Mapping genomic loci implicates genes and synaptic biology in schizophrenia.

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.

Profiles of Subjective Daytime Sleepiness through Cluster Analysis.

Sleepiness propensity and sleepiness perception are two relevant dimensions of the general multidimensional sleepiness construct. In the current study, the aim was to identify eventual homogeneous subgroups when sleepiness propensity and sleepiness perception measures are combined. Data from 678 undergraduate students (aged 17 to 24 years) from a medical school were analyzed. A Two-Step Cluster Analysis was performed taken into consideration sleepiness propensity and sleepiness perception measures as clustering variables. Four different clusters were identified. Additionally, the two groups comprising higher levels of sleepiness perception (i.e., "high perception, low propensity" and "high subjective daytime sleepiness" clusters) had the most compromised results in some of the sleep-related variables examined - sleep needs, sleep latency, sleep quality, sleep sufficiency, self-reported insomnia, sleep reactivity to stress, and cognitive arousal - and in some of non-sleep related variables, such as neuroticism and affect. As to non-sleep variables, those groups reported higher scores in neuroticism, arousability, self-reported mental health and affective states. The identification of distinct groups concerning self-reported sleepiness may bring new avenues for research and understanding of the specific and differential role of sleepiness and its dimensions in sleep health and sleep disturbances, in particular, insomnia disorder.

Assessing Stress-Induced Sleep Reactivity in College Students: The European Portuguese Version of the Ford Insomnia Response to Stress Test (FIRST).

OBJECTIVE AND BACKGROUND: Over the past few years, the comprehensive models of insomnia have exhibited impressive developments. However, there is scarce knowledge on predisposing or vulnerability factors for insomnia. One of the most promising constructs to aid in filling this gap is stress-induced sleep reactivity assessed through self-report. Our aim was to study the psychometric properties of the European Portuguese version of the Ford Insomnia Response to Stress Test (FIRST). PARTICIPANTS: We recruited a large sample of students attending medical school (N = 699). METHODS: Several analyses were carried out such as internal consistency, construct validity, and discriminant groups' analysis. RESULTS: It was observed that FIRST-PT shows good internal consistency (Cronbach´s alpha = .81) and validity indicators. Interestingly, and contrary to what was observed in the previously published studies on psychometric properties of the FIRST, it was observed that a two-factor solution (Factor I = rumination, Factor II = worry) was the most adequate one to explain the correlation matrix, accounting for approximately 44% of the total variance. CONCLUSIONS: The FIRST-PT proved to be a useful and reliable tool to measure stress-induced sleep reactivity. However, these results should be replicated in other groups, particularly clinical samples, in order to verify the stability of its factorial dimension.

Sleep-wake patterns reported by parents in hyperactive children diagnosed according to ICD-10, as compared to paired controls.

This study aimed primarily to compare the parent-reported sleep of children with ICD-10 hyperkinetic disorder (HKD) versus community children. Thirty children aged 5-13 years (83.3% boys) diagnosed with HKD by their child and adolescent psychiatrists took part in this study, plus 30 community children, matched for sex, age, and school year. Compared to the controls, the HKD children showed significantly later bedtimes, stronger bedtime resistance, longer sleep latency, shorter sleep; more frequent behaviors and symptoms concerning falling asleep into parents bed, needing something special to initiate sleep, nightmares, sleep talking, sleep bruxism, fear from darkness, bedwetting, and, most notably, loud snoring (26.7%); they also tended to show higher daytime somnolence. Attention deficit/hyperactivity disorder (ADHD)/HKD children may thus have more sleep-related problems than typically developing children. Alternatively, our results may reflect misdiagnoses; thus, special attention should be directed to comorbidity and differential diagnosis issues between sleep disturbances and ADHD/HKD.

Daytime sleepiness in insomnia: Are we focusing on what truly matters?

Insomnia, the most prevalent sleep disorder, is commonly associated with other mental and somatic disorders, making it a significant health concern. It is characterized by nighttime symptoms and daytime dysfunction, with sleepiness being a potential criterion for the latter. Sleepiness is a normal physiological state that is typically experienced near usual bedtime, in normal circumstances. In insomnia, it seems somewhat logical the idea that there is significant daytime sleepiness. However, the topic has been the subject of various discussions in sleep medicine, with studies yielding contradictory and inconsistent results. In this article, we aim to critically examine daytime sleepiness in individuals with insomnia disorder and propose an alternative approach to addressing it, both in clinical practice and research settings. It is crucial to further investigate the role of daytime sleepiness in insomnia, particularly by focusing on sleepiness perception as a more relevant dimension to explore in majority of patients. It is plausible that certain insomnia phenotypes are objectively sleepy during the day, but more studies are necessary, particularly with well-defined clinical samples. The implications of assessing sleepiness perception in insomnia for clinical practice are discussed, and new avenues for research are suggested.

