Characterization of the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) in Lung Transplant Candidates.

The SIPAT is a standardized measure for pre-transplant psychosocial evaluation. Previous SIPAT studies utilized a relatively small lung transplant sample and only included listed patients. This study characterized the SIPAT in 147 lung transplant candidates to better elucidate its utility. The average score corresponded to a minimally acceptable rating and nearly half of the patients had relative or absolute contraindications. Interstitial Lung Disease (ILD) patients scored more favorably than non-ILD patients (U = 7.69, p < .05). The Total (ß = - .05, SE = .018, p < .01), Social Support Subscale (ß = - .133, SE = .058, p < .05), and Psychosocial Stability and Psychopathology Subscale (ß = - .103, SE = .040, p < .05) significantly predicted listing status. The SIPAT has a unique profile in lung transplant candidates and demonstrated utility for guiding transplant decisions. Future research should examine which lung transplant outcomes are significantly associated with SIPAT scores.

Dispositional Negative Emotionality in Childhood and Adolescence Predicts Structural Variation in the Amygdala and Caudal Anterior Cingulate During Early Adulthood: Theoretically and Empirically Based Tests.

Substantial evidence implicates the amygdala and related structures in the processing of negative emotions. Furthermore, neuroimaging evidence suggests that variations in amygdala volumes are related to trait-like individual differences in neuroticism/negative emotionality, although many questions remain about the nature of such associations. We conducted planned tests of the directional prediction that dispositional negative emotionality measured at 10-17 years using parent and youth ratings on the Child and Adolescent Dispositions Scale (CADS) would predict larger volumes of the amygdala in adulthood and conducted exploratory tests of associations with other regions implicated in emotion processing. Participants were 433 twins strategically selected for neuroimaging during wave 2 from wave 1 of the Tennessee Twins Study (TTS) by oversampling on internalizing and/or externalizing psychopathology risk. Controlling for age, sex, race-ethnicity, handedness, scanner, and total brain volume, youth-rated negative emotionality positively predicted bilateral amygdala volumes after correction for multiple testing. Each unit difference of one standard deviation (SD) in negative emotionality was associated with a .12 SD unit difference in larger volumes of both amygdalae. Parent-rated negative emotionality predicted greater thickness of the left caudal/dorsal anterior cingulate cortex (ß = 0.28). Associations of brain structure with negative emotionality were not moderated by sex. These results are striking because dispositions assessed at 10-17 years of age were predictive of grey matter volumes measured 12-13 years later in adulthood. Future longitudinal studies should examine the timing of amygdala/cingulate associations with dispositional negative emotionality to determine when these associations emerge during development.

COVID-19 highlights the pitfalls of reliance on the carceral system as a response to addiction.

People who are incarcerated are likely to meet criteria for at least one substance use disorder and need access to treatment. Access to such interventions was limited prior to the COVID-19 pandemic and has almost certainly been restricted further due to implementation of procedures intended to stop the spread of the virus. In this brief commentary, we discuss how COVID-19 has revealed the already tenuous access that people who are incarcerated have to behavioral health services, and the pitfalls of reliance on the U.S. carceral system as a response to addiction.

Sex differences in associations of socioemotional dispositions measured in childhood and adolescence with brain white matter microstructure 12 years later.

Predictive associations were estimated between socioemotional dispositions measured at 10-17 years using the Child and Adolescent Dispositions Scale (CADS) and future individual differences in white matter microstructure measured at 22-31 years of age. Participants were 410 twins (48.3% monozygotic) selected for later neuroimaging by oversampling on risk for psychopathology from a representative sample of child and adolescent twins. Controlling for demographic covariates and total intracranial volume (TICV), each CADS disposition (negative emotionality, prosociality, and daring) rated by one of the informants (parent or youth) significantly predicted global fractional anisotropy (FA) averaged across the major white matter tracts in brain in adulthood, but did so through significant interactions with sex after false discovery rate (FDR) correction. In females, each 1 SD difference in greater parent-rated prosociality was associated with 0.43 SD greater FA (p < 0.0008). In males, each 1 SD difference in greater parent-rated daring was associated with 0.24 SD lower FA (p < 0.0008), and each 1 SD difference in greater youth-rated negative emotionality was associated with 0.18 SD greater average FA (p < 0.0040). These findings suggest that CADS dispositions are associated with FA, but associations differ by sex. Exploratory analyses suggest that FA may mediate the associations between dispositions and psychopathology in some cases. These associations over 12 years could reflect enduring brain-behavior associations in spite of transactions with the environment, but could equally reflect processes in which dispositional differences in behavior influence the development of white matter. Future longitudinal studies are needed to resolve the causal nature of these sex-moderated associations.

White matter microstructure correlates of general and specific second-order factors of psychopathology.

