| 1. |
- Almby, Kristina E., et al.
(författare)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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| 2. |
- Bengtsson, Johan, et al.
(författare)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
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Tidskriftsartikel (refereegranskat)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 3. |
- Costache, Madalina Elena, et al.
(författare)
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Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder
- 2020
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.
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| 4. |
- Frick, Andreas, Docent, et al.
(författare)
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Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 261, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD). Methods: Forty-seven SAD patients (mean±SD age 33.9 ± 9.4 years, 24 women) were randomized and commenced 9 weeks’ Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n = 24) or placebo (placebo+CBT, n = 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI-I ≤ 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation. Results: The best model separated treatment responders (n = 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P = 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model. Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available. Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.
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| 5. |
- Hjorth, Olof, et al.
(författare)
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Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder : a randomized clinical trial
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.
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| 6. |
- Hjorth, Olof, et al.
(författare)
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Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder : a multitracer positron emission tomography study
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 3970-3979
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.
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| 7. |
- Luders, Eileen, et al.
(författare)
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From baby brain to mommy brain : Widespread gray matter gain after giving birth
- 2020
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Ingår i: Cortex. - : ELSEVIER MASSON, CORP OFF. - 0010-9452 .- 1973-8102. ; 126, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy results in obvious physiological changes to the female body, but data as to what happens to the maternal brain after giving birth are sparse as well as inconsistent. The overall goal of this study is to determine the nature of cerebral change in the postpartum period. For this purpose, we analyzed T1-weighted brain images of 14 healthy women (age range: 25-38 years) at two time points, specifically within 1-2 days of childbirth (immediate postpartum) and at 4-6 weeks after childbirth (late postpartum). When comparing voxel-wise gray matter between these two time points, there was no evidence of any significant decrease. Instead, we detected a pronounced gray matter increase involving both cortical and subcortical regions, such as the pre- and postcentral gyrus, the frontal and central operculum, the inferior frontal gyrus, the precuneus, and the middle occipital gyrus, as well as the thalamus and caudate. These structural changes occurring within only 4-6 weeks after delivery are reflective of a high degree of neuroplasticity and massive adaptations in the maternal brain. They may suggest a restoration of brain tissue following pregnancy and/or a substantial brain reorganization, possibly to accommodate a multifaceted repertoire of complex behaviors associated with being a mother.
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| 8. |
- Luders, Eileen, et al.
(författare)
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Gray matter increases within subregions of the hippocampal complex after pregnancy
- 2021
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Ingår i: Brain Imaging and Behavior. - : Springer Nature. - 1931-7557 .- 1931-7565. ; 15:6, s. 2790-2794
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Tidskriftsartikel (refereegranskat)abstract
- Neuroimaging findings - although still relatively sparse in the realm of postpartum research - suggest significant tissue increases within the hippocampus or its vicinity after giving birth. Given that the hippocampus is not a homogenous structure, effects may manifest differently across the hippocampal complex. Thus, the goal of this study was to determine the presence, magnitude, and direction of postpartum gray matter changes within five hippocampal subregions, specifically the dentate gyrus, the subiculum, and the subfields of the cornu ammonis (CA1, CA2 and CA3). For this purpose, we analyzed brain images of 14 healthy women acquired at immediate postpartum (within 1-2 days of childbirth) and at late postpartum (at 4-6 weeks after childbirth). Changes in hippocampal gray matter between both time points were calculated for all subregions as well as the hippocampal complex as a whole by integrating imaging-based intensity information with microscopically defined cytoarchitectonic probabilities. Hippocampal gray matter increased significantly within the right subiculum, right CA2, and right CA3. These findings may suggest that brain tissue lost during pregnancy is being restored after giving birth, perhaps even expanded compared to before pregnancy. Possible events on the microanatomical level include dendritic branching as well as the generation of new synapses, glia cells, and blood vessels. Altogether, the outcomes of our study confirm that hippocampal gray matter increases in the female human brain after giving birth, with differential effects across the hippocampal complex.
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| 9. |
- Luders, Eileen, et al.
(författare)
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Postpartum Gray Matter Changes in the Auditory Cortex
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:23
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Tidskriftsartikel (refereegranskat)abstract
- After giving birth, a mother's brain undergoes functional adaptations fostering the ability to properly respond to the needs of her newborn. Tuning into and understanding her baby's crying is among the top skills required and executed in the early stages of motherhood. However, surprisingly little is known about potential changes in the anatomy of the maternal auditory cortex. Therefore, in this longitudinal study, we compared the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), focusing on areas of the primary, secondary, and higher auditory cortex. We observed significant volume increases within all auditory regions and subregions examined, which might reflect rapid adaptations of the mother's brain in relation to reliably interpreting her newborn's cries. There was also a trend for a larger postpartum increase within right-hemispheric regions compared to left-hemispheric regions that might be specifically linked to the ability to discern the pitch, sound, and volume of a baby's crying. Follow-up research is warranted to replicate these findings and evaluate their current interpretation.
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| 10. |
- Luders, Eileen, et al.
(författare)
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Significant increases of the amygdala between immediate and late postpartum : Pronounced effects within the superficial subregion
- 2021
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Ingår i: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:9, s. 2261-2270
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Tidskriftsartikel (refereegranskat)abstract
- Research exploring the underlying neuroanatomical correlates of early motherhood seems to suggest that the period after giving birth is marked by tissue increases in the mother's brain. While some studies point to the amygdala as one of the areas undergoing postpartum changes, existing analyses did not discriminate between the different subregions of this functionally heterogeneous structure. Thus, to further extend this understudied field of research and to better understand the potential role of the amygdala when transitioning to motherhood, we applied an advanced region-of-interest technique that enabled us to analyze the amygdala as a whole as well as its different subareas, specifically the left and right centromedian (CM), laterobasal (LB), and superficial (SF) regions. Comparing the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), we revealed increases of the amygdala. However, effects manifested differentially across subareas, with particularly strong effects for the SF region, moderate effects for the CM region, and no effects for the LB region. These findings might reflect region-specific adaptations of the mother's brain tuning into the distinct and ever-changing needs of a newborn, either as a cause for it or as a consequence thereof.
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