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Journal of Neural Transmission
Journal Prestige (SJR): 1.232
Citation Impact (citeScore): 3
Number of Followers: 2  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0300-9564 - ISSN (Online) 1435-1463
Published by Springer-Verlag Homepage  [2352 journals]
  • The brain as a “hyper-network”: the key role of neural networks as
           main producers of the integrated brain actions especially via the
           “broadcasted” neuroconnectomics
    • Authors: Luigi F. Agnati; Manuela Marcoli; Guido Maura; Amina Woods; Diego Guidolin
      Pages: 883 - 897
      Abstract: Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the “core components” of the brain hyper-network that has as special “nodes” the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1855-7
      Issue No: Vol. 125, No. 6 (2018)
  • Kynurenic acid and its derivatives are able to modulate the adhesion and
           locomotion of brain endothelial cells
    • Authors: Eszter Lajkó; Bernadett Tuka; Ferenc Fülöp; István Krizbai; József Toldi; Kálmán Magyar; László Vécsei; László Kőhidai
      Pages: 899 - 912
      Abstract: The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood–brain barrier (BBB)] are well established. Cell–extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium. The effects of KYNA and its derivatives on cell adhesion were measured using an impedance-based technique, the xCELLigence SP system. Holographic microscopy (Holomonitor™ M4) was used to analyse both chemokinetic responses and morphometry. The GP8 cells proved to be a suitable model cell line for investigating cell adhesion and the locomotion modulator effects of kynurenines. KYNA enhanced cell adhesion and spreading, and also decreased the migration/motility of GP8 cells at physiological concentrations (10−9 and 10−7 mol/L). The derivatives containing an amide side-chain at the C2 position (KYNA-A1 and A2) had lower adhesion inducer effects compared to KYNA. All synthetic analogues (except KYNA-A5) had a time-dependent inhibitory effect on GP8 cell adhesion at a supraphysiological concentration (10−3 mol/L). The immobilization promoting effect of KYNA and the adhesion inducer activity of its derivatives indicate that these compounds could contribute to maintaining or restoring the protective function of brain endothelium; they also suggest that cell–ECM adhesion and related cell responses (e.g. migration/motility) could be potential new targets of KYNA.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1839-7
      Issue No: Vol. 125, No. 6 (2018)
  • Expression of the ADHD candidate gene Diras2 in the brain
    • Authors: Lena Grünewald; Nils Becker; Annika Camphausen; Aet O‘Leary; Klaus-Peter Lesch; Florian Freudenberg; Andreas Reif
      Pages: 913 - 923
      Abstract: The distinct subgroup of the Ras family member 2 (DIRAS2) gene has been found to be associated with attention-deficit/hyperactivity disorder (ADHD) in one of our previous studies. This gene is coding for a small Ras GTPase with unknown function. DIRAS2 is highly expressed in the brain. However, the exact neural expression pattern of this gene was unknown so far. Therefore, we investigated the expressional profile of DIRAS2 in the human and murine brain. In the present study, qPCR analyses in the human and in the developing mouse brain, immunocytological double staining on murine hippocampal primary cells and RNA in situ hybridization (ISH) on brain sections of C57BL/6J wild-type mice, have been used to reveal the expression pattern of DIRAS2 in the brain. We could show that DIRAS2 expression in the human brain is the highest in the hippocampus and the cerebral cortex, which is in line with the ISH results in the mouse brain. During mouse brain development, Diras2 levels strongly increase from prenatal to late postnatal stages. Co-expression studies indicate Diras2 expression in glutamatergic and catecholaminergic neurons. Our findings support the idea of DIRAS2 as a candidate gene for ADHD as the timeline of its expression as well as the brain regions and cell types that show Diras2 expression correspond to those assumed to underlie the pathomechanisms of the disease.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1867-3
      Issue No: Vol. 125, No. 6 (2018)
  • Flavor perception and the risk of malnutrition in patients with
           Parkinson’s disease
    • Authors: Dareia S. Roos; Oscar J. M. Oranje; Anneleen F. D. Freriksen; Henk W. Berendse; Sanne Boesveldt
      Pages: 925 - 930
