| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 2. |
- Bloomfield, Madeleine, et al.
(författare)
-
European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry
- 2024
-
Ingår i: BMJ OPEN. - 2044-6055. ; 14:6
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles.Methods and analysis EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms.Ethics and dissemination To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).
|
|
| 3. |
- Bodén, Robert, 1973-, et al.
(författare)
-
Psychomotor and cognitive deficits as predictors of 5-year outcome in first-episode schizophrenia
- 2014
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 68:4, s. 282-288
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive deficits are common in schizophrenia but the predictive value of these deficits for long-term outcome in first-episode patients is unclear. Aims: We aimed to investigate associations of performance in psychomotor and cognitive tests with a 5-year functional and symptomatic outcome. Methods: After clinical stabilization, patients with a first schizophrenia spectrum diagnosis (n = 46) were assessed for global cognitive function [Synonyms, Reasoning, and Block Design (SRB)], psychomotor speed [Trail Making Test (TMT) and finger tapping] and verbal learning (Claeson-Dahl Verbal Learning Test). The subsequent 5-year outcome regarding independent living, occupational and social function, and symptomatic remission status was assessed. Results: Low psychomotor speed was associated with poor social function 5 years later, with an odds ratio (OR) of 3.37 and a 95% confidence interval (CI) of 1.08-10.51, adjusted for antipsychotic drug use. Better performance on finger tapping with the non-dominant hand was associated with an increased risk of a 5-year symptomatic non-remission (adjusted OR = 0.42, CI 0.19-0.96). Occupational function and independent living were not significantly associated with any of the investigated tests. Conclusions: Psychomotor speed is associated with a long-term outcome regarding social function and symptom remission in patients with first-episode schizophrenia.
|
|
| 4. |
- Borg, Jacqueline
(författare)
-
Molecular imaging of the serotonin system in human behaviour
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The serotonin (5-HT) neurotransmission system has a role in essential physiological and psychological functions such as sleep, eating behaviour, sexuality, perception, emotion and cognition. Individual measures of serotonin biomarkers in the living human brain can be obtained using positron emission tomography (PET) imaging, direct measures of. The interindividual variability in these measures can then be related to human behavioural output. In combination with genotyping, this strategy provides an approach to complex chain of events linking the genetic endowment to higher brain functions. The present thesis includes a series of PET studies aimed to increase understanding of the role of serotonin in higher brain functions in man. In study I, fifteen control subjects were examined with PET and [11C]WAY100635, a radioligand that is selective for the serotonin 5-HT1A receptor. Personality traits were assessed with the Temperament and Character Inventory (TCI) self-report questionnaire. Availability of 5-HT1A receptor was found to correlate inversely with scores for self-transcendence, a personality trait covering religious behaviour and attitudes. This finding indicates that the serotonin system may serve as a biological underpinning for spiritual experiences. Interestingly, the observed several-fold variability in 5-HT1A receptor density may partly explain why people vary greatly in spiritual zeal. In study II, twenty-four control subjects were examined with [11C]WAY100635 PET and a battery of tests covering all major cognitive domains. There were no significant correlations between regional 5-HT1A binding and cognitive performance. The results do not provide support for involvement of the 5-HT1A receptor in cognitive functioning in man, thereby questioning the predictive validity of some currently used animal models in translational neuroscience. In study III, seventeen volunteers were examined with [11C]MADAM PET and a battery of cognitive tests. Serotonin transporter (5-HTT) availability in cortical regions correlated significantly with performance in sustained attention. The results support a role for the serotonin system in some but not all cognitive functions in man. In study IV, fifty-four control subjects were examined with [11C]WAY100635 PET and a battery of cognitive tests. Subjects were genotyped for the 5-HTT linked polymorphic region (5-HTTLPR), a functional polymorphism in the promoter region of the 5-HTT gene. The short (S) allele of the 5-HTTLPR has been associated with depression as well as anxiety-related personality traits. Carriers of the S allele of the 5-HTTLPR did not differ from non-carriers with respect to [11C]WAY100635 binding potential in any of the brain regions studied. S-carriers however performed significantly better in the Wisconsin Card Sorting Test. These observations suggest that functional implications of the 5-HTTLPR are not likely to be mediated by differences in 5-HT1A density and that other biomarkers must be considered for future investigations at phenotype level. The present studies of serotonergic biomarkers in man provide new evidence for a role of the serotonin system in complex human behaviour such as cognitive functions and personality traits.
|
|
| 5. |
- Borg, Jacqueline, et al.
