Célia Barreto Carvalho

Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis.

Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31–5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at markers D5S2112–D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia (peak NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases.

Identification of a Highly Homogenous Population for Genetic Study of Psychiatric Disorders

Many psychiatric disorders are influenced by genetic factors, but the genetic components of complex diseases may not follow clear inheritance patterns. Although the patients may share a common clinical phenotype, the cause of the syndrome may consist of a heterogeneous collection of both genetic and/or environmental components. One method to minimize genetic heterogeneity in studies of complex disorders is to select a very homogenous study population. The average number of families with the same last name, when corrected for population size, is an excellent marker for the degree of homogeneity. We used surname analysis to evaluate the homogeneity of the Portuguese population of Madeira, comparing it with previous data on the homogeneity of populations of mainland Portugal, the Azores, and both rural and urban US populations. The average number of families with the same last name corrected for population size was 33.84 in Madeira, 30.88 in the Azores, and 21.42 in Coimbra (mainland Portugal) compared with 1.13 in rural and 0.38 in urban United States. This surname analysis supports the premise that the Portuguese population is a highly homogenous population, with the highest homogeneity in Madeira and the Azores, making it a good study population for molecular genetic analyses.

Influence of Family and Childhood Memories in the Development and Manifestation of Paranoid Ideation

Several studies point out to the influence of social experiences on perceptions of the environment and others in cognitive functioning and different aspects of psychopathology. The current study aimed at studying the influence of the psychosocial risk factors in a mixed sample of participants from the general population and affected by paranoid schizophrenia. The extent to which the existence of negative life events and events that are threatening to the inner models of the self (i.e., history of maltreatment, physical, social or psychological abuse) or the memories of these traumatic events occurring during childhood are related to the existence of paranoid beliefs in adulthood was explored. Results suggested that memories of parental behaviours characterized by antipathy from both parental figures, submissiveness and bullying victimization were important predictors of paranoid ideation in adult life. This further emphasizes the need for understanding the family and social dynamics of people presenting paranoid ideations to the development of therapeutic interventions that can effectively reduce the invalidation caused by severe psychopathology, as is the case of schizophrenia. Copyright

Genetic overlap of schizophrenia and bipolar disorder in a high‐density linkage survey in the Portuguese Island population

Recent family and genome‐wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome‐wide overlap between them. Forty‐seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene‐dropping simulations. Significance of genome‐wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54–15.71 MB, LOD = 3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32–90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL ≥ 1.98, which was more than would be expected by chance (empirical P = 0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high‐density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles.

Paranoia in the general population: A revised version of the General Paranoia Scale for adults

Background Paranoid ideation has been regarded as a cognitive and a social process used as a defence against perceived threats. According to this perspective, paranoid ideation can be understood as a process extending across the normal–pathological continuum. Methods In order to refine the construct of paranoid ideation and to validate a measure of paranoia, 906 Portuguese participants from the general population and 91 patients were administered the General Paranoia Scale (GPS), and two conceptual models (one- and tridimensional) were compared through confirmatory factor analysis (CFA). Results Results from the CFA of the GPS confirmed a different model than the one-dimensional model proposed by Fenigstein and Vanable, which comprised three dimensions (mistrust thoughts, persecutory ideas, and self-deprecation). This alternative model presented a better fit and increased sensitivity when compared with the one-dimensional model. Further data analysis of the scale revealed that the GPS is an adequate assessment tool for adults, with good psychometric characteristics and high internal consistency. Conclusion The model proposed in the current work leads to further refinements and enrichment of the construct of paranoia in different populations, allowing the assessment of three dimensions of paranoia and the risk of clinical paranoia in a single measure for the general population.

Association study of 83 candidate genes for bipolar disorder in chromosome 6q selected using an evidence-based prioritization algorithm

Prior genome‐scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci.

