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The hypothalamus–pituitary–adrenal axis is the main physiological stress response system and regulating the release of cortisol. The two corticoid receptors encoded by the genes NR3C1 and NR3C2 are the main players in regulating the physiological response to cortisol. This biological system has been linked to neurocognitive processes and memory, yet the mechanisms remain largely unclear. In two independent general population studies (SHIP, total sample size > 5500), we aim to diseantangle the effects of genetic variation, gene expression and cortisol on verbal memory and memory associated brain volume. Especially for NR3C1 results exhibited a consistent pattern of direct an interactive effects. All three biological layers, genetic variation (rs56149945), gene expression for NR3C1 and cortisol levels, were directly associated with verbal memory. Interactions between these components showed significant effects on verbal memory as well as hippocampal volume. For NR3C2 such a complex association pattern could not be observed. Our analyses revealed that different components of the stress response system are acting together on different aspects of cognition. Complex phenotypes, such as cognition and memory function are regulated by a complex interplay between different genetic and epigenetic features. We promote the glucocorticoid receptor NR3C1 as a main target to focus in the context of verbal memory and provided a mechanistic concept of the interaction between various biological layers spanning NR3C1 function and its effects on memory. Especially the NR3C1 transcript seemed to be a key element in this complex system.
Childhood abuse was inconsistently related to whole-brain cortical thickness in former studies. However, both childhood abuse and cortical thickness have been associated with depressive symptoms. We hypothesised that childhood abuse moderates the association between depressive symptoms and cortical thickness. In 1551 individuals of the general population, associations between whole-brain cortical thickness and the interaction of childhood abuse (emotional, physical, and sexual) and depressive symptoms were analysed using an ANCOVA. Linear regression analyses were used to estimate the same effect on the cortical thickness of 34 separate regions (Desikan-Killiany-atlas). A significant interaction effect of childhood abuse and depressive symptoms was observed for whole-brain cortical thickness (F(2, 1534) = 5.28, p = 0.007). A thinner cortex was associated with depressive symptoms in abused (t value = 2.78, p = 0.025) but not in non-abused participants (t value = − 1.50, p = 0.224). Focussing on non-depressed participants, a thicker whole-brain cortex was found in abused compared to non-abused participants (t value = − 2.79, p = 0.025). Similar interaction effects were observed in 12 out of 34 cortical regions. Our results suggest that childhood abuse is associated with reduced cortical thickness in subjects with depressive symptoms. In abused subjects without depressive symptoms, larger cortical thickness might act compensatory and thus reflect resilience against depressive symptoms.
The aim of this study was to investigate the impact of resilience, alexithymia and the subjectively perceived severity (fear of death, pain intensity, helplessness) of myocardial infarction (MI) on posttraumatic symptom severity (PTSS) after MI. Patients were assessed with the Posttraumatic Diagnostic Scale (PDS), Resilience Scale (RS-11) and Toronto Alexithymia Scale (TAS-20). Subjectively perceived severity of MI was measured with three items on a 10-point Likert scale. To test our hypothesis, we applied Pearson correlations as well as multiple hierarchical linear regression analyses. A higher resilience score was significantly associated with lower (r = − .39, p < .001) PTSS. Higher scores of alexithymia (r = .38, p < .01) and subjectively perceived helplessness (r = .42, p < .001) were associated with higher PTSS. Multiple hierarchical linear regression analyses revealed that resilience, the TAS-20 subscale difficulty identifying feelings (DIF) and especially subjectively perceived helplessness were independent significant predictors for the PTSS, adjusted R2 = .29, F(5, 102) = 9.57, p < .001. Our results suggest that resilience reduces the PTSS whereas alexithymia and subjectively perceived helplessness increase the risk. Especially the subjectively perceived helplessness explains a high degree of variance of PTSS and should be assessed to hindering further mental health burden.
The relationship between Alzheimer's-related brain atrophy patterns and sleep macro-architecture
(2022)
Introduction
Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD).
Methods
Using an magnetic resonance imaging (MRI)–based AD score based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case-control cohort, we investigated the associations between polysomnography-based sleep macro-architecture and AD-related brain atrophy patterns in 712 pre-symptomatic, healthy subjects from the population-based Study of Health in Pomerania.