      Abstract: Flavor perception involves both olfactory and gustatory function. In patients with Parkinson’s disease (PD), hyposmia is a frequent finding, as well as an increased risk of malnutrition. We performed a pilot study to investigate the relationship between flavor perception and risk of malnutrition in PD patients. 63 PD patients participated to perform an olfactory (Sniffin’ Sticks) and gustatory (Taste Strips) task, and a questionnaire to establish nutritional risk (MUST), which includes BMI measurements. The relationship between olfactory and gustatory function and BMI was analyzed using partial correlations, corrected for disease duration, and regression analysis. Patients displayed a high prevalence of hyposmia (68.3%), and a low prevalence (6.3%) of hypogeusia. A small, but significant correlation was found between olfactory function and BMI (r = 0.261, p = 0.038), and not for gustatory function and BMI (r = 0.137, p = 0.284). Hyposmia, and not hypogeusia, may contribute to weight loss in Parkinson’s disease, and hence increase the risk of malnutrition.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1862-8
      Issue No: Vol. 125, No. 6 (2018)
  • In vivo exploration of retinal nerve fiber layer morphology in
           Parkinson’s disease patients
    • Authors: Femke Visser; Koenraad A. Vermeer; Babak Ghafaryasl; Annemarie M. M. Vlaar; Valentin Apostolov; Jan van Hellenberg Hubar; Henry C. Weinstein; Johannes F. de Boer; Henk W. Berendse
      Pages: 931 - 936
      Abstract: Thinning of the retinal nerve fiber layer (RNFL) is a recently discovered feature of Parkinson’s disease (PD). Its exact pathological mechanism is yet unknown. We aimed to determine whether morphological changes of the RNFL are limited to RNFL thinning or also comprise an altered internal structure of this layer. Therefore, we investigated RNFL thickness and applied the RNFL attenuation coefficient (RNFL-AC), a novel method derived from optical coherence tomography, in PD patients and healthy controls (HCs). In this pilot study, we included 20 PD patients and 20 HCs matched for age, sex, and ethnicity. An ophthalmologist investigated all participants thoroughly, and we acquired retinal images from both eyes of each participant with a Spectralis optical coherence tomography system. We obtained both the RNFL-AC and RNFL thickness from peripapillary RNFL scans for the entire RNFL, as well as for each quadrant separately. We found no significant differences in the average RNFL-AC or the RNFL-AC of the separate retinal quadrants between PD patients and the HC group. However, compared to the HC group, PD patients had a significantly thinner RNFL in the temporal retinal quadrant. RNFL thinning was found in the temporal quadrant in PD patients without a corresponding change in the RNFL-AC. These findings suggest a reduction in the number of RNFL axons (atrophy) without other major changes in the structural integrity of the remaining RNFL.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1872-6
      Issue No: Vol. 125, No. 6 (2018)
  • The relationship between gait variability and cognitive functions differs
           between fallers and non-fallers in MS
    • Authors: Alon Kalron; Roy Aloni; Mark Dolev; Lior Frid; Uri Givon; Shay Menascu
      Pages: 945 - 952
      Abstract: The objective of the study was to determine if cognitive function is associated with step time variability in people with multiple sclerosis (PwMS). The study included 355 PwMS (218 women), average age 41.1 (SD = 13.5), disease duration 5.9 (SD = 7.3) years, and a median expanded disability status scale score of 2.5. We separately analyzed the sample group of fallers and non-fallers based on their fall history. Gait variability was measured by an electronic walkway and all participants completed a computerized cognitive test battery designed to evaluate multiple cognitive domains. Fallers (43.7%) demonstrated elevated step time variability (%CV), 5.0 (SD = 3.4) vs. 3.5 (SD = 1.6), P < 0.001 compared to the non-faller subjects. According to the regression analysis in the non-fallers’ group, step time variability was found significantly associated with the global cognitive score (P = 0.001), executive function subcategory (P = 0.038), and motor skills subcategory (P < 0.001). No relationship between step time variability and any cognitive domain was demonstrated in the faller group. This study illustrated that the association between gait variability and cognition occurs only in PwMS without a fall history. From a clinical standpoint, these findings might help medical professionals to create improved assessment tests and rehabilitation strategies in the MS population.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1843-y
      Issue No: Vol. 125, No. 6 (2018)
  • An observational study of rotigotine transdermal patch and other currently
           prescribed therapies in patients with Parkinson’s disease
    • Authors: Thomas Müller; Eduardo Tolosa; Letitia Badea; Mahnaz Asgharnejad; Frank Grieger; Michael Markowitz; Xavier Nondonfaz; Lars Bauer; Lars Timmermann
      Pages: 953 - 963
      Abstract: Real-world data from large cohorts of patients with Parkinson’s disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1860-x