(författare)
-
The serotonin system and spiritual experiences
- 2003
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 160:11, s. 1965-1969
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The serotonin system has long been of interest in biological models of human personality. The purpose of this positron emission tomography (PET) study was to search for relationships between serotonin 5-HT(1A) receptor density and personality traits. METHOD: Fifteen normal male subjects, ages 20-45 years, were examined with PET and the radioligand [(11)C]WAY100635. Personality traits were assessed with the Swedish version of the Temperament and Character Inventory self-report questionnaire. Binding potential, an index for the density of available 5-HT(1A) receptors, was calculated for the dorsal raphe nuclei, the hippocampal formation, and the neocortex. For each region, correlation coefficients between 5-HT(1A) receptor binding potential and Temperament and Character Inventory personality dimensions were calculated and analyzed in two-tailed tests for significance. RESULTS: The authors found that the binding potential correlated inversely with scores for self-transcendence, a personality trait covering religious behavior and attitudes. No correlations were found for any of the other six Temperament and Character Inventory dimensions. The self-transcendence dimension consists of three distinct subscales, and further analysis showed that the subscale for spiritual acceptance correlated significantly with binding potential but not with the other two subscales. CONCLUSIONS: This finding in normal male subjects indicated that the serotonin system may serve as a biological basis for spiritual experiences. The authors speculated that the several-fold variability in 5-HT(1A) receptor density may explain why people vary greatly in spiritual zeal.
|
|
| 6. |
- Caravaggio, Fernando, et al.
(författare)
-
Trait impulsivity is not related to post-commissural putamen volumes : A replication study in healthy men
- 2018
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
-
Tidskriftsartikel (refereegranskat)abstract
- High levels of trait impulsivity are considered a risk factor for substance abuse and drug addiction. We recently found that non-planning trait impulsivity was negatively correlated with post-commissural putamen volumes in men, but not women, using the Karolinska Scales of Personality (KSP). Here, we attempted to replicate this finding in an independent sample using an updated version of the KSP: the Swedish Universities Scales of Personality (SSP). Data from 88 healthy male participants (Mean Age: 28.16 +/- 3.34), who provided structural T1-weighted magnetic resonance images (MRIs) and self-reported SSP impulsivity scores, were analyzed. Striatal sub-region volumes were acquired using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Contrary to our previous findings trait impulsivity measured using SSP was not a significant predictor of post-commissural putamen volumes (beta = .14, df = 84, p = .94). A replication Bayes Factors analysis strongly supported this null result. Consistent with our previous findings, secondary exploratory analyses found no relationship between ventral striatum volumes and SSP trait impulsivity (beta = -.05, df = 84, p = .28). An exploratory analysis of the other striatal compartments showed that there were no significant associations with trait impulsivity. While we could not replicate our previous findings in the current sample, we believe this work will aide future studies aimed at establishing meaningful brain biomarkers for addiction vulnerability in healthy humans.
|
|
| 7. |
- Farde, Lars, et al.
(författare)
-
Brain neuroreceptor density and personality traits : towards dimensional biomarkers for psychiatric disorders.
- 2018
-
Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 373:1744
-
Forskningsöversikt (refereegranskat)abstract
- Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
|
|
| 8. |
- Gaudet, Mia M., et al.
(författare)
-
Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
|
|
| 9. |
- Griffioen, Gina, et al.
