Associations between multi-method latent factors of puberty and brain structure in adolescent girls.

Pubertal processes are associated with structural brain development, but studies have produced inconsistent findings that may relate to different measurements of puberty. Measuring both hormones and physical characteristics is important for capturing variation in neurobiological development. The current study explored associations between cortical thickness and latent factors from multi-method pubertal data in 174 early adolescent girls aged 10-13 years in the Transitions in Adolescent Girls (TAG) Study. Our multi-method approach used self-reported physical characteristics and hormone levels (dehydroepiandrosterone (DHEA), testosterone (T), and estradiol (E2) from saliva) to estimate an overall pubertal factor and for each process of adrenarche and gonadarche. There were negative associations between the overall puberty factor representing later stage and thickness in the posterior cortex, including the occipital cortices and extending laterally to the parietal lobe. However, the multi-method latent factor had weaker cortical associations when examining the adnearcheal process alone, suggesting physical characteristics and hormones capture different aspects of neurobiological development during adrenarche. Controlling for age weakened some of these associations. These findings show that associations between pubertal stage and cortical thickness differ depending on the measurement method and the pubertal process, and both should be considered in future confirmatory studies on the developing brain.

Longitudinal Change in Adolescent Depression and Anxiety Symptoms from before to during the COVID-19 Pandemic.

This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.

Socio-ecological Resilience Relates to Lower Internalizing Symptoms among Adolescents during the Strictest Period of COVID-19 Lockdown in Perú.

The COVID-19 pandemic has touched the lives of adolescents around the world. This short-term longitudinal, observational study followed 1,334 adolescents (11-17 yo) to investigate whether social-ecological resilience relates to intra- and inter-personal resources and/or the caregiver relationship relates to changes in internalizing symptoms during five stressful weeks of COVID-19 lockdown in Perú. In this work, we contextualize social-ecological resilience in relation to culturally-relevant personal and caregiver resources that youth can use to adapt to stressful situations. We found that adolescents who reported higher levels of personal, caregiver, and overall resilience had lower levels of anxiety and depressive symptoms at week six. We also find that personal, caregiver, and overall resilience moderated the change in anxiety symptoms from week 6 to week 11 of lockdown in 2020. Our findings underscore the importance of social-ecological resilience related to both intra/interpersonal resources and the caregiver relationship for minimizing the harmful impacts of COVID-19 on adolescent internalizing symptoms.

Associations Between Parenting Behavior and Neural Processing of Adolescent Faces in Mothers With and Without Depression.

BACKGROUND: This study first examined how mothers with and without depression differ in neural activation in response to adolescents' affective faces. Second, it examined the extent to which these neural activation patterns are related to observed positive and aggressive parenting behavior. METHODS: Mothers with and without depression (based on self-reported symptoms and treatment history; n = 77 and n = 64, respectively; meanage = 40 years) from low-income families completed an interaction task with their adolescents (meanage = 12.8 years), which was coded for parents' aggressive and positive affective behavior. During functional magnetic resonance imaging, mothers viewed blurry, happy, sad, and angry faces of unfamiliar adolescents, with an instruction to either label the emotion or determine the clarity of the image. RESULTS: The depression group showed less activation in the posterior midcingulate than the control subject group while labeling happy faces. Higher activation in the insula and dorsomedial prefrontal cortex (PFC) was related to less positive parenting behavior. Ventrolateral PFC activation was most pronounced when labeling negative emotions, but stronger ventrolateral PFC response to happy faces was associated with more aggressive parenting behavior. CONCLUSIONS: This demonstrates the association between parents' neural responses to adolescent faces and their behavior during interactions with their own adolescents, with relatively low insula and dorsomedial PFC activation supporting positive parenting and affect-dependent response in the ventrolateral PFC as being important to limit aggressive behavior.

The impact of depression on mothers' neural processing of their adolescents' affective behavior.

