Mother's personality and infant temperament.

We examined if perfectionism and the perception of being an anxious person were associated with more negative infant temperament ratings by the mothers. 386 women (mean age=30.08; standard deviation=4.21) in their last trimester of pregnancy completed the Multidimensional Perfectionism Scale (MPS), the Beck Depression Inventory-II (BDI-II) and an item about their perception of being or not an anxious person. The Portuguese version of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness were used to generate diagnoses according to DSM-IV and ICD-10 criteria. After delivery, women completed eight items of the Difficult Infant Temperament Questionnaire (developed by our team) and filled in, again, the BDI-II and were interviewed with the DIGS. Women with depression (DSM-IV/ICD-10) and probable cases of depression using different cut-offs adjusted to Portuguese prevalence (BDI-II), in pregnancy and postpartum, were excluded. The Difficult Infant Temperament Questionnaire showed to have factorial validity and internal consistency. There was a statistically significant negative correlation between perfectionism total scale score and item 6 from the temperament scale ("is your baby irritable or fussy?"). Considering MPS 3-factor solution found for pregnancy there was also a statistically significant negative correlation between SOP and the same item. Women with low SOP differed from those with medium and high SOP in the total temperament score. Moreover, the low SOP group differed from the medium group on items three and four scores. There were no significant associations with SPP, which is the dimension more closely associated with negative outcomes. There was an association between anxiety trait status (having it or not) and scoring low, medium or high in the infant temperament scale. The proportion of anxious vs. non-anxious women presenting a high score on the infant temperament scale was higher (24.2% vs. 12.9%). Linear regressions showed that SOP (low vs. medium/high) offered a significant contribution to the prediction of total temperament scale score and items 3 and 4 scores, but a logistic regression did not confirm trait anxiety as a significant predictor of mother's infant temperament perception. Concluding, a major result concerns the fact that higher levels of adaptive perfectionism (i.e. SOP) are associated (and predict) a less negative view of their infant's temperament. These results on the effect of mother's anxiety and perfectionism on the child temperament perception might have treatment implications. As perfectionism is not always maladaptive, some of its positive features could be used to enhance women's self-efficacy/sense of parental competence in their role as mothers and positive affect towards their infants. Also, antenatal interventions aimed at minimising anxiety could help to optimise infant temperament outcomes, which could, eventually, also, lead to subsequent maternal and infant mental health better outcomes.

Perfectionism and eating behaviour in Portuguese adolescents.

OBJECTIVES: The main objective was to investigate the association between perfectionism and eating behaviour in a non-clinical sample of adolescents of both genders. METHOD: 997 middle and high school students completed the Portuguese versions of the child-adolescent perfectionism scale (CAPS) and of the eating attitudes test -25 (EAT-25). RESULTS: In both genders, the perfectionism total score and the sociallyprescribed perfectionism (SPP) score were positive and significantly correlated with the EAT total score and with all EAT dimensions: Drive for Thinness (DT), Bulimic Related Behaviour (BRB), Social Pressure to Eat (SPE). In girls, self-oriented perfectionism (SOP) was also associated with the EAT total score and its dimensions, whereas in boys it was only associated with EAT total score and DT. In both genders SPP was a useful predictor of the EAT-25 total score and of all its dimensions. In which respects SOP, there were some gender differences showing that in boys this dimension should not be considered a predictor of eating behaviours. CONCLUSION: These results confirm that high levels of perfectionism (SOP and SPP) are associated with abnormal eating behaviour in both genders.

[Sleep-wake patterns in Portuguese undergraduates]. / Padrões de sono em estudantes universitários Portugueses.