(författare)
-
Serotonin 5-HT1A receptor binding and self-transcendence in healthy control subjects : a replication study using Bayesian hypothesis testing
- 2018
-
Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. A putative relationship between markers for the serotonin system and the personality scale self-transcendence (ST) and its subscale spiritual acceptance (SA) has been demonstrated in a previous PET study of 5-HT1A receptor binding in healthy control subjects. The results could however not be replicated in a subsequent PET study at an independent centre. In this study, we performed a replication of our original study in a larger sample using Bayesian hypothesis testing to evaluate relative evidence both for and against this hypothesis. Methods. Regional 5-HT1A receptor binding potential (BPND) was examined in 50 healthy male subjects using PET with the radioligand [C-11]WAY100635. 5-HT1A availability was calculated using the simplified reference tissue model (SRTM) yielding regional BPND. ST and SA were measured using the Temperament and Character Inventory (TCI) questionnaire. Correlations between ST/SA scores and 5-HT1A BPND in frontal cortex, hippocampus and raphe nuclei were examined by calculation of default correlation Bayes factors (BFs) and replication BFs. Results. There were no significant correlations between 5-HT1A receptor binding and ST/SA scores. Rather, five of six replication BFs provided moderate to strong evidence for no association between 5-HT1A availability and ST/SA, while the remaining BF provided only weak evidence. Conclusion. We could not replicate our previous findings of an association between 5-HT1A availability and the personality trait ST/SA. Rather, the Bayesian analysis provided evidence for a lack of correlation. Further research should focus on whether other components of the serotonin system may be related to ST or SA. This study also illustrates how Bayesian hypothesis testing allows for greater flexibility and more informative conclusions than traditional p-values, suggesting that this approach may be advantageous for analysis of molecular imaging data.
|
|
| 10. |
- Gustavsson, Peter, et al.
(författare)
-
Duplication 16q12.1-q22.1 characterized by array CGH in a girl with spina bifida
- 2007
-
Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 50:3, s. 237-241
-
Tidskriftsartikel (refereegranskat)abstract
- We report a 7-year-old girl with spina bifida carrying a complex chromosome abnormality resulting in duplication 16q12.1–q22.1. An abnormal karyotype was identified involving the long arm of chromosome 11 and fluorescent in situ hybridization (FISH) to metaphase chromosomes revealed an insertion of part of chromosome 16 on chromosome 11. A detailed mapping of the chromosome abnormality using whole genome array based comparative genomic hybridization (CGH) of the patient DNA revealed a duplication 16q12.1–q22.1 corresponding to gain of 19.8 Mb of DNA without any detectable loss of genetic material on chromosome 11. The karyotype is defined as 46,XX,der(11)ins(11;16)(q13;q12.1q22.1). We present here the clinical findings and a fine mapping of the associated structural chromosome abnormalities. We suggest that a gene dosage imbalance of 16q12.1–q22.1 is associated with spina bifida in the patient.
|
|
| 11. |
- Henningsson, Susanne, 1977, et al.
(författare)
-
Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men
- 2009
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:5, s. 477-485
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). Methods: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [C-11]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [C-11]WAY-100635. Results: Several single nucleotide polymorphisms were associated with [C-11]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [C-11]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with I-123-beta-CIT as ligand. Conclusions: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.
|
|
| 12. |
- Higier, Rachel G, et al.
(författare)
-
Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder
- 2014
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 171:11, s. 1191-1198
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls.METHOD: Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores.RESULTS: Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts.CONCLUSIONS: These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.
|
|
| 13. |
- Jangard, Simon, et al.
(författare)
-
Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.
- 2023
-
Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 118:6, s. 1053-1061
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8-to-16-years post PET scan, in social drinkers.DESIGN: Longitudinal study following healthy individuals.SETTING: Academic research imaging centre in Stockholm, Sweden.PARTICIPANTS: 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies.MEASUREMENTS: One PET examination with the D2R antagonist radioligand [11 C]raclopride at baseline, and self-report measures assessing alcohol use, drug use, impulsivity, reward sensitivity, and family history of alcohol- or substance use disorder at follow-up.FINDINGS: We found no evidence for an association between D2R availability and later alcohol use (B = -.019, B 95% confidence interval [CI] = -.043-(-).006, p = .147), nor for the majority of the alcohol-related factors (B 95 % CI = -.034-.004, p = .273-.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = -.017, B 95% CI = -.034-(-).001, p = .046).CONCLUSIONS: Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.
|
|
| 14. |
- Johansson, Viktoria, et al.