Contextual Cognitive-Behavioral Therapies Across the Psychosis Continuum

Considering several etiologic, therapeutic, and comorbidity-related factors, a psychosis continuum model has been proposed for the understanding and treatment of psychotic disorders. Within the new emerging treatment approaches, Contextual Cognitive-Behavioral Therapies (CCBT) seem to hold promise for the psychosis continuum. However, considering their novelty for this specific population, the quality of efficacy evidence remains unclear. Objective: To examine, critically analyze, and summarize the results from studies based on therapeutic models within the CCBT approach (Mindfulness and Acceptance-based interventions, Compassion-Focused Therapy, Dialectical Behavior Therapy, and Metacognitive Therapy) for patients with a diagnosis within the psychosis continuum (schizophrenia, schizoaffective disorder, bipolar disorder). Methods: Three leading electronic databases (MEDLINE/PUBMED; PsycINFO; Cochrane Library), a grey literature database (OpenGrey), and registered clinical trials (ClinicalTrials.Gov) were searched using combinations of key terms regarding the CCBT models and the diagnosis considered. Reference lists of the relevant studies and reviews were searched. Only Randomized Controlled Trials (RCTs) were included. The “Cochrane Risk of Bias Assessment Tool” was used for quality assessment. Results: A total of 17 articles were included. This review was based on a majority of unclear or low risk of bias studies. Benefits regarding clinical variables such as psychotic symptoms, anxiety and depression, functioning or quality of life were found. Conclusion: Overall the studies supported some benefits of CCBT approaches for the psychosis continuum. The conceptual perspective on treatment has changed, nevertheless the outcomes assessed are still symptom-focused and there is still need for improvement. Methodological considerations and future directions are presented.

Genetics of Schizophrenia: Current Findings and Issues

The genetics of schizophrenia are characterized by a set of complex questions, with few answers forthcoming. However, molecular genetic approaches remain the most promising avenue to the understanding of etiologic mechanisms. Powerful discoveries may arise in the near future from candidate gene studies that are benefiting from the extensive neurobiology research in schizophrenia over the past decades. Furthermore, there are promising new divisions of the phenotype into more manageable subtypes that may make both candidate gene and genome scan studies more revealing. The following review discusses selected highlights of the epidemiology, molecular genetic strategies, candidate genes, and genome scan investigations in schizophrenia.

Pathways from paranoid conviction to distress: exploring the mediator role of Fears of Compassion in a sample of people with psychosis

Abstract Fears of Compassion (FOC) relate to experiencing defensive emotions and avoidance reactions when receiving and giving compassion. Three different flows have been identified: giving compassion to others, receiving compassion, and self-compassion. This study sought to explore: FOC within a sample of patients with psychosis; the associations between FOC and paranoia; and the mediator role of FOC in the relationship between paranoid conviction and distress. Seventy-two patients with psychosis (74% diagnosed with schizophrenia), mostly male (85%), with a mean age of 33.46 (SD = 9.43), were recruited and assessed with measures of paranoia (conviction and distress) and FOC. Participants presented significantly higher levels of FOC than non-clinical samples and lower levels than depressed patients. Different flows of FOC were associated with each other and with paranoia-related measures. A mediation effect of FOC from others and fears of self-compassion was found. Results support the relevance of including FOC in formulation and treatment protocols for psychosis.

Attitudes towards mental health problems scale: Confirmatory factor analysis and validation in the Portuguese population

ABSTRACT Several studies about stigmatization and shame toward mental health problems have contributed to minimizing the impact of these negative attitudes on people diagnosed with mental illnesses, on their families and on their communities. The Attitudes Towards Mental Health Problems Scale (ATMHP) is a self-report scale aimed at the assessment of attitudes toward mental health that involve several factors relating to attitudes and shame (internal, external, and reflected shame) when facing mental health problems. The goal of the current study was to translate, and to adapt this scale to the Portuguese population, and to study its psychometric properties in a sample of Azorean adults with and without psychiatric problems. The scale was administered to 411 participants with ages between 19 and 81 years. Confirmatory factor analysis was carried out on the initial model proposed by the authors of the ATMHP, and results showed a poor adjustment. An alternative model comprising an additional factor was tested and presented good model fit indices. Based on the alternative model, further analysis revealed that the scale has good psychometric properties.