Short forms of the postpartum depression screening scale: as accurate as the original form.

The aims of the present study were to develop three shorter forms of the Portuguese version of the Postpartum Depression Screening Scale (PDSS) as adapted and translated in Portugal, to analyse their psychometrics and to determine their cut-off points and associated conditional probabilities to screen for perinatal depression according to DSM-IV and ICD-10 criteria. In this study, 441 women in the third trimester of pregnancy and 453 in the third month of postpartum were interviewed for diagnostic purposes according to the Portuguese versions of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness. DSM-IV and ICD-10 classifications of depression were our gold standards for caseness. Three different shorter forms of the original Portuguese version of the PDSS were developed on the basis of reliability and factorial analysis. PDSS short versions, composed of seven and 21 (postpartum)/24 (pregnancy) items, presented significant reliability and validity and showed satisfactory combinations of sensitivity and specificity (≅80 %). The short forms of the original Portuguese version of the PDSS are valid alternatives to the 35-item version, given their equally precise screening performances, more concise structures and ease of completion.

Psychometric Properties of the Sleep Locus of Control (SLOC) Scale in a Portuguese Sample.

Over the past few decades, research has suggested that cognitive variables play a key role in sleep disorders, particularly, in insomnia. The SLOC (Sleep Locus of Control Scale) evaluates the sleep locus of control, which is associated with the degree to which an individual attributes her/his experiences of sleep to chance or internal causes. The aim of this study was to develop the first translation and adaptation of the SLOC into the European Portuguese, as well as to analyze its psychometric properties. In this study, it was recruited a sample of 2029 Portuguese Higher Education students, aged ≥ 18 years, where approximately 75% of the sample were women and 25% men. The results showed that the SLOC had acceptable internal consistency value (α = .64), considering that it is a measure with a reduced number of items. As in the original study, a principal component analysis with varimax rotation identified two components. A parallel analysis was also conducted, identifying two factors. The correlation between the two subscales "internal sleep locus of control" and "chance sleep locus of control" was positive albeit of low magnitude (r = .15). Through the analysis carried out, it was also observed that individuals with "insomnia", relative to those without, had a more chance sleep locus of control. Overall, these findings show similarities with the original study. The SLOC seems to be a useful psychological assessment measure to be used in clinical and research settings.

Is insomnia in late pregnancy a risk factor for postpartum depression/depressive symptomatology?

The aim of the present work was to investigate if insomnia in late pregnancy is a risk factor for postpartum depressive symptomatology/postpartum depression (PPD). 581 women in their last trimester of pregnancy answered questions/questionnaires about lifetime history of insomnia, current sleep perception, current mood and depressive symptomatology. They were interviewed with the Portuguese version of the Diagnostic Interview for Genetic Studies. After delivery 382 (65.7%) mothers participated again in the study. Insomnia in pregnancy was not a risk factor for PPD (DSM-IV or ICD-10) but was a significant predictor of postpartum depressive symptomatology. Negative Affect (NA) was a significant predictor of postpartum depressive symptomatology. Women with higher NA were 4.6 (CI95%=1.69-12.74) and 5.3 times (CI95%=2.26-12.58) more likely of experiencing PPD (DSM-IV/ICD-10, respectively) than women with lower NA. Lifetime Depression was a significant predictor of postpartum depressive symptomatology and ICD-10/PPD (OR=2.6; CI95%=1.16-4.38). Positive Affect (PA) showed to be a protective factor for postpartum depressive symptomatology and DSM-IV/PPD (OR=1.5; CI95%=1.20-2.33). Controlling NA, PA and Lifetime Depression, insomnia lost its predictive role, suggesting these variables might work as mediators. Associations between insomnia, NA, PA and Lifetime Depression should be assessed in pregnancy. This might help to preventively target NA, enhance PA and reduce the likelihood of experiencing postpartum depressive symptomatology.

The postpartum depression screening scale: is it valid to screen for antenatal depression?

