Vertical locomotion improves horizontal locomotion: effects of climbing on gait and other mobility aspects in Parkinson's disease. A secondary analysis from a randomized controlled trial.

BACKGROUND: In the Climb Up! Head Up! trial, we showed that sport climbing reduces bradykinesia, tremor, and rigidity in mildly to moderately affected participants with Parkinson's disease. This secondary analysis aimed to evaluate the effects of sport climbing on gait and functional mobility in this cohort. METHODS: Climb Up! Head Up! was a 1:1 randomized controlled trial. Forty-eight PD participants (Hoehn and Yahr stage 2-3) either participated in a 12-week, 90-min-per-week sport climbing course (intervention group) or were engaged in regular unsupervised physical activity (control group). Relevant outcome measures for this analysis were extracted from six inertial measurement units placed on the extremities, chest, and lower back, that were worn during supervised gait and functional mobility assessments before and after the intervention. Assessments included normal and fast walking, dual-tasking walking, Timed Up and Go test, Instrumented Stand and Walk test, and Five Times Sit to Stand test. RESULTS: Compared to baseline, climbing improved gait speed during normal walking by 0.09 m/s (p = 0.005) and during fast walking by 0.1 m/s. Climbing also reduced the time spent in the stance phase during fast walking by 0.03 s. Climbing improved the walking speed in the 7-m- Timed Up and Go test by 0.1 m/s (p < 0.001) and the turning speed by 0.39 s (p = 0.052), the speed in the Instrumented Stand and Walk test by 0.1 m/s (p < 0.001), and the speed in the Five Times Sit to Stand test by 2.5 s (p = 0.014). There was no effect of sport climbing on gait speed or gait variables during dual-task walking. CONCLUSIONS: Sport climbing improves gait speed during normal and fast walking, as well as functional mobility in people with Parkinson's disease. Trial registration This study was registered within the U.S. National Library of Medicine (No: NCT04569981, date of registration September 30th, 2020).

Seasonality of benign paroxysmal positional vertigo : A retrospective study from Central Europe.

BACKGROUND: Although benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in clinical practice, factors influencing the pathophysiology remain not fully understood. OBJECTIVE: Here we aim to investigate possible seasonal influences on the occurrence of BPPV in Vienna, a city located in a Central European country with pronounced seasonal fluctuations. METHODS: We retrospectively investigated data from 503 patients presenting with BPPV to the outpatient clinics of the Medical University of Vienna between 2007 and 2012. Analyses included age, gender, type of BPPV, seasonal assignment, as well as daylight hours and the temperature in Vienna at symptom onset. RESULTS: Out of 503 patients (159 male, 344 female, ratio 1:2.2; mean age 60 ± 15.80 years), most patients presented with posterior (89.7%) and left-sided (43.1%) BPPV. There was a significant seasonal difference (χ2 p = 0.036) with the majority of symptoms occurring in winter seasons (n = 142), followed by springtime (n = 139). Symptom onset did not correlate with the average temperature (p = 0.24) but on the other hand very well with daylight hours (p < 0.05), which ranged from 8.4 h per day in December, to an average of 15.6 h in July. CONCLUSION: Our results show a seasonal accumulation of BPPV during winter and springtime, which is in line with previous studies from other climatic zones, suggesting an association of this seasonality with varying vitamin D levels.

Climb up! Head up! Climbing improves posture in Parkinson's disease. A secondary analysis from a randomized controlled trial.