Depression affects neural processing of emotional stimuli and could, therefore, impact parent-child interactions. However, the neural processes with which mothers with depression process their adolescents' affective interpersonal signals and how this relates to mothers' parenting behavior are poorly understood. Mothers with and without depression (N = 64 and N = 51, respectively; Mage = 40 years) from low-income families completed an interaction task with their adolescents (Mage = 12.8 years), which was coded for both individuals' aggressive, dysphoric, positive and neutral affective behavior. While undergoing fMRI, mothers viewed video clips from this task of affective behavior from their own and an unfamiliar adolescent. Relative to non-depressed mothers, those with depression showed more aggressive and less positive affective behavior during the interaction task and more activation in the bilateral insula, superior temporal gyrus and striatum but less in the lateral prefrontal cortex while viewing aggressive and neutral affect. Findings were comparable for own and unfamiliar adolescents' affect. Heightened limbic, striatal and sensory responses were associated with more aggressive and dysphoric parenting behavior during the interactions, while reduced lateral prefrontal activation was associated with less positive parenting behavior. These results highlight the importance of depressed mothers' affective information processing for understanding mothers' behavior during interactions with their adolescents.

Multimethod assessment of pubertal timing and associations with internalizing psychopathology in early adolescent girls.

Early pubertal timing has consistently been associated with internalizing psychopathology in adolescent girls. Here, we aimed to examine whether the association between timing and mental health outcomes varies by measurement of pubertal timing and internalizing psychopathology, differs between adrenarcheal and gonadarcheal processes, and is stronger concurrently or prospectively. We assessed 174 female adolescents (age 10.0-13.0 at Time 1) twice, with an 18-month interval. Participants provided self-reported assessments of depression/anxiety symptoms and pubertal development, subjective pubertal timing, and date of menarche. Their parents/guardians also reported on the adolescent's pubertal development and subjective pubertal timing. We assessed salivary dehydroepiandrosterone (DHEA), testosterone, and estradiol levels and conducted clinical interviews to determine the presence of case level internalizing disorders. From these data, we computed 11 measures of pubertal timing at both time points, as well as seven measures of internalizing psychopathology, and entered these in a Specification Curve Analysis. Overall, earlier pubertal timing was associated with increased internalizing psychopathology. Associations were stronger prospectively than concurrently, suggesting that timing of early pubertal processes might be especially important for later risk of mental illness. Associations were strongest when pubertal timing was based on the Tanner Stage Line Drawings and when the outcome was case-level Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) depression or Hierarchical Taxonomy of Psychopathology (HiTOP) distress disorders. Timing based on hormone levels was not associated with internalizing psychopathology, suggesting that psychosocial mechanisms, captured by timing measures of visible physical characteristics might be more meaningful determinants of internalizing psychopathology than biological ones in adolescent girls. Future research should precisely examine these psychosocial mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Researcher's Guide to the Measurement and Modeling of Puberty in the ABCD Study® at Baseline.

The Adolescent Brain Cognitive Development℠ (ABCD) Study is an ongoing, diverse, longitudinal, and multi-site study of 11,880 adolescents in the United States. The ABCD Study provides open access to data about pubertal development at a large scale, and this article is a researcher's guide that both describes its pubertal variables and outlines recommendations for use. These considerations are contextualized with reference to cross-sectional empirical analyses of pubertal measures within the baseline ABCD dataset by Herting, Uban, and colleagues (2021). We discuss strategies to capitalize on strengths, mitigate weaknesses, and appropriately interpret study limitations for researchers using pubertal variables within the ABCD dataset, with the aim of building toward a robust science of adolescent development.

Adrenarcheal hormone-related development of white matter during late childhood.

The aim of the current study was to longitudinally examine how adrenarcheal hormones influence the development of white matter structure from age 8.5 to 10 years. Participants were 120 children (66 female; mean age 8.45 years at Time 1 and 9.97 years at Time 2) who completed two diffusion-weighted imaging scans 1.5 years apart. Morning saliva samples were taken at both assessment time points to measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. Fixel-based analysis was performed to examine how changes in white matter fibre density (FD) and cross-section (FC) over time were associated with initial levels of hormones, and changes in hormone levels over time. Both FD and FC increased over time in a wide range of white matter tracts. Increases in testosterone over time were related to relatively weaker increases in FC in the inferior fronto-occipital fasciculus. Levels and change in DHEA and DHEAS were not related to FD or FC changes. The results demonstrated development of white matter fibre density and cross-section from age 8.5 to 10 years. Changes in adrenarcheal hormone levels showed limited, localized associations with development of white matter FC. Future research should examine the relevance of adrenarcheal hormone-related white matter development for cognitive functioning; as well as directly compare analysis techniques of white matter structure.

Neural correlates of self-evaluation in relation to age and pubertal development in early adolescent girls.

