| 1. |
- Cannavacciuolo, Antonio, et al.
(författare)
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Facial emotion expressivity in patients with Parkinson's and Alzheimer's disease
- 2024
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Ingår i: Journal of neural transmission. - 0300-9564 .- 1435-1463. ; 31, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters’ responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters’ response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.
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| 2. |
- Checknita, Dave, et al.
(författare)
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Associations of Age, Sex, Sexual Abuse, and Genotype with Monoamine Oxidase A Gene Methylation
- 2021
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Ingår i: Journal of neural transmission. - : Springer Nature. - 0300-9564 .- 1435-1463. ; 128:11, s. 1721-1739
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Tidskriftsartikel (refereegranskat)abstract
- Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation of monoamine oxidase A (MAOA). Methylation of the first exonic and partial first intronic region of MAOA has been shown to strengthen associations of interactions of MAOA-uVNTR genotypes and adversity with aggression and substance misuse. Our study examined associations of sex and age with MAOA first exon and intron methylation levels in 252 women and 157 men aged 14–73 years. Participants included adolescents recruited at a substance misuse clinic, their siblings and parents, and healthy women. Women showed ~ 50% higher levels of exonic, and ~ 15% higher intronic, methylation than men. Methylation levels were similar between younger (M = 22.7 years) and older (M = 46.1 years) participants, and stable across age. Age modified few associations of methylation levels with sex. MAOA genotypes modified few associations of methylation with sex and age. Higher methylation levels among women were not explained by genotype, nor interaction of genotype and sexual abuse. Findings were similar after adjusting for lifetime diagnoses of substance dependence (women = 24.3%; men = 34.2%). Methylation levels were higher among women who experienced sexual abuse than women who did not. Results extend on prior studies by showing that women display higher levels of methylation than men within first intronic/exonic regions of MAOA, which did not decrease with age in either sex. Findings were not conditioned by genotype nor interactions of genotype and trauma, and indicate X-chromosome inactivation.
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| 3. |
- de Vries, Lyssa, et al.
(författare)
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Investigating the development of the autonomic nervous system in infancy through pupillometry
- 2023
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Ingår i: Journal of neural transmission. - : Springer. - 0300-9564 .- 1435-1463. ; 130, s. 723-734
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Tidskriftsartikel (refereegranskat)abstract
- We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, eta(2)(p) = 0.13), latency to constriction (F(3,326.41) =3.84, p = 0.010,eta(2)(p) = 0.03) and relative constriction amplitude(F(3,282.53) =3.70, p = 0.012,eta(2)(p)= 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001,eta(2)(p) = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, eta(2)(p) = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.
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| 4. |
- Delaby, C., et al.
(författare)
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Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles
- 2022
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 129, s. 231-237
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined. Methods We studied in two independent cohorts, the performance of blood biomarkers in detecting "nonpathological" (A-/T-/N-), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles. Results Plasma A beta(1-42)/A beta(1-40) ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A-/T-/N-) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection. Conclusion The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents an attractive stratification strategy in the clinical management of patients visiting memory clinics. This could reduce the need for lumbar puncture and foreshadow the use of blood testing on larger populations.
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| 5. |
- Fornstedt Wallin, Bodil
(författare)
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Oxidation of dopamine and related catechols in dopaminergic brain regions in Parkinson’s disease and during ageing in non-Parkinsonian subjects
- 2024
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Ingår i: Journal of Neural Transmission. - 0300-9564 .- 1435-1463.
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Tidskriftsartikel (refereegranskat)abstract
- The present study was performed to examine if catechol oxidation is higher in brains from patients with Parkinson’s disease compared to age-matched controls, and if catechol oxidation increases with age. Brain tissue from Parkinson patients and age-matched controls was examined for oxidation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) to corresponding quinones, by measurement of 5-S-cysteinyl-dopamine, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA. The cysteinyl catechols are assumed to be biomarkers for DA, DOPAC and DOPA autoxidation and part of the biosynthetic pathway of neuromelanin. The concentrations of the 5-S-cysteinyl catechols were lower, whereas the 5-S-cysteinyl-DA/DA and 5-S-cysteinyl-DOPAC/DOPAC ratios tended to be higher in the Parkinson group compared to controls, which was interpreted as a higher degree of oxidation. High 5-S-cysteinyl-DA/DA ratios were found in the substantia nigra of a sub-population of the Parkinson group. Based on 5-S-cysteinyl-DA/DA ratios, dopamine oxidation was found to increase statistically significantly with age in the caudate nucleus, and non-significantly in the substantia nigra. In conclusion, the occurrence of 5-S-cysteinyl-DA, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA was demonstrated in dopaminergic brain areas of humans, a tendency for higher oxidation of DA in the Parkinson group compared to controls was observed as well as a statistically significant increase in DA oxidation with age. Possibly, autoxidation of DA and other catechols are involved in both normal and pathological ageing of the brain. This study confirms one earlier but small study, as well as complements one study on non-PD cases and one study on both PD cases and controls on NM bound or integrated markers or catechols.
