Positive psychotic symptoms as a marker of clinical severity in a transdiagnostic sample of help-seeking adolescents.

The present study aimed to examine the association between the presence, number, and type of positive psychotic symptoms (PPS) and clinical severity in adolescent patients. Five hundred-six patients aged 11-17 years were assigned to either the noPPS (n = 341), the delusional beliefs only (del; n = 32), the hallucinations only (hall; n = 80), or the delusional beliefs and hallucinations (del&hall; n = 53) group. Generalized Structural Equation Modeling was applied to identify the best-fitting model representing clinical severity indicated by psychiatric diagnoses, depressivity, personality pathology, non-suicidal self-injury, suicide attempts, perceived stress, and psychosocial impairments, assessed by interviews and questionnaires. The groups were compared concerning the final model's factors. The final model consisted of three factors representing psychopathology and functional impairments, self-harming behavior, and perceived stress (BIC difference to reference model: 103.99). Participants with any PPS scored higher on all factors than the noPPS group (differences in SD: 0.49-1.48). Additionally, the del&hall group scored 1.31 SD higher on psychopathology and functional impairments than the hall group, and 1.16 SD higher on self-harming behavior compared to the del group. Finally, the hall group scored 0.84 SD higher on self-harming behavior than the del group, with no group differences in the other factors. In adolescent patients, the presence of PPS may represent a marker for a more severe form of mental disorder, with hallucinations being indicative of self-harming behavior. Early transdiagnostic assessment of PPS seems indicated as it may inform treatment in the context of clinical staging.

An examination of sociodemographic and clinical factors influencing help-seeking attitudes and behaviors among adolescents with mental health problems.

This study investigated sociodemographic and clinical factors influencing help-seeking attitudes and behavior among adolescents with mental health problems. As part of the ProHEAD ("Promoting Help-seeking using E-technology for ADolescents") consortium a school-based, online assessment of sociodemographic information, psychopathology, risk-taking and self-harming behavior, help-seeking attitudes and behavior, and barriers to help-seeking was conducted in adolescents aged ≥ 12 years recruited from randomly selected schools in five regions of Germany. Linear regression analyses with the LMG formula were performed to explore predictors of help-seeking attitudes and behavior and assess their relative importance. Nine thousand five hundred and nine participants (95.5%) completed the online assessment (mean age: 15.1 years, 58.6% female). In total, 1606 participants (16.9%) showed relevant mental health problems (e.g., depressive and eating disorder symptoms, alcohol problems, and thoughts of self-harming behavior). Among them, 895 (55.7%) reported having sought help (lifetime), with higher rates for informal (n = 842, 52.4%) compared to professional (n = 380, 23.7%) sources. High help-seeking propensity emerged as the most important factor contributing to professional help-seeking, followed by elevated levels of psychopathology and perceived barriers, with sociodemographic factors being less impactful. Psychopathological severity also outweighed sociodemographic factors in predicting negative help-seeking attitudes. These findings indicate that attitudes towards seeking professional help, perceived barriers, and psychopathology severity critically influence limited adolescent help-seeking behavior. This emphasizes the need for initiatives that promote help-seeking, reduce negative attitudes, and address structural barriers in adolescent mental health care.

Age-related decline in the brain: a longitudinal study on inter-individual variability of cortical thickness, area, volume, and cognition.

Magnetic Resonance Imaging (MRI) studies have shown that cortical volume declines with age. Although volume is a multiplicative measure consisting of thickness and area, few studies have focused on both its components. Information on decline variability and associations between person-specific changes of different brain metrics, brain regions, and cognition is sparse. In addition, the estimates have often been biased by the measurement error, because three repeated measures are minimally required to separate the measurement error from person-specific changes. With a sample size of N = 231, five repeated measures, and an observational time span of seven years, this study explores the associations between changes of different brain metrics, brain regions, and cognitive abilities in aging. Person-specific changes were obtained by latent growth curve models using Bayesian estimation. Our data indicate that both thickness and area are important contributors to volumetric changes. In most brain regions, area clearly declined on average over the years, while thickness showed only little decline. However, there was also substantial variation around the average slope in thickness and area. The correlation pattern of changes in thickness between brain regions was strong and largely homogenous. The pattern for changes in area was similar but weaker, indicating that factors affecting area may be more region-specific. Changes in thickness and volume were substantially correlated with changes in cognition. In some brain regions, changes in area were also related to changes in cognition. Overall, studying the associations between the trajectories of brain regions in different brain metrics provides insights into the regional heterogeneity of structural changes. SIGNIFICANCE STATEMENT: Many studies have described volumetric brain changes in aging. Few studies have focused on both its individual components: area and thickness. Longitudinal studies with three or more time points are highly needed, because they provide more precise average change estimates and, more importantly, allow us to quantify the associations between changes in the different brain metrics, brain regions, and other variables (e.g. cognitive abilities). Studying these associations is important because they can provide information regarding possible underlying factors of these changes. Our study, with a large sample size, five repeated measures, and an observational time span of seven years, provides new insights about the associations between person-specific changes in thickness, area, volume, and cognitive abilities.