Early adolescence is marked by puberty, and is also a time of flux in self-perception. However, there is limited research on the neural correlates of self-evaluation in relation to pubertal development. The current study examined relationships between neural activation during self-evaluation of social traits and maturation (age and pubertal development) in a community sample of female adolescents. Participants (N = 143; age M = 11.65, range = 10.0-13.0) completed a functional MRI task in which they judged the self-descriptiveness of adjectives for prosocial, antisocial and social status-related traits. Pubertal development was based on self-report, and was also examined using morning salivary testosterone, dehydroepiandrosterone, and estradiol. Contrary to preregistered hypotheses, neither age nor pubertal development were related to neural activation during self-evaluation. We further examined whether activation in two regions-of-interest, the ventromedial prefrontal cortex (vmPFC) and perigenual anterior cingulate (pgACC), was associated with trial-level self-evaluative behavior. In line with preregistered hypotheses, higher vmPFC and pgACC activation during self-evaluation were both associated with a higher probability of endorsing negative adjectives, and a lower probability of endorsing positive adjectives. Future studies should examine neural trajectories of self-evaluation longitudinally, and investigate the predictive value of the neural correlates of self-evaluation for adolescent mental health.

Investigating microstructure of white matter tracts as candidate endophenotypes of Social Anxiety Disorder - Findings from the Leiden Family Lab study on Social Anxiety Disorder (LFLSAD).

BACKGROUND: Social anxiety disorder (SAD) is a mental illness with a complex, partially genetic background. Differences in characteristics of white matter (WM) microstructure have been reported in patients with SAD compared to healthy controls. Also, WM characteristics are moderately to highly heritable. Endophenotypes are measurable characteristics on the road from genotype to phenotype, putatively reflective of genetically based disease mechanisms. In search of candidate endophenotypes of SAD we used a unique sample of SAD patients and their family members of two generations to explore microstructure of WM tracts as candidate endophenotypes. We focused on two endophenotype criteria: co-segregation with social anxiety within the families, and heritability. METHODS: Participants (n = 94 from 8 families genetically vulnerable for SAD) took part in the Leiden Family Lab Study on Social Anxiety Disorder (LFLSAD). We employed tract-based spatial statistics to examine structural WM characteristics, being fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD), in three a-priori defined tracts of interest: uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF). Associations with social anxiety symptoms and heritability were estimated. RESULTS: Increased FA in the left and right SLF co-segregated with symptoms of social anxiety. These findings were coupled with decreased RD and MD. All characteristics of WM microstructure were estimated to be at least moderately heritable. CONCLUSION: These findings suggest that alterations in WM microstructure in the SLF could be candidate endophenotypes of SAD, as they co-segregated within families genetically vulnerable for SAD and are heritable. These findings further elucidate the genetic susceptibility to SAD and improve our understanding of the overall etiology.

Adrenarcheal Timing Longitudinally Predicts Anxiety Symptoms via Amygdala Connectivity During Emotion Processing.

OBJECTIVE: This study aimed to examine longitudinally whether adrenarcheal timing (adrenarcheal hormone levels independent of age) and tempo (change in hormone levels over time) were associated with amygdala functional connectivity and how this in turn related to anxiety symptoms in the transition from childhood to adolescence. METHOD: Participants were 64 children (34 girls) who completed the Spence Children's Anxiety Scale and saliva collections to measure levels of testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate at two time points (mean age 9.5 years at time 1 [T1], 12.2 years at time 2 [T2]). Participants also viewed fearful and calm facial expressions while undergoing functional magnetic resonance imaging scanning at both time points. Amygdala functional connectivity was assessed with psychophysiological interaction analysis and modeled longitudinally with the Multivariate and Repeated Measures MATLAB toolbox. RESULTS: Controlling for age, higher dehydroepiandrosterone sulfate at T1 was related to an increase in amygdala to inferior frontal gyrus connectivity over time (T1 to T2) in boys, but the opposite pattern was found in girls. Dehydroepiandrosterone at T1 showed a positive association with amygdala connectivity to several lateral prefrontal areas and the anterior cingulate across time. Higher dehydroepiandrosterone at T1 was indirectly related to more anxiety symptoms at T2, controlling for symptoms at T1, via more positive amygdala to inferior frontal gyrus connectivity. Changes in hormone levels did not relate to changes in amygdala connectivity (from T1 to T2). CONCLUSION: The results suggest that amygdala to prefrontal cortex connectivity may be a mechanism through which early adrenarcheal timing predicts the development of anxiety symptoms during adrenarche.