The purpose of the study was to analyse for the first time the validity of a slightly modified version of the Portuguese Postpartum Depression Screening Scale (PDSS), to be used as a screening instrument for antenatal depression. Specifically, the aims were to analyse its psychometric properties, to determine PDSS cutoff points and associated conditional probabilities to screen for depression according to DSM-IV and ICD-10 criteria and to compare its screening performance with that of the Beck Depression Inventory-II (BDI-II). Five hundred and three pregnant women in the third trimester of pregnancy completed both questionnaires and were interviewed face-to-face with the Portuguese version of the Diagnostic Interview for Genetic Studies. The Portuguese version of the Operational Criteria Checklist for Psychotic Illness was used to obtain DSM-IV and ICD-10 diagnoses of depression, our gold standards for caseness. PDSS reliability and validity were very good and comparable to those obtained in the postpartum validation studies developed in Portugal and in other countries, showing satisfactory sensitivity and specificity combinations (≅80%). Compared with BDI-II, it has the advantage of being more specific for the motherhood context. Although developed for postpartum depression, PDSS is accurate to screen for antenatal depression, and it could be very useful for clinical and epidemiologic purposes.

Perfectionism dimensions in pregnancy--a study in Portuguese women.

Pregnancy is essentially a physiological event, but neuroendocrinal and psychosocial changes are also important components of this experience. In this context, perceived stress may be enhanced by the activation of certain personality traits, like perfectionism, which in turn may be associated with more psychological distress (PD). The aim of this study was to investigate if perfectionism could be associated with more negative emotional outcomes (PD) in the transition to motherhood and to look at which of the perfectionism dimensions these consequences are specifically linked. The sample comprises 421 pregnant women (mean = 29.8, SD = 4.48 years) who completed measures of perfectionism and mood symptoms. A two-factor model with self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) dimensions and a three-factor model with SOP, SPP-others' high standards and SPP-conditional acceptance (CA) factors were explored. Correlations and linear regressions were calculated between perfectionism factors and mood variables. Results showed that higher levels of SPP factors were associated with increased anxiety, depression, anger, fatigue and confusion, with decreased vigour and with more severe depressive symptoms. Our results, in contrast with those from the study of Campbell and DiPaula (2002, In: Flett G, Hewitt P (eds) Perfectionism. Theory, research, and practice. American Psychological Association, Washington, pp 181-198), did not confirm a preferential association between SPP-CA and PD, revealing that both components of SPP were associated with PD.

The BDI-II factor structure in pregnancy and postpartum: Two or three factors?

The purpose of the present study was to investigate the factor structure of the Beck Depression Inventory-II (BDI-II) in pregnancy and postpartum. Women were asked to fill in the BDI-II in their last trimester of pregnancy and at 3 months after delivery. A total of 331 pregnant women, with a mean age of 29.7 years (SD=4.6), and 354 mothers, aged 30.6 years (SD=4.6 years), answered the BDI-II. The first group was mainly nulliparas (65.6%) and the second group was mostly primiparas (57.4%). Factor analyses with principal components solution and varimax rotation were performed. Based on the scree test of Cattell a 2-factor solution and a 3-factor solution were explored. The 2-factor solution was identical in pregnancy and postpartum. Items loading in the Cognitive-Affective factor and in the Somatic-Anxiety factor were almost the same, though the Cognitive-Affective factor explained more of the BDI-II total variance in pregnancy, whereas in postpartum both factors explained similar total variances. The 3-factor solution of the BDI-II in pregnancy and postpartum slightly diverged. Besides the Cognitive-Affective and the Somatic-Anxiety factors, a third factor, Fatigue, was obtained in pregnancy while Guilt was the third factor identified in postpartum. This study reveals that the BDI-II 3-factor solution might be more appropriate to assess depressive symptoms in pregnancy and postpartum.

Perfectionism and eating attitudes in Portuguese students: a longitudinal study.

AIM: To investigate the role of perfectionism in the development of disordered eating behaviours. METHOD: 382 female university students completed the Hewitt & Flett MPS and the EAT-40 at baseline, and 1 year after (T1) and 206 2 years later (T2). RESULTS: Perfectionism at baseline was significantly associated with long-term abnormal eating attitudes/behaviours. Self-Oriented Perfectionism (SOP) and Socially Prescribed Perfectionism (SPP) were significant predictors of disordered eating behaviours. Regression analysis revealed that SOP at baseline was predictive of Diet Concerns and overall eating disturbance (EAT total score), at T1 and T2. SPP was a significant predictor of Social Pressure to Eat at T1 and T2 and of Bulimic Behaviours only at T1. CONCLUSION: Our findings contribute to a more clear understanding of the association between perfectionism and eating disorders. SOP and SPP were prospectively associated with abnormal eating attitudes/behaviours and SOP was found to be predictive of diet concerns and overall eating disturbance.

