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Although the common pathology of Alzheimer’s disease (AD) and white matter hyperintensities (WMH) is disputed, the gene TREML2 has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (APOE) ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant’s AD-related brain atrophy. In our study, increased whole-blood TREML2 gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The APOE status did not influence the associations. In sum, TREML2 robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin TREML2’s role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight TREML2 as a worthwhile target for disentangling the two pathologies.
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.
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.
Introduction: It has been shown that Alzheimer’s disease (AD) is accompanied by marked structural brain changes that can be detected several years before clinical diagnosis via structural magnetic resonance (MR) imaging. In this study, we developed a structural MR-based biomarker for in vivo detection of AD using a supervised machine learning approach. Based on an individual’s pattern of brain atrophy a continuous AD score is assigned which measures the similarity with brain atrophy patterns seen in clinical cases of AD.
Methods: The underlying statistical model was trained with MR scans of patients and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-1 screening). Validation was performed within ADNI-1 and in an independent patient sample from the Open Access Series of Imaging Studies (OASIS-1). In addition, our analyses included data from a large general population sample of the Study of Health in Pomerania (SHIP-Trend).
Results: Based on the proposed AD score we were able to differentiate patients from healthy controls in ADNI-1 and OASIS-1 with an accuracy of 89% (AUC = 95%) and 87% (AUC = 93%), respectively. Moreover, we found the AD score to be significantly associated with cognitive functioning as assessed by the Mini-Mental State Examination in the OASIS-1 sample after correcting for diagnosis, age, sex, age·sex, and total intracranial volume (Cohen’s f2 = 0.13). Additional analyses showed that the prediction accuracy of AD status based on both the AD score and the MMSE score is significantly higher than when using just one of them. In SHIP-Trend we found the AD score to be weakly but significantly associated with a test of verbal memory consisting of an immediate and a delayed word list recall (again after correcting for age, sex, age·sex, and total intracranial volume, Cohen’s f2 = 0.009). This association was mainly driven by the immediate recall performance.
Discussion: In summary, our proposed biomarker well differentiated between patients and healthy controls in an independent test sample. It was associated with measures of cognitive functioning both in a patient sample and a general population sample. Our approach might be useful for defining robust MR-based biomarkers for other neurodegenerative diseases, too.
Background: There is evidence that the borderline symptomatology of the mother longitudinally predicts the number of borderline criteria met by the children. However, possible underlying mechanisms have rarely been examined. In line with transactional models of borderline personality disorder (BPD), we analyzed a broad concept of maladaptive mother-child interactions of mothers with BPD symptoms towards their children, including insensitive parenting and mother-child discrepancies, in reporting the child's psychopathological behavior. Sampling/Methods: The sample was drawn from the population-based Greifswald Family Study and consisted of 295 children and their biological mothers. Both were examined at two points in time, first when the children were about 15 years old (T₀) and again 5 years later (T<sub>1</sub>), using path analyses. Results: Maladaptive mother-child interactions (especially an overprotective and rejecting parenting style and high discrepancies regarding internalizing problems) mediate the longitudinal transmission of borderline symptoms from mother to child. Furthermore, our data revealed that this result is consistent for various youth symptoms which are associated with BPD such as impulsivity or dissociation. Conclusion: The data of the current study imply that the transmission of borderline symptoms from mother to child is mediated by maladaptive mother-child interactions. For this reason early and professional support may be useful to prevent these children from developing severe psychopathology.