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Multiple Sklerose (MS) ist die häufigste entzündliche Erkrankung des zentralen Nervensystems (ZNS) im jungen Erwachsenenalter. Weltweit sind mehr als 2,3 Mio. Menschen betroffen – Frauen doppelt so häufig wie Männer. Die Erkrankung ist gekennzeichnet durch eine autoimmunvermittelte Demyelinisierung im ZNS einhergehend mit motorischen, sensorischen und neuropsychiatrischen Defiziten.
Bereits Charcot beschrieb im 19. Jahrhundert auch psychiatrische Syndrome als Teil der Erkrankung. Am häufigsten treten Depressionen und Angststörungen auf [1]. Im Krankheitsverlauf können auch kognitive Defizite und organische Persönlichkeitsveränderungen hinzukommen [8]. Psychotische Symptome sind selten und spielen eher eine Rolle als Nebenwirkung der MS-Therapie mit Kortikosteroiden und seltener β‑Interferonen [5].
Bei unserer Patientin trat die akute psychotische Störung als erste klinische Manifestation der MS auf und führte zur Diagnosestellung.
In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen’s d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder.
Background: Understanding which factors influence dietary intake, particularly in daily life, is crucial given the impact diet has on physical as well as mental health. However, a factor might influence whether but not how much an individual eats and vice versa or a factor’s importance may differ across these two facets. Distinguishing between these two facets, hence, studying dietary intake as a dual process is conceptually promising and not only allows further insights, but also solves a statistical issue. When assessing the association between a predictor (e.g. momentary affect) and subsequent dietary intake in daily life through ecological momentary assessment (EMA), the outcome variable (e.g. energy intake within a predefined time-interval) is semicontinuous. That is, one part is equal to zero (i.e. no dietary intake occurred) and the other contains right-skewed positive values (i.e. dietary intake occurred, but often only small amounts are consumed). However, linear multilevel modelling which is commonly used for EMA data to account for repeated measures within individuals cannot be applied to semicontinuous outcomes. A highly informative statistical approach for semicontinuous outcomes is multilevel two-part modelling which treats the outcome as generated by a dual process, combining a multilevel logistic/probit regression for zeros and a multilevel (generalized) linear regression for nonzero values. Methods: A multilevel two-part model combining a multilevel logistic regression to predict whether an individual eats and a multilevel gamma regression to predict how much is eaten, if an individual eats, is proposed. Its general implementation in R, a widely used and freely available statistical software, using the R-package brms is described. To illustrate its practical application, the analytical approach is applied exemplary to data from the Eat2beNICE-APPetite-study. Results: Results highlight that the proposed multilevel two-part model reveals process-specific associations which cannot be detected through traditional multilevel modelling. Conclusions: This paper is the first to introduce multilevel two-part modelling as a novel analytical approach to study dietary intake in daily life. Studying dietary intake through multilevel two-part modelling is conceptually as well as methodologically promising. Findings can be translated to tailored nutritional interventions targeting either the occurrence or the amount of dietary intake.
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30–40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify central mechanism of dystonia development. Dystonia-like movements (DLM) were assessed using the tail suspension test and implementing a pipeline of deep learning applications. Neuron numbers of striatal parvalbumin+, nNOS+, calretinin+, ChAT+ interneurons and Nissl+ cells were estimated by unbiased stereology. Striatal dopaminergic metabolism was analyzed via in vivo microdialysis, qPCR and western blot. Local field potentials (LFP) were recorded from the central motor network. Deep brain stimulation (DBS) of the entopeduncular nucleus (EP) was performed. Nerve-injured ∆ETorA rats developed long-lasting DLM over 12 weeks. No changes in striatal structure were observed. Dystonic-like ∆ETorA rats presented a higher striatal dopaminergic turnover and stimulus-induced elevation of dopamine efflux compared to the control groups. Higher LFP theta power in the EP of dystonic-like ∆ETorA compared to wt rats was recorded. Chronic EP-DBS over 3 weeks led to improvement of DLM. Our data emphasizes the role of environmental factors in TOR1A symptomatogenesis. LFP analyses indicate that the pathologically enhanced theta power is a physiomarker of DLM. This TOR1A model replicates key features of the human TOR1A pathology on multiple biological levels and is therefore suited for further analysis of dystonia pathomechanism.
The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ = − 3.46, t(165) = − 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ = − 1.00, t(165) = − 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results.
