did not across migrant generations. The American instrument performed adequately in the measurement of psychotic symptoms across generations, but not across ethnic groups. The effect of measurement noninvariance on the estimation of risk across groups was, however, modest in size. Finally, there was evidence for risk of reporting psychotic symptoms being raised among those who were exposed to racial discrimination. These findings suggest that these self-reported psychotic symptoms constitute clinically relevant phenomena which appear phenotypically similar to the clinical symptoms in diagnosed psychotic disorder. Risk is distributed unevenly over ethnic groups in Britain and the US, is higher among minorities who were exposed to social adversity, and higher among the second generation (in most cases). These patterns are, therefore, highly suggestive of social causation in the aetiology of these self-reported symptoms.

Recent studies have found associations between prolonged stress response and white matter (WM) microstructure in individuals with schizophrenia, as well as correlations between early life trauma and WM integrity in individuals with schizophrenia and non-psychiatric controls; however, psychosocial correlates of WM dysfunction have not yet been adequately explored in individuals experiencing attenuated psychotic symptoms (APS, subthreshold versions of positive psychotic symptoms). This study examines WM microstructure using traditional and free-water corrected diffusion metrics within a community sample of 66 16 to 30-year-olds experiencing a range of APS to examine the contribution of perceived stress and childhood trauma to the relationship between APS and WM abnormalities, as well as examine the moderating influence of sex assigned at birth (herein referred to as sex) to these relationships. We found that overall symptom severity on the Structured Interview for Psychosis-risk Syndromes (SIPS) was associated with higher extracellular free-water (FW) across the whole brain, lower free-water corrected fractional anisotropy values (FAT), and higher free-water corrected radial diffusivity (RDT). Further, childhood trauma significantly moderated the relationship between SIPS scores and both FAT and RDT, controlling for biological sex at birth, such that in the presence of APS, childhood trauma was associated with higher FAT and lower RDT, and in lower APS the opposite pattern was seen, with childhood trauma associated with lower FAT and lower RDT. After stratifying for sex, childhood trauma moderated the SIPS – FAT and RDT relationships in males similar to findings in the whole sample, though this relationship was not present in females. Perceived stress was not a significant moderator in the total sample, though was a significant moderator of the APS – FA relationship in males only. This study represents an important step toward identifying mechanisms for WM dysfunction within individuals with psychosis spectrum disorders, as well as identifying important targets for interventions. / Psychology

Psychosis has intrigued and confused neuroscientists for many years, yet there seems to be no clear explanation for why and how it occurs. There is also not just one disorder of psychosis, such as schizophrenia, some epileptic patients experience the same symptoms.That is called schizophrenia-like psychosis of epilepsy (SLPE), which is similar to primary schizophrenia but also very different. This systematic review will explain SLPE as a disorder in itself, compare it to other psychotic disorders, provide research findings and conclude what we can learn from better understanding psychosis in general.

Pouco se sabe sobre a presença de sintomas psicóticos em idosos sem diagnóstico de demência, levando a dificuldades no esclarecimento da etiologia, na ausência de informações quanto a possíveis diagnósticos e no manejo clínico. Os estudos sobre a incidência de sintomas psicóticos nessa população são ainda mais escassos e limitados. Os dados disponíveis na literatura são todos provenientes de estudos em populações de países desenvolvidos. A prevalência de sintomas psicóticos em idosos sem diagnóstico de demência varia de 0,9 a 10,5%, já a incidência na literatura varia entre 4,8 e 8,0%. É possível especular sobre alguns fatores de risco para o desenvolvimento de sintomas psicóticos em indivíduos sem demência: idade avançada, gênero feminino, comprometimento sensorial, pior desempenho cognitivo, isolamento social, pior funcionalidade. Dados recentes sugerem os sintomas psicóticos como uma expressão prodrômica da demência, devido a sintomas como alucinações, delírios e ideação paranoide estarem associados ao aumento da incidência de