INTRODUCTION: Sleep habits of Portuguese undergraduates are almost unknown, and very few international published articles have addressed whether demographic and academic variables such as residence, university year and academic field, might be associated to the sleep-wake patterns of university students. The aims of the present work were thus to characterize perceived sleep habits, behaviours and problems of Portuguese undergraduates, and to examine them by gender, residence status, university year and academic field. POPULATION AND METHODS: The selected participants were 1654 undergraduates (55% female) of a public Portuguese university, aged 17-25 years (M = 19.98, SD = 1.65), at the 1st, 2nd a 3rd university years, studying Engineering, Management, Sciences, Languages and Education, in its majority living outside their parents/family home (<> students). Participants answered to a self-response questionnaire about sleep-wake patterns, developed for the main research. RESULTS: Compared to men, women showed more regular and earlier sleep-wake schedules, fewer sleeplessness nights, and less napping, but more troubles initiating/maintaining sleep and use of pills to fall asleep. <> students had the latest sleep-wake schedules on week nights, and felt more disturbed by noise; <> men reported more sleeplessness nights to complete academic tasks and greater changes of sleep habits since high school. Across university years (1st-3rd), there was a rising of perceived change of sleep habits, a delay of bedtime on school nights, and a decrease, in men, of week-weekend irregularity of rise time and of sleeplessness nights. Engineering students had the fewest difficulties initiating/maintaining sleep and the lowest use of sleeping promoting pills but, together with Sciences and Management, later sleep-wake schedules, than Languages and Education students. DISCUSSION AND CONCLUSION: Differences on sleep-wake patterns were found between men and women, in accordance to the sleep literature. On addition to gender, the present study highlights that university year and, most importantly, residence circumstances, are also important variables to be considered for a better understanding of sleep habits and behaviours in undergraduates. Thus, we hope our findings constitute a contribution for the improvement of health prevention and intervention strategies directed to university students.

Sleep and behavioral/emotional problems in children: a population-based study.

BACKGROUND: The potential relationships between sleep-wake behaviors and emotional/disruptive problems in otherwise healthy school-aged children are unclear. METHODS: A parental questionnaire was developed for the epidemiologic survey of children's sleep and wake behavioral patterns. The questions covered a wide range of features including sleep length (school days, weekends), time to fall asleep, night awakenings, bedtime and nighttime sleep-related behaviors, daytime sleepiness, irritability, and tiredness. To assess psychiatric symptomatology, the Rutter Scale B2 was completed by teachers. In addition to the total score, sub-scores of emotional, hyperactivity, and conduct problems were obtained. The representative population sample comprised 779 children (403 girls), with an age range of 6-11 years. RESULTS: Hyperactivity and conduct problems at school in boys were both associated with parental reports of bedtime resistance. Hyperactivity was also associated with longer sleep duration during weekends. Conduct and emotional problems in girls were associated with earlier bedtime during school days. Emotional problems in girls were also associated with longer sleep durations in school days and weekends. CONCLUSION: Bedtime resistance was the only sleep behavior associated with either hyperactivity or conduct problems in children, and longer sleep durations appear to occur more frequently in children with both hyperactive or emotional problems. Information about good sleep hygiene at bedtime may help parents setting sleep limits.

Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia.

We previously performed a genome-wide linkage scan in Portuguese schizophrenia families that identified a risk locus on chromosome 5q31-q35. This finding was supported by meta-analysis of 20 other schizophrenia genome-wide scans that identified 5q23.2-q34 as the second most compelling susceptibility locus in the genome. In the present report, we took a two-stage candidate gene association approach to investigate a group of gamma-aminobutyric acid (GABA) A receptor subunit genes (GABRA1, GABRA6, GABRB2, GABRG2, and GABRP) within our linkage peak. These genes are plausible candidates based on prior evidence for GABA system involvement in schizophrenia. In the first stage, associations were detected in a Portuguese patient sample with single nucleotide polymorphisms (SNPs) and haplotypes in GABRA1 (P=0.00062-0.048), GABRP (P=0.0024-0.042), and GABRA6 (P=0.0065-0.0088). The GABRA1 and GABRP findings were replicated in the second stage in an independent German family-based sample (P=0.0015-0.043). Supportive evidence for association was also obtained for a previously reported GABRB2 risk haplotype. Exploratory analyses of the effects of associated GABRA1 haplotypes on transcript levels found altered expression of GABRA6 and coexpressed genes of GABRA1 and GABRB2. Comparison of transcript levels in schizophrenia patients and unaffected siblings found lower patient expression of GABRA6 and coexpressed genes of GABRA1. Interestingly, the GABRA1 coexpressed genes include synaptic and vesicle-associated genes previously found altered in schizophrenia prefrontal cortex. Taken together, these results support the involvement of the chromosome 5q GABAA receptor gene cluster in schizophrenia, and suggest that schizophrenia-associated haplotypes may alter expression of GABA-related genes.