Physical inactivity is discussed as one of the most detrimental influences for lifestyle-related medical complications such as obesity, heart disease, hypertension, diabetes and premature mortality in in- and outpatients with major depressive disorder (MDD). In contrast, intervention studies indicate that moderate-to-vigorous-intensity physical activity (MVPA) might reduce complications and depression symptoms itself. Self-reported data on depression [Beck-Depression-Inventory-II (BDI-II)], general habitual well-being (FAHW), self-esteem and physical self-perception (FAHW, MSWS) were administrated in a cross-sectional study with 76 in- and outpatients with MDD. MVPA was documented using ActiGraph wGT3X + ® accelerometers and fitness was measured using cardiopulmonary exercise testing (CPET). Subgroups were built according to activity level (low PA defined as MVPA < 30 min/day, moderate PA defined as MVPA 30–45 min/day, high PA defined as MVPA > 45 min/day). Statistical analysis was performed using a Mann–Whitney U and Kruskal–Wallis test, Spearman correlation and mediation analysis. BDI-II scores and MVPA values of in- and outpatients were comparable, but fitness differed between the two groups. Analysis of the outpatient group showed a negative correlation between BDI-II and MVPA. No association of inpatient MVPA and psychopathology was found. General habitual well-being and self-esteem mediated the relationship between outpatient MVPA and BDI-II. The level of depression determined by the BDI-II score was significantly higher in the outpatient low- and moderate PA subgroups compared to outpatients with high PA. Fitness showed no association to depression symptoms or well-being. To ameliorate depressive symptoms of MDD outpatients, intervention strategies should promote habitual MVPA and exercise exceeding the duration recommended for general health (≥ 30 min/day). Further studies need to investigate sufficient MVPA strategies to impact MDD symptoms in inpatient settings. Exercise effects seem to be driven by changes of well-being rather than increased physical fitness.
Background: Diet and physical activity (PA) have a major impact on physical and mental health. However, there is a lack of effective strategies for sustaining these health-protective behaviors. A shift to a microtemporal, within-person approach is needed to capture dynamic processes underlying eating behavior and PA, as they change rapidly across minutes or hours and differ among individuals. However, a tool that captures these microtemporal, within-person processes in daily life is currently not present.
Objective: The APPetite-mobile-app is developed for the ecological momentary assessment of microtemporal, within-person processes of complex dietary intake, objectively recorded PA, and related factors. This study aims to evaluate the feasibility and usability of the APPetite-mobile-app and the validity of the incorporated APPetite-food record.
Methods: The APPetite-mobile-app captures dietary intake event-contingently through a food record, captures PA continuously through accelerometers, and captures related factors (eg, stress) signal-contingently through 8 prompts per day. Empirical data on feasibility (n=157), usability (n=84), and validity (n=44) were collected within the Eat2beNICE-APPetite-study. Feasibility and usability were examined in healthy participants and psychiatric patients. The relative validity of the APPetite-food record was assessed with a subgroup of healthy participants by using a counterbalanced crossover design. The reference method was a 24-hour recall. In addition, the energy intake was compared with the total energy expenditure estimated from accelerometry.
Results: Good feasibility, with compliance rates above 80% for prompts and the accelerometer, as well as reasonable average response and recording durations (prompt: 2.04 min; food record per day: 17.66 min) and latencies (prompts: 3.16 min; food record: 58.35 min) were found. Usability was rated as moderate, with a score of 61.9 of 100 on the System Usability Scale. The evaluation of validity identified large differences in energy and macronutrient intake between the two methods at the group and individual levels. The APPetite-food record captured higher dietary intakes, indicating a lower level of underreporting, compared with the 24-hour recall. Energy intake was assessed fairly accurately by the APPetite-food record at the group level on 2 of 3 days when compared with total energy expenditure. The comparison with mean total energy expenditure (2417.8 kcal, SD 410) showed that the 24-hour recall (1909.2 kcal, SD 478.8) underestimated habitual energy intake to a larger degree than the APPetite-food record (2146.4 kcal, SD 574.5).
Conclusions: The APPetite-mobile-app is a promising tool for capturing microtemporal, within-person processes of diet, PA, and related factors in real time or near real time and is, to the best of our knowledge, the first of its kind. First evidence supports the good feasibility and moderate usability of the APPetite-mobile-app and the validity of the APPetite-food record. Future findings in this context will build the foundation for the development of personalized lifestyle modification interventions, such as just-in-time adaptive interventions.
ADHD is a neurodevelopmental disorder with a long trajectory into adulthood where it is often comorbid with depression, substance use disorder (SUD) or obesity. Previous studies described a dysregulated dopaminergic system, reflected by abnormal reward processing, both in ADHD as well as in depression, SUD or obesity. No study so far however tested systematically whether pathologies in the brain’s reward system explain the frequent comorbidity in adult ADHD. To test this, we acquired MRI scans from 137 participants probing the reward system by a monetary incentive delay task (MIDT) as well as assessing resting-state connectivity with ventral striatum as a seed mask. No differences were found between comorbid disorders, but a significant linear effect pointed toward less left intrastriatal connectivity in patients depending on the number of comorbidities. This points towards a neurobiologically impaired reward- and decision-making ability in patients with more comorbid disorders. This suggests that less intrastriatal connectivity parallels disorder severity but not disorder specificity, while MIDT abnormalities seem mainly to be driven by ADHD.