(författare)
-
The schizophrenia and bipolar twin study in Sweden (STAR)
- 2019
-
Ingår i: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509. ; 204, s. 183-192
-
Tidskriftsartikel (refereegranskat)abstract
- The schizophrenia and bipolar twin study in Sweden (STAR) is a large nation-wide cohort of monozygotic (MZ) and dizygotic (DZ) same-sex twins with schizophrenia or bipolar disorder and healthy control pairs, extensively characterized with brain imaging, neuropsychological tests, biomarkers, genetic testing, psychiatric symptoms and personality traits. The purpose is to investigate genetic and environmental mechanisms that give rise to schizophrenia and bipolar disorder as well as the intermediate phenotypes. This article describes the design, recruitment, data collection, measures, collected twins' characteristics, diagnostic procedures as well as ongoing and planned analyses. Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes for schizophrenia and bipolar disorder are potential gains from this cohort.
|
|
| 15. |
- Kuchinskaya, Ekaterina, et al.
(författare)
-
Array-CGH reveals hidden gene dose changes in children with acute lymphoblastic leukaemia and a normal or failed karyotype by G-banding
- 2008
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 140:5, s. 572-577
-
Tidskriftsartikel (refereegranskat)abstract
- A tiling path 33K BAC array was used to study 28 children with acute lymphoblastic leukaemia (ALL) who had normal or failed G-banded karyotypes. Twenty-two patients (79%) had a total of 135 copy number alterations (CNA) (69 gains and 66 losses); most of these patients showed CNA that were below the resolution of G-banding. Molecular cytogenetic and array comparative genomic hybridization results enabled the division of B-precursor ALL patients into five groups: high hyperdiploidy, intrachromosomal amplification of 21q, ETV6/RUNX1 rearrangement, others and no CNA. Apart from a shared deletion of 9p21.3, T-ALL patients had additional small CNA, with no region in common.
|
|
| 16. |
- Larsson, Cornelia, et al.
(författare)
-
Facial affect recognition in first-episode psychosis is impaired but not associated with psychotic symptoms.
- 2022
-
Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 8:9
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Social dysfunction is a key feature of psychotic disorders such as schizophrenia linked to disability. Less is known about social functioning in the early stages of the disorder and if there is an association to psychotic symptoms.Aims: Investigate if antipsychotic drug-naïve or briefly medicated individuals with first-episode psychosis (FEP), have impaired facial affect recognition (FAR) compared to control participants and if psychotic symptoms are associated with the FAR ability.Method: Individuals with FEP (n = 67) and control participants (n = 51) performed a computer-aided FAR task on basic emotions. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Group performances were compared using age and gender as covariates. The associations between FAR and performance on the subscales of PANSS were analyzed.Results: Compared to control participants, individuals with FEP were impaired in general FAR (Beta = -2.04 [95 % conf: -3.75/-1.62], p < 0.001) and FAR of negative emotions (Beta = -1.74 [95 % conf: -3.08/-1.22], p < 0.001), driven by difficulties in recognition of anger and disgust. In both groups, there was a pattern of mistaking negative emotions for other negative emotions. There were no significant group differences in FAR of happiness. No significant associations between FAR and psychotic symptoms were observed.Discussion: The results indicate that FAR, an underlying mechanism of social functioning is impaired early in the course of psychotic disorders. Current findings do not support the hypothesis that misinterpretation of facial expressions in individuals with FEP underlies or contributes to symptoms of psychosis.
|
|
| 17. |
- Lee, Maria, et al.
(författare)
-
Cognitive Function and Variability in Antipsychotic Drug-Naive Patients With First-Episode Psychosis : A Systematic Review and Meta-Analysis.
- 2024
-
Ingår i: JAMA psychiatry. - 2168-6238.
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.OBJECTIVE: To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.DATA SOURCES: In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.STUDY SELECTION: Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included.DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.MAIN OUTCOMES AND MEASURES: The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.RESULTS: Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.
|
|
| 18. |
|
|
| 19. |
- Matheson, Granville J., et al.
(författare)
-
Diurnal and seasonal variation of the brain serotonin system in healthy male subjects
- 2015
-
Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 112, s. 225-231
-
Tidskriftsartikel (refereegranskat)abstract
- The mammalian circadian clock underlies both diurnal and seasonal changes in physiology, and its function is thought to be disturbed in both seasonal and non-seasonal depression. In humans, molecular imaging studies have reported seasonal changes in the serotonin system. Despite the role of the circadian clock in generating seasonal physiological changes, however, diurnal variation of serotonin receptors and transporters has never been directly studied in humans. We used positron emission tomography to examine diurnal and seasonal changes in the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of healthy male subjects, employing a cross-sectional design. In 56 subjects measured with [C-11] WAY-100635, we observed diurnal increases in the availability of 5-HT1A receptors in the cortex. In 40 subjects measured with [C-11] MADAM, a decrease in 5-HTT was observed in the midbrain across the day. We also found seasonal changes in the 5-HT1A receptor in serotonin projection regions, with higher availability on days with a longer duration of daylight. Our observation that serotonin receptor and transporter levels may change across the day in humans is corroborated by experimental research in rodents. These findings have important implications for understanding the relationship between the circadian and serotonin systems in both the healthy brain and in affective disorders, as well as for the design of future molecular imaging studies. (C) 2015 Elsevier Inc. All rights reserved.
|
|
| 20. |
- Matheson, Granville J, et al.
(författare)
-
Dopamine D1 receptor availability is not associated with delusional ideation measures of psychosis proneness
- 2020
-
Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 222, s. 175-184
-
Tidskriftsartikel (refereegranskat)abstract
- The dopamine D1 receptor (D1R) is thought to play a role in psychosis and schizophrenia, however positron emission tomography studies comparing patients and controls have been inconsistent. To circumvent some of the limitations of clinical studies, such as antipsychotic exposure, an alternative approach is to examine subclinical psychotic symptoms within the general population, i.e. psychosis proneness traits. In this study, we investigated whether D1R availability is associated with delusional ideation in healthy controls, in four experiments, using [11C]SCH23390 PET (n = 76) and psychometric questionnaires (n = 217). We performed exploratory analyses, direct self-replication, and confirmatory analyses using Bayesian statistical modelling. Collectively, we found strong evidence that there is little to no linear association between delusional ideation and D1R. If hypothesised changes in D1R in drug-naive psychosis patients can be confirmed, our results suggest that they may either occur at disease onset, or that they are associated with specific aspects of psychosis other than delusional ideation.
|
|
| 21. |
- Plaven-Sigray, Pontus, et al.
(författare)
-
Dopamine D1 receptor availability is related to social behavior : A positron emission tomography study
- 2014
-
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 102, s. 590-595
-
Tidskriftsartikel (refereegranskat)abstract
- Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human interpersonal behavior. Twenty-three healthy subjects were examined using positron emission tomography and the radioligand [C-11] SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions. D1-R binding potential values in the limbic striatum(r= .52; p= .015), associative striatum(r= .55; p= .009), and sensorimotor striatum(r= .67; p= .001) were positively related to Social Desirability scores. D1-R binding potential in the limbic striatum (r= -.51; p = .019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in the amygdala (r = .60; p = .006) and medial frontal cortex (r= .60; p = .004). This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles.
|
|
| 22. |
|
|
| 23. |
- Schoumans, Jacqueline, et al.
(författare)
-
Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
- 2007
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:2, s. 143-149
-
Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
|
|
| 24. |
- Tangen, Ämma, et al.
(författare)
-
Associations between cognition and serotonin receptor 1B binding in patients with major depressive disorder : a pilot study
- 2017
-
Ingår i: Psychiatry Research: Neuroimaging. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 0925-4927 .- 1872-7506.
-
Tidskriftsartikel (refereegranskat)abstract
- The neurotransmitter serotonin has been widely implicated in the pathophysiology of major depressive disorder (MDD). In animal studies and human neuroimaging studies, involvement of the serotonin receptor 1B (5-HT1BR) in MDD and memory performance has been reported. However, the role of the 5-HT1BR in cognitive functions affected in MDD remains to be clarified. Ten patients with MDD diagnosis were examined with positron emission tomography (PET) and a battery of cognitive tests before and after Internet-based Cognitive Behavioral Therapy (ICBT). The results were compared to ten matched control subjects in order to investigate putative changes in 5-HT1BR availability and cognitive performance. Patients treated with ICBT showed statistically significant improvement relative to baseline in Verbal fluency, both letter and category production. Significant correlations were found between improvement in letter production and changes in 5-HT1BR availability in ventral striatum, between category production and amygdala, as well as between the improvement in Trailmaking test B and change in 5-HT1BR binding in dorsal brainstem, in amygdala and in hippocampus. The results suggest an association between 5-HT1BR binding and improvement in cognitive functioning. Replications in larger-scale studies are required to confirm these findings.
|
|
| 25. |
- Willfors, Charlotte, et al.
(författare)
-
Symptoms of autism in Williams syndrome: a transdiagnostic approach
- 2024
-
Ingår i: SCIENTIFIC REPORTS. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Williams syndrome (WS) is associated with atypical social communication and cognition reminiscent of the behaviours observed in autism. Nonetheless, WS also differs significantly from autism, such as regarding social motivation, which is typically enhanced in WS and reduced in autism. This study sought to examine the conditions' transdiagnostic similarities and differences for autistic symptoms and social functioning, and their developmental trajectories, by comparing individuals with WS (n = 24) and those diagnosed with idiopathic autism (n = 24) and attention deficit hyperactivity disorder (ADHD; n = 24), aged 9 to 53 years, on measures of autism, social functioning, IQ and cooccurring psychiatric conditions. Although only 12.5% in the WS group met the criteria for an autism diagnosis, a majority exhibited distinct difficulties within social communication, social cognition, repetitive behaviours, and atypical sensory reactivity resembling autism. Conversely, elevated social motivation and a high number of social initiatives accompany these characteristics. No group differences in the developmental trajectories of autism symptoms were found. Our results demonstrate that autistic behaviours are more frequent in individuals with WS, than in individuals with idiopathic ADHD, and emphasize the need for clinical management of these behaviours.
|
|
| 26. |
- Zhang, Zhong-Fa, et al.
(författare)
-
Detection of submicroscopic constitutional chromosome aberrations in clinical diagnostics: a validation of the practical performance of different array platforms
- 2008
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 16:7, s. 786-792
-
Tidskriftsartikel (refereegranskat)abstract
- For several decades etiological diagnosis of patients with idiopathic mental retardation (MR) and multiple congenital anomalies (MCA) has relied on chromosome analysis by karyotyping. Conventional karyotyping allows a genome-wide detection of chromosomal abnormalities but has a limited resolution. Recently, array-based comparative genomic hybridization (array CGH) technologies have been developed to evaluate DNA copy-number alterations across the whole-genome at a much higher resolution. It has proven to be an effective tool for detection of submicroscopic chromosome abnormalities causing congenital disorders and has recently been adopted for clinical applications. Here, we investigated four high-density array platforms with a theoretical resolution <= 100 kb: 33K tiling path BAC array, 500K Affymetrix SNP array, 385K NimbleGen oligonucleotide array and 244K Agilent oligonucleotide array for their robustness and implementation in our diagnostic setting. We evaluated the practical performance based on the detection of 10 previously characterized abnormalities whose size ranged from 100 kb to 3 Mb. Furthermore, array data analysis was performed using four computer programs developed for each corresponding platform to test their effective ability of reliable copy-number detection and their user-friendliness. All tested platforms provided sensitive performances, but our experience showed that accurate and user-friendly computer programs are of crucial importance for reliable copy-number detection.
|
|