demência no acompanhamento, à maior presença deles à medida que a faixa etária sobe e à menor média no escore do Miniexame do Estado Mental (MEEM) em indivíduos com tais sintomas. Objetivamos determinar a incidência de sintomas psicóticos, correlacioná-los com características clínicas e estabelecer uma taxa de conversão em idosos sem comprometimento cognitivo. Este estudo foi realizado em uma amostra de idosos de comunidade de São Paulo, sendo a amostra inicial composta por 1.125 indivíduos acima de 60 anos. Destes, 547 foram reavaliados em 2011 e submetidos ao mesmo protocolo inicial. Não tinham sintomas psicóticos na primeira fase 199 e 64 já possuíam em 2006. A incidência de ao menos um sintoma psicótico em 7 anos foi 8,0% (alucinações visuais/táteis: 4,5%; ideias persecutórias: 3,0%; alucinações auditivas: 2,5%). A incidência esteve relacionada à epilepsia (OR: 7,75 e 15,83), baixa pontuação no MEEM (OR: 0,72) e depressão referida (OR: 6,48). 57,8% dos indivíduos com sintomas psicóticos, mas sem demência na fase I, desenvolveram comprometimento cognitivo em 7 anos (alucinações visuais/táteis foram preditivas - OR: 5,66), o que estava relacionado a baixo MEEM e comprometimento funcional. A incidência de sintomas psicóticos e a taxa de conversão em comprometimento cognitivo estão no limite superior dos dados da literatura. Alucinações visuais/táteis foram os sintomas mais incidentes e os únicos preditivos para a evolução para comprometimento cognitivo em 5 anos. Encontramos importantes relações entre sintomas psicóticos e MEEM, crises convulsivas, depressão referida, diabetes e sífilis / Background: Studies of the incidence of psychotic symptoms in elderly people at risk of dementia are scarce. This is a seven year follow up study aiming to determine the incidence of psychotic symptoms and their correlation with other clinical aspects as well as conversion rates to cognitive impairment. Objectives: To determine the incidence of psychotic symptoms, correlate these symptoms with clinical characteristics and establish the conversion rate to cognitively impaired individuals. Design: Cross-sectional study of a community-based sample of elderly subjects. Setting: City of Sao Paulo, State of Sao Paulo, Brazil. Participants: The original sample was composed of 1,125 individuals aged 60 years and older from a community. Among this sample, 547 subjects were re-evaluated in 2011 and submitted to the same protocol. Of these, 199 did not have psychotic symptoms at phase I and 64 already had psychotic symptoms in 2006. Results: The incidence of at least one psychotic symptom in 7 years was 8.0% (Visual/tactile hallucinations: 4.5%; Persecutory delusions: 3.0%; Auditory hallucinations: 2.5%). Psychotic symptom incidence was associated with epilepsy (OR: 7.75 and 15.83), lower MMSE (OR: 0.72) and reported depression (OR: 6.48). A total of 57.8% of individuals with psychotic symptoms but without dementia at phase I developed cognitive impairment after 7 years (visual/tactile hallucinations were the only psychotic symptom predictive of this impairment - OR: 5.66), which was related to lower MMSE and increased functional impairment. Conclusions: The incidence of psychotic symptoms and the conversion rate to cognitive impairment was in the upper range of previous literature reports. Visual/tactile hallucinations were the most incident symptoms and the only predictive psychotic symptoms for cognitive impairment in 5 years. Important relationships were found between psychotic symptoms incidence and MMSE, epilepsy, reported depression, diabetes and syphilis

Background. The reported link between psychological trauma and onset of psychosis remains controversial. Aims. To examine associations between self-reported psychological trauma and psychotic symptoms as a function of prior evidence of vulnerability to psychosis (psychosis proneness). Method. At baseline, 2524 adolescents aged 14-24 years provided self-reports on psychological trauma and psychosis proneness, and at follow-up (on average 42 months later) participants were interviewed for presence of psychotic symptoms. Results. Self-reported trauma was associated with psychotic symptoms, in particular at more severe levels (adjusted OR1.89,95% CI1.16-3.08) and following trauma associated with intense fear, helplessness or horror. The risk difference between those with and without self-reported trauma at baseline was 7% in the group with baseline psychosis proneness, but only 1.8% in those without (adjusted test for difference between these two effect sizes: χ2=4.6, P=0.032). Conclusions. Exposure to psychological trauma may increase the risk of psychotic symptoms in people vulnerable to psychosis.

