Visuo-Cognitive Phenotypes in Early Multiple Sclerosis: A Multisystem Model of Visual Processing.

BACKGROUND: Cognitive impairment can emerge in the earliest stages of multiple sclerosis (MS), with heterogeneity in cognitive deficits often hindering symptom identification and management. Sensory-motor dysfunction, such as visual processing impairment, is also common in early disease and can impact neuropsychological task performance in MS. However, cognitive phenotype research in MS does not currently consider the relationship between early cognitive changes and visual processing impairment. OBJECTIVES: This study explored the relationship between cognition and visual processing in early MS by adopting a three-system model of afferent sensory, central cognitive and efferent ocular motor visual processing to identify distinct visuo-cognitive phenotypes. METHODS: Patients with clinically isolated syndrome and relapsing-remitting MS underwent neuro-ophthalmic, ocular motor and neuropsychological evaluation to assess each visual processing system. The factor structure of ocular motor variables was examined using exploratory factor analysis, and phenotypes were identified using latent profile analysis. RESULTS: Analyses revealed three ocular-motor constructs (cognitive control, cognitive processing speed and basic visual processing) and four visuo-cognitive phenotypes (early visual changes, efferent-cognitive, cognitive control and afferent-processing speed). While the efferent-cognitive phenotype was present in significantly older patients than was the early visual changes phenotype, there were no other demographic differences between phenotypes. The efferent-cognitive and cognitive control phenotypes had poorer performance on the Symbol Digit Modalities Test compared to that of other phenotypes; however, no other differences in performance were detected. CONCLUSION: Our findings suggest that distinct visual processing deficits in early MS may differentially impact cognition, which is not captured using standard neuropsychological evaluation. Further research may facilitate improved symptom identification and intervention in early disease.

The Hitchhiker's guide to longitudinal models: A primer on model selection for repeated-measures methods.

Longitudinal data are becoming increasingly available in developmental neuroimaging. To maximize the promise of this wealth of information on how biology, behavior, and cognition change over time, there is a need to incorporate broad and rigorous training in longitudinal methods into the repertoire of developmental neuroscientists. Fortunately, these models have an incredibly rich tradition in the broader developmental sciences that we can draw from. Here, we provide a primer on longitudinal models, written in a beginner-friendly (and slightly irreverent) manner, with a particular focus on selecting among different modeling frameworks (e.g., multilevel versus latent curve models) to build the theoretical model of development a researcher wishes to test. Our aims are three-fold: (1) lay out a heuristic framework for longitudinal model selection, (2) build a repository of references that ground each model in its tradition of methodological development and practical implementation with a focus on connecting researchers to resources outside traditional neuroimaging journals, and (3) provide practical resources in the form of a codebook companion demonstrating how to fit these models. These resources together aim to enhance training for the next generation of developmental neuroscientists by providing a solid foundation for future forays into advanced modeling applications.

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.

The Link Between Positive and Negative Parenting Behaviors and Child Inflammation: A Systematic Review.

Children's inflammation may be an important link between parenting behaviors and health outcomes. The aims of this systematic review were to: (1) describe associations between parenting behaviors and child inflammatory markers, and (2) evaluate the relevance of existing literature to the review question. Database searches identified 19 studies that included a measure of positive or negative parenting behaviors and a marker of child inflammation, 53% of which measured parental responsiveness/warmth. Greater parental responsiveness/warmth was associated with lower levels of child pro-inflammatory markers in 60% of studies. Across studies, the association between parenting and child inflammation varied as a function of parenting construct, inflammatory measure, and sample characteristics. Studies were highly relevant, with 42% rated 5 + out of 6 for study's ability to address links between parenting behavior and child inflammation. If future research uncovers causal effects of parenting behaviors on inflammation, parenting interventions could be employed as a preventative tool.

Insomnia is a key risk factor for persistent anxiety and depressive symptoms: A 12-month longitudinal cohort study during the COVID-19 pandemic.