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories, ignoring the highly correlated nature of psychopathology. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of mental disorders, nearly all such studies used case-control designs, leaving it unclear whether observed relations reflect disorder-specific characteristics or transdiagnostic associations. Using a representative sample of 410 young adult twins oversampled for psychopathology risk, we tested the hypothesis that some previously observed relations between white matter microstructure properties in major tracts and specific disorders are related to second-order factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple statistical tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that some features of white matter within specific tracts may be transdiagnostically associated multiple forms of psychopathology through second-order factors of psychopathology rather with than individual mental disorders.

Right Fronto-Subcortical White Matter Microstructure Predicts Cognitive Control Ability on the Go/No-go Task in a Community Sample.

Go/no-go tasks are widely used to index cognitive control. This construct has been linked to white matter microstructure in a circuit connecting the right inferior frontal gyrus (IFG), subthalamic nucleus (STN), and pre-supplementary motor area. However, the specificity of this association has not been tested. A general factor of white matter has been identified that is related to processing speed. Given the strong processing speed component in successful performance on the go/no-go task, this general factor could contribute to task performance, but the general factor has often not been accounted for in past studies of cognitive control. Further, studies on cognitive control have generally employed small unrepresentative case-control designs. The present study examined the relationship between go/no-go performance and white matter microstructure in a large community sample of 378 subjects that included participants with a range of both clinical and subclinical nonpsychotic psychopathology. We found that white matter microstructure properties in the right IFG-STN tract significantly predicted task performance, and remained significant after controlling for dimensional psychopathology. The general factor of white matter only reached statistical significance when controlling for dimensional psychopathology. Although the IFG-STN and general factor tracts were highly correlated, when both were included in the model, only the IFG-STN remained a significant predictor of performance. Overall, these findings suggest that while a general factor of white matter can be identified in a young community sample, white matter microstructure properties in the right IFG-STN tract show a specific relationship to cognitive control. The findings highlight the importance of examining both specific and general correlates of cognition, especially in tasks with a speeded component.

Convergent individual differences in visual cortices, but not the amygdala across standard amygdalar fMRI probe tasks.

The amygdala (AMG) has been repeatedly implicated in the processing of threatening and negatively valenced stimuli and multiple fMRI paradigms have reported personality, genetic, and psychopathological associations with individual differences in AMG activation in these paradigms. Yet the interchangeability of activations in these probes has not been established, thus it remains unclear if we can interpret AMG responses on specific tasks as general markers of its reactivity. In this study we aimed to assess if different tasks that have been widely used within the Affective Neuroscience literature consistently recruit the AMG. METHOD: Thirty-two young healthy subjects completed four fMRI tasks that have all been previously shown to probe the AMG during processing of threatening stimuli: the Threat Face Matching (TFM), the Cued Aversive Picture (CAP), the Aversive and Erotica Pictures (AEP) and the Screaming Lady paradigm (SLp) tasks. Contrasts testing response to aversive stimuli relative to baseline or neutral stimuli were generated and correlations between activations in the AMG were calculated across tasks were performed for ROIs of the AMG. RESULTS: The TFM, CAP and AEP, but not the SLp, successfully recruit the AMG, among other brain regions, especially when contrasts were against baseline or nonsocial stimuli. Conjunction analysis across contrasts showed that visual cortices (VisCtx) were also consistently recruited. Correlation analysis between the extracted data for right and left AMG did not yield significant associations across tasks. By contrast, the extracted signal in VisCtx showed significant associations across tasks (range r=0.511-r=0.630). CONCLUSIONS: Three of the four paradigms revealed significant AMG reactivity, but individual differences in the magnitudes of AMG reactivity were not correlated across paradigms. By contrast, VisCtx activation appears to be a better candidate than the AMG as a measure of individual differences with convergent validity across negative emotion processing paradigms.

Evaluation of Atlas-Based White Matter Segmentation with Eve.

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

A prospective study of severe irritability in youths: 2- and 4-year follow-up.

BACKGROUND: Severe, chronic irritability is receiving increased research attention, and is the cardinal symptom of a new diagnostic category, disruptive mood dysregulation disorder (DMDD). Although data from epidemiological community samples suggest that childhood chronic irritability predicts unipolar depression and anxiety in adulthood, whether these symptoms are stable and cause ongoing clinical impairment is unknown. The present study presents 4-year prospective and longitudinal diagnostic and impairment data on a clinical sample of children selected for symptoms of severe irritability (operationalized as severe mood dysregulation [SMD]). METHODS: Youth meeting criteria for SMD (n = 200) were evaluated at baseline using standard diagnostic methods. Two-year (n = 78) and 4-year (n = 46) follow-up diagnostic and clinical impairment ratings collected at 6-month intervals were completed with those youths enrolled in the study for a sufficient time. RESULTS: Although the number of youth meeting strict categorical SMD criteria declined over time (49 and 40% at 2 and 4 years, respectively), many individuals not meeting full criteria continued to display clinically significant irritability symptoms (2 years: 42%; 4 years: 37%). Impairment due to these irritability symptoms remained consistently in the moderate range on the Clinical Global Impressions Scale. CONCLUSIONS: By the 4-year follow-up, only 40% of youths meet strict SMD criteria; however, most continue to display clinically impairing symptoms and significant impairment warranting psychiatric treatment. These findings provide evidence for the course of irritability, with implications for DMDD. Future research with populations meeting DMDD criteria and followed through the ages of high risk for psychiatric diagnoses is necessary.