Pouco se sabe sobre a presença de sintomas psicóticos em idosos sem diagnóstico de demência, levando a dificuldades no esclarecimento da etiologia, na ausência de informações quanto a possíveis diagnósticos e no manejo clínico. Os estudos sobre a incidência de sintomas psicóticos nessa população são ainda mais escassos e limitados. Os dados disponíveis na literatura são todos provenientes de estudos em populações de países desenvolvidos. A prevalência de sintomas psicóticos em idosos sem diagnóstico de demência varia de 0,9 a 10,5%, já a incidência na literatura varia entre 4,8 e 8,0%. É possível especular sobre alguns fatores de risco para o desenvolvimento de sintomas psicóticos em indivíduos sem demência: idade avançada, gênero feminino, comprometimento sensorial, pior desempenho cognitivo, isolamento social, pior funcionalidade. Dados recentes sugerem os sintomas psicóticos como uma expressão prodrômica da demência, devido a sintomas como alucinações, delírios e ideação paranoide estarem associados ao aumento da incidência de demência no acompanhamento, à maior presença deles à medida que a faixa etária sobe e à menor média no escore do Miniexame do Estado Mental (MEEM) em indivíduos com tais sintomas. Objetivamos determinar a incidência de sintomas psicóticos, correlacioná-los com características clínicas e estabelecer uma taxa de conversão em idosos sem comprometimento cognitivo. Este estudo foi realizado em uma amostra de idosos de comunidade de São Paulo, sendo a amostra inicial composta por 1.125 indivíduos acima de 60 anos. Destes, 547 foram reavaliados em 2011 e submetidos ao mesmo protocolo inicial. Não tinham sintomas psicóticos na primeira fase 199 e 64 já possuíam em 2006. A incidência de ao menos um sintoma psicótico em 7 anos foi 8,0% (alucinações visuais/táteis: 4,5%; ideias persecutórias: 3,0%; alucinações auditivas: 2,5%). A incidência esteve relacionada à epilepsia (OR: 7,75 e 15,83), baixa pontuação no MEEM (OR: 0,72) e depressão referida (OR: 6,48). 57,8% dos indivíduos com sintomas psicóticos, mas sem demência na fase I, desenvolveram comprometimento cognitivo em 7 anos (alucinações visuais/táteis foram preditivas - OR: 5,66), o que estava relacionado a baixo MEEM e comprometimento funcional. A incidência de sintomas psicóticos e a taxa de conversão em comprometimento cognitivo estão no limite superior dos dados da literatura. Alucinações visuais/táteis foram os sintomas mais incidentes e os únicos preditivos para a evolução para comprometimento cognitivo em 5 anos. Encontramos importantes relações entre sintomas psicóticos e MEEM, crises convulsivas, depressão referida, diabetes e sífilis / Background: Studies of the incidence of psychotic symptoms in elderly people at risk of dementia are scarce. This is a seven year follow up study aiming to determine the incidence of psychotic symptoms and their correlation with other clinical aspects as well as conversion rates to cognitive impairment. Objectives: To determine the incidence of psychotic symptoms, correlate these symptoms with clinical characteristics and establish the conversion rate to cognitively impaired individuals. Design: Cross-sectional study of a community-based sample of elderly subjects. Setting: City of Sao Paulo, State of Sao Paulo, Brazil. Participants: The original sample was composed of 1,125 individuals aged 60 years and older from a community. Among this sample, 547 subjects were re-evaluated in 2011 and submitted to the same protocol. Of these, 199 did not have psychotic symptoms at phase I and 64 already had psychotic symptoms in 2006. Results: The incidence of at least one psychotic symptom in 7 years was 8.0% (Visual/tactile hallucinations: 4.5%; Persecutory delusions: 3.0%; Auditory hallucinations: 2.5%). Psychotic symptom incidence was associated with epilepsy (OR: 7.75 and 15.83), lower MMSE (OR: 0.72) and reported depression (OR: 6.48). A total of 57.8% of individuals with psychotic symptoms but without dementia at phase I developed cognitive impairment after 7 years (visual/tactile hallucinations were the only psychotic symptom predictive of this impairment - OR: 5.66), which was related to lower MMSE and increased functional impairment. Conclusions: The incidence of psychotic symptoms and the conversion rate to cognitive impairment was in the upper range of previous literature reports. Visual/tactile hallucinations were the most incident symptoms and the only predictive psychotic symptoms for cognitive impairment in 5 years. Important relationships were found between psychotic symptoms incidence and MMSE, epilepsy, reported depression, diabetes and syphilis