OBJECTIVE: To investigate the effect of sport climbing on a biomechanical marker of axial posture in patients with Parkinson's disease, as well as its association with age, body mass index and health-related quality-of-life outcome measures. DESIGN: Pre-planned secondary analysis of our randomized controlled, semi-blind trial (unblinded patients, blinded assessors) comparing sport climbing to unsupervised exercise. SETTING: Single-centre study conducted at the Department of Neurology of the Medical University of Vienna, Austria. PARTICIPANTS: Forty-eight Parkinson's disease patients (aged 64 ± 8 years, Hoehn & Yahr stage 2-3) were included. INTERVENTION: Sport climbers (n = 24) followed a 12-week, 90 min/week supervised top-rope sport climbing course in an indoor climbing gym. The unsupervised training group (n = 24) independently followed the 'European Physiotherapy Guidelines for Parkinson's Disease' and World Health Organization recommendations for an active lifestyle for 12 weeks. MAIN MEASURES: Posture was assessed with the horizontal distance of the seventh cervical vertebra to the wall at baseline and after the intervention. RESULTS: Participating in the sport climbing group significantly predicted the biomechanical marker of axial posture (P = 0.044). The improvement in the biomechanical marker did not affect the quality of life, depression, fatigue, physical activity or fear of falling. Participants in the sport climbing group showed a significantly decreased horizontal distance of the seventh cervical vertebra to the wall after the intervention (-1.7 cm (95%CI [-2.6, -0.8]). In the unsupervised training group, no difference was found (-0.5 cm; 95%CI -1.3, 0.2]). CONCLUSIONS: We conclude that sport climbing improves a biomechanical marker of axial posture in Parkinson's disease.

Therapeutic climbing in Parkinson's disease: Differences in self-reported health and well-being, feasibility and clinical changes.

BACKGROUND: Therapeutic climbing (TC) is a whole-body workout that stimulates and improves physical and psychosocial abilities. It has been used in neurological rehabilitation, but there is scarce evidence of specific benefits for people with Parkinson's (PwP). OBJECTIVE: To investigate and evaluate self-reported differences in health and well-being among trial participants, the overall feasibility of TC and clinical changes caused as a rehabilitation measure for PwP. METHODS: A 3-level Likert scale survey was completed by 26 PwP (100% response rate) after a TC course (mean 16 sessions) at the Neurological Rehabilitation Center assessing self-perceived differences in health and well-being in terms of physical, psychological, and social parameters. We investigated the feasibility of TC in terms of adherence, practicability and acceptability during a multidisciplinary inpatient rehabilitation program and determined several clinical outcomes (10-meter distance and 2-minute duration walking tests, Functional Gait Assessment, Nine-Hole-Peg tests, and Tinetti Assessment Tool). RESULTS: Improvements are based on self-reported perceptions of PwP. We observed an improvement of overall physical (average 65%), psychological (average 59%) and social (average 39%) aspects after TC. PwP improved strength (96%), balance (88%), range of motion (88%), body awareness (85%), physical well-being (77%), and fatigue (75%). Furthermore, they self-reported admiration in their social surrounding (42%) and felt more sociable and outgoing (40%). Concerning adherence, practicability and acceptability, TC seems to be feasible for PwP. Treatment adherence was 100%, 70% declared motivation to continue TC, and 96% intended to recommend TC to peers. Furthermore, PwP showed statistically significant improvements in 10-meter walking tests (T0: 7.5 (1.1-13.9), T1: 6.5 (0.1-12.9); p < .01; n = 16), 2-minute walking tests (T0: 149.5 (-111.0-410.0), T1: 177.0 (-140.7-494.7); p < .01; n = 19), Functional Gait Assessment (T0: 26.0 (-24.8-76.8), T1: 28.0 (2.6-53.4); p < .01; n = 15), and Nine-Hole-Peg tests (left: T0: 26.5 (24.3-28.7), T1: 24.1 (22.0-26.3); p < .01; n = 15; right: T0: 26.7 (24.1-29.2), T1: 23.3 (20.8-25.7); p < .01; n = 15). CONCLUSION: The preliminary findings suggest that TC offers an effective and feasible training method that may positively affect PwP overall perceptions of physical and psychosocial health status. The methodological limitations and small sample size limit the study's interpretability. More research is needed to definitely show the scientifically significant benefits of TC to PwP.

Individual Perception of Telehealth: Validation of a German Translation of the Telemedicine Perception Questionnaire and a Derived Short Version.

