Anxiety impacts the quality of everyday life and may facilitate the development of affective disorders, possibly through concurrent alterations in neural circuitry. Findings from multimodal neuroimaging studies suggest that trait-anxious individuals may have a reduced capacity for efficient communication between the amygdala and the ventral prefrontal cortex (vPFC). A diffusion-weighted imaging protocol with 61 directions was used to identify lateral and medial amygdala-vPFC white matter pathways. The structural integrity of both pathways was inversely correlated with self-reported levels of trait anxiety. When this mask from our first dataset was then applied to an independent validation dataset, both pathways again showed a consistent inverse relationship with trait anxiety. Importantly, a moderating effect of sex was found, demonstrating that the observed brain-anxiety relationship was stronger in females. These data reveal a potential neuroanatomical mediator of previously documented functional alterations in amygdala-prefrontal connectivity that is associated with trait anxiety, which might prove informative for future studies of psychopathology.

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. General Scientific SummaryEarly pubertal timing is a risk factor for the development of anxiety and depression in adolescence. The findings of this article show that this link depends on how pubertal timing is measured and that timing of early pubertal processes might be especially important for later risk of mental illness in adolescent girls. It suggests that psychosocial mechanisms, captured by timing measures of visible physical characteristics, might be more meaningful predictors of depression and anxiety than hormonal ones.

Oversensitivity to uncertain future threat is usefully conceptualized as intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely focused on its relationship with brain function, but few studies have documented the association between IU and the quantitative properties of brain structure. Here, we examined potential gray and white matter brain structural correlates of IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a robust positive correlation between IU and striatal volume, particularly the putamen. Conversely, tract-based spatial statistical analysis showed no evidence for a relationship between IU and the structural integrity of white matter fiber tracts. Current results converge upon findings from individuals with anxiety disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD), where abnormally increased IU and striatal volume are consistently reported. They also converge with neurobehavioral data implicating the putamen in predictive coding. Most notably, the relationship between IU and striatal volume is observed at a preclinical level, suggesting that the volumetric properties of the striatum reflect the processing of uncertainty per se as it relates to this dimensional personality characteristic – such a relationship could then potentially contribute to the onset of OCD or GAD, rather than being unique to their pathophysiology.

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 selfperception 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.