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- Martino, Davide, et al.
(författare)
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Association and Familial Coaggregation of Idiopathic Dystonia with Psychiatric Outcomes
- 2020
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Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35:12, s. 2270-2278
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Tidskriftsartikel (refereegranskat)abstract
- Background Psychiatric comorbidities are common and major determinants of quality of life in idiopathic dystonia. Their prevalence estimates from service-based studies are heterogeneous. Objective We explored the association between idiopathic dystonia and depressive disorders, anxiety disorders, suicide attempts, and death by suicide using Swedish population-based registers. Methods Diagnoses of idiopathic dystonia and psychiatric outcomes from inpatient and outpatient specialist services (1997-2013) were collected from the National Patient Register and the Cause of Death Register. Familial associations were explored using the Multi-Generation Register. Adjusted logistic regression analyses measured associations with psychiatric disorders in individuals with dystonia compared with general population individuals and their unaffected siblings, as well as in full siblings of individuals with dystonia compared with full siblings of unaffected individuals. Results Individuals with dystonia were more likely than those without to have a diagnosis of depressive disorder (adjusted odds ratio = 2.00, 95% confidence interval: 1.77-2.26), anxiety disorder (adjusted odds ratio = 2.13, 95% confidence interval: 1.90-2.39), and suicide attempts/death by suicide combined (adjusted odds ratio = 1.80, 95% confidence interval: 1.50-2.17), with odds higher in most idiopathic dystonia forms. In the full sibling comparison, estimates followed the same pattern, with overall attenuated magnitude. Full siblings of individuals with dystonia had higher likelihood of depressive or anxiety disorders and suicide attempts/death by suicide combined compared with siblings of individuals without dystonia. Conclusions Different forms of idiopathic dystonia confirm its association with increased risk for depressive and anxiety disorders and suicide attempts. Familial coaggregation of dystonia and these psychiatric comorbidities supports shared genetic and extragenetic factors. (c) 2020 International Parkinson and Movement Disorder Society
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| 2. |
- Mataix-Cols, David, et al.
(författare)
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Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder
- 2021
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 36:1, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents.OBJECTIVES: The aim of this study was to investigate the risk for injuries or death caused by transport and motor vehicle accidents in individuals with Tourette syndrome or chronic tic disorder.METHODS: This population-based, sibling-controlled cohort study included all individuals aged ≥18 years living in Sweden between 1997 and 2013 (N = 6,127,290). A total of 3449 individuals had a registered diagnosis of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. We also identified 2191 families with full siblings discordant for tic disorders. Cox proportional hazards regression modeling was used to estimate the risk for injuries or deaths as a result of transport accidents in individuals with a lifetime diagnosis of Tourette syndrome or chronic tic disorder compared with unexposed individuals and siblings.RESULTS: Individuals with tic disorders had a higher risk for transport injuries or death compared with the general population (adjusted hazard ratio, 1.50 [95% confidence interval: 1.33-1.69]) and their unaffected siblings (adjusted hazard ratio, 1.41 [95% confidence interval: 1.18-1.68]). The risks were similar across sexes. The exclusion of most psychiatric comorbidities did not alter the magnitude of the estimates. However, the risks were no longer significant after exclusion of individuals with comorbid attention deficit hyperactivity disorder.CONCLUSIONS: The marginally increased risk for serious transport accidents in tic disorders is mainly driven by attention deficit hyperactivity disorder comorbidity. Improved detection and management of attention deficit hyperactivity disorder symptoms in this patient group are warranted.
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| 3. |
- Niemelä, Valter, et al.
(författare)
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Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:2, s. 481-491
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Tidskriftsartikel (refereegranskat)abstract
- Objective Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies. Methods We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 pre-manifest (preHD), and 38 controls. A biologically plausible and significant possible biomarker was validated in samples from a separate cohort of patients and controls consisting of 23 ManHD patients and 23 controls. Results In ManHD compared to preHD, 10 proteins were downregulated and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin were closely linked to HD symptom severity, whereas levels of 15 upregulated proteins were associated with symptom severity. The decreased PENK levels were replicated in the separate cohort where absolute quantitation was performed. Conclusions We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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| 4. |
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| 5. |
- Svenningsson, P., et al.
(författare)
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A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:6, s. 1046-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 mu M on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. (c) 2020 International Parkinson and Movement Disorder Society
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