Telehealth is a growing domain with particular relevance for remote patient monitoring. With respect to the biopsychosocial model of health, it is important to evaluate perception and satisfaction with new methods in telehealth as part of an integrative approach. The Telemedicine Perception Questionnaire (TMPQ) is a 17-item questionnaire measuring patients' perception of and satisfaction with telecare. We translated this survey into German and determined its validity and reliability in 32 adolescents and adults. Furthermore, we derived a short version of the TMPQ, named Patient and Physician Satisfaction with Monitoring (PPSM), which is a 5-item questionnaire that can be administered to both patients and physicians. Validity and reliability were tested in 32 patients and 32 physicians. Crohnbach's α for the translated TMPQ was 0.76, and the German version yielded high validity (intraclass correlation coefficient (ICC) 0.995). We tested the PPSM in both patients and physicians and found acceptable values for Crohnbach's α (0.72 and 0.78) with excellent validity (ICC 0.965). We therefore concluded from this small study that both German versions of the TMPQ and PPSM can be used to investigate the acceptance of telehealth applications.

Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

OBJECTIVE: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment. DESIGN: Explorative, nonrandomized, clinical trial. SETTING: Patients receiving ambulatory care and control participants from the general community. PARTICIPANTS: Volunteer sample (N=84) of patients (n=21) with blepharospasm or hemifacial spasm who received facial BTX injections. Control participants included patients (n=30) with cervical dystonia who received cervical BTX injections and individuals without neurological disorders (n=33). INTERVENTIONS: The 2 groups receiving injections were tested before and 3 weeks after their treatment. The group without neurological disorders received no injections. MAIN OUTCOME MEASURES: Verbal and nonverbal reasoning scores. RESULTS: The key unexpected finding was that patients who received facial BTX injections perform significantly worse in nonverbal reasoning tasks, when compared with those who did not receive injections (P=.022). There was no significant difference in the baseline reasoning scores and at follow-up for verbal reasoning between the 3 groups. There was no correlation between toxin dose and reasoning scores (verbal: P=.132; nonverbal: P=.294). CONCLUSIONS: Because of potential confounders, the results do not yet allow any conclusion on causality. Further research is needed to confirm our findings.

A randomised controlled trial on effectiveness and feasibility of sport climbing in Parkinson's disease.

Physical activity is of prime importance in non-pharmacological Parkinson's disease (PD) treatment. The current study examines the effectiveness and feasibility of sport climbing in PD patients in a single-centre, randomised controlled, semi-blind trial. A total of 48 PD patients without experience in climbing (average age 64 ± 8 years, Hoehn & Yahr stage 2-3) were assigned either to participate in a 12-week sport climbing course (SC) or to attend an unsupervised physical training group (UT). The primary outcome was the improvement of symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III). Sport climbing was associated with a significant reduction of the MDS-UPDRS-III (-12.9 points; 95% CI -15.9 to -9.8), while no significant improvement was to be found in the UT (-3.0 points; 95% CI -6.0 to 0.1). Bradykinesia, rigidity and tremor subscales significantly improved in SC, but not in the unsupervised control group. In terms of feasibility, the study showed a 99% adherence of participants to climbing sessions and a drop-out rate of only 8%. No adverse events occurred. This trial provides class III evidence that sport climbing is highly effective and feasible in mildly to moderately affected PD patients.

Electrophysiological correlates of conventional metaphor, irony, and literal language processing - An event-related potentials and eLORETA study.

Conventional metaphor, irony, and literal language processing were compared. Thirty right-handed participants (21-34 years) performed a sequential-statement ERP-paradigm. A left-frontal Late Anterior Negative Slow Wave (LANSW, 450-1000 ms) was significantly greater for metaphors and by visual tendency greater for irony, compared to literal statements. A centroparietal N400 (300-450 ms) and a centroparietal right-dominant "Late N400" (450-600 ms) were by statistical and visual tendency greater for metaphors. Left PCC and left lingual gyrus activity was significantly higher in metaphors compared to literal statements (eLORETA; 450-1000 ms). A statistical trend indicated higher parahippocampal gyrus activity in metaphors and ironies. N400 results are discussed considering changing processing techniques and a renewed semantic conflict. The Late N400 was associated with the construct of "associativeness". The LANSW was related to metaphorical mapping, frame-shifting processes, integration of meanings, and memory processes. eLORETA results were discussed considering metaphorical mapping, creation of mental images, conventionality, valence, memory processes, and divergent thinking.