BACKGROUND: Insomnia is a risk factor for affective disorders. This study examined whether individuals with insomnia symptoms early in the pandemic, either pre-existing or new-onset, were more vulnerable to anxiety and depressive symptoms over time than those who maintained normal sleep. Additionally, sleep-related factors such as pre-sleep arousal were assessed for their influence on clinically significant anxiety and depression risk. METHODS: Using a global online survey with 3-, 6-, and 12-month follow-ups between April 2020 and May 2021, data from 2069 participants (M = 46.16 ± 13.42 years; 75.3 % female) with pre-existing, new-onset, or no insomnia symptoms was examined using mixed-effects and logistic regression models. RESULTS: New-onset and pre-existing insomnia predicted persistent anxiety and depressive symptoms longitudinally (p's < 0.001), over other known risk factors, including age, sex, and previous psychiatric diagnoses. Anxiety and depressive symptoms in both insomnia groups remained above clinically significant thresholds at most time points, whereas normal sleepers remained subclinical. Pre-sleep arousal was found to increase the risk of clinically significant anxiety (OR = 1.05) and depressive symptoms (OR = 1.09) at 12-months. Sleep effort contributed to anxiety (OR = 1.06), whereas dysfunctional sleep-related beliefs and attitudes predicted clinically significant depression (OR = 1.22). LIMITATIONS: Insomnia group categorization was based on self-report at baseline supported by a validated measure. High participant attrition was observed at 3-months (53 %; n = 971), but retention remained steady till 12-months (63 %, n = 779). CONCLUSIONS: Insomnia is a modifiable risk factor for persistent anxiety and depressive symptoms that needs to be addressed in mental healthcare. Additionally, pre-sleep arousal may be an important transdiagnostic process linking insomnia with affective disorders.

Estradiol variability is associated with brain structure in early adolescent females.

One-third of adolescents are diagnosed with a psychiatric disorder by age 16, with female adolescents twice as likely to experience an internalizing (i.e., depression or anxiety) disorder as their male peers. Individual differences in pubertal factors may partially underlie this disparity, potentially via the role of pubertal hormones in shaping brain development. While research has examined links between estradiol levels and brain structure, individual variation in estradiol levels has not been considered. Using longitudinal data from 44 female adolescents (baseline age M = 11.7; follow-up age M= 13.3), we examined associations between both average estradiol and estradiol variability, and brain gray matter structure at baseline. We used a hypothesis-driven region of interest (ROI) approach focusing on subcortical and ventromedial prefrontal regions, in addition to an exploratory whole-brain analysis. We also investigated whether brain structure mediated the association between estradiol measures and internalizing (i.e., anxious and depressive) symptoms at follow-up. ROI analyses revealed a significant negative association between estradiol variability and thickness of the right medial orbitofrontal cortex (OFC, ß = -0.39, FDR corrected p = .010). There were, however, no significant associations between average estradiol or estradiol variability and internalizing symptoms, nor was there evidence of mediation. Our results indicate that increased variation in estradiol levels across a month is associated with decreased cortical thickness in a brain region implicated in emotion processing, although implications for mental health are unclear. Findings, however, highlight the importance of considering individual variation in estradiol when examining links to brain development.

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).

Using mobile sensing data to assess stress: Associations with perceived and lifetime stress, mental health, sleep, and inflammation.

BACKGROUND: Although stress is a risk factor for mental and physical health problems, it can be difficult to assess, especially on a continual, non-invasive basis. Mobile sensing data, which are continuously collected from naturalistic smartphone use, may estimate exposure to acute and chronic stressors that have health-damaging effects. This initial validation study validated a mobile-sensing collection tool against assessments of perceived and lifetime stress, mental health, sleep duration, and inflammation. METHODS: Participants were 25 well-characterized healthy young adults (M age = 20.64 years, SD = 2.74; 13 men, 12 women). We collected affective text language use with a custom smartphone keyboard. We assessed participants' perceived and lifetime stress, depression and anxiety levels, sleep duration, and basal inflammatory activity (i.e. salivary C-reactive protein and interleukin-1ß). RESULTS: Three measures of affective language (i.e. total positive words, total negative words, and total affective words) were strongly associated with lifetime stress exposure, and total negative words typed was related to fewer hours slept (all large effect sizes: r = 0.50 - 0.78). Total positive words, total negative words, and total affective words typed were also associated with higher perceived stress and lower salivary C-reactive protein levels (medium effect sizes; r = 0.22 - 0.32). CONCLUSIONS: Data from this initial longitudinal validation study suggest that total and affective text use may be useful mobile sensing measures insofar as they are associated with several other stress, mental health, behavioral, and biological outcomes. This tool may thus help identify individuals at increased risk for stress-related health problems.

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.

Maternal parenting behavior and functional connectivity development in children: A longitudinal fMRI study.

Parenting behavior is associated with internalizing symptoms in children, and cross-sectional research suggests that this association may be mediated by the influence of parenting on the development of frontoamygdala circuitry. However, longitudinal studies are lacking. Moreover, there is a paucity of studies that have investigated parenting and large-scale networks implicated in affective functioning. In this longitudinal study, data from 95 (52 female) children and their mothers were included. Children underwent magnetic resonance imaging that included a 6 min resting state sequence at wave 1 (mean age = 8.4 years) and wave 2 (mean age = 9.9 years). At wave 1, observational measures of positive and negative maternal behavior were collected during mother-child interactions. Region-of-interest analysis of the amygdala, and independent component and dual-regression analyses of the Default Mode Network (DMN), Executive Control Network (ECN) and the Salience Network (SN) were carried out. We identified developmental effects as a function of parenting: positive parenting was associated with decreased coactivation of the superior parietal lobule with the ECN at wave 2 compared to wave 1. Thus our findings provide preliminary longitudinal evidence that positive maternal behavior is associated with maturation of the connectivity between higher-order control networks.