      Issue No: Vol. 125, No. 6 (2018)
  • Neuropathology and biochemistry of early onset familial Alzheimer’s
           disease caused by presenilin-1 missense mutation Thr116Asn
    • Authors: Stanislav Sutovsky; Tomas Smolek; Peter Turcani; Robert Petrovic; Petra Brandoburova; Santosh Jadhav; Petr Novak; Johannes Attems; Norbert Zilka
      Pages: 965 - 976
      Abstract: The majority (~ 55%) of early onset familial Alzheimer disease (FAD) is caused by mutations in the presenilin 1 gene (PSEN1). Here, we describe a family with early onset FAD with a missense mutation in the PSEN1 gene (Thr116Asn). Five family members developed dementia in the third decade of life. One subject underwent autopsy. The onset of clinical symptoms was at the age of 37 years and the disease progressed rapidly. The clinical picture was characterised by progressive memory impairment, amnestic aphasia, and gait disturbances. Neuropathological assessment revealed widespread β-amyloid (Thal phase 5) and tau (Braak stage 6) pathology. Abundant deposition of diffuse and cored plaques was distributed in cortical and subcortical areas, as well as in the cerebellum, while cotton wool plaques were observed mainly in the occipital cortex. Cerebral amyloid angiopathy was present throughout the brain. In the neocortex, tau pathology, especially neuropil threads, was more abundant in the frontal and occipital cortex and in the hippocampus. Proteomic analyses revealed that the pattern of sarkosyl-insoluble tau was similar to the one seen in sporadic AD. No α-synuclein or TDP-43 pathology was found either in cortical nor in subcortical areas. Here, we present the first comprehensive neuropathological and biochemical study of early onset FAD with a missense mutation Thr116Asn in the presenilin 1 gene. In contrast to other PS1-linked AD patients, the present subject developed cotton wool plaques which were not associated with spastic paraparesis.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1850-z
      Issue No: Vol. 125, No. 6 (2018)
  • Individual biological sensitivity to environmental influences: testing the
           differential susceptibility properties of the 5HTTLPR polymorphism in
           relation to depressive symptoms and delinquency in two adolescent general
    • Authors: Cecilia Åslund; Kent W. Nilsson
      Pages: 977 - 993
      Abstract: The gene–environment interaction research field in psychiatry has traditionally been dominated by the diathesis–stress framework, where certain genotypes are assumed to confer increased risk for adverse outcomes in a stressful environment. In later years, theories of differential susceptibility, or biological sensitivity, suggest that candidate genes that interact with environmental events do not exclusively confer a risk for behavioural or psychiatric disorders but rather seem to alter the sensitivity to both positive and negative environmental influences. The present study investigates the susceptibility properties of the serotonin transporter-linked polymorphic region (5HTTLPR) in relation to depressive symptoms and delinquency in two separate adolescent community samples: n = 1457, collected in 2006; and n = 191, collected in 2001. Two-, three-, and four-way interactions between the 5HTTLPR, positive and negative family environment, and sex were found in relation to both depressive symptoms and delinquency. However, the susceptibility properties of the 5HTTLPR were distinctly less pronounced in relation to depressive symptoms. If the assumption that the 5HTTLPR induces differential susceptibility to both positive and negative environmental influences is correct, the previous failures to measure and control for positive environmental factors might be a possible explanation for former inconsistent findings within the research field.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1854-8
      Issue No: Vol. 125, No. 6 (2018)
  • Antidepressant treatment effects on dopamine transporter availability in
           patients with major depression: a prospective 123 I-FP-CIT SPECT imaging
           genetic study
    • Authors: Sabine Hellwig; Lars Frings; Annette Masuch; Werner Vach; Katharina Domschke; Claus Normann; Philipp T. Meyer
      Pages: 995 - 1005
