Interaction of perceived social support and childhood maltreatment on limbic responsivity towards negative emotional stimuli in healthy individuals.

Childhood maltreatment (CM) is associated with increased limbic activity, while social support is linked to decreased limbic activity towards negative stimuli. Our study aimed to explore the interaction of perceived social support with CM, and their combined impact on limbic activity in negative emotion processing. A total of 130 healthy individuals (HC) underwent a negative emotional face processing paradigm. They were divided into two groups based on the Childhood Trauma Questionnaire: n = 65 HC without CM matched with n = 65 HC with CM. In a region-of-interest approach of the bilateral amygdala-hippocampus-complex (AHC), regression analyses investigating the association of CM and perceived social support with limbic activity and a social support x CM ANCOVA were conducted. CM was associated with increased AHC activity, while perceived social support tended to be associated with decreased AHC activity during negative emotion processing. The ANCOVA showed a significant interaction in bilateral AHC activity (pFWE ≤ 0.024) driven by a negative association between perceived social support and bilateral AHC activity in HC without CM. No significant association was observed in HC with CM. Exploratory analyses using continuous CM scores support this finding. Our results suggest that CM moderates the link between perceived social support and limbic activity, with a protective effect of perceived social support only in HC without CM. The lack of this effect in HC with CM suggests that CM may alter the buffering effect of perceived social support on limbic functioning, highlighting the potential need for preventive interventions targeting social perception of HC with CM.

How movies move us - movie preferences are linked to differences in neuronal emotion processing of fear and anger: an fMRI study.

Introduction: As a source of audio-visual stimulation, movies expose people to various emotions. Interestingly, several genres are characterized by negative emotional content. Albeit theoretical approaches exist, little is known about preferences for specific movie genres and the neuronal processing of negative emotions. Methods: We investigated associations between movie genre preference and limbic and reward-related brain reactivity to close this gap by employing an fMRI paradigm with negative emotional faces in 257 healthy participants. We compared the functional activity of the amygdala and the nucleus accumbens (NAcc) between individuals with a preference for a particular movie genre and those without such preference. Results and discussion: Amygdala activation was relatively higher in individuals with action movie preference (p TFCE-FWE = 0.013). Comedy genre preference was associated with increased amygdala (p TFCE-FWE = 0.038) and NAcc activity (p TFCE-FWE = 0.011). In contrast, crime/thriller preference (amygdala: p TFCE-FWE ≤ 0.010, NAcc: p TFCE-FWE = 0.036), as well as documentary preference, was linked to the decreased amygdala (p TFCE-FWE = 0.012) and NAcc activity (p TFCE-FWE = 0.015). The study revealed associations between participants' genre preferences and brain reactivity to negative affective stimuli. Interestingly, preferences for genres with similar emotion profiles (action, crime/thriller) were associated with oppositely directed neural activity. Potential links between brain reactivity and susceptibility to different movie-related gratifications are discussed.

The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression.

Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients. Processing speed performance of n = 284 acutely depressed, n = 177 partially and n = 198 fully remitted patients, and n = 743 healthy controls (HC) was estimated based on five neuropsychological tests. Network-based statistic was used to identify a brain network associated with processing speed. We employed general linear models to examine the association between TNF-α PGS and processing speed. We investigated whether network connectivity mediates the association between TNF-α PGS and processing speed. We identified a structural network positively associated with processing speed in the whole sample. We observed a significant negative association between TNF-α PGS and processing speed in acutely depressed patients, whereas no association was found in remitted patients and HC. The mediation analysis revealed that brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD. The present study provides evidence that TNF-α PGS is associated with decreased processing speed exclusively in patients with acute depression. This association was partially mediated by structural brain connectivity. Using multimodal data, the current findings advance our understanding of cognitive dysfunction in MDD and highlight the involvement of genetic-immunological processes in its pathomechanisms.

2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. / 2-Hydroxyglutarat als MR-spektroskopisch erfassbarer Prädiktor einer IDH-Mutation bei Gliomen.

The mutated enzyme isocitrate dehydrogenase (IDH) 1 and 2 has been detected in various tumor entities such as gliomas and can convert α-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG). This neuro-oncologically significant metabolic product can be detected by MR spectroscopy and is therefore suitable for noninvasive glioma classification and therapy monitoring.This paper provides an up-to-date overview of the methodology and relevance of 1H-MR spectroscopy (MRS) in the oncological primary and follow-up diagnosis of gliomas. The possibilities and limitations of this MR spectroscopic examination are evaluated on the basis of the available literature.By detecting 2-HG, MRS can in principle offer a noninvasive alternative to immunohistological analysis thus avoiding surgical intervention in some cases. However, in addition to an adapted and optimized examination protocol, the individual measurement conditions in the examination region are of decisive importance. Due to the inherently small signal of 2-HG, unfavorable measurement conditions can influence the reliability of detection. · MR spectroscopy enables the non-invasive detection of 2-hydroxyglutarate.. · The measurement of this metabolite allows the detection of an IDH mutation in gliomas.. · The choice of MR examination method is particularly important.. · Detection reliability is influenced by glioma size, necrotic tissue and the existing measurement conditions.. · Bauer J, Raum HN, Kugel H et al. 2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. Fortschr Röntgenstr 2024; DOI 10.1055/a-2285-4923.

A Systematic Evaluation of Machine Learning-Based Biomarkers for Major Depressive Disorder.

Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no informative biomarkers have been identified. Objective: To evaluate whether machine learning (ML) can identify a multivariate biomarker for MDD. Design, Setting, and Participants: This study used data from the Marburg-Münster Affective Disorders Cohort Study, a case-control clinical neuroimaging study. Patients with acute or lifetime MDD and healthy controls aged 18 to 65 years were recruited from primary care and the general population in Münster and Marburg, Germany, from September 11, 2014, to September 26, 2018. The Münster Neuroimaging Cohort (MNC) was used as an independent partial replication sample. Data were analyzed from April 2022 to June 2023. Exposure: Patients with MDD and healthy controls. Main Outcome and Measure: Diagnostic classification accuracy was quantified on an individual level using an extensive ML-based multivariate approach across a comprehensive range of neuroimaging modalities, including structural and functional magnetic resonance imaging and diffusion tensor imaging as well as a polygenic risk score for depression. Results: Of 1801 included participants, 1162 (64.5%) were female, and the mean (SD) age was 36.1 (13.1) years. There were a total of 856 patients with MDD (47.5%) and 945 healthy controls (52.5%). The MNC replication sample included 1198 individuals (362 with MDD [30.1%] and 836 healthy controls [69.9%]). Training and testing a total of 4 million ML models, mean (SD) accuracies for diagnostic classification ranged between 48.1% (3.6%) and 62.0% (4.8%). Integrating neuroimaging modalities and stratifying individuals based on age, sex, treatment, or remission status does not enhance model performance. Findings were replicated within study sites and also observed in structural magnetic resonance imaging within MNC. Under simulated conditions of perfect reliability, performance did not significantly improve. Analyzing model errors suggests that symptom severity could be a potential focus for identifying MDD subgroups. Conclusion and Relevance: Despite the improved predictive capability of multivariate compared with univariate neuroimaging markers, no informative individual-level MDD biomarker-even under extensive ML optimization in a large sample of diagnosed patients-could be identified.

Persistence of amygdala hyperactivity to subliminal negative emotion processing in the long-term course of depression.

Biased emotion processing has been suggested to underlie the etiology and maintenance of depression. Neuroimaging studies have shown mood-congruent alterations in amygdala activity in patients with acute depression, even during early, automatic stages of emotion processing. However, due to a lack of prospective studies over periods longer than 8 weeks, it is unclear whether these neurofunctional abnormalities represent a persistent correlate of depression even in remission. In this prospective case-control study, we aimed to examine brain functional correlates of automatic emotion processing in the long-term course of depression. In a naturalistic design, n = 57 patients with acute major depressive disorder (MDD) and n = 37 healthy controls (HC) were assessed with functional magnetic resonance imaging (fMRI) at baseline and after 2 years. Patients were divided into two subgroups according to their course of illness during the study period (n = 37 relapse, n = 20 no-relapse). During fMRI, participants underwent an affective priming task that assessed emotion processing of subliminally presented sad and happy compared to neutral face stimuli. A group × time × condition (3 × 2 × 2) ANOVA was performed for the amygdala as region-of-interest (ROI). At baseline, there was a significant group × condition interaction, resulting from amygdala hyperactivity to sad primes in patients with MDD compared to HC, whereas no difference between groups emerged for happy primes. In both patient subgroups, amygdala hyperactivity to sad primes persisted after 2 years, regardless of relapse or remission at follow-up. The results suggest that amygdala hyperactivity during automatic processing of negative stimuli persists during remission and represents a trait rather than a state marker of depression. Enduring neurofunctional abnormalities may reflect a consequence of or a vulnerability to depression.

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers.

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

Robustness of apparent diffusion coefficient-based lymph node classification for diagnosis of prostate cancer metastasis.

OBJECTIVES: The aim of this proof-of-principle study combining data analysis and computer simulation was to evaluate the robustness of apparent diffusion coefficient (ADC) values for lymph node classification in prostate cancer under conditions comparable to clinical practice. MATERIALS AND METHODS: To assess differences in ADC and inter-rater variability, ADC values of 359 lymph nodes in 101 patients undergoing simultaneous prostate-specific membrane antigen (PSMA)-PET/MRI were retrospectively measured by two blinded readers and compared in a node-by-node analysis with respect to lymph node status. In addition, a phantom and 13 patients with 86 lymph nodes were prospectively measured on two different MRI scanners to analyze inter-scanner agreement. To estimate the diagnostic quality of the ADC in real-world application, a computer simulation was used to emulate the blurring caused by scanner and reader variability. To account for intra-individual correlation, the statistical analyses and simulations were based on linear mixed models. RESULTS: The mean ADC of lymph nodes showing PSMA signals in PET was markedly lower (0.77 × 10-3 mm2/s) compared to inconspicuous nodes (1.46 × 10-3 mm2/s, p < 0.001). High inter-reader agreement was observed for ADC measurements (ICC 0.93, 95%CI [0.92, 0.95]). Good inter-scanner agreement was observed in the phantom study and confirmed in vivo (ICC 0.89, 95%CI [0.84, 0.93]). With a median AUC of 0.95 (95%CI [0.92, 0.97]), the simulation study confirmed the diagnostic potential of ADC for lymph node classification in prostate cancer. CONCLUSION: Our model-based simulation approach implicates a high potential of ADC for lymph node classification in prostate cancer, even when inter-rater and inter-scanner variability are considered. CLINICAL RELEVANCE STATEMENT: The ADC value shows a high diagnostic potential for lymph node classification in prostate cancer. The robustness to scanner and reader variability implicates that this easy to measure and widely available method could be readily integrated into clinical routine. KEY POINTS: • The diagnostic value of the apparent diffusion coefficient (ADC) for lymph node classification in prostate cancer is unclear in the light of inter-rater and inter-scanner variability. • Metastatic and inconspicuous lymph nodes differ significantly in ADC, resulting in a high diagnostic potential that is robust to inter-scanner and inter-rater variability. • ADC has a high potential for lymph node classification in prostate cancer that is maintained under conditions comparable to clinical practice.