Support for involvement of neuregulin 1 in schizophrenia pathophysiology.

Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ("Hap(ICE)"), and two haplotypes located in the 3' end of NRG1 (all P<0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.

Genomewide linkage analysis of bipolar disorder by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay: a comparison with microsatellite marker assays and finding of significant linkage to chromosome 6q22.

We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11.

Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11.

As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley-Liss, Inc.

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. Molecular Psychiatry (2004) 9, 213-218. doi:10.1038/sj.mp.4001418 Published online 30 December 2003

Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3eta gene.

Although the genetic contribution to schizophrenia is substantial, positive findings in whole-genome linkage scans have not been consistently replicated. We analyzed gene expression in various rat conditions to identify novel candidate genes for schizophrenia. Suppression subtraction hybridization (SSH), with polyA mRNA from temporal and frontal cortex of rats, was used to identify differentially expressed genes. Expression of mRNA was compared between adult Lewis and Fischer 344 (F344) rats, adult and postnatal day 6 (d6) F344, and adult F344 treated with haloperidol or control vehicle. These groups were chosen because each highlights a particular aspect of schizophrenia: differences in strain vulnerability to behavioral analogs of psychosis; factors that may relate to disease onset in relation to CNS development; and improvement of symptoms by haloperidol. The 14-3-3 gene family, as represented by 14-3-3gamma and 14-3-3zeta isoforms in the SSH study, and SNAP-25 were among the candidate genes. Genetic association between schizophrenia and the 14-3-3eta gene, positioned close to a genomic locus implicated in schizophrenia, and SNAP-25 genes was analyzed in 168 schizophrenia probands and their families. These findings address three different genes in the 14-3-3 family. We find a significant association with schizophrenia for two polymorphisms in the 14-3-3eta gene: a 7 bp variable number of tandem repeats in the 5' noncoding region (P=0.036, 1 df), and a 3' untranslated region SNP (753G/A) that is an RFLP visualized with Ava II (P=0.028). There was no significant genetic association with SNAP-25. The candidate genes identified may be of functional importance in the etiology, pathophysiology or treatment response of schizophrenia or psychotic symptoms. This is to our knowledge the first report of a significant association between the 14-3-3eta-chain gene and schizophrenia in a family-based sample, strengthening prior association reports in case-control studies and microarray gene expression studies.

Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population.

A functional polymorphism in the promoter region of the DRD2 gene has been found to be associated with schizophrenia in Japanese(1,2) and Swedish populations.(3) We attempted to replicate these findings in a genetically homogeneous Portuguese population using a family-based study design. Analysis of 78 trios revealed evidence for association between the -141 C Ins allele and schizophrenia using the haplotype relative risk (HRR) method (chi(2) = 9.30, P = 0.0023). Further examination of this sample using an alternative family-based association analysis method, the transmission disequilibrium test (TDT), of 33 informative matings from the Portuguese trios provided evidence for an allelic association and linkage disequilibrium between the insertion allele and schizophrenia (chi(2) = 8.76, P = 0.0031). These consistent results using two alternative family-based association analysis methods replicate the findings of previous reports, and thus further implicate a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia.

Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families.

Recent studies have suggested that the alpha 7-nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7-nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13-14 regions. The human gene is partially duplicated (exons 5-10) with four novel upstream exons. The marker D15S1360 has been shown to be significantly linked with the phenotype of abnormal P50 suppression in schizophrenia families. The marker L76630 is 3 kb in the 3' direction from the last exon of the CHRNA7 gene and is located in the duplicated region. The function of the two L76630 copies is unknown. We genotyped three polymorphic markers D15S1360, D15S165, and L76630 that are localized in a genomic fragment containing the CHRNA7 in 31 Azorean schizophrenia families/trios (including 41 schizophrenia individuals and 97 unaffected families members). An overall analysis utilizing the family-based association test revealed significant linkage disequilibrium between L76630 and schizophrenia (P = 0.0004). Using the extended transmission disequilibrium test and limiting the analysis to one triad per family, transmission disequilibrium of D15S1360 was near significance (P = 0.078). The 15q13 region overlaps with the location of two well-known genomically imprinted disorders: Angelman syndrome and Prader-Willi syndrome. Therefore, we investigated maternal and paternal meioses. We found significant transmission disequilibrium for D15S1360 through paternal transmission (P = 0.0006) in our schizophrenia families. The L76630 marker showed a significant disequilibrium in maternal transmissions (P = 0.028). No parent-of-origin effect was found in D15S165. Overall, our results suggest that the CHRNA7 may play a role in schizophrenia in these families. A parent of origin effect may be present and requires further study.