      Abstract: We investigated if sleep deprivation (SD) and electroconvulsive therapy (ECT) affect striatal dopamine transporter (DAT) availability assessed by single-photon emission computed tomography (SPECT) and 123I-FP-CIT, if dopamine transporter gene (SLC6A3; DAT) variation modifies aforementioned parameters, and if SD response or SD-induced DAT changes correlate with ECT response. Sixteen patients with major depression (MDD) referred for ECT and 12 matched controls were prospectively recruited for imaging and SLC6A3 VNTR genotyping. After withdrawal from any psychiatric medication, 123I-FP-CIT-SPECT was acquired at baseline, after SD and after ECT series. Striatal DAT availability was assessed by volume-of-interest analysis of SPECT data. Eleven patients underwent combined treatment with SD and ECT (five ECT responders and six non-responders). Per-protocol analyses yielded no significant effect of SD or ECT on striatal DAT availability using repeated-measures ANOVA. However, intention-to-treat analysis indicated a significant decrease of striatal DAT availability due to SD (paired t test, p < 0.01). Stratification by SLC6A3 VNTR genotype suggested the 9R allele to drive this effect. In an exploratory analysis, SD-induced change in DAT availability of the left caudate nucleus predicted ECT response. This study revealed a treatment effect of SD on striatal DAT availability—possibly depending on SLC6A3 VNTR genotype. This and the observed association between SD-induced change of striatal DAT availability and response to ECT may help to identify treatment mechanisms and response predictors useful for precision medicine approaches in the treatment of MDD.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1863-7
      Issue No: Vol. 125, No. 6 (2018)
  • Who will remain tremor dominant' The possible role of cognitive
           reserve in the time course of two common Parkinson’s disease motor
    • Authors: Talia Herman; S. Shema-Shiratzky; L. Arie; N. Giladi; J. M. Hausdorff
      Pages: 1007 - 1011
      Abstract: In a prospective 5-year study among Parkinson’s disease (PD) tremor-dominant (TD) patients, we investigated who will remain TD and who will later convert into the postural instability gait difficulty (PIGD) phenotype. At follow-up, 38% were still considered TD. At baseline the TD non-convertors had more years of education and better cognitive function than the convertors and significantly smaller deterioration in gait, balance, cognitive function and other non-motor symptoms. These results highlight the potential role of cognition in protecting against the development of PIGD symptoms.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1859-3
      Issue No: Vol. 125, No. 6 (2018)
  • Neuroinflammation in neurodegeneration: role in pathophysiology,
           therapeutic opportunities and clinical perspectives
    • Authors: Guillaume Dorothée
      Pages: 749 - 750
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1880-6
      Issue No: Vol. 125, No. 5 (2018)
  • Kynurenine is correlated with IL-1β in plasma of schizophrenia
    • Authors: Helena P. G. Joaquim; Alana C. Costa; Wagner F. Gattaz; Leda Leme Talib
      Pages: 869 - 873
      Abstract: The etiology of schizophrenia is still unclear. It is well-known that pro-inflammatory cytokines are higher in schizophrenia patients since the first episode psychosis comparing to healthy controls. Inflammatory downstream cascades influence different cellular pathways, like the displacement of the tryptophan (TRP) metabolism to the production of kynurenine (KYN) instead of serotonin, which results in the generation of several neuro and immunoactive metabolites. The aim of this study was to determine TRP, KYN and IL-1β plasma levels in first-onset schizophrenia (n = 28) and healthy controls (n = 30). The plasmatic levels of TRP and KYN were decreased in schizophrenic patients (p = 0.004 and p = 0.002, respectively), but there was no difference in the ratio of KYN/TRP (p = 0.554) or either in IL-1β (p = 0.101). Positive correlation was observed between KYN and IL-1β only in the schizophrenia group (r = 0.461, p = 0.021). And, there was also positive correlation between KYN and Positive and Negative Symptoms Scale (PANSS) (r = 0.395, p = 0.037). There is no correlation between the other analytes and other parameters of PANSS. Although our results of KYN have been different than expected and there was no difference in the KYN/TRP ratio, we observed a positive correlation between IL-1β and KYN, corroborating findings that pro-inflammatory agents hold up the KYN pathway.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1838-8
      Issue No: Vol. 125, No. 5 (2018)
  • Interleukin 6 and complement serum level study in Parkinson’s
    • Authors: Branislav Veselý; Michal Dufek; Vojtech Thon; Miroslav Brozman; Silvia Királová; Tatiana Halászová; Eva Koriťáková; Ivan Rektor
      Pages: 875 - 881