Temperament and Symptom Pathways to the Development of Adolescent Depression.

This study examined the associations between internalizing and externalizing symptoms during early adolescence and the subsequent development of Major Depressive Disorder. The role that temperament plays in predisposing individuals to these particular pathways was also examined. Temperament at approximately age 12 was used to produce a risk-enriched subsample of 243 (124 female) participants. Data was collected in four waves over 6-7 years roughly corresponding to ages 13, 15, 17 and 19. Participants were excluded from the study, prior to the first wave, based on current or prior depressive, substance-use, or eating disorders. Logistic regression analyses revealed that internalizing symptoms and social-externalizing problems were significant risk pathways to the development of depression. Moreover, mediation analyses revealed that high temperamental negative emotionality, high affiliation, low effortful control, and low surgency were significant vulnerability factors for depression via the internalizing symptom pathway, whereas low effortful control was the only significant predictor for depression via the social-externalizing problem pathway. As such, high levels of effortful control acted as a protective factor for the development of depression across both symptom pathways, suggesting that is may be an important target for prevention strategies.

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.

Factor Structure of the Early Adolescent Temperament Questionnaire-Revised.

Early adolescence (typically aged 9-15 years) is a period of dramatic developmental change, and individual differences in temperament is likely to be an important predictor of the success with which individuals negotiate this period of life. Moreover, early adolescent temperament cannot be adequately captured by measures designed for other age groups. This study examined the empirical validity of the proposed temperament factors of the Early Adolescent Temperament Questionnaire-Revised (EATQ-R) in a large representative sample of 2,453 early adolescents aged between 10 and 12 years of age, and compared it with models that include cross-loadings between items and first-order factors, as well as first- and second-order factors. Furthermore, the reproducibility of the factor structure established by using a cross validation approach. Adding cross-loadings to the EATQ-R fit the data substantially better, resulting in an overall good fit that the original EATQ-R model did not achieve. However, the conceptual interpretation of the first- and second-order factor structures were not substantially altered even with this addition of cross-loadings. Future research should establish the construct validity of the first- and second-order factors as measured by this empirically based factor structure.

Neurodevelopmental Trajectories Related to Attention Problems Predict Driving-Related Risk Behaviors.

Objective: Investigate neurodevelopmental trajectories related to attention/hyperactivity problems (AP) in a community sample of adolescents and whether these trajectories predict later-emerging health risk behaviors. Method: One hundred sixty-six participants underwent up to three magnetic resonance imaging (MRI) scans (n = 367) between 11 and 20 years of age. AP were measured during early adolescence using the Child Behaviour Checklist, and engagement in risk behaviors was measured during late adolescence using the "DRIVE" survey (i.e., driving risks) and items assessing alcohol-harms. Results: Greater AP scores during early adolescence were related to less reduction over time of left dorsal prefrontal, left ventrolateral prefrontal, and right orbitofrontal thickness. Less thinning of the orbitofrontal cortex was related to greater driving-related risk behaviors at late adolescence. Conclusion: Findings highlight altered neurodevelopmental trajectories in adolescents with AP. Furthermore, altered orbitofrontal development was related to later-emerging driving-related risk, and this neurobiological change mediated the association between attention problems and risk behaviors.

Early adolescent drinking and cannabis use predicts later sleep-quality problems.

A range of biopsychosocial changes occur during adolescence that contribute to changes in the sleep-wake system. Use of alcohol and cannabis also increases during early adolescence; however, limited studies have examined the associations between changes in the use of alcohol and cannabis and later sleep problems. Participants (n = 245) aged 12 years were recruited from schools and completed a baseline assessment, which included questions about their alcohol and cannabis use. Three subsequent follow-up assessments took place approximately 2.5 years (age 14 years), 4 years (age 16 years), and 6 years (age 18 years) after baseline, with sleep quality assessed at age 18 years. Earlier drug use was associated with poorer sleep quality at age 18 years, with different facets of alcohol and cannabis important in these associations. For alcohol, heavy episodic drinking across time was associated with poorer sleep; lifetime use at age 18 years (but not prior) was also associated with poorer sleep. For cannabis, recent use at age 18 years was associated with poor sleep quality. Our findings suggest that there are associations between specific facets of alcohol and cannabis use that are related to poor sleep in adolescents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).