Publikasjoner

Genetic loci shared between major depression and intelligence with mixed directions of effect.

Nat Hum Behav. 2021 Jan 18;:

Authors: Bahrami S, Shadrin A, Frei O, O'Connell KS, Bettella F, Krull F, Fan CC, Røssberg JI, Hindley G, Ueland T, Dale AM, Djurovic S, Steen NE, Smeland OB, Andreassen OA

Abstract Genome-wide association studies (GWAS) have identified several common genetic variants influencing major depression and general cognitive abilities, but little is known about whether the two share any of their genetic aetiology. Here we investigate shared genomic architectures between major depression (MD) and general intelligence (INT) with the MiXeR statistical tool and their overlapping susceptibility loci with conjunctional false discovery rate (conjFDR), which evaluate the level of overlap in genetic variants and improve the power for gene discovery between two phenotypes. We analysed GWAS data on MD (n = 480,359) and INT (n = 269,867) to characterize polygenic architecture and identify genetic loci shared between these phenotypes. Despite non-significant genetic correlation (rg = -0.0148, P = 0.50), we observed large polygenic overlap and identified 92 loci shared between MD and INT at conjFDR < 0.05. Among the shared loci, 69 and 64 are new for MD and INT, respectively. Our study demonstrates polygenic overlap between these phenotypes with a balanced mixture of effect.

PMID: 33462475 [PubMed - as supplied by publisher]

Runaway multi-allelic copy number variation at the α-defensin locus in African and Asian populations.

Sci Rep. 2020 06 04;10(1):9101

Authors: Hughes T, Hansson L, Akkouh I, Hajdarevic R, Bringsli JS, Torsvik A, Inderhaug E, Steen VM, Djurovic S

Abstract Alpha defensins are anti-microbial peptides of the innate immune system. The defensin A1 and A3 genes are located in a repeat array of variable copy number (the DEFA1A3 locus) and encode the human neutrophil peptides 1, 2 and 3. The possibility that copy number variation (CNV) may be associated with infection susceptibility and autoimmune pathology motivated the study of DEFA1A3 CNV across populations. We enhanced two existing methods (one qPCR-based and one sequencing-based) to enable copy number estimation that discriminates between DEFA1 and DEFA3 genes. We used these methods to quantify A1/A3 copy number variation in 2504 samples from the 1000 Genomes high-coverage dataset as well as performing FiberFISH assays on selected samples to visualize the haplotypes. These methods produce accurate estimates and show that there are substantial differences between populations. The African population is a clear outlier with a high frequency of the ancestral pure DEFA1 haplotype, but also harbours exceptionally long haplotypes of 24 copies of both DEFA1 and DEFA3, whilst the East Asian population displays the highest mean level of DEFA3 copy number. Further, our findings demonstrate that qPCR can be an accurate method for CNV estimation and that defensins substantially extend the known range of copy number variation for a human protein-coding gene.

PMID: 32499510 [PubMed - indexed for MEDLINE]

Higher vitamin B12 levels in neurodevelopmental disorders than in healthy controls and schizophrenia: A comparison among participants between 2 and 53 years.

FASEB J. 2020 06;34(6):8114-8124

Authors: Hope S, Naerland T, Høiland AL, Torske T, Malt E, Abrahamsen T, Nerhus M, Wedervang-Resell K, Lonning V, Johannessen J, Steen NE, Agartz I, Stenberg N, Hundhausen T, Mørkrid L, Andreassen OA

Abstract Recent studies suggest that both high and low levels of vitamin B12 (vitB12) may have negative health impacts. We measured VitB12 in patients with the Neurodevelopmental disorders (ND) (n = 222), comprised of Autism Spectrum Disorders, specific Developmental disorders, and Intellectual Disability (aged 2-53 years), schizophrenia (n = 401), and healthy controls (HC) (n = 483). Age-and gender-adjusted vitB12 z-scores were calculated by comparisons with a reference population (n = 76 148). We found higher vitB12 in ND (median 420 pmol/L, mean z-score: 0.30) than in HC (316 pmol/L, z-score: 0.06, P < .01) and schizophrenia (306 pmol/L, z-score: -0.02, P < .001), which was significant after adjusting for age, gender, vitB12 supplement, folate, hemoglobin, leukocytes, liver, and kidney function (P < .02). In ND, 20% (n = 44) had vitB12 above 650 pmol/L, and 1% (n = 3) had below 150 pmol/L (common reference limits). In 6.3% (n = 14) of ND, vitB12 was above 2SD of mean in the age-and gender-adjusted reference population, which was more frequent than in HC (n = 8, 1.6%), OR: 4.0, P = .001. Low vitB12 was equally frequent as in HC, and vitB12 z-scores were equal across the age groups. To conclude, vitB12 was higher in ND than in HC and schizophrenia, suggesting a specific feature of ND, which warrants further studies to investigate the underlying mechanisms.