      Abstract: The objective of this study is to assess whether elevation of serum inflammatory markers levels may indicate the progression of clinical impairment in Parkinson’s disease (PD) patients. In 47 PD patients, the serum levels of the C3 and C4 part of the complement and Interleukin-6 (IL-6) were measured. The results at baseline and after 2 years were correlated with scales measuring memory, depression, motor symptoms, and quality of life. Patients with higher levels of C3 and C4 at baseline had decreased quality of life, verbal ability, and memory. Patients with higher IL-6 at baseline showed worse depression scores at 2 years. Patients with persistently higher levels of C3 and C4 at 2 years had worse quality of life and memory ability. Uncorrected p values are reported due to the exploratory nature of the study. The results indicate an impact of inflammation on non-motor signs and quality of life in PD. The increase of levels of serum inflammatory biomarkers may indicate the progression of non-motor impairment in PD.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1857-5
      Issue No: Vol. 125, No. 5 (2018)
  • Hippocampal subfield atrophy in patients with Parkinson’s disease
           and psychosis
    • Authors: Abhishek Lenka; Madhura Ingalhalikar; Apurva Shah; Jitender Saini; Shyam Sundar Arumugham; Shantala Hegde; Lija George; Venkateswara Reddy; Y. C. Janardhana Reddy; Ravi Yadav; Pramod Kumar Pal
      Abstract: Psychosis, manifested through formed visual hallucinations or minor hallucinations, is a common non-motor symptom of Parkinson’s disease (PD). The pathogenesis of psychosis in PD remains unclear; however, is possibly linked to structural and functional alterations in the hippocampus. To explore the role of hippocampus in psychosis, a detailed hippocampal subfield analysis was performed on PD patients with (PD-P) and without psychosis (PD-NP), and healthy controls (HC). An automated subfield parcellation was performed on T1 MRI images of 141 subjects (PD-P:42, PD-NP:51, and HC:48). The volumes of 12 subfields on each side were estimated and analyzed between the three groups and were corrected for multiple comparisons using false discovery rates. The volumes were also correlated to psychosis severity and specific neuropsychological tests and finally were employed to predict the psychosis severity in PD-P using a support vector regression (SVR) model. Compared to controls, PD-NP group did not demonstrate any significant differences; however, the PD-P group had significantly lower total hippocampal volume. Bilateral molecular layer, granule cell-dentate gyrus, left subiculum, and hippocampal tail and right CA3, CA4, and HATA illustrated significantly lower volumes, while bilateral hippocampal fissure demonstrated a significant widening. Compared to PD-NP, the PD-P group had higher volume of the bilateral hippocampal fissures. Finally, SVR could significantly predict the psychosis severity from all the subfield volumes. Our findings indicate a higher degeneration of specific hippocampal subfields in PD-P compared to controls and a trend of higher volume of hippocampal fissures in PD-P group than in PD-NP.
      PubDate: 2018-06-01
      DOI: 10.1007/s00702-018-1891-3
  • Levodopa-responsive breathing discomfort in Parkinson’s disease
    • Authors: Nicola Tambasco; Nicola Murgia; Pasquale Nigro; Federico Paolini Paoletti; Michele Romoli; Elona Brahimi; Marta Filidei; Simone Simoni; Giacomo Muzi; Paolo Calabresi
      Abstract: In Parkinson’s disease (PD), respiratory disturbances have been reported and the effect of levodopa on respiratory function remains controversial. The objective of this study was to evaluate pulmonary function utilizing spirometric and subjective evaluations in mild to moderated PD. Thirty-four consecutive sporadic PD patients (Hoehn and Yahr scale: 1–3) were prospectively evaluated using clinimetric scales, spirometry and modified Borg scale, all in off- and on-conditions. To check the respiratory function, a follow-up was performed at 4 years in a subgroup of these patients. Spirometric results were normal for all patients in both the on- and off-conditions at baseline. After levodopa administration, in addition to a significant improvement in subjective state of breathing discomfort, the mean forced expiratory volume in 1 s (FEV1), vital capacity (VC), forced vital capacity (FVC) values and their mean percentages predicted values (FEV1%, VC%, FVC%) were significantly increased (p < 0.05). Moreover, residual volume, total lung capacity, and the FEV1/FVC ratio were not significantly different for the ON and OFF conditions. At 4-year follow-up no resulting variations in the baseline values for FEV1%, FVC% or VC% were revealed. The results from this prospective study suggest that PD patients report frequently pulmonary discomfort. Levodopa improves respiratory symptoms. Pulmonary restrictive and obstructive dysfunctions, when not present at baseline, might not be present at 4-year follow-up.
      PubDate: 2018-05-29
      DOI: 10.1007/s00702-018-1890-4
  • Correlations between abnormal iron metabolism and non-motor symptoms in
           Parkinson’s disease
    • Authors: Wu Xu; Yan Zhi; Yongsheng Yuan; Bingfeng Zhang; Yuting Shen; Hui Zhang; Kezhong Zhang; Yun Xu
      Abstract: Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson’s disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.