Detection of expansion regions in Portuguese bipolar families.

We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000.

Long repeat tracts at SCA8 in major psychosis.

Expansion at a recently identified unstable trinucleotide repeat on chromosome 13q21 has been reported as the molecular cause for spinocerebellar ataxia type 8 (SCA8). The trinucleotide repeat, which consists of a [CTA]n repeat and adjacent [CTG]n repeat, was reported to have a pathogenic range of 107-127 CTG repeats (or 110-130 combined CTA and CTG repeats) in a large ataxia kindred. This repeat region was also cloned by our group from a bipolar affective disorder (BPAD) patient, who has approximately 600 combined repeats, and large alleles (>100 repeats) were reported to be present in 0.7% of controls and 1.5% of major psychosis patients (n = 710 and n = 1,120, respectively). We have followed up these findings by screening three new samples of BPAD and schizophrenia (SCZ) patients and controls, including 272 individuals from 14 BPAD families from Sweden, 130 individuals from 32 SCZ and BPAD families/trios from the Azores Islands, and 206 SCZ individuals from the United Kingdom and Ireland, and 219 matched controls. We found large repeat alleles above the SCA8 pathogenic range in individuals from 3 of 32 Azorean pedigrees and in 1 of 206 SCZ individuals from the United Kingdom, and repeat alleles within the SCA8 pathogenic range in 1 of 14 Swedish families. Although the rarity of major psychosis patients carrying the SCA8 expansion mutation would require a much larger sample size to reach statistical significance, these results support the previously reported observation of increased occurrence of large repeats at SCA8 in major psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:873-876, 2000.

Snoring in Portuguese primary school children.

OBJECTIVE: To determine the prevalence of snoring and its potential associations with sleep problems, such as daytime symptoms, medical conditions, school performance, and behavioral disturbances in Portuguese children attending primary school. METHODS: A previously validated questionnaire was sent to the parents of 1381 children attending primary schools in a parish of Coimbra, Portugal. To assess behavioral disturbances, the Portuguese version of Rutter's Children's Behavior Questionnaire for completion by teachers was used. RESULTS: Of the 988 questionnaires returned (71.5%), complete information concerning snoring was obtained for 976 children (496 girls and 480 boys; mean age: 8.1 +/- 1.5 years). Loud snoring during sleep was reported as frequent or constantly present (LSn) in 84 children (8.6%), as occasionally present in 299 children (30.6%), and as never present (NSn) by 593 children (60.8%). The LSn and NSn groups did not differ with respect to age, gender, sleep duration, time to fall asleep, frequency of night wakings, bedwetting, daytime tiredness, and school achievement. However, LSn was significantly associated with increased bedtime problems (fears and struggles), increased need for comforting activities to fall asleep, behaviors suggestive of parasomnias (sleep talking, teeth grinding, and night terrors), increased daytime sleepiness and irritability, and behavioral disturbances. Children in the LSn group were also more likely to report recurrent medical problems particularly those involving infections of the respiratory tract. CONCLUSIONS: Snoring is a common symptom in Portuguese children that is associated with behavioral daytime and sleep time disturbances. Children with loud snoring may benefit from early evaluation and intervention.

Using consensus OPCRIT diagnoses. An efficient procedure for best-estimate lifetime diagnoses.

BACKGROUND: The Operational Criteria Checklist (OPCRIT) generates diagnoses according to 12 operational diagnostic systems (e.g. DSM-III, DSM-III-R, Research Diagnostic Criteria, ICD-10). AIMS: To examine the agreement between diagnoses generated by the OPCRIT, as completed by the interviewer, with a best-estimate lifetime procedure using the OPCRIT. METHOD: Subjects came from large multi-generational bipolar or schizophrenia pedigrees (n = 100), and from a sample of unrelated subjects with schizophrenia (n = 40). We analysed the diagnostic agreement between OPCRIT diagnoses generated by the interviewer and our best-estimate OPCRIT diagnoses, according to DSM-III-R and ICD-10, using Cohen kappa statistics. RESULTS: Excellent agreement was found between interviewer OPCRIT diagnoses and OPCRIT diagnoses made by the best-estimate lifetime consensus procedure for DSM-III-R (kappa = 0.83) and ICD-10 (kappa = 0.81). CONCLUSIONS: Results suggest that this procedure for diagnostic assessment is an efficient alternative to classic best-estimate diagnosis procedures.