Cognitive and affective Theory of Mind in adolescence: developmental aspects and associated neuropsychological variables.

Theory of Mind (ToM) is the ability to represent and attribute mental states to oneself and others. So far, research regarding ToM processing across adolescence is scarce. Existing studies either yield inconsistent results or did not or not thoroughly investigate aspects like higher order ToM and associated neuropsychological variables which the current study tried to address. 643 typically developing early, middle, and late adolescents (age groups 13-14; 15-16; 17-18) performed cognitive and affective ToM tasks as well as neuropsychological tasks tapping the cognitive or affective domain. Regarding both ToM types, 15- to 16-year-olds and 17- to 18-year-olds outperformed 13- to 14-year-olds, whereas females were superior regarding cognitive ToM. Across adolescence, cognitive and affective ToM correlated with attention and affective intelligence, whereas working memory, language comprehension, and figural intelligence additionally correlated with cognitive ToM. In early adolescence, attention correlated with both ToM types, whereas cognitive ToM further correlated with language comprehension and affective ToM with verbal intelligence, verbal fluency, and verbal flexibility. In middle and late adolescence, affective intelligence correlated with both ToM types, whereas cognitive ToM additionally correlated with working memory, language comprehension, and figural intelligence. The current study shows a developmental step regarding cognitive and affective ToM in middle adolescence as well as gender differences in cognitive ToM processing. Associations between neuropsychological variables and ToM processing were shown across adolescence and within age groups. Results give new insights into social cognition in adolescence and are well supported by neuroscientific and neurobiological studies regarding ToM and the integration of cognitive and affective processes.

Electrophysiological Correlates of Basic and Higher Order Cognitive and Affective Theory of Mind Processing in Emerging and Early Adulthood-An Explorative Event-Related Potentials Study to Investigate First-, Second-, and Third-Order Theory of Mind Processing Based on Visual Cues.

Attributing mental states to others in social interactions [Theory of Mind (ToM)] often depends on visual social cues like eye gaze or mimic. This study presents an event-related potentials task (Brainy-ERP) that was developed in order to investigate the electrophysiological correlates of first-, second-, and third-order cognitive and affective ToM processing. The task was based on social visual cues and involved electroencephalographic event-related potential (ERP) analyses and exact low-resolution brain electromagnetic tomography analyses (eLORETA) source localization analyses. Results showed that in cognitive and affective conditions, first-order trials elicited greater Anterior P2 (180-370 ms) amplitudes. In the cognitive condition, third-order trials elicited greatest amplitudes in the broadly distributed early negative slow wave (eNSW, 260-470 ms) and the late NSW (LNSW, 460-1,000 ms). In the affective condition, third-order and second-order trials elicited greatest amplitudes in a broadly distributed NSW (250-1,000 ms). Regarding affective trials in the NSW time span, statistical significant differences and trends were shown regarding activation of underlying brain regions. Third-order trials elicited greatest activation in a number of regions typically associated with the ToM network, especially the posterior cingulate cortex (PCC), cuneus, and temporoparietal junction (TPJ). Furthermore, ToM low performers (participants with high accuracy but longer reaction times) showed by trend smaller Posterior N1 and significantly smaller eNSW amplitudes compared to average and high performers. This study offers new insights into electrophysiological correlates of basic and higher order cognitive and affective ToM processing and its precise time course.

Subjective emotional arousal: an explorative study on the role of gender, age, intensity, emotion regulation difficulties, depression and anxiety symptoms, and meta-emotion.

