Subclinical post-traumatic stress symptomology and brain structure in youth with chronic headaches.

BACKGROUND/AIMS: Post-traumatic stress symptoms (PTSS) and chronic pain often co-occur at high rates in youth. PTSS may alter brain structure thereby contributing to headache chronicity. This study examined whether PTSS and altered limbic circuitry were associated with headache frequency in youth. METHODS: Thirty youth aged 10-18 years with chronic headaches and 30 age- and sex-matched controls underwent a 3T MRI scan. Volumes of the hippocampus and amygdala were obtained from T1-weighted images. Mean fractional anisotropy (FA, an index of white matter structure) axial and radial diffusivity values of the cingulum and uncinate fasciculus were extracted from diffusion-weighted images. Youth reported on their headaches daily, for one-month, and self-reported pubertal status, emotion regulation, adverse childhood experiences (ACEs) and PTSS using validated measures. Volumes of the hippocampus and amygdala and diffusivity values of the cingulum and uncinate were compared between patients and controls. Hierarchical linear regressions were used to examine the association between PTSS, subcortical volumes and/or diffusivity values and headache frequency. RESULTS: Mean FA values of the cingulum were higher in patients compared to controls (P = 0.02, Cohen's d = 0.69). Greater PTSS (P = 0.04), smaller amygdala volumes (P = 0.01) and lower FA of the cingulum (P = 0.04) were associated with greater headache frequency, after accounting for age, puberty, pain duration, emotion regulation, and ACEs (Adjusted R2 ≥ 0.15). Headache frequency was associated with increases in radial diffusivity (P = 0.002, Adjusted R2 = 0.59), as opposed to axial diffusivity (n.s.). CONCLUSIONS: PTSS, smaller amygdalar volume, and poorer cingulum structural connectivity were associated with headache frequency in youth, and may underlie headache chronicity.

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1-weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7-16 years. Twenty-one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE-), and 33 were age- and gender-matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent-Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico-limbic white matter tracts between groups, and to assess brain-mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE- group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE- group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.

Brain structure and internalizing and externalizing behavior in typically developing children and adolescents.

Mental health problems often emerge in adolescence and are associated with reduced gray matter thickness or volume in the prefrontal cortex (PFC) and limbic system and reduced fractional anisotropy (FA) and increased mean diffusivity (MD) of white matter linking these regions. However, few studies have investigated whether internalizing and externalizing behavior are associated with brain structure in children and adolescents without mental health disorders, which is important for understanding the progression of symptoms. 67 T1-weighted and diffusion tensor imaging datasets were obtained from 48 typically developing participants aged 6-16 years (37M/30F; 19 participants had two visits). Volume was calculated in the prefrontal and limbic structures, and diffusion parameters were assessed in limbic white matter. Linear mixed effects models were used to compute associations between brain structure and internalizing and externalizing behavior, assessed using the Behavioral Assessment System for Children (BASC-2) Parent Rating Scale. Internalizing behavior was positively associated with MD of the bilateral cingulum. Gender interactions were found in the cingulum, with stronger positive relationships between MD and internalizing behavior in females. Externalizing behavior was negatively associated with FA of the left cingulum, and the left uncinate fasciculus showed an age-behavior interaction. No relationships between behavior and brain volumes survived multiple comparison correction. These results show altered limbic white matter FA and MD related to sub-clinical internalizing and externalizing behavior and further our understanding of neurological markers that may underlie risk for future mental health disorders.

Characterizing adverse prenatal and postnatal experiences in children.

BACKGROUND: Prenatal and postnatal adversities, including prenatal alcohol exposure (PAE), prenatal exposure to other substances, toxic stress, lack of adequate resources, and postnatal abuse or neglect, often co-occur. These exposures can have cumulative effects, or interact with each other, leading to worse outcomes than single exposures. However, given their complexity and heterogeneity, exposures can be difficult to characterize. Clinical services and research often overlook additional exposures and attribute outcomes solely to one factor. METHODS: We propose a framework for characterizing adverse prenatal and postnatal exposures and apply it to a cohort of 77 children. Our approach considers type, timing, and frequency to quantify PAE, other prenatal substance exposure, prenatal toxic stress, postnatal threat (harm or threat of harm), and postnatal deprivation (failure to meet basic needs) using a 4-point Likert-type scale. Postnatal deprivation and harm were separated into early (<24 months of age) and late (≥24 months) time periods, giving seven exposure variables. Exposures were ascertained via health records, child welfare records, interviews with birth parents, caregivers, and/or close family/friends. RESULTS: Nearly all children had co-occurring prenatal exposures, and two-thirds had both prenatal and postnatal adversities. Children with high PAE were more likely to experience late postnatal adversities, and children with other prenatal substance exposure were more likely to have early postnatal deprivation. Postnatal adversities were more likely to co-occur. CONCLUSION: This framework provides a comprehensive picture of a child's adverse exposures, which can inform assessment and intervention approaches and policy and will be useful for future research.