BaSIQS - basic scale on insomnia complaints and quality of sleep: reliability, norms, validity, and accuracy studies, based on clinical and community samples.

This research focused on the Basic Scale on Insomnia Symptoms and Quality of Sleep (BaSIQS), formerly validated in undergraduates using the Pittsburgh Sleep Quality Index (PSQI), and aimed to expand internal consistency analysis, examine thoroughly its validity, and determine its clinical accuracy. Considering objective and subjective measures, recruiting non-clinical and clinical samples, this research implemented a comprehensive approach to examine convergent and discriminant validity, confirmatory factor analyses, and the BaSIQS sensitivity and specificity. The BaSIQS was filled out along with the Insomnia Severity Index (ISI), questions on sleep-wake schedules, Composite Scale of Morningness (CSM) and Brief Symptom Inventory-18 (BSI-18) by 1198 adults, 18-64 years old, plus another 30 who wore actimeters, recruited in community settings. A clinical group of 30 chronic insomnia disorder patients also participated. Cronbach alpha coefficient was 0.80. A two-factor structure was confirmed. The association between BaSIQS and ISI was large, whereas actigraphy correlations were medium or small. Medium to non-significant correlations were found concerning conceptually different self-report measures. Comparing the clinic and control groups, the former showed poorer sleep, with a large effect size. Receiver operating characteristic analysis revealed an area under curve = 0.9, and an optimal cut-off score >15. In conclusion, results on reliability, validity, and accuracy provide support to the utility of the BaSIQS both in community and clinical settings, for research and practical purposes.

Organization and quantification of the elements in the intertubular space in the adult jaguar testis (Panthera onca, LINNAEUS, 1758).

The endocrine portion of mammal testicle is represented by Leydig cells which, together with connective cells, leukocytes, blood and lymphatic vessels, form the intertubular space. The arrangement and proportion of these components vary in the different species of mammals and form mechanisms that keep the testosterone level--the main product of the Leydig cell--two to three times higher in the interstitial fluid than in the testicular blood vessels and 40-250 times higher in these than in the peripheral blood. Marked differences are observed among animal species regarding the abundance of Leydig cells, loose connective tissue, development degree and location of the lymphatic vessels and their topographical relationship with seminiferous tubules. In the jaguar about 13% of the testicular parenchyma is occupied by Leydig cells, 8.3% by connective tissue and 0.3% by lymphatic vessels. Although included in standard II, as described in the literature, concerning the arrangement of the intertubular space, the jaguar has grouped lymphatic vessels in the intertubular space instead of isolated ones. In the jaguar the average volume of the Leydig cell was 2386 microm3 and its average nuclear diameter was 7.7 microm. A great quantity of 2.3 microm diameter lipidic drops was observed in the Leydig cell cytoplasm of the jaguar. The Leydig cells in the jaguar occupy an average 0.0036% of the body weight and the average number per gram of testicle was within the range for most mammals: between 20 and 40 million.

The Portuguese short form of the Eating Attitudes Test-40.

To develop a Portuguese short form, the Eating Attitudes Test-40 (EAT-40) was administered to a community sample of 922 female students and to a clinical sample of 63 females suffering from an eating disorder. With the EAT responses of the community sample a factor analysis was performed and items with factor loadings > or = 0.30 were selected. Internal consistency was computed for both the instrument and the factors. To study the discriminant capacity the proportion of symptomatic answers and the mean scores were compared between the clinical (N = 63) and control (N = 63) samples. Three factors were extracted: Drive for Thinness (14 items, alpha = .839), Bulimic Behaviours (8 items, alpha = .670), Social Pressure to Eat (3 items, alpha = .758). The short form is composed of 25 items and shows good internal consistency = 0.839. Symptomatic answers for all items (except one) and total mean scores were significantly higher (p < .001) in the clinical sample than in community sample.

Factor structure of the Rutter Teacher Questionnaire in Portuguese children.

