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Sökning: WFRF:(Hartberg CB)

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1.
  • Haukvik, Unn Kristin, et al. (författare)
  • Cerebral cortical thickness and a history of obstetric complications in schizophrenia
  • 2009
  • Ingår i: Journal of Psychiatric Research. - : Elsevier. - 1879-1379. ; 43:16, s. 1287-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have thinner brain cortices compared with healthy control subjects. Neurodevelopment is vulnerable to obstetric complications (OCs) such as hypoxia and birth trauma, factors that are also related to increased risk of developing schizophrenia. With the hypothesis that OCs might explain the thinner cortices found in schizophrenia, we studied patients with schizophrenia and healthy controls subjects for association between number and severity of OCs and variation in cortical thickness. Methods: MRI scans of 54 adults with schizophrenia or schizoaffective disorder and 54 healthy controls were acquired at Karolinska Institutet, Stockholm, Sweden. Measures of brain cortical thickness were obtained using automated computer processing (FreeSurfer). OCs were assessed from obstetric records and scored blindly according to the McNeil-Sjostrom scale. At numerous cortical locations, putative effects of OCs on cortical thickness variation were tested for each trimester, for labour, for composite OC scores, severe OC scores, and hypoxia scores among patients and controls separately. Results: Number and severity of OCs varied among both patient and control subjects but were not associated with cortical thickness in either of the groups. Patients demonstrated thinner brain cortices but there were no significant differences in number and severity of OC scores across groups. Conclusion: In the present study, number and severity of obstetric complications were not associated with brain cortical thickness, in patients with schizophrenia or in healthy control subjects. The thinner brain cortices found in patients with schizophrenia were not explained by a history of OCs. (C) 2009 Elsevier Ltd. All rights reserved.
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  • Haukvik, U. K., et al. (författare)
  • Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls
  • 2012
  • Ingår i: Psychological Medicine. - : Cambridge University Press. - 1469-8978. ; 42:6, s. 1329-1337
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The increased occurrence of obstetric complications (OCs) in patients with schizophrenia suggests that alterations in neurodevelopment may be of importance to the aetiology of the illness. Abnormal cortical folding may reflect subtle deviation from normal neurodevelopment during the foetal or neonatal period. In the present study, we hypothesized that OCs would be related to cortical folding abnormalities in schizophrenia patients corresponding to areas where patients with schizophrenia display altered cortical folding when compared with healthy controls. Method. In total, 54 schizophrenia patients and 54 healthy control subjects underwent clinical examination and magnetic resonance image scanning on a 1.5 T scanner. Information on OCs was collected from original birth records. An automated algorithm was used to calculate a three-dimensional local gyrification index (lGI) at numerous points across the cortical mantle. Results. In both schizophrenia patients and healthy controls, an increasing number of OCs was significantly related to lower lGI in the left pars triangularis (p<0.0005) in Broca's area. For five other anatomical cortical parcellations in the left hemisphere, a similar trend was demonstrated. No significant relationships between OCs and lGI were found in the right hemisphere and there were no significant case-control differences in lGI. Conclusions. The reduced cortical folding in the left pars triangularis, associated with OCs in both patients and control subjects suggests that the cortical effect of OCs is caused by factors shared by schizophrenia patients and healthy controls rather than factors related to schizophrenia alone.
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  • Hibar, Derrek P., et al. (författare)
  • Common genetic variants influence human subcortical brain structures
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 520:7546, s. 224-U216
  • Tidskriftsartikel (refereegranskat)abstract
    • The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
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  • Hibar, D. P., et al. (författare)
  • Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
  • 2018
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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6.
  • Hibar, D. P., et al. (författare)
  • Subcortical volumetric abnormalities in bipolar disorder
  • 2016
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
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