Impaired Caregiving, Trauma Exposure, and Psychosocial Functioning in a National Sample of Children and Adolescents.

Impairments in Caregiving (ICG) secondary to mental illness and substance use have been linked to adverse outcomes in children. Little is known, however, about whether outcomes vary by type of ICG, exposure to co-occurring traumas, or mechanisms of maladaptive outcomes. Clinic-referred youth age 7-18 years (n = 3988) were compared on ICG history, demographics, trauma history, and mental health symptoms. Child trauma exposure was tested as a mediator of ICG and child symptoms. Youth with ICG were at heightened risk for trauma exposure, PTSD, internalizing symptoms, total behavioral problems, and attachment problems, particularly youth with multiple types of ICG. Effect sizes were moderate to large for PTSD, internalizing symptoms, and total behavioral problems. Number of trauma types mediated the relationship between ICG and child symptoms. ICG was related to trauma exposure within and outside the family context. Understanding these links has important implications for interrupting intergenerational trauma and psychopathology.

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

A Stress-Induced Shift From Trace to Delay Conditioning Depends on the Mineralocorticoid Receptor.

BACKGROUND: Fear learning in stressful situations is highly adaptive for survival by steering behavior in subsequent situations, but fear learning can become disproportionate in vulnerable individuals. Despite the potential clinical significance, the mechanism by which stress modulates fear learning is poorly understood. Memory theories state that stress can cause a shift away from more controlled processing depending on the hippocampus toward more reflexive processing supported by the amygdala and striatum. This shift may be mediated by activation of the mineralocorticoid receptor (MR) for cortisol. We investigated how stress shifts processes underlying cognitively demanding learning versus less demanding fear learning using a combined trace and delay fear conditioning paradigm. METHODS: In a pharmacological functional magnetic resonance imaging study, we tested 101 healthy men probing the effects of stress (socially evaluated cold pressor vs. control procedure) and MR-availability (400 mg spironolactone vs. placebo) in a randomized, placebo-controlled, full-factorial, between-subjects design. RESULTS: Effective stress induction and successful conditioning were confirmed by subjective, physiologic, and somatic data. In line with a stress-induced shift, stress enhanced later recall of delay compared with trace conditioning in the MR-available groups as indexed by skin conductance responses. During learning, this was accompanied by a stress-induced reduction of learning-related hippocampal activity for trace conditioning. The stress-induced shift in fear and neural processing was absent in the MR-blocked groups. CONCLUSIONS: Our results are in line with a stress-induced shift in fear learning, mediated by the MR, resulting in a dominance of cognitively less demanding amygdala-based learning, which might be particularly prominent in individuals with high MR sensitivity.

Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum.

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol.

Cell-Type and State-Dependent Synchronization among Rodent Somatosensory, Visual, Perirhinal Cortex, and Hippocampus CA1.

Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1). S1BF spiking activity was strongly entrained by both beta and gamma S1BF oscillations, which were associated with deactivations and activations, respectively. We identified multiple classes of fast spiking and excitatory cells in S1BF, which showed prominent differences in rhythmic entrainment and in the extent to which phase locking was modulated by behavioral state. Using an additional dataset acquired by whole-cell recordings in head-fixed mice, these cell classes could be compared with identified phenotypes showing gamma rhythmicity in their membrane potential. We next examined how S1BF cells were entrained by rhythmic fluctuations in connected brain areas. Gamma-synchronization was detected in all four areas, however we did not detect significant gamma coherence among these areas. Instead, we only found long-range coherence in the theta-beta range among these areas. In contrast to local S1BF synchronization, we found long-range S1BF-spike to CA1-LFP synchronization to be homogeneous across inhibitory and excitatory cell types. These findings suggest distinct, cell-type contributions of low and high-frequency synchronization to intra- and inter-areal neuronal interactions.

Racial disparities in outcomes of spinal surgery for lumbar stenosis.