OBJECTIVE: To examine the factor structure of the Rutter Teacher Questionnaire in Portuguese primary school children. METHOD: The Rutter Teacher Questionnaire, a 26-item scale covering a variety of behavioral problems, was completed by teachers of 877 children, aged 6 to 11 years. Data were subjected to factor analysis using the principal components solution with varimax rotation. RESULTS: The factorial analysis in total sample revealed three factors explaining 38.88% of the total variance. The factors contained items representing hyperactivity/conduct (Factor 1), anxious/depressive (Factor 2) and truancy/stealing (Factor 3). The highest correlations between factors scores were for Factor 1 and Factor 3. These Factors scores were higher in boys than girls and correlated with lower social class. All three Factors scores correlated with school performance. The comparison between separate factorial structures for the samples of boys and girls revealed a considerable overlap. CONCLUSIONS: The pattern of the items contained on Factor 1 appears to be related with the category of hyperkinetic conduct disorder used by the International Classification of Diseases-10. Results suggest that the Portuguese language version of the Rutter Teacher Questionnaire possesses good psychometric properties and may be considered a useful instrument for measuring children's behavior problems.

Portuguese Version of the Arousal Predisposition Scale: Preliminary Evidence for a Two-Factor Structure in a Nonclinical Sample.

It is known that there is significant variability in arousal levels of the individuals. The Arousal Predisposition Scale (APS) is a questionnaire intended to measure individual differences in arousability. In the current work, our aim was to present the initial psychometric properties of the Portuguese version of the APS. Three hundred forty-five undergraduate medical students from both genders were enrolled. All participants filled out a set of questionnaires-which contained the APS-at the end of their lectures and out of the evaluation period. The APS showed good internal consistency (α = .85) and discriminated individuals with extreme scores. Further, in general, the scale discriminated as well both genders pertaining to the individual items and total score. In terms of scale structure, two related factors were extracted (F1 = emotional reactivity and F2 = trait anxiety). Significant associations among APS and other sleep and psychological self-report variables were also observed. The APS seems to be a reliable and valid instrument to assess self-reported physiological arousability, at least in a sample of young adults. The two-factor composition will require more studies to be replicated in similar groups and, particularly, in clinical samples.

Pre-Sleep Arousal Scale (PSAS): psychometric study of a European Portuguese version.

OBJECTIVE/BACKGROUND: Pre-sleep arousal constitutes one of the major features of insomnia. As such, it is imperative to have adequate instruments to measure this construct in both clinical and research settings. The Pre-Sleep Arousal Scale (PSAS) is the most well-known measure to evaluate pre-sleep arousal. The current study aimed to examine some of the psychometric properties of a European Portuguese version of the scale. PARTICIPANTS/METHODS: For this purpose, data from 691 undergraduate students from a medical school were analyzed. Internal consistency indices and factor analysis were performed. In addition, the association between the PSAS and its subscales with other measures was also examined. Finally, PSAS scores of self-reported insomniacs were compared with those of self-reported non-insomniacs. RESULTS: The results indicated that the PSAS comprises a cognitive scale and a somatic scale, both with adequate internal consistency indices (α = 0.82 and 0.79, respectively). However, a three-factor solution also seemed plausible, suggesting that the original somatic arousal subscale might be divided into two subscales. Significant associations between the PSAS total score and its subscales were found with other concurrent measures such as sleep reactivity to stress, arousability and neuroticism. Self-defined insomniacs presented higher levels of cognitive and somatic arousal than healthy individuals. CONCLUSIONS: Further investigations of the PSAS are needed to refine its psychometric properties and explore its research and clinical utility in other populations.

Perfectionism and eating attitudes in Portuguese university students.

OBJECTIVES: The main objective was to explore which are the dimensions of perfectionism that are linked to disordered eating behaviour (EB) in a large non-clinical sample of both genders. METHOD: One thousand one hundred and sixty-three undergraduate students of the University of Coimbra completed the Portuguese versions of the multidimensional perfectionism scale (MPS) and the eating attitudes test (EAT-40). RESULTS: In both genders, the MPS total score was associated with the EAT total score and all EAT dimensions (except for socially prescribed perfectionism in females). Self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) were associated with EAT total score, diet concerns (DC) and bulimic behaviour (BB) in females while in males the social prescribed perfectionism (SPP) was the useful predictor of EAT total score, BB and social pressure to eat (SPE). CONCLUSION: These results confirm that in general high levels of perfectionism are associated with abnormal EB. This was the case for both genders for SPP but for SOP for females only. The association for other oriented perfectionism (OOP) was greater for males than for females.