Subjective emotional arousal in typically developing adults was investigated in an explorative study. 177 participants (20-70 years) rated facial expressions and words for self-experienced arousal and perceived intensity, and completed the Difficulties in Emotion Regulation scale and the Hospital Anxiety and Depression scale (HADS-D). Exclusion criteria were psychiatric or neurological diseases, or clinically relevant scores in the HADS-D. Arousal regarding faces and words was significantly predicted by emotional clarity. Separate analyses showed following significant results: arousal regarding faces and arousal regarding words constantly predicted each other; negative faces were predicted by age and intensity; neutral faces by gender and impulse control; positive faces by gender and intensity; negative words by emotional clarity; and neutral words by gender. Males showed higher arousal scores than females regarding neutral faces and neutral words; for the other arousal scores, no explicit group differences were shown. Cluster analysis yielded three distinguished emotional characteristics groups: "emotional difficulties disposition group" (mainly females; highest emotion regulation difficulties, depression and anxiety scores; by trend highest arousal), "low emotional awareness group" (exclusively males; lowest awareness regarding currently experienced emotions; by trend intermediate arousal), and a "low emotional difficulties group" (exclusively females; lowest values throughout). No age effect was shown. Results suggest that arousal elicited by facial expressions and words are specialized parts of a greater emotional processing system and that typically developing adults show some kind of stable, modality-unspecific dispositional baseline of emotional arousal. Emotional awareness and clarity, and impulse control probably are trait aspects of emotion regulation that influence emotional arousal in typically developing adults and can be regarded as aspects of meta-emotion. Different emotional personality styles were shown between as well as within gender groups.

How influenceable is our metamemory for pictorial material? The impact of framing and emotionality on metamemory judgments.

Metamemory refers to the ability to monitor and control one´s own memory processes which plays an important role in everyday life when accuracy of memory is required. The present study intends to give new insights into the complex relationship between confidence in memory and accuracy of metamemory judgments for negative emotional and neutral pictorial stimuli. Judgments of learning (JOLs) were investigated in order to provide important theoretical information for practical applications in everyday life. A balanced 2×2 factorial experimental design was used to explore the impact of framing in terms of remembering or forgetting as well as emotionality on JOLs. With respect to the already known complex relationship of confidence in memory and accuracy of confidence statements, the present results emphasize this complexity by showing that there is no interaction between the factors framing and emotionality but significant main effects of these two factors with respect to JOLs. Furthermore, accuracy of JOLs is not influenced by framing in terms of remembering and forgetting. Both framing conditions lead to overconfident judgments, regardless of whether confidence in memory is influenced by framing. Emotionality, on the other hand, enhances memory accuracy regardless of whether the subjective feeling of remembering influences confidence in memory or not. The present findings highlight the need to strengthen the collective consciousness about the influenceability of confidence in memory and the fact that a high confidence in memory is not inevitably accompanied by accurate memories.

Metaphor processing in middle childhood and at the transition to early adolescence: the role of chronological age, mental age, and verbal intelligence.

Metaphor development in conjunction with verbal intelligence and linguistic competence in middle childhood and at the transition to early adolescence was investigated. 298 individuals between seven and ten years (chronological age) who attended grades two-four (mental age) were tested for metaphor processing by the Metaphoric Triads Task, for linguistic competence (HELD), and verbal intelligence (WISC-III). Chronological age significantly predicted metaphor processing with a breakpoint of 8.2 years regarding identification and comprehension, and 10.2 years regarding preference. Fourth-graders showed highest metaphor processing scores. Verbal intelligence significantly predicted metaphor processing; this effect became stronger with increasing age. Attributional metaphors were best understood and most preferred. Chronological and mental age are associated with metaphor processing in an age span that is seemingly crucial for metaphor development. Verbal analogical reasoning, concept formation, verbal abstraction, and semantic knowledge predicted metaphor comprehension. Understanding facts, principles, and social situations, and resultant inferential verbal reasoning predicted metaphor preference.

Clinical and magnetic resonance imaging features of children, adolescents, and adults with a clinically isolated syndrome.