Selection of homogeneous populations for genetic study: the Portugal genetics of psychosis project.

Molecular genetic studies of psychiatric disorders must face the possibility that despite the significant contribution of genetic factors to the expression of syndromes like schizophrenia, these syndromes may be a heterogeneous collection of genetic and non-genetic illnesses. These illnesses may be etiologically distinct from each other and still share many clinical features in common. Linkage studies of families with multiple affected members tend to favor the selection of genetic forms of a syndrome but can still represent a heterogeneous set of different genetic illnesses. To limit the potential genetic heterogeneity of a study sample, we selected a population that was geographically isolated and was historically relatively genetically homogeneous. We then assessed the relative level of homogeneity utilizing a surname analysis of the population of the Azores, mainland Portugal, rural USA, and urban USA. The average number of families with the same last name corrected for population size in the Azores is 30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population and 0.38 in an urban American population. The results of this analysis indicate that the Azores have the highest degree of homogeneity, and mainland Portugal has a high degree of homogeneity.

[Acromegaly with the sleep apnea syndrome]. / Acromegalia com síndrome de apneia do sono.

The authors present the clinical of a male patient aged 45 years whose main complaints were loud snoring and excessive daytime sleepiness. Polysomnographic study revealed a sleep obstructive apnea syndrome with an apnea/hypopnea index of 86.5. After being treated with nasal continuous positive air pressure, (12 cm H2O), the apneas ended and sleep architecture was corrected. Physical examination also indicated the presence of an acromegaly, and therefore, the patient was subjected to endocrinological and cerebral imagiological studies; the diagnosis confirmed it as a predisposing factor to the sleep breathing disorder. A brief literature review about the incidence of sleep apnea syndrome in acromegaly is also made; the authors conclude that there is still the need for a systematic screening of sleep breathing disorders in acromegalic patients in order to optimise the treatment and prognosis of this disorders.

Expanded CAG/CTG repeats in schizophrenia. A study of clinical correlates.

BACKGROUND: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia. METHOD: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist. Patient's maximum CAG/CTG repeat length was measured using repeat expansion detection (RED). Significant differences were sought for repeat lengths in subjects categorised according to dimensional and categorical schizophrenia subsyndromes, affective episodes, individual symptoms, and a range of demographic variables. RESULTS: Maximum CAG/CTG repeat length did not differ significantly for any of the clinical or demographic variables studied. CONCLUSION: There are no subsyndromes or other clinical features of schizophrenia associated with CAG/CTG repeat expansion. Therefore, the identification of the gene(s) that contain expanded CAG/CTG repeats and which are associated with schizophrenia is unlikely to be facilitated at present by using any subsyndromes of schizophrenia as phenotypes.

Seleçäo de fungos predadores do gênero Arthrobotrys para passar através do trato gastrintestinal de bezerros / Screening parasitic nematode-trapping fungi Arthrobotrys for passage through the gastrointestinal tract of calves

Experimentos "in vivo" foram realizados para selecionar três isolados de fungos predadores de nematódeos, um isolado de Arthrobotrys musiformis e dois isolados de A. robusta, para passar através do trato gastrintestinal de bezerros sem perda de viabilidade para predar larvas infectantes de Haemonchus placei. Após a administraçäo de 20 x 10 elevado à sexta potência conídios divididos em quatro doses de 5 x 10 elevado à sexta potência de três em três horas por via oral aos bezerros, somente um isolado de A. robusta cumpriu este objetivo ao ser coletado de amostras fecais e, posteriormente, conseguir predar as larvas infectantes de H. placei, enquanto que nos demais isolados a passagem pelo trato gastrintestinal dos bezerros näo foi evidenciada. Este isolamento das fezes ocorreu entre 24 a 48 horas após a primeira administraçäo de conídios e de 15 a 39 horas após a última