      PubDate: 2018-05-10
      DOI: 10.1007/s00702-018-1889-x
  • From aggression to autism: new perspectives on the behavioral sequelae of
           monoamine oxidase deficiency
    • Authors: Marco Bortolato; Gabriele Floris; Jean C. Shih
      Abstract: The two monoamine oxidase (MAO) enzymes, A and B, catalyze the metabolism of monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine. The phenotypic outcomes of MAO congenital deficiency have been studied in humans and animal models, to explore the role of these enzymes in behavioral regulation. The clinical condition caused by MAOA deficiency, Brunner syndrome, was first described as a disorder characterized by overt antisocial and aggressive conduct. Building on this discovery, subsequent studies were focused on the characterization of the role of MAOA in the neurobiology of antisocial conduct. MAO A knockout mice were found to display high levels of intermale aggression; however, further analyses of these mutants unveiled additional behavioral abnormalities mimicking the core symptoms of autism-spectrum disorder. These findings were strikingly confirmed in newly reported cases of Brunner syndrome. The role of MAOB in behavioral regulation remains less well-understood, even though Maob-deficient mice have been found to exhibit greater behavioral disinhibition and risk-taking responses, supporting previous clinical studies showing associations between low MAO B activity and impulsivity. Furthermore, lack of MAOB was found to exacerbate the severity of psychopathological deficits induced by concurrent MAOA deficiency. Here, we summarize how the convergence of clinical reports and behavioral phenotyping in mutant mice has helped frame a complex picture of psychopathological features in MAO-deficient individuals, which encompass a broad spectrum of neurodevelopmental problems. This emerging knowledge poses novel conceptual challenges towards the identification of the endophenotypes shared by autism-spectrum disorder, antisocial behavior and impulse-control problems, as well as their monoaminergic underpinnings.
      PubDate: 2018-05-10
      DOI: 10.1007/s00702-018-1888-y
  • Patient characteristics driving clinical utility in psychiatric
           pharmacogenetics: a reanalysis from the AB-GEN multicentric trial
    • Authors: J. M. Menchón; J. Espadaler; M. Tuson; J. Saiz-Ruiz; J. Bobes; E. Vieta; E. Álvarez; V. Pérez
      Abstract: Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode. Trial registration NCT02529462.
      PubDate: 2018-05-04
      DOI: 10.1007/s00702-018-1879-z
  • COQ2 variants in Parkinson’s disease and multiple system atrophy
    • Authors: Michitaka Mikasa; Kazuaki Kanai; Yuanzhe Li; Hiroyo Yoshino; Kaoru Mogushi; Arisa Hayashida; Aya Ikeda; Sumihiro Kawajiri; Yasuyuki Okuma; Kenichi Kashihara; Tatsuya Sato; Hiroshi Kondo; Manabu Funayama; Kenya Nishioka; Nobutaka Hattori
      Abstract: Coenzyme Q2, polyprenyltransferase (COQ2) variants have been reported to be associated with multiple system atrophy (MSA). However, the relationship between COQ2 variants and familial Parkinson’s disease (PD) remains unclear. We investigated the frequency of COQ2 variants and clinical symptoms among familial PD and MSA. We screened COQ2 using the Sanger method in 123 patients with familial PD, 52 patients with sporadic PD, and 39 patients with clinically diagnosed MSA. Clinical information was collected from medical records for the patients with COQ2 variants. Allele frequencies of detected rare non-synonymous variants were compared by public database of the Exome Aggregation Consortium (ExAC) and Japanese genetic variation database, using Fisher’s exact test. We detected two probands with rare variants in COQ2, the p.P157S from Family A, whose patient was clinically diagnosed as having juvenile PD, and the p.H15 N/p.G331S from Family B, whose patients shared common symptoms of PD. Furthermore, in an association study comparing these familial PD and MSA cases with a public variant database, eight non synonymous variants were detected in COQ2. Three of these were very rare variants, namely, p.P157S, p.L261Qfs*4, and p.G331S, and one variant, p.G21S, was found to show a significant association with familial PD. COQ2 variants rarely may associate with the disease onset of familial PD. Our findings contribute to an understanding of COQ2 variants in neurodegenerative disorders.
      PubDate: 2018-04-11
      DOI: 10.1007/s00702-018-1885-1
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