Results
We identified a robust inverse association between slow-wave sleep and the AD marker (estimate: −0.019; 95% confidence interval: −0.03 to −0.0076; false discovery rate [FDR] = 0.0041), as well as with gray matter (GM) thicknesses in typical individual cortical AD-signature regions. No effects were identified regarding rapid eye movement or non–rapid eye movement (NREM) stage 2 sleep, and NREM stage 1 was positively associated with GM thickness, mainly in the prefrontal cortical regions.
Discussion
There is a cross-sectional relationship between AD-related neurodegenerative patterns and the proportion of sleep spent in slow-wave sleep.
The experience of abuse in the period of childhood and youth is a key stressor that has con-sequences on the developing brain and is associated with the genesis of mental disorders. Childhood abuse and depression often cooccur together and have both been associated with cortical thickness resulting in a difficulty to detangle the influence of each factor. In prior studies, childhood abuse and depression were inconsistently related to whole-brain cortical thickness. Thus, this thesis aims to investigate the link between childhood abuse, depres-sive symptoms, and alterations of the cortex.
Therefore, this study analyses 1,551 individuals of the general population. A significant in-teraction effect of childhood abuse and depressive symptoms is observed for whole-brain cortical thickness. Yet, the results indicate no influence of childhood abuse or depression alone. A thinner cortex was associated with more severe depressive symptoms in the abused, but not in the non-abused group. In non-depressed participants, an increased whole-brain cortex was found in the abused, compared to the non-abused group. Similar interaction effects were observed in 12 out of 34 cortical regions.
The results suggest, in line with prior findings, that depressed individuals with a history of childhood abuse are a specific ecophenotype which is also reflected in specific brain altera-tions. Cortical regions that are distinct associated with the interaction of depressive symp-toms and childhood abuse are involved in various fields such as sensory processing, self-conception, and memory. Greater cortical thickness in subjects with childhood abuse and without depressive symptoms might act compensatory and thus reflect resilience against depressive symptoms.
Practical implications concern the treatment and diagnostic system as well as the im-portance of early prevention programs. An individualised treatment is necessary as various studies found a less favourable outcome in depressive patients with a history of maltreat-ment. Therefore, it seems urgent to assess experiences of childhood abuse at the beginning of psychiatric and psychotherapeutic treatment. In addition, early prevention programs are in need to support vulnerable family systems and thereby strengthening the economic, health and social system.
Abstract
Purpose
Depressive disorders in children and adolescents have an enormous impact on their general quality of life. There is a clear need to effectively treat depression in this age group. Effects of psychotherapy can be enhanced by involving caregivers. In our systematic review and meta‐analysis, we examine for the first time the effects of caregiver involvement in depression‐specific interventions for children and adolescents.
Methods
We included randomized controlled trials examining the effects of interventions for children and adolescents with depression involving their caregivers or families compared to interventions without including caregivers. Primary outcome was the severity of childhood and adolescent depression.
Results
Overall, 19 randomized controlled trials could be included (N = 1553) that were highly heterogeneous regarding outcome measures or the extent of caregiver integration. We were able to include k = 17 studies in our meta‐analysis and find a small but significant effect for family‐involved interventions against active control conditions without family‐involvement at post intervention (α = 0.05, d = 0.34; [0.07; 0.60]; p = .01).
Conclusions
We detected an overall significant but small effect of family/caregivers’ involvement compared to control groups without it. Structured, guideline‐based research is urgently needed to identify for which children/adolescents with depression, under what circumstances, and in what form the family should be effectively involved in their psychotherapy.
Zur Messqualität des Beck-Depressionsinventars (BDI-II) in
unterschiedlichen klinischen Stichproben
(2022)
Theoretischer Hintergrund: Das BDI-II ist ein Selbstbeurteilungsinstrument zur Erfassung des Schweregrads einer Depression. Es liegen kaum Analysen mit Modellen aus der Item-Response-Theorie (IRT) vor. Fragestellung: Wie hoch ist die Messgenauigkeit des BDI-II über die unterschiedlichen Ausprägungen des latenten Traits (Depressivität) hinweg und sind die Kategorien der Items jeweils aufsteigend geordnet? Methode: Anhand von sechs großen Datensätzen aus verschiedenen klinischen Bereichen wurden psychometrische Analysen mit dem Graded Response Model durchgeführt. Ergebnisse: In allen Stichproben fand sich eine hohe interne Konsistenz. Die Schwellenwerte waren mit Ausnahme von Item 6 („Bestrafungsgefühle“) geordnet. Gemäß Testinformationsfunktion misst das BDI-II im mittleren bis hohen Depressionsbereich sehr gut (Reliabilität > .90) und im unteren Bereich gut. Schlussfolgerung: Für das BDI-II ergibt sich eine hohe und relativ gleichbleibende Messpräzision über einen weiten Bereich des latenten Traits, weshalb es insbesondere im klinischen, aber auch im nicht klinisch relevanten Wertebereich zur Erhebung des Schweregrades einer Depression gut geeignet ist.