Cyclotorsion Measurement on Scanning Laser Ophthalmoscopy Imaging Compared With Fundus Photography in Patients With Fourth Nerve Palsy and Healthy Controls: CySLO-IV Study.

BACKGROUND: The purpose of the study is to evaluate the agreement of the foveopapillary angle (FPA) on conventional fundus photography (c-FPA) with the FPA on scanning laser ophthalmoscopy (SLO) imaging (SLO-FPA) in patients with fourth nerve palsy and healthy controls (HCs). METHODS: The FPA was measured in both eyes of 25 patients and 25 HCs in synedra View (c-FPA) and with the integrated algorithm of the Heidelberg Spectralis OCT (SLO-FPA). The primary endpoint was the agreement of both measurements. Furthermore, we evaluated the influence of the eye tracker, the influence of fixation on objective torsion, and the FPA cutoff between patients and HCs. RESULTS: The mean SLO-FPA in patients (6/25 acquired palsies) was 11.3 ± 3.6° and 6.4 ± 2.1° in HCs. The mean c-FPA was 11.4 ± 4.0° and 5.8 ± 2.2°, respectively. The Bland-Altman plot of c-FPA vs SLO-FPA in patients and HCs shows no systematic bias (mean of -0.28°). Limits of agreement were -6.58 and 6.02°. Using the eye tracker had no systematic effect. There was no evidence for an immediate shift of torsion with change of fixation (24/25 patients and 23/25 HCs). Discrimination between patients and HCs by the SLO-FPA is very good with an area under the curve = 0.92 (95% confidence interval: 0.84-0.99). CONCLUSIONS: SLO-FPA measurement allows convenient and consistent assessment of objective cyclotorsion. There was no systematic bias in the difference between SLO-FPA and traditional c-FPA; thus, SLO-FPA is a valuable alternative to the commonly used c-FPA. Using the eye tracker is recommended for proper centering of the ring scan.

Neural patterns reveal single-trial information on absolute pitch and relative pitch perception.

Pitch is a fundamental attribute of sounds and yet is not perceived equally by all humans. Absolute pitch (AP) musicians perceive, recognize, and name pitches in absolute terms, whereas relative pitch (RP) musicians, representing the large majority of musicians, perceive pitches in relation to other pitches. In this study, we used electroencephalography (EEG) to investigate the neural representations underlying tone listening and tone labeling in a large sample of musicians (n = 105). Participants performed a pitch processing task with a listening and a labeling condition during EEG acquisition. Using a brain-decoding framework, we tested a prediction derived from both theoretical and empirical accounts of AP, namely that the representational similarity of listening and labeling is higher in AP musicians than in RP musicians. Consistent with the prediction, time-resolved single-trial EEG decoding revealed a higher representational similarity in AP musicians during late stages of pitch perception. Time-frequency-resolved EEG decoding further showed that the higher representational similarity was present in oscillations in the theta and beta frequency bands. Supplemental univariate analyses were less sensitive in detecting subtle group differences in the frequency domain. Taken together, the results suggest differences between AP and RP musicians in late pitch processing stages associated with cognition, rather than in early processing stages associated with perception.

Prefrontal oxygenation during experimental pain in adolescents engaging in non-suicidal self-injury.