La dépendance à la cocaïne est un problème de santé publique d’importance croissante. Il n’existe pas actuellement de traitement pharmacologique validé dans la dépendance à la cocaïne. Les essais thérapeutiques nécessitent une méthodologie qui permette d’évaluer l’efficacité des médicaments employés. Il n’existait pas à ce jour de mesure d’efficacité des traitements pharmacologiques dans la dépendance à la cocaïne validée en français. Nous avons mis au point et validé des questionnaires pouvant servir de mesures intermédiaires d’efficacité pour les essais pharmacologiques dans la dépendance à la cocaïne. Nous avons choisi de nous intéresser à deux types de variables intermédiaires : le craving et les symptômes psychotiques. Le craving est le besoin impérieux de reconsommer une drogue. Ce concept psychologique est un marqueur de dépendance. Nous avons conçu un questionnaire de craving en langue française : l’OCCS (Obsessive Compulsive Cocaïne Scale), en nous basant sur les travaux de plusieurs équipes travaillant dans le domaine de la dépendance à l’alcool. Nous avons validé ce questionnaire sur une population de 119 sujets cocaïnomanes suivis en centre de soins (Vorspan et al 2012). Nous avons notamment montré que les scores à ce questionnaire étaient corrélés à une mesure de craving par échelle visuelle analogique, étaient supérieurs chez les sujets dépendants par rapport aux sujets abuseurs de cocaïne, et étaient sensible au changement. Nous avons déjà utilisé le questionnaire de craving OCCS dans un essai thérapeutique en ouvert d’aripiprazole chez 10 patients dépendants du crack non schizophrènes (Vorspan et al 2008). Nous proposons également de l’utiliser pour évaluer l’efficacité d’interventions non pharmacologiques dans la dépendance à la cocaïne, comme la stimulation cérébrale profonde (Vorspan et al 2011), ou des interventions psychothérapeutiques. Les symptômes psychotiques se composent de différentes manifestations (hallucinations, idées délirantes et modifications comportementales). Nous avons choisi d’adapter en français un questionnaire évaluant les symptômes psychotiques transitoires survenant dans les quelques minutes à quelques heures suivant une consommation de cocaïne : le SAPS-CIP (Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis). Nous avons montré que ces symptômes sont fréquents mais d’intensité variable dans une population de patients cocaïnomanes suivis en centre de soins (Vorspan et al, soumis), et qu’ils étaient sensibles au changement (Vorspan et al 2011). Il existe des hypothèses de vulnérabilité génétique à la survenue des symptômes psychotiques lors de l’usage de cocaïne. La vulnérabilité à cette complication pourrait être un facteur de protection vis-à-vis de l’acquisition d’une dépendance à la cocaïne (Brousse et al 2010). La mesure des symptômes psychotiques survenant lors de l’usage de drogue permet de modéliser une vulnérabilité pharmacogénétique vis-à-vis des addictions. Nous proposons d’utiliser ces deux mesures (OCCS pour le craving et SAPS-CIP pour les symptômes psychotiques) dans les essais thérapeutiques dans la dépendance à la cocaïne. En effet, il paraît pertinent, au regard des particularités cliniques de la dépendance à la cocaïne, de viser une réduction ou une disparition de ces deux ordres de symptômes. Une diminution du craving pourrait constituer une variable intermédiaire de l’objectif final d’obtenir une abstinence de la drogue. Une diminution des symptômes psychotiques pourrait constituer un moyen de réduction de la morbi-mortalité liée à l’usage de cocaïne. / Cocaine dependence is a growing public health concern in France. There is no pharmacological treatment validated for cocaine dependence treatment. Clinical trials require that validated methods are used to ascertain the efficacy of new drugs that are tested. There was no validated tool available to conduct pharmacological trials for cocaine dependence in French. We conceptualized and validated questionnaires that could be used as surrogate endpoints in pharmacological trials for cocaine dependence. We choose to work on two types of surrogate variables: craving and psychotic symptoms.Craving is the overwhelming desire to use a drug. It is a psychological construct that can be used as a biomarker of dependence. We designed a craving questionnaire in French named OCCS (Obsessive Compulsive Cocaïne Scale) after the work of several research teams working in the field of alcohol dependence. We validated