STUDY DESIGN: A retrospective, cross-sectional study. OBJECTIVE: To evaluate racial disparities in outcomes of lumbar stenosis surgery. SUMMARY OF BACKGROUND DATA: Racial inequalities have been described in the outcomes of cardiovascular and orthopedic procedures. There have been minimal investigation of racial disparities in complications and costs of lumbar laminectomies and fusions. METHODS: We analyzed the Medicaid data set of Thomson Reuter's MarketScan database. African-American and non-Hispanic white patients who underwent laminectomy or fusion for lumbar stenosis with at least 2 years postoperative data were included. We examined the effect of race on the rate of reoperations, complications, and the cost associated with surgery. RESULTS: African-American patients in the Medicaid database were at no higher risk for reoperation in the 2 years after an operation for lumbar stenosis than white patients (7.14% vs. 7.89%, P = 0.7895). However, we did find that African-American patients were more likely to experience postoperative complications of any kind, even after adjusting for length of hospital stay, comorbidities, sex, and age (adjusted odds ratio = 1.819, P = 0.0123 for immediate complication; adjusted odds ratio = 1.746, P = 0.0141 for 30-d complication; and adjusted odds ratio = 1.611, P = 0.0410 for 90-d complication). White patients had a significantly shorter length of stay (3 vs. 5 d, P < 0.007) and accrued fewer hospital-related costs ($16,148 vs. $24,267, P < 0.0007). African-American patients, despite having more comorbidities in our sample, were prescribed significantly fewer medications in the 2 years after index procedures (91 vs. 138 prescriptions, P < 0.0007) and had fewer medication costs during the 2 years after surgery ($5297 vs. $8450, P < 0.0007). CONCLUSION: At the national level, there are several racial disparities in the rate of complications, length of stay, and costs after surgery for lumbar spinal stenosis. LEVEL OF EVIDENCE: 3.

Comparison of calcaneus ultrasound and dual X-ray absorptiometry in children at risk of osteopenia.

The optimal method to assess pediatric bone mass remains controversial. Dual X-ray absorptiometry (DXA) is used most commonly for clinical assessments in children, but calcaneus ultrasound (CUS) is less costly, is free of ionizing radiation, and predicts fracture as well as DXA in adults. This study was designed to compare CUS and DXA in 42 young patients (ages 9-21) with chronic disease and/or fragility fractures. Zscores for broadband ultrasound attenuation (BUA) and speed of sound (SOS) determined using the Lunar Achilles Plus ultrasonometer were compared with Z-scores for areal bone mineral density (BMD) and volumetric BMD using DXA (Hologic). Logistic regression was employed to predict low bone density measured by DXA (defined as spinal BMD Z-score < -2) from CUS measurements. Sensitivity/specificity analysis was performed to compare CUS and spinal DXA Z-scores as predictors of previous low-impact fracture. Correlations between CUS and DXA Z-scores were in the range of r = 0.3-0.6. Areas under the receiver operator characteristic (ROC) curves for BUA and SOS predicting low bone density by DXA were similar: 0.81 and 0.82, respectively. ROC curve areas for spinal DXA, BUA, and SOS predicting previous fracture were also similar: 0.85, 0.84, and 0.84, respectively. While CUS correlates only modestly with DXA, ROC curve areas indicate that CUS detects low bone mineral in children with fragility fractures as well as DXA and may be a viable initial screen for osteopenia.

Ethnic differences in bone mass of young women vary with method of assessment.

To examine ethnic differences in bone mass measured by calcaneus ultrasound (CUS) and dual energy X-ray absorptiometry (DXA), and to compare the two methodologies, CUS was performed in 904 healthy Asian, African American, Latina, and Caucasian women 20-26 yr old using the Lunar Achilles Plus ultrasonometer. CUS measurements (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) were made following standard methodology (standard CUS) and repeated adjusting for foot size using shims (with-shim CUS). Areal bone mineral density (BMD) and estimated volumetric bone density (BMAD) at the spine, femoral neck, and whole body were determined using the Lunar DPX-IQ. African Americans had greater height- and weight-adjusted BUA than Caucasians, while Asians and African Americans had greater SOS than Caucasians and Latinas. Additionally, African Americans had greater height- and weight-adjusted BMD and BMAD than all other groups. CUS and DXA measurements correlated moderately (r = 0.2-0.5). With-shim CUS values were 0.9-7.8% lower than standard CUS values. In conclusion, African American women had greater DXA measurements than all others and greater CUS measurements than Caucasians. In contrast to DXA, CUS measurements in Asians and Latinas were not significantly lower than those in African Americans. Most notably, Asians had greater values for SOS than Caucasians and Latinas. Discrepancies in ethnic comparisons and modest correlations suggest that CUS and DXA methods may capture different bone qualities.