Examining putamen resting-state connectivity markers of suicide attempt history in depressed adolescents.

Introduction: Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt. Methods: We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (MAge [SD] = 16.4[0.3], 41% male) and 13 with AT (MAge [SD] = 16.2[0.3], 31% male). Results: Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise p<.001, cluster-wise p<.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted. Discussion: The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome.

Simple Incisionless Temporary Stabilization: An Adjunct to Lower Blepharoplasty.

Background: Lateral canthal tightening is indicated for patients undergoing lower eyelid blepharoplasty who have preexisting lower eyelid laxity or ectropion. A canthoplasty or canthopexy is indicated at the time of lower blepharoplasty to avoid postoperative complications, such as eyelid retraction or ectropion. Various surgical techniques are described to accomplish this goal, including canthopexy procedures, which usually access the lateral canthal tendon through an upper eyelid blepharoplasty or lateral canthal incision. Objectives: To describe an incisionless technique adjunctive to lower blepharoplasty, which stabilizes the lower eyelid in the week following blepharoplasty. Methods: This operative technique description and retrospective case series includes 15 patients who underwent a simple incisionless temporary stabilization (SITS) during lower eyelid blepharoplasty. The procedures were performed at the same outpatient office-based surgery center and were performed by the author surgeons. Patients were followed from 3 to 6 months postoperatively. Results: The SITS procedure during lower eyelid blepharoplasty successfully maintained a desirable functional and aesthetic eyelid position with minimal complications. One patient reported tearing postoperatively which was determined to be unrelated to the SITS and resolved by the 1-month follow-up visit. No patient had any other complications during the follow-up period. Conclusions: The SITS procedure was successfully utilized in patients with mild-to-moderate lower eyelid laxity and/or a negative vector to prevent postoperative ectropion and eyelid retraction. It is a more favorable alternative to temporary tarsorrhaphy, as it does not obstruct vision during healing and better secures the eyelid. It should not be used in patients with significant lower eyelid laxity that would place the patient at significant risk of ectropion and lower eyelid retraction related to swelling and inappropriate eyelid position during the early postoperative course.

Threat- and reward-related brain circuitry, perceived stress, and anxiety in adolescents during the COVID-19 pandemic: a longitudinal investigation.

The Coronavirus disease (COVID-19) pandemic led to heightened anxiety in adolescents. The basolateral amygdala (BLA) and the nucleus accumbens (NAcc) are implicated in response to stress and may contribute to anxiety. The role of threat- and reward-related circuitry in adolescent anxiety during the COVID-19 pandemic, however, is not clear. Ninety-nine adolescents underwent resting-state fMRI ∼1 year before the pandemic. Following shelter-in-place orders, adolescents reported their perceived stress and, 1 month later, their anxiety. Generalized multivariate analyses identified BLA and NAcc seed-based whole-brain functional connectivity maps with perceived stress. In the resulting significant clusters, we examined the association between seed-based connectivityand subsequent anxiety. Perceived stress was associated with bilateral BLA and NAcc connectivity across distributed clusters that included prefrontal, limbic, temporal, and cerebellar regions. Several NAcc connectivity clusters located in ventromedial prefrontal, parahippocampal, and temporal cortices were positively associated with anxiety; NAcc connectivity with the inferior frontal gyrus was negatively associated. BLA connectivity was not associated with anxiety. These results underscore the integrative role of the NAcc in responding to acute stressors and its relation to anxiety in adolescents. Elucidating the involvement of subcortical-cortical circuitry in adolescents' capacity to respond adaptively to environmental challenges can inform treatment for anxiety-related disorders.

Socioeconomic Disadvantage Moderates the Association of Systemic Inflammation With Amