| 1. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-ChiP data
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative trait loci (QTL) mapping is a first step to identify chromosomal regions harboring genetic polymorphisms that regulate complex traits. Searching causative mutations for observed effects is sometimes a daunting task as even after fine mapping of the QTL, millions of base pairs including many genes will typically need to be explored. There is thus a great need for efficient bioinformatics strategies to trace the causative mutation(s). Here, we searched for gene transcripts along with mutations regulating body weight at 56 days traits in the Virginia chicken lines – an experimental population comprising two lines that have been divergently selected for 56 days body weight for more than 50 generations. Several QTL regions have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line (AIL). Candidate transcripts and mutations were here sought in the parts of the QTL regions where the highest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, 47 Mbp or 35% of the actual QTL regions, were identified by comparing the allele frequencies in the genomes of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions with 12X ABI SOLID genome resequencing of DNA pools. Gene transcripts in the target segments, obtained using the Ensembl genome browser 67, were analyzed with DAVID bioinformatic database to investigate their role in any growth-related functions. Single nucleotide polymorphisms (SNPs) in target segments obtained from resequencing data were analyzed with Variant Effect Predictor (VEP) tool to find their location and functional consequences in gene transcripts. Non-synonymous SNPs (nsSNPs) were scored for their effects on protein function with PASE software (Li et al., submitted). Finally, we present most important candidate gene transcripts from each QTL segment for further functional validation. For example, the cysteine rich transmembrane BMP regulator 1 (chordin-like) gene has growth factor binding and cell growth functions. It carries a nsSNP with high allele frequency difference (0.97) between lines, PASE (0.67) and conservation scores (0.63). Another candidate, glucagon is involved in anorexia and appetite regulation carrying a CpG mutation with high allele frequency difference (0.87) between lines.
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| 2. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-chip data.
- 2013
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Mapping of chromosomal regions harboring genetic polymorphisms that regulate complex traits is usually followed by a search for the causative mutations underlying the observed effects. This is often a challenging task even after fine mapping, as millions of base pairs including many genes will typically need to be investigated. Thus to trace the causative mutation(s) there is a great need for efficient bioinformatic strategies. Here, we searched for genes and mutations regulating growth in the Virginia chicken lines - an experimental population comprising two lines that have been divergently selected for body weight at 56 days for more than 50 generations. Several quantitative trait loci (QTL) have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line. We have further analyzed the QTL regions where the largest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, covering about 37% of the actual QTL regions, were identified by comparing the allele frequencies of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions from genome resequencing of DNA pools. Based on a combination of criteria including significance of the QTL, allele frequency difference of identified mutations between the selected lines, gene information on relevance for growth, and the predicted functional effects of identified mutations we propose here a subset of candidate mutations of highest priority for further evaluation in functional studies. The candidate mutations were identified within the GCG, IGFBP2, GRB14, CRIM1, FGF16, VEGFR-2, ALG11, EDN1, SNX6, and BIRC7 genes. We believe that the proposed method of combining different types of genomic information increases the probability that the genes underlying the observed QTL effects are represented among the candidate mutations identified.
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| 3. |
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| 4. |
- Brus, Ole, 1982-, et al.
(författare)
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Long-Term Effect of Maintenance Electroconvulsive Therapy in Patients With Depression-Data From a Small Randomized Controlled Trial
- 2024
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Ingår i: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to compare the long-term effects of maintenance electroconvulsive therapy (M-ECT) with medication and medication only in patients with depression.METHODS: A randomized controlled trial of 1 year of M-ECT with medication or medication only investigated relapse/recurrence among 56 patients in remission after electroconvulsive therapy (ECT) for depression was conducted. The results of the first year are published already and showed a significant advantage of M-ECT with medication.The current study was a long-term follow-up. When the randomized treatment allocation ended, medication was continued in both groups but M-ECT was terminated. Patients were followed for up to 10 years via Swedish national registers until the study endpoint of a new psychiatric diagnosis as an inpatient, suicide, suspected suicide, or death of another cause. Time to relapse was compared between the M-ECT with medication group and the medication-only group using Kaplan-Meier estimates.RESULTS: The median follow-up time was 6.5 years for the M-ECT and medication group and 3.1 years for the medication-only group. One year after randomization 22 patients remained in the M-ECT and medication group, and 14 patients remained in the medication-only group. Relapse patterns between the treatment groups after the completion of M-ECT seemed to be similar according to visual inspection.CONCLUSIONS: This long-term follow-up study suggests that most of the benefit achieved during the treatment period with M-ECT is maintained over several years, but the small sample size, with accompanying large statistical imprecision, makes the results uncertain. More long-term studies of M-ECT are required.Trial registration: ClinicalTrials.gov identifier: NCT00627887.
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| 5. |
- Carlborg, Andreas, et al.