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| 6. |
- Hollmann, K., et al.
(författare)
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Internet-based cognitive behavioral therapy in children and adolescents with obsessive compulsive disorder: a feasibility study
- 2021
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 1445-1459
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavioral therapy (CBT) is the first choice of treatment of obsessive-compulsive disorder (OCD) in children and adolescents. However, there is often a lack of access to appropriate treatment close to the home of the patients. An internet-based CBT via videoconferencing could facilitate access to state-of-the-art treatment even in remote areas. The aim of this study was to investigate feasibility and acceptability of this telemedical approach. A total of nine children received 14 sessions of CBT. The first session took place face-to-face, the remaining 13 sessions via videoconference. OCD symptoms were recorded with a smartphone app and therapy materials were made accessible in a data cloud. We assessed diagnostic data before and after treatment and obtained measures to feasibility, treatment satisfaction and acceptability. Outcomes showed high acceptance and satisfaction on the part of patients with online treatment (89%) and that face-to-face therapy was not preferred over an internet-based approach (67%). The majority of patients and their parents classified the quality of treatment as high. They emphasized the usefulness of exposures with response prevention (E/RP) in triggering situations at home. The app itself was rated as easy to operate and useful. In addition to feasibility, a significant decrease in obsessive-compulsive symptoms was also achieved. Internet-based CBT for pediatric OCD is feasible and well received by the patients and their parents. Furthermore, obsessive-compulsive symptomatology decreased in all patients. The results of this study are encouraging and suggest the significance of further research regarding this technology-supported approach, with a specific focus on efficacy. Trial registration number: Clinical trials AZ53-5400.1-004/44.
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| 7. |
- Ivarsson, Tord, 1946, et al.
(författare)
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Neurochemical properties measured by H-1 magnetic resonance spectroscopy may predict cognitive behaviour therapy outcome in paediatric OCD: a pilot study
- 2021
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 1361-1370
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Tidskriftsartikel (refereegranskat)abstract
- To identify neurochemical factors measured pre-treatment that may predict cognitive behavioural treatment (CBT) outcome, aiming at understanding possible causes of poor CBT response. 1H magnetic resonance spectroscopy was used before treatment with CBT in treatment naive 11-18 year-old patients with moderate-severe OCD. Diagnoses and assessment of OCD severity were based on semi-structured interviews. Linear mixed effects models were used to analyse the association between metabolite level and treatment outcome. Worse CBT outcome was associated with higher concentration of glutamine and glutamate combined (Glx) in middle cingulate cortex (MCC) (F = + 3.35, p = 0.004) and of N-acetylaspartate and N-acetylaspartylglutamate combined (tNAA) (F = + 2.59, p = 0.019). Also, we noted a tendency towards higher thalamic Glx concentration (F = + 1.91, p = 0.077) to be associated with worse CBT outcome. In general, the findings of the current pilot study are compatible with the hypothesis of an overweight of excitatory to inhibitory factors in brain circuits driving goal-directed behaviours (GDB). Higher MCC Glx and tNAA may be involved in the selection of GDB. A more detailed understanding of how these brain areas function in health and illness is needed.
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| 8. |
- Keijser, Rebecka, et al.
(författare)
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Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population
- 2021
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Ingår i: Journal of neural transmission. - : Springer Nature. - 0300-9564 .- 1435-1463. ; 128, s. 1409-1424
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Tidskriftsartikel (refereegranskat)abstract
- FKBP5 gene–environment interaction (cG × E) studies have shown diverse results, some indicating significant interaction effects between the gene and environmental stressors on depression, while others lack such results. Moreover, FKBP5 has a potential role in the diathesis stress and differential susceptibility theorem. The aim of the present study was to evaluate whether a cG × E interaction effect of FKBP5 single-nucleotide polymorphisms (SNPs) or haplotype and early life stress (ELS) on depressive symptoms among young adults was moderated by a positive parenting style (PASCQpos), through the frameworks of the diathesis stress and differential susceptibility theorem. Data were obtained from the Survey of Adolescent Life in Västmanland Cohort Study, including 1006 participants and their guardians. Data were collected during 2012, when the participants were 13 and 15 years old (Wave I: DNA), 2015, when participants were 16 and 18 years old (Wave II: PASCQpos, depressive symptomology and ELS) and 2018, when participants were 19 and 21 years old (Wave III: depressive symptomology). Significant three-way interactions were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309, moderated by ELS and PASCQpos, on depressive symptoms among young adults. Diathesis stress patterns of interaction were observed for the FKBP5 SNPs rs1360780, rs4713916 and rs9394309, and differential susceptibility patterns of interaction were observed for the FKBP5 SNP rs7748266. Findings emphasize the possible role of FKBP5 in the development of depressive symptoms among young adults and contribute to the understanding of possible differential susceptibility effects of FKBP5.
