1. |
|
|
2. |
- Hibar, D. P., et al.
(author)
-
Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
-
Journal article (peer-reviewed)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.
|
|
3. |
- Ching, C. R. K., et al.
(author)
-
What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group
- 2022
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 56-82
-
Journal article (peer-reviewed)abstract
- MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
|
|
4. |
|
|
5. |
- Hibar, D. P., et al.
(author)
-
Subcortical volumetric abnormalities in bipolar disorder
- 2016
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
-
Journal article (peer-reviewed)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.
|
|
6. |
|
|
7. |
|
|
8. |
- Gröning, L., et al.
(author)
-
Remodelling criminal insanity: Exploring philosophical, legal, and medical premises of the medical model used in Norwegian law
- 2022
-
In: International Journal of Law and Psychiatry. - : Elsevier BV. - 0160-2527. ; 81
-
Journal article (peer-reviewed)abstract
- This paper clarifies the conceptual space of discussion of legal insanity by considering the virtues of the ‘medical model’ model that has been used in Norway for almost a century. The medical model identifies insanity exclusively with mental disorder, and especially with psychosis, without any requirement that the disorder causally influenced the commission of the crime. We explore the medical model from a transdisciplinary perspective and show how it can be utilised to systematise and reconsider the central philosophical, legal and medical premises involved in the insanity debate. A key concern is how recent transdiagnostic and dimensional approaches to psychosis can illuminate the law's understanding of insanity and its relation to mental disorder. The authors eventually raise the question whether the medical model can be reconstructed into a unified insanity model that is valid across the related disciplinary perspectives, and that moves beyond current insanity models. © 2022 The Authors
|
|
9. |
- Haukvik, U. K., et al.
(author)
-
Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls
- 2012
-
In: Psychological Medicine. - 1469-8978. ; 42:6, s. 1329-1337
-
Journal article (peer-reviewed)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.
|
|
10. |
- Haukvik, U. K., et al.
(author)
-
Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder
- 2014
-
In: Psychological Medicine. - 1469-8978. ; 44:5, s. 975-985
-
Journal article (peer-reviewed)abstract
- Background Pre- and perinatal adversities may increase the risk for schizophrenia and bipolar disorder. Hypoxia-related obstetric complications (OCs) are associated with brain anatomical abnormalities in schizophrenia, but their association with brain anatomy variation in bipolar disorder is unknown. Method Magnetic resonance imaging brain scans, clinical examinations and data from the Medical Birth Registry of Norway were obtained for 219 adults, including 79 patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d.=11.8 years, 39% male) and 140 healthy controls (age 30.8 years, s.d.=12.0 years, 53% male). Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala, obtained with FreeSurfer), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied. Results Perinatal asphyxia was associated with smaller left amygdala volume (t=-2.59, p=0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t=-2.69, p=0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t=-2.60, p=0.015) and severe OCs (t=-3.25, p=0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found. Conclusions Pre- and perinatal hypoxia-related OCs are related to brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.
|
|