BACKGROUND: The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and magnetic resonance imaging (MRI) features according to the McDonald criteria. Little is known about differences in the presentation between pre-pubertal children, adolescents, and adult patients at disease onset. OBJECTIVE: To compare (1) the clinical, cerebrospinal fluid (CSF), and MRI characteristics, and (2) the diagnostic performance of the 2010 McDonald criteria between pre-pubertal, adolescent, and adult patients with a clinically isolated syndrome (CIS). METHODS: We performed a retrospective analysis of the initial brain and spinal cord MRI scans from 11 pre-pubertal children, 46 adolescents, and 56 adults with a CIS. Furthermore, clinical, CSF characteristics, and the performance of the 2010 McDonald criteria were compared. RESULTS: The first inter-attack interval tended to increase with age. With respect to MRI presentation, significantly fewer pre-pubertal children presented with juxtacortical and callosal lesions. We found no significant differences in the fulfillment of the 2010 McDonald criteria between the groups. CONCLUSION: In this retrospective series, subtle differences between children, adolescents, and adults with a CIS were noted. Larger samples are required in order to establish distinct features of the different age groups.

Maternal bonding behavior, adult intimate relationship, and quality of life.

Continuity and discontinuity in the development of social relationships have been investigated by reviewing the course of social bonds and by analyzing the effects of a sound intimate relationship in adulthood in conjunction with recalled maternal bonding on the quality of life among students.A questionnaire-based study of 207 students was conducted. Perceptions of maternal bonding were designated as being representative of one of the two contrasting bonding types "optimal maternal bonding" and "affectionless maternal control" assessed by the Parental Bonding Instrument (PBI) and combined with perceptions of a sound intimate adult relationship measured by the Family Assessment Measure III Dyadic Relationships Scale (FAM-III-D). Quality of life and general health data were determined by using the World Health Organization Quality of Life (WHOQOL-BREF) instrument.Students who reported "optimal maternal bonding" had intimate relationships in adulthood that were of significantly higher quality than those who recalled "affectionless maternal control". Students who recalled "optimal maternal bonding" and described their intimate relationship as sound showed significantly higher scores in all domains of quality of life and indicated having better general health than those who reported "affectionless maternal control" and a sound intimate relationship.A sound intimate relationship in adulthood does not appear to compensate the impact of a recalled maternal bonding behavior in terms of affectionless control, on quality of life. Furthermore, results seem to support the hypothesis of continuity of the development of social relationships among psychologically well individuals based on the association between maternal bonding and later intimate relationships.

Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test.

Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler Preschool-and-Primary-Scale-of-Intelligence-WPPSI). Group differences were analyzed using t tests, as well as direct and stepwise discriminant analyses. The predictive value of the WPPSI with respect to TT performance was analyzed using regression analyses. SLI-children performed significantly worse on both TT and WPPSI ([Formula: see text]). The TT alone yielded an overall classification rate of 79%, the TT and the WPPSI together yielded an overall classification rate of 80%. TT performance was significantly predicted by verbal intelligence in SLI-children and nonverbal intelligence in controls whilst WPPSI subtest arithmetic was predictive in both groups. Without further research, the Token Test cannot be seen as a valid and sufficient tool for the screening of SLI in preschool children but rather as a tool for the assessment of more general intellectual capacities. SLI-children at this age already show impairments typically associated with SLI which indicates the necessity of early developmental support or training. Token Test performance is possibly an indicator for a more general developmental factor rather than an exclusive indicator for language difficulties.

Cognitive and emotional demands of black humour processing: the role of intelligence, aggressiveness and mood.

Humour processing is a complex information-processing task that is dependent on cognitive and emotional aspects which presumably influence frame-shifting and conceptual blending, mental operations that underlie humour processing. The aim of the current study was to find distinctive groups of subjects with respect to black humour processing, intellectual capacities, mood disturbance and aggressiveness. A total of 156 adults rated black humour cartoons and conducted measurements of verbal and nonverbal intelligence, mood disturbance and aggressiveness. Cluster analysis yields three groups comprising following properties: (1) moderate black humour preference and moderate comprehension; average nonverbal and verbal intelligence; low mood disturbance and moderate aggressiveness; (2) low black humour preference and moderate comprehension; average nonverbal and verbal intelligence, high mood disturbance and high aggressiveness; and (3) high black humour preference and high comprehension; high nonverbal and verbal intelligence; no mood disturbance and low aggressiveness. Age and gender do not differ significantly, differences in education level can be found. Black humour preference and comprehension are positively associated with higher verbal and nonverbal intelligence as well as higher levels of education. Emotional instability and higher aggressiveness apparently lead to decreased levels of pleasure when dealing with black humour. These results support the hypothesis that humour processing involves cognitive as well as affective components and suggest that these variables influence the execution of frame-shifting and conceptual blending in the course of humour processing.

Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender.

OBJECTIVES: Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender. METHODS: Out of 977 retrieved articles, 21 included case-control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender-subgroups. RESULTS: In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs. CONCLUSIONS: The results imply a complex nature of the genotype × phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes.

Brain-derived neurotrophic factor (BDNF)-epigenetic regulation in unipolar and bipolar affective disorder.

BACKGROUND: Alterations of brain-derived neurotrophic factor (BDNF) DNA methylation at specific BDNF promoters and corresponding gene expressions are associated with pathology and the response to antidepressant (AD) therapy in affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Genomic DNA was derived from peripheral blood mononuclear cells (PBMCs) and was bisulfite converted. Percentage of methylated reference (PMR) was calculated based on results from quantitative real-time PCR following the MethyLight protocol. For statistical analysis parametric procedures were performed as appropriate. RESULTS: In this study 544 subjects were included, 207 MDD subjects, 59 BD subjects and 278 control subjects. The BDNF exon I promoter methylation resulted to be significantly increased in MDD subjects compared to BD subjects (p=0.0089) and control subjects (p<0.001). Furthermore, the increase of methylation in MDD subjects was significantly associated with AD therapy (p=0.0019) but not to the clinical features of depression such as the severity of symptoms (p=n.s.). None of the 12 investigated single nucleotide polymorphisms (SNP) showed significant genotype-methylation interactions. LIMITATIONS: Although based on previous findings, the DNA methylation was evaluated within only one CpG island of the different alternative BDNF gene transcripts. CONCLUSIONS: The results suggest that the methylation status might not only be affected by the disease phenotype but might also be further influenced by pharmacological treatment, therefore harbouring the possibility of identifying new insights for treatment options.

Comprehension of metaphors in patients with schizophrenia-spectrum disorders.

BACKGROUND: Metaphors, mainly proverbs and idiomatic expressions of ordinary life are commonly used as a model for concretism. Previous studies have shown impaired metaphor comprehension in patients with schizophrenia-spectrum disorders compared to either psychiatric or non-psychiatric control subject. The aim of this study was to detect possible quantitative differences in figurative processing between patients with schizophrenia-spectrum disorders and healthy controls. METHODS: In order to analyse possible dissociations of different aspects of figurative speech, a range of metaphor tasks was used to distinguish between recognition of familiar metaphors, paraphrasing the meaning of the latter and generating novel metaphors: we used a standard proverb test for conventional metaphors consisting of a multiple-choice and a paraphrasing task, and the Metaphoric Triads Test for the assessment of novel metaphors. We included 40 patients with schizophrenia-spectrum disorders and 43 healthy control subjects. RESULTS: Our results showed that patients had impaired figurative speech processing regarding novel and conventional metaphors. Associations with cognitive functions were detected. Performance on the paraphrasing task was associated with the severity of negative symptoms. CONCLUSION: We conclude that patients with schizophrenia-spectrum disorders do exhibit impairments in the recognition and paraphrasing of conventional and the generation of novel metaphors and that some cognitive domains as well the extent of negative symptoms might be associated with these deficits.