| 1. |
- Hibar, D. P., et al.
(författare)
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Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
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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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| 2. |
- Hibar, D. P., et al.
(författare)
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Subcortical volumetric abnormalities in bipolar disorder
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
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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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| 3. |
- Sellgren, C. M., et al.
(författare)
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A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:10, s. 1342-1350
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Tidskriftsartikel (refereegranskat)abstract
- Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant-associated with reduced SNX7 expression-to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1 beta and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder.
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| 4. |
- Abé, C, et al.
(författare)
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Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.
- 2018
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Ingår i: Acta psychiatrica Scandinavica. - : Wiley. - 1600-0447 .- 0001-690X. ; 138:4, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects.Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160).We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions.Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes.
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| 5. |
- Ahmad, I., et al.
(författare)
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Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy
- 2022
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 76:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery angstrom sberg Depression Rating Scale between the Q-ECT and the patient record. Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.
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| 6. |
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| 7. |
- Goterfelt, L., et al.
(författare)
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The Incidence of Dental Fracturing in Electroconvulsive Therapy in Sweden
- 2020
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Ingår i: Journal of Ect. - : Ovid Technologies (Wolters Kluwer Health). - 1095-0680 .- 1533-4112. ; 36:3, s. 168-171
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Tidskriftsartikel (refereegranskat)abstract
- Objectives One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions. Methods This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions. Results Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture. Conclusions There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant.
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| 8. |
- Johansson, Viktoria, et al.
(författare)
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Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. Methodology/Principal Findings: We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 mu m in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR = 48, 95% CL: 8.2-550, p<0.0001) and the co-twin-group (OR = 16, 95% CL: 2.0-218, p = 0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. Conclusion: Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder.
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| 9. |
- Liberg, B., et al.
(författare)
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Vertex-based morphometry in euthymic bipolar disorder implicates striatal regions involved in psychomotor function
- 2014
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Ingår i: Psychiatry Research-Neuroimaging. - : Elsevier BV. - 0925-4927 .- 1872-7123. ; 221:3, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that psychomotor disturbances in patients with bipolar disorder are associated with morphometric changes in functionally specific regions of the basal ganglia and thalamus. We used structural magnetic resonance imaging and vertex-based morphometry to investigate whether psychomotor performance is associated with changes in volume and shape in euthymic subjects with bipolar disorder (n=27) compared with matched healthy controls (n=27). We saw no significant differences between age- and sex-matched groups in motor performance. We found a statistically significant group difference in the shape of the right putamen in the absence of psychomotor disturbances. There was an association between shape and motor performance in controls that was lacking in patients. We conclude that euthymic subjects with bipolar disorder without psychomotor disturbances show shape changes in regions of the right putamen that contribute to executive functions and motor function. It may be that other brain regions sustain the psychomotor functions that produce nearly identical motor performance in both groups. (C) 2014 Elsevier Ireland Ltd. All rights reserved
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| 10. |
- Pålsson, Erik, 1975, et al.
(författare)
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Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls
- 2015
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 25:1, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Goran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.
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