In den letzten Jahrzehnten hat sich durch randomisiert-kontrollierte Studien (RCTs) eine breite Evidenzbasis von Psychotherapie mit mittleren bis großen Effekten für verschiedene psychische Störungen gebildet. Neben der Bestimmung dieser Wirksamkeit („Efficacy“) ebneten Studien zur Wirksamkeit unter alltäglichen Routinebedingungen („Effectiveness“) historisch den Weg zur Entwicklung eines praxisorientierten Forschungsparadigmas. Im Beitrag wird argumentiert, dass im Rahmen dieses Paradigmas praxisbasierte Studien eine wertvolle Ergänzung zu RCTs darstellen, da sie existierende Probleme in der Psychotherapieforschung adressieren können. In der gegenwärtigen praxisorientierten Forschung liefern dabei neue Ansätze aus der personalisierten Medizin und Methoden aus der ‚Computational Psychiatry‘ wichtige Anhaltspunkte zur Optimierung von Effekten in der Psychotherapie. Im Kontext der Personalisierung werden bspw. klinische multivariable Prädiktionsmodelle entwickelt, welche durch Rückmeldeschleifen an Praktiker_innen kurzfristig ein evidenzbasiertes Outcome-Monitoring ermöglicht und langfristig das Praxis-Forschungsnetzwerk in Deutschland stärkt. Am Ende des Beitrags werden zukünftige Richtungen für die praxisorientierte Forschung im Sinne des ‘Precision Mental Health Care’ -Paradigmas abgeleitet und diskutiert.
Complex problem solving (CPS) can be interpreted as the number of psychological mechanisms that allow us to reach our targets in difficult situations, that can be classified as complex, dynamic, non-transparent, interconnected, and multilayered, and also polytelic. The previous results demonstrated associations between the personality dimensions neuroticism, conscientiousness, and extraversion and problem-solving performance. However, there are no studies dealing with personality disorders in connection with CPS skills. Therefore, the current study examines a clinical sample consisting of people with personality and/or depressive disorders. As we have data for all the potential personality disorders and also data from each patient regarding to potential depression, we meet the whole range from healthy to impaired for each personality disorder and for depression. We make use of a unique operationalization: CPS was surveyed in a simulation game, making use of the microworld approach. This study was designed to investigate the hypothesis that personality traits are related to CPS performance. Results show that schizotypal, histrionic, dependent, and depressive persons are less likely to successfully solve problems, while persons having the additional behavioral characteristics of resilience, action orientation, and motivation for creation are more likely to successfully solve complex problems.
Objective
Obesity, often associated with non-alcoholic fatty liver disease (NAFLD), is characterized by an imbalance between energy expenditure and food intake, which is also reflected by desensitization of fibroblast growth factor 21 (FGF21). FGF21 is strongly influenced, among others, by TNFα, which is known to be upregulated in obesity-induced inflammation. Successful long-term treatments of NAFLD might be dietary modification, exercise, or fasting.
Materials and methods
Whether succeeded NAFLD recovery is linked with improved FGF21 sensitivity and finally reverted FGF21 resistance was the focus of the present study. For this purpose, mice received a high-fat diet (HFD) for 6 months to establish obesity. Afterward, the mice were subjected to three different weight loss interventions, namely, dietary change to low-fat diet (LFD), treadmill training, and/or time-restricted feeding for additional 6 months, whereas one group remained on HFD.
Results
In addition to the expected decrease in NAFLD activity with dietary change, this was also observed in the HFD group with additional time-restricted feeding. There was also an associated decrease in hepatic TNFα and FGF21 expression and an increase in ß-klotho expression, demonstrated mainly by using principal component analysis. Pearson correlation analysis shows that independent of any intervention, TNFα expression decreased with improved NAFLD recovery. This was accompanied with higher FGF21 sensitivity, as expressed by an increase in β-klotho and FGFR1c expression and concomitantly decreased FGF21 levels.
Conclusion
In summary, we conclude that successful NAFLD therapy is associated with a reversion of the TNFα-triggered FGF21-resistant state or desensitization.