(författare)
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Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis
- 2010
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 68-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor.AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide.METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records.RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters.CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.
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| 6. |
- Carlborg, Andreas
(författare)
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Biomarkers of suicide risk in psychosis
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Suicide and attempted suicide are major health problems. Approximately 1400 people die from suicide every year in Sweden and ten times more attempt suicide. Patients with schizophrenia spectrum psychosis have an increased risk of suicide and suicide rates have been suggested to be as high as 10%. Important risk factors include a prior suicide attempt and depressive disorder. Low concentrations of monoamine metabolites in cerebrospinal fluid (CSF) have been related to suicidal behavior in patients diagnosed with mood disorders. Few studies have investigated patients with schizophrenia spectrum psychosis and they suffer from small numbers of patients, short periods of follow-up and contradictory results. The main objective of this study was to investigate the long-term suicide risk in schizophrenia spectrum psychosis, whether concentrations of the CSF monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) are related to suicidal behavior and to the overall mortality. The importance of other factors influencing suicide risk such as a prior suicide attempt, gender and CSF kynurenic acid (KYNA) was also investigated. Inpatients (n=385) with schizophrenia like symptoms were lumbar punctured at admittance and followed up for a median period of 26 years. Information about prior suicide attempts was retrieved from the medical records. Causes of death were obtained from the Causes of Death Register. During the follow-up period nearly equal percentages of men (6.5 %) and women (6.9 %) died by suicide. Eighteen percent of suicide attempters and 2% of the non-attempters died by suicide. The suicide risk was almost three times higher in male attempters than in females. Thus, attempted suicide and male gender were significant risk factors for suicide. There were neither any associations between CSF concentrations of 5-HIAA and HVA, or their ratio, nor between CSF KYNA concentrations and suicide or attempted suicide. CSF 5-HIAA and HVA concentrations were not a risk factor for early death from natural causes. Patients with schizophrenia spectrum psychosis have a high long-term risk of suicide. Attempted suicide was a very important risk factor for suicide in both genders, especially in males. In contrast to patients diagnosed with mood disorders, CSF 5-HIAA and HVA concentrations were not associated with suicidal behavior in schizophrenia spectrum psychosis patients.
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| 7. |
- Carlborg, Andreas, et al.
(författare)
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CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis
- 2013
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 205:1-2, s. 165-7
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Tidskriftsartikel (refereegranskat)abstract
- Relationships between concentrations of cerebrospinal fluid (CSF) kynurenic acid (KYNA) and suicidal behavior were evaluated in 59 patients with psychosis after 22 years of follow-up. Three patients died from suicide and nine patients had a history of attempted suicide. Patients with attempted suicide had significantly lower concentrations of CSF KYNA.
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| 8. |
- Carlborg, Andreas, et al.
(författare)
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Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis
- 2011
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:2, s. 101-5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers.AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA.METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register.RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age.CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.
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| 9. |
- Carlborg, Andreas, et al.
(författare)
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Suicide in schizophrenia
- 2010
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Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 10:7, s. 1153-64
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Forskningsöversikt (refereegranskat)abstract
- Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.
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| 10. |
- Eckerström, Joachim, et al.
(författare)
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Brief admission for patients with emotional instability and self-harm : A qualitative analysis of patients' experiences during crisis
- 2020
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Ingår i: International Journal of Mental Health Nursing. - : John Wiley & Sons. - 1445-8330 .- 1447-0349. ; 29:5, s. 962-971
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies report that individuals diagnosed with borderline personality disorder have been met by negative attitudes from healthcare professionals and their care needs have often been neglected during hospitalizations. When symptoms of emotional instability are combined with self-harm, the resulting crisis often becomes difficult to handle for patients and healthcare professionals. To meet their care needs during these crises, an intervention called 'brief admission' (BA) has been developed. The purpose of BA is to provide a timeout, in situations of increased stress and threat, in order to foster self-management in a safe environment. In the present study, we explored the following research questions: What are patients' experiences with BA? What do patients consider to be the key components of BA? What improvements are considered relevant by patients? A qualitative design was employed, and 15 patients (13 females, 2 males; mean age 38.5 ± 12.9, range 20-67 years) were interviewed using a semi-structured interview guide. Thematic analyses were performed, which yielded four themes related to the patients' experiences: 'a timeout when life is tough', 'it is comforting to know that help exists', 'encouraged to take personal responsibility', and 'it is helpful to see the problems from a different perspective'. Four themes also described the key components: 'a clear treatment plan', 'a smooth admission procedure', 'a friendly and welcoming approach from the staff', and 'daily conversations'. Lastly, three themes described areas for improvements: 'feeling guilty about seeking BA', 'room occupancy issues', and 'differences in staff's competence'. Collectively, the findings indicate that BA constructively supports patients with emotional instability and self-harm during a period of crisis.
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