BACKGROUND: The intricate role of pain in non-suicidal self-injury (NSSI) makes the investigation of alterations in brain function during pain processing a critical yet underexplored topic. The aim of this study was to investigate fNIRS correlates of experimental pain and how these differed between adolescent patients engaging in NSSI and healthy controls. METHODS: 154 adolescent patients with NSSI and 48 healthy controls underwent a heat pain stimulation with linearly increasing temperature from 32 °C to max. 50 °C, during which fNIRS activity was recorded. Associations between fNIRS activity and pain perception (i.e. pain threshold, pain tolerance and pain intensity) were examined using linear mixed models and linear regression analyses. RESULTS: Across groups, we found a decrease in prefrontal oxygenation during increasing pain stimulation: Oxygenated hemoglobin was higher during baseline than during pain threshold (b = -0.36, p < .001) and higher during pain threshold than during pain tolerance (b = -0.10, p < .001). We did not find differential patterns of prefrontal oxygenation across the pain assessment between patients and healthy controls. Also, no association between pain intensity and fNIRS activity was found. LIMITATIONS: fNIRS was only recorded in prefrontal regions and our design did not include a non-painful stimulation as a control condition. CONCLUSION: While our study adds to the understanding of prefrontal hemodynamic changes associated with pain processing, it did not contribute further evidence to the few existing findings regarding altered neural processing of pain in adolescents engaging in NSSI.

Longitudinal investigation in children and adolescents with ADHD and healthy controls: A 2-year ERP study.

Cross-sectional group comparisons have shown altered neurocognitive and neurophysiological profiles in individuals with attention-deficit/hyperactivity disorder (ADHD). We report a two-year longitudinal observational study of ADHD children and adolescents (N = 239) regarding ADHD symptoms, behavioral metrics, and event-related potentials (ERP) and compared them to healthy controls (N = 91). The participants were assessed up to five times with a cued Go/NoGo task while ERPs were recorded. We fitted the trajectories of our variables of interest with univariate and bivariate latent growth curve models. At baseline, the ADHD group had increased reaction time variability, higher number of omission and commission errors, and attenuated CNV and P3d amplitudes compared to controls. The task performance in terms of behavioral metrics improved in both groups over two years; however, with differential patterns: the decrease in reaction time and omission errors were stronger in the control group, and the reduction of commission errors was more substantial in the ADHD group. The cueP3, CNV, and N2d amplitudes changed slightly over two years, with negligible differences between both groups. Furthermore, the parent-rated symptom burden in the ADHD group decreased by 22 % (DSM-5-based questionnaire). We did not identify any associations between the changes in symptoms and the changes in the behavioral or neurophysiological metrics. The lack of association between the changes in symptoms and the behavioral or ERP metrics supports the trait liability hypothesis, which claims that the neurocognitive deficits are independent of symptom alleviation. Furthermore, the change in symptom burden was substantial, questioning the stability of the reported ADHD symptoms.

Prenatal stress and child externalizing behavior: effects of maternal perceived stress and cortisol are moderated by child sex.

BACKGROUND: Externalizing behavior problems are related to social maladjustment. Evidence indicates associations between prenatal stress and child behavioral outcomes. It remains unclear how psychological distress vs. biological correlates of stress (cortisol) differentially predict externalizing behavior, and how their effects might differ as a function of child sex. METHOD: 108 pregnant women from the community collected salivary cortisol and reported their perceived stress during each trimester of pregnancy. At child age 9 years (M = 9.01, SD = 0.55), 70 mothers and children reported on child behavior. Structural equation modelling was used to analyze how cortisol levels and perceived stress during pregnancy predicted current child externalizing behavior, considering the moderating effect of child sex. RESULTS: Perceived stress predicted higher externalizing behavior in boys (ß = 0.42, p = 0.009) and lower externalizing behavior in girls (ß = - 0.56, p = 0.014). Cortisol predicted lower externalizing behavior in boys (ß = - 0.81, p < .001) and was not related to girls' externalizing behavior (ß = 0.37, p = 0.200). DISCUSSION/CONCLUSION: Prenatal stress affected externalizing behavior differently in girls vs. boys. These response patters in turn differed for indicators of psychological vs. biological maternal stress, encouraging an integrated approach. Findings indicate that perceived stress and cortisol may affect child development via different trajectories.

Longitudinal Analysis of Self-Reported Symptoms, Behavioral Measures, and Event-Related Potential Components of a Cued Go/NoGo Task in Adults With Attention-Deficit/Hyperactivity Disorder and Controls.