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| 9. |
- Olsson, Yasmin, et al.
(författare)
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Effects of systemic glycine on accumbal glycine and dopamine levels and ethanol intake in male Wistar rats
- 2021
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 83-94
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Tidskriftsartikel (refereegranskat)abstract
- Approved medications for alcohol use disorder (AUD) display modest effect sizes. Pharmacotherapy aimed at the mechanism(s) by which ethanol activates the dopamine reward pathway may offer improved outcomes. Basal and ethanol-induced accumbal dopamine release in the rat involve glycine receptors (GlyR) in the nucleus accumbens (nAc). Glycine transporter 1 (GlyT-1) inhibitors, which raise extracellular glycine levels, have repeatedly been shown to decrease ethanol intake in the rat. To further explore the rational for elevating glycine levels in the treatment of AUD, this study examined accumbal extracellular glycine and dopamine levels and voluntary ethanol intake and preference in the rat, after systemic treatment with glycine. The effects of three different doses of glycine i.p. on accumbal glycine and dopamine levels were examined using in vivo microdialysis in Wistar rats. In addition, the effects of the intermediate dose of glycine on voluntary ethanol intake and preference were examined in a limited access two-bottle ethanol/water model in the rat. Systemic glycine treatment increased accumbal glycine levels in a dose-related manner, whereas accumbal dopamine levels were elevated in a subpopulation of animals, defined as dopamine responders. Ethanol intake and preference decreased after systemic glycine treatment. These results give further support to the concept of elevating central glycine levels to reduce ethanol intake and indicate that targeting the glycinergic system may represent a pharmacologic treatment principle for AUD.
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| 10. |
- Olsson, Yasmin, et al.
(författare)
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The glycine-containing dipeptide leucine-glycine raises accumbal dopamine levels in a subpopulation of rats presenting a lower endogenous dopamine tone
- 2022
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 129:4, s. 395-407
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Tidskriftsartikel (refereegranskat)abstract
- Interventions that elevate glycine levels and target the glycine receptor (GlyR) in the nucleus Accumbens (nAc) reduce ethanol intake in rats, supposedly by acting on the brain reward system via increased basal and attenuated ethanol-induced nAc dopamine release. Glycine transport across the blood brain barrier (BBB) appears inefficient, but glycine-containing dipeptides elevate whole brain tissue dopamine levels in mice. This study explores whether treatment with the glycine-containing dipeptides leucine-glycine (Leu-Gly) and glycine-leucine (Gly-Leu) by means of a hypothesized, facilitated BBB passage, alter nAc glycine and dopamine levels and locomotor activity in two rodent models. The acute effects of Leu-Gly and Gly-Leu (1-1000 mg/kg, i.p.) alone or Leu-Gly in combination with ethanol on locomotion in male NMRI mice were examined in locomotor activity boxes. Striatal and brainstem slices were obtained for ex vivo HPLC analyses of tissue levels of glycine and dopamine. Furthermore, the effects of Leu-Gly i.p. (1-1000 mg/kg) on glycine and dopamine output in the nAc were examined using in vivo microdialysis coupled to HPLC in freely moving male Wistar rats. Leu-Gly and Gly-Leu did not significantly alter locomotion, ethanol-induced hyperlocomotor activity or tissue levels of glycine or dopamine, apart from Gly-Leu 10 mg/kg that slightly raised nAc dopamine. Microdialysis revealed no significant alterations in nAc glycine or dopamine levels when regarding all rats as a homogenous group. In a subgroup of rats defined as dopamine responders, a significant elevation of nAc dopamine (20%) was seen following Leu-Gly 10-1000 mg/kg i.p, and this group of animals presented lower baseline dopamine levels compared to dopamine non-responders. To conclude, peripheral injection of glycine-containing dipeptides appears inefficient in elevating central glycine levels but raises accumbal dopamine levels in a subgroup of rats with a lower endogenous dopamine tone. The tentative relationship between dopamine baseline and ensuing response to glycinergic treatment and presumptive direct interactions between glycine-containing dipeptides and the GlyR bear insights for refinement of the glycinergic treatment concept for alcohol use disorder (AUD).
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