Parametric modulation of neural activity during face emotion processing in unaffected youth at familial risk for bipolar disorder.

OBJECTIVES: Both patients with pediatric bipolar disorder (BD) and unaffected youth at familial risk (AR) for the illness show impairments in face emotion labeling. Few studies, however, have examined brain regions engaged in AR youth when processing emotional faces. Moreover, studies have yet to explore neural responsiveness to subtle changes in face emotion in AR youth. METHODS: Sixty-four unrelated youth, including 20 patients with BD, 15 unaffected AR youth, and 29 healthy comparisons (HC), completed functional magnetic resonance imaging. Neutral faces were morphed with angry or happy faces in 25% intervals. In specific phases of the task, youth alternatively made explicit (hostility) or implicit (nose width) ratings of the faces. The slope of blood oxygenated level-dependent activity was calculated across neutral to angry and neutral to happy face stimuli. RESULTS: Behaviorally, both subjects with BD (p ≤ 0.001) and AR youth (p ≤ 0.05) rated faces as less hostile relative to HC. Consistent with this, in response to increasing anger on the face, patients with BD and AR youth showed decreased modulation in the amygdala and inferior frontal gyrus (IFG; BA 46) compared to HC (all p ≤ 0.05). Amygdala dysfunction was present across both implicit and explicit rating conditions, but IFG modulation deficits were specific to the explicit condition. With increasing happiness, AR youth showed aberrant modulation in the IFG, which was also sensitive to task demands (all p ≤ 0.05). CONCLUSIONS: Decreased amygdala and IFG modulation in patients with BD and AR youth may be pathophysiological risk markers for BD, and may underlie the social cognition and face emotion labeling deficits observed in BD and AR youth.

Neural response during explicit and implicit face processing varies developmentally in bipolar disorder.

Both children and adults with bipolar disorder (BD) exhibit face emotion labeling deficits and neural circuitry dysfunction in response to emotional faces. However, few studies have compared these groups directly to distinguish effects of age and diagnosis. Such studies are important to begin to elucidate the developmental trajectory of BD and facilitate its diagnosis, prevention and treatment. This functional magnetic resonance imaging study compares 41 individuals with BD (19 children; 22 adults) and 44 age-matched healthy individuals (25 children; 19 adults) when making explicit or implicit judgments about angry or happy face morphs across a range of emotion intensity. Linear trend analyses revealed that BD patients, irrespective of age, failed to recruit the amygdala in response to increasing angry face. This finding was no longer significant when the group was restricted to euthymic youth or those without comorbid attention deficit hyperactivity disorder although this may reflect low statistical power. Deficits in subgenual anterior cingulate modulation were observed in both patient groups but were related to implicit processing for child patients and explicit processing for adult patients. Abnormalities in face emotion labeling and the circuitry mediating it may be biomarkers of BD that are present across development.

Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder.

A major controversy in child psychiatry is whether bipolar disorder (BD) presents in children as severe, non-episodic irritability (operationalized here as severe mood dysregulation, SMD), rather than with manic episodes as in adults. Both classic, episodic BD and SMD are severe mood disorders characterized by deficits in processing emotional stimuli. Neuroimaging techniques can be used to test whether the pathophysiology mediating these deficits are similar across the two phenotypes. Amygdala dysfunction during face emotion processing is well-documented in BD, but little is known about amygdala dysfunction in chronically irritable youth. We compared neural activation in SMD (n=19), BD (n=19), and healthy volunteer (HV; n=15) youths during an implicit face-emotion processing task with angry, fearful and neutral expressions. In the right amygdala, both SMD and BD exhibited greater activity across all expressions than HV. However, SMD and BD differed from each other and HV in posterior cingulate cortex, posterior insula, and inferior parietal lobe. In these regions, only SMD showed deactivation in response to fearful expressions, whereas only BD showed deactivation in response to angry expressions. Thus, during implicit face emotion processing, youth with BD and those with SMD exhibit similar amygdala dysfunction but different abnormalities in regions involved in information monitoring and integration.