Computerized Cognitive Training for Older Adults at Higher Dementia Risk due to Diabetes: Findings From a Randomized Controlled Trial.

BACKGROUND: To evaluate the effects of adaptive and tailored computerized cognitive training on cognition and disease self-management in older adults with diabetes. METHODS: This was a single-blind trial. Eighty-four community-dwelling older adults with diabetes were randomized into a tailored and adaptive computerized cognitive training or a generic, non-tailored or adaptive computerized cognitive training condition. Both groups trained for 8 weeks on the commercially available CogniFit program and were supported by a range of behavior change techniques. Participants in each condition were further randomized into a global or cognition-specific self-efficacy intervention, or to a no self-efficacy condition. The primary outcome was global cognition immediately following the intervention. Secondary outcomes included diabetes self-management, meta-memory, mood, and self-efficacy. Assessments were conducted at baseline, immediately after the training, and at a 6-month follow-up. RESULTS: Adherence and retention were lower in the generic computerized cognitive training condition, but the self-efficacy intervention was not associated with adherence. Moderate improvements in performance on a global cognitive composite at the posttreatment assessments were observed in both cognitive training conditions, with further small improvement observed at the 6-month follow-up. Results for diabetes self-management showed a modest improvement on self-rated diabetes care for both intervention conditions following the treatment, which was maintained at the 6-month follow-up. CONCLUSIONS: Our findings suggest that older adults at higher dementia risk due to diabetes can show improvements in both cognition and disease self-management following home-based multidomain computerized cognitive training. These findings also suggest that adaptive difficulty and individual task tailoring may not be critical components of such interventions. TRIAL REGISTRATION: NCT02709629.

Study Protocol: Transitions in Adolescent Girls (TAG).

BACKGROUND: Despite recent studies linking pubertal processes to brain development, as well as research demonstrating the importance of both pubertal and neurodevelopmental processes for adolescent mental health, there is limited knowledge of the full pathways and mechanisms behind the emergence of mental illnesses such as depression and anxiety disorders in adolescence. The Transitions in Adolescent Girls (TAG) study aims to understand the complex relationships between pubertal development, brain structure and connectivity, the behavioral and neural correlates of social and self-perception processes, and adolescent mental health in female adolescents. METHODS: The TAG study includes 174 female adolescents aged 10.0 to 13.0 years, recruited from the local community in Lane County, Oregon, USA. The participants, along with a parent/guardian, will complete three waves of assessment over the course of 3 years; the third wave is currently underway. Each wave includes collection of four saliva samples (one per week) and one hair sample for the assessment of hormone levels and immune factors; an MRI session including structural, diffusion, resting-state functional and task-based functional scans; the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), a diagnostic interview on current and lifetime mental health; production of a short self-narrative video; and measurement of height, weight, and waist circumference. The functional MRI tasks include a self-evaluation paradigm and a self-disclosure paradigm. In addition, adolescents and their parents/guardians complete a number of surveys to report on the adolescent's pubertal development, mental health, social environment and life events; adolescents also report on various indices of self-perception and social-emotional functioning. DISCUSSION: The knowledge gained from this study will include developmental trajectories of pubertal, neurological, and social processes and their roles as mechanisms in predicting emergence of mental illness in female adolescents. This knowledge will help identify modifiable, developmentally specific risk factors as targets for early intervention and prevention efforts.

Associations between adrenarcheal hormones, amygdala functional connectivity and anxiety symptoms in children.

OBJECTIVE: The transition from childhood to adolescence is a vulnerable period for the development of anxiety symptoms. There is some evidence that hormonal changes occurring during adrenarche, an early pubertal phase, might play a role in this increased vulnerability. Little is known about underlying brain mechanisms. Given the role of the amygdala-based fear circuit in anxiety, the current study aimed to investigate whether children's adrenarcheal hormone levels were associated with functional connectivity of the amygdala while processing fearful facial expressions, and how this in turn related to anxiety symptoms. METHOD: Participants were 83 children (M age 9.53 years) who completed two morning saliva collections to measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. They also completed the Spence Children's Anxiety Scale (SCAS), and viewed fearful and calm facial expressions while undergoing a functional MRI scan. Psychophysiological interaction (PPI) analyses were performed to examine amygdala connectivity and significant clusters were fed into a bootstrapping mediation model. RESULTS: In boys, mediation analyses showed an indirect positive effect of testosterone on anxiety symptoms, which was mediated by amygdala-secondary visual cortex connectivity as well as amygdala-anterior cingulate connectivity. In girls, DHEAS showed a negative indirect association with anxiety symptoms mediated by amygdala connectivity to the fusiform face area and insula. CONCLUSION: The results indicate unique roles for adrenarcheal hormones in anxiety and suggest that amygdala connectivity may represent an important neural mechanism in these associations. Importantly, results reveal prominent sex differences in the biological mechanisms associated with anxiety in children undergoing adrenarche.