this questionnaire in a sample of 119 cocaine addicts in a clinical setting (Vorspan et al 2012). We could demonstrate that the scores obtained on this questionnaire were correlated to those obtain on a visual analogue scale of craving. We could also demonstrate that the scores were higher in cocaine dependent that in cocaine abusing subjects. Lastly, we could demonstrate that the scores were time-sensitive. We used this questionnaire OCCS in an open-label trial of aripiprazole in 10 non-schizophrenic crack dependent patients (Vorspan et al 2008). We propose that this questionnaire could be used in clinical trials assessing the efficacy of various therapeutic interventions in cocaine dependent subjects, pharmacological treatments, but also deep brain stimulation (Vorspan et al 2011) and psychological interventions. Psychotic symptoms are composed of various phenomenons (hallucinations, delusions and behavioural modifications). We choose to adapt in French a validated questionnaire that assesses psychotic symptoms occurring between a few minutes to a few hours after cocaine intake: the SAPS-CIP (Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis). We could demonstrate that those symptoms are frequent but of variable intensity in a sample of French cocaine addicts in a clinical setting (Vorspan et al, soumis). We could also demonstrate that those symptoms are change sensitive (Vorspan et al 2011). We hypothesized that there is a genetic vulnerability to cocaine-induced psychotic symptoms, and that being sensitive to the occurrence of psychotic symptoms could be a protective factor toward the development of cocaine dependence (Brousse et al 2010). The variability of cocaine-induced psychotic symptoms helps to conceptualize a pharmacogenetic model of drug dependence. We propose that those two questionnaires (OCCS for craving and SAPS-CIP for psychotic symptoms) could be used in clinical trial in cocaine dependent subjects. It seems very helpful indeed, knowing the clinical pattern of cocaine dependence, to design trails aimed at reducing or suppressing craving and psychotic symptoms. Reducing or suppressing craving could be a surrogate endpoint for cocaine abstinence. Reducing or suppressing cocaine-induced psychotic symptoms could reduce the morbidity and mortality associated with cocaine use.

Background. The reported link between psychological trauma and onset of psychosis remains controversial. Aims. To examine associations between self-reported psychological trauma and psychotic symptoms as a function of prior evidence of vulnerability to psychosis (psychosis proneness). Method. At baseline, 2524 adolescents aged 14-24 years provided self-reports on psychological trauma and psychosis proneness, and at follow-up (on average 42 months later) participants were interviewed for presence of psychotic symptoms. Results. Self-reported trauma was associated with psychotic symptoms, in particular at more severe levels (adjusted OR1.89,95% CI1.16-3.08) and following trauma associated with intense fear, helplessness or horror. The risk difference between those with and without self-reported trauma at baseline was 7% in the group with baseline psychosis proneness, but only 1.8% in those without (adjusted test for difference between these two effect sizes: χ2=4.6, P=0.032). Conclusions. Exposure to psychological trauma may increase the risk of psychotic symptoms in people vulnerable to psychosis.

The study examines to what degree well-documented present and life-time psychotic symptoms in a group of former psychiatric inpatients are ascertained when using the Diagnostic Interview Schedule (DIS). The Inpatient Multidimensional Psychiatric Scale (IMPS) and the Manual for the Assessment and Documentation of Psychopathology/Diagnostische Sichtlochkartei (AMDP/DiaSika) Interview-Checklist approach were used for the “clinical” evaluations of symptoms. The results indicate fair concordance between the two clinical approaches and the DIS with regard to the presence of any delusional or hallucination symptoms. Low to poor agreement was found in the assessment of many of the rather specific hallucinations and delusions. Generally, the concordance found was higher when compared to the more clinical AMDP/DiaSiKa approach than to the IMPS. More detailed comparisons with diagnostic subgroups of schizophrenic and schizoaffective patients substantiated the findings in the overall sample. Overall it was reconfirmed that the DIS approach is limited to those patients who are cooperative and at least partly remitted.