PMID: 32323402 [PubMed - indexed for MEDLINE]

Anabolic androgenic steroid dependence is associated with executive dysfunction.

Drug Alcohol Depend. 2020 03 01;208:107874

Authors: Hauger LE, Westlye LT, Bjørnebekk A

Abstract BACKGROUND: Anabolic androgenic steroid (AAS) dependence is associated with a high prevalence of intra- and interpersonal problems, hence it is central to identify cognitive factors related to the development and maintenance of dependence. METHODS: The study explores executive functions (EFs) in a sample of 174 male weightlifters, divided into three groups; 1) AAS dependents; n = 58, 2) AAS non-dependents; n = 38 and 3) AAS non-users; n = 78, using a targeted battery of neuropsychological (NP) tests, and self-report questionnaires assessing EFs in everyday life, ADHD symptoms and psychological distress. RESULTS: Multivariate analysis of variance showed significant between-group differences on several EFs, including working memory [F (2, 169) = 13.79, p < .001, ηp² = 0.14], mental flexibility [F (2, 169) = 4.82, p = .009, ηp² = 0.05], problem-solving [F (2, 169) = 4.77 p = .010, ηp² = 0.05] and inhibition [F (2, 163) = 4.15, p = .017, ηp² = 0.05]. Additionally, significant between-group differences were seen for self-reported problems with EFs [F (2, 124) = 4.38 p = .015, ηp² = 0.07], ADHD symptoms [F (2, 124) = 7.02 p = .001, ηp² = 0.10], and psychological distress [F (2, 124) = 4.11 p = .019, ηp² = 0.06]. Post hoc tests showed that AAS dependents exhibited poorer EFs and reported more psychological distress compared to non-users. CONCLUSION: AAS dependence is associated with executive dysfunction, which might be related to continued abuse despite adverse side-effects and social consequences. Increased awareness of executive dysfunction could have important implications for treatment and rehabilitation.

PMID: 31972519 [PubMed - indexed for MEDLINE]

Biological stress response in women at risk of postpartum psychosis: The role of life events and inflammation.

Psychoneuroendocrinology. 2020 03;113:104558

Authors: Aas M, Vecchio C, Pauls A, Mehta M, Williams S, Hazelgrove K, Biaggi A, Pawlby S, Conroy S, Seneviratne G, Mondelli V, Pariante CM, Dazzan P

Abstract BACKGROUND: Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high in women with a history of bipolar disorder, schizoaffective disorder or in those who have suffered previous episodes of PP. While studies in patients with psychosis not related to the puerperium have demonstrated that abnormalities in stress response are important risk factors for psychosis, it remains unknown whether this is also the case for PP. METHODS: This study includes 30 postpartum women, assessed, on average, at postpartum week 14.8 ± 10.1 either with a current episode of PP (n = 14), or at-risk of PP because of a history of bipolar/schizoaffective disorder but who were well (n = 16), and a group of healthy women (n = 26). Details about recent stressful life events were obtained using the List of Threatening Experiences questionnaire, while perceived stress was evaluated using the Perceived Stress Scale. We estimated hypothalamic-pituitary adrenal (HPA) activity by measuring salivary cortisol at awakening; at 15, 30, and 60 min after awakening; at noon; and at 8 pm. An Area Under the Curve analysis was performed to assess the awakening response (AUCi) and cortisol levels during the day (AUCg). Immune markers, including high sensitivity C-Reactive Protein (hs-CRP) and Interleukin (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, Tumor Necrosis Factor (TNFa), Vascular Endothelial Growth Factor (VEGF), Interferon gamma (INFγ), Monocyte Chemoattractant Protein 1 (MCP-1), and Epidermal Growth Factor (EGF) were evaluated from peripheral blood samples. RESULTS: Women with current PP reported more frequent recent stressful life events, and higher perceived stress than healthy women. They also showed an activation of the stress and immune response, with higher levels of cortisol AUCg and hs-CRP (but not of other inflammatory markers) than healthy controls. Women at-risk of PP who remained well had values on these measures that were intermediate between those of women with a current episode of PP and those of healthy women. Stress measures and markers of stress and immune response explained 78 % of the variance of in group status between PP and healthy women, and 46 % of variance of in group status between women at-risk and healthy women. CONCLUSION: These findings suggest that an immune-HPA axis dysregulation, together with current stress may represent an important underlying pathophysiological mechanism in the onset of psychosis after childbirth in vulnerable women.

PMID: 31923613 [PubMed - indexed for MEDLINE]