Brain structural connectivity during adrenarche: Associations between hormone levels and white matter microstructure.

Levels of the adrenal hormones dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and testosterone, have all been linked to behavior and mental health during adrenarche, and preclinical studies suggest that these hormones influence brain development. However, little is known about how variation in these hormones is associated with white matter structure during this period of life. The current study aimed to examine associations between DHEA, DHEAS, and testosterone, and white matter microstructure during adrenarche. To avoid the confounding effect of age on hormone levels, we tested these associations in 87 children within a narrow age range (mean age 9.56 years, SD=0.34) but varying in hormone levels. All children provided saliva samples directly after waking and completed a diffusion-weighted MRI scan. Higher levels of DHEA were associated with higher mean diffusivity (MD) in a widespread cluster of white matter tracts, which was partially explained by higher radial diffusivity (RD) and partially by higher axial diffusivity (AD). In addition, there was an interaction between DHEA and testosterone, with higher levels of testosterone being associated with higher fractional anisotropy (FA) and lower MD and RD when DHEA levels were relatively high, but with lower FA and higher MD and RD when DHEA levels were low. These findings suggest that relatively early exposure to DHEA, as well as an imbalance between the adrenal hormones, may be associated with alterations in white matter microstructure. These findings highlight the potential relevance of adrenarcheal hormones for structural brain development.

Prefrontal-Amygdala Connectivity and State Anxiety during Fear Extinction Recall in Adolescents.

While deficits in fear extinction recall have been suggested to underlie vulnerability to anxiety disorders in adolescents, the neurobiology of these deficits remain underexplored. Here we investigate the functional connectivity (FC) of the ventromedial prefrontal cortex (vmPFC) and dorsolateral PFC (dlPFC) underlying extinction recall in healthy adolescents, and assess associations between FC and state/trait anxiety. Adolescents (17) and adults (14, for comparison) completed a fear-learning paradigm involving extinction and extinction recall during a functional magnetic resonance imaging session, in which skin conductance response (SCR) was recorded. Psychophysiological interaction analyses revealed that during extinction recall there was significant negative connectivity between the vmPFC and amygdala in adults, but not adolescents. vmPFC-amygdala connectivity was positively correlated with SCR. Adolescents showed significant negative FC between the dlPFC and the left and right hippocampus, and the amygdala, which was positively correlated with state anxiety. Recall was also associated with negative connectivity between the dlPFC and thalamus, posterior cingulate cortex, fusiform gyrus, and pallidum in adolescents. These results demonstrate that fear extinction recall in healthy adolescents is associated with FC between prefrontal and limbic brain regions, and suggest that alterations in connectivity may be associated with vulnerability to anxiety in adolescence.

Subtypes of trait impulsivity differentially correlate with neural responses to food choices.

Impulsivity is a personality trait that is linked to unhealthy eating and overweight. A few studies assessed how impulsivity relates to neural responses to anticipating and tasting food, but it is unknown how impulsivity relates to neural responses during food choice. Although impulsivity is a multi-faceted construct, it is unknown whether impulsivity subtypes have different underlying neural mechanisms. We investigated how impulsivity correlates with brain responses during food choice and in how far different impulsivity subtypes modulate brain responses during food choice differently. Twenty weight-concerned females performed an fMRI task in which they indicated for high and low energy snacks whether or not they wanted to eat them. Impulsivity subtypes were measured by the monetary delay discounting task and the Barratt Impulsiveness Scale (total BIS-11 and subscales). Only temporal subtypes of impulsivity, namely delay discounting and the BIS-11 non-planning subscale, modulated responses to food choice; both measures correlated positively with striatum activation during high versus low energy choices. However, only delay discounting predicted high energy choices, whereas BIS-11 non-planning independently related to a striatum region that reflects subjective stimulus value. To conclude, the brain mechanisms underlying subtypes of impulsivity have a common ground but differ in specific aspects of food-related decision-making. The findings advance our understanding of the neural correlates of different impulsivity subtypes in the food domain.