This study characterizes a large sample of adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls regarding their task performance and neurophysiology; cross-sectionally and longitudinally. Self-reported symptoms, behavioral measures, and event-related potentials from a classical cued Go/NoGo task were used to outline the symptom burden, executive function deficits and neurophysiological features, and the associations between these domains. The study participants (N = 210 ADHD, N = 158 controls, age: 18-62 years) were assessed five (ADHD) or three (controls) times over two years. We describe cross-sectional and longitudinal group differences, and associations between symptom burden, and behavioral and event-related potential (ERP) components variables by latent growth curve models, including random slopes and intercepts. The ADHD group showed increased reaction time variability, increased commission and omission errors, and attenuated cueP3, CNV, N2d, and P3d amplitudes. We observed a decrease in self-reported symptoms in the ADHD group over the two years. The behavioral measures (reaction time variability, number of omission, and commission errors) did not change over time, whereas the cueP3, P3d, and N2d amplitude attenuated in both groups. There was no evidence for a robust association between symptom burden and behavioral or ERP measures. The changes in the ERP components with stable task performance, potentially indicate more efficient neuronal processing over the two years. Whether the lack of association between symptom burden and behavioral or ERP measures might be due to the low reliability of the ADHD assessment criteria, or the inappropriateness of the objective measures cannot be inferred.

Decline Variability of Cortical and Subcortical Regions in Aging: A Longitudinal Study.

Describing the trajectories of age-related change for different brain structures has been of interest in many recent studies. However, our knowledge regarding these trajectories and their associations is still limited due to small sample sizes and low numbers of repeated measures. For the present study, we used a large longitudinal dataset (four measurements over 4 years) comprising anatomical data from a sample of healthy older adults (N = 231 at baseline). This dataset enables us to gain new insights about volumetric cortical and subcortical changes and their associations in the context of healthy aging. Brain structure volumes were derived from T1-weighted MRI scans using FreeSurfer segmentation tools. Brain structure trajectories were fitted using mixed models and latent growth curve models to gain information about the mean extent and variability of decline trajectories for different brain structures as well as the associations between individual trajectories. On the group level, our analyses indicate similar linear changes for frontal and parietal brain regions, while medial temporal regions showed an accelerated decline with advancing age. Regarding subcortical regions, some structures showed strong declines (e.g., hippocampus), others showed little decline (e.g., pallidum). Our data provide little evidence for sex differences regarding the aforementioned trajectories. Between-person variability of the person-specific slopes (random slopes) was largest in subcortical and medial temporal brain structures. When looking at the associations between the random slopes from each brain structure, we found that the decline is largely homogenous across the majority of cortical brain structures. In subcortical and medial temporal brain structures, however, more heterogeneity of the decline was observed, meaning that the extent of the decline in one structure is less predictive of the decline in another structure. Taken together, our study contributes to enhancing our understanding of structural brain aging by demonstrating (1) that average volumetric change differs across the brain and (2) that there are regional differences with respect to between-person variability in the slopes. Moreover, our data suggest (3) that random slopes are highly correlated across large parts of the cerebral cortex but (4) that some brain regions (i.e., medial temporal regions) deviate from this homogeneity.

Heterogeneity of EEG resting-state brain networks in absolute pitch.

The neural basis of absolute pitch (AP), the ability to effortlessly identify a musical tone without an external reference, is poorly understood. One of the key questions is whether perceptual or cognitive processes underlie the phenomenon, as both sensory and higher-order brain regions have been associated with AP. To integrate the perceptual and cognitive views on AP, here, we investigated joint contributions of sensory and higher-order brain regions to AP resting-state networks. We performed a comprehensive functional network analysis of source-level EEG in a large sample of AP musicians (n = 54) and non-AP musicians (n = 51), adopting two analysis approaches: First, we applied an ROI-based analysis to examine the connectivity between the auditory cortex and the dorsolateral prefrontal cortex (DLPFC) using several established functional connectivity measures. This analysis is a replication of a previous study which reported increased connectivity between these two regions in AP musicians. Second, we performed a whole-brain network-based analysis on the same functional connectivity measures to gain a more complete picture of the brain regions involved in a possibly large-scale network supporting AP ability. In our sample, the ROI-based analysis did not provide evidence for an AP-specific connectivity increase between the auditory cortex and the DLPFC. The whole-brain analysis revealed three networks with increased connectivity in AP musicians comprising nodes in frontal, temporal, subcortical, and occipital areas. Commonalities of the networks were found in both sensory and higher-order brain regions of the perisylvian area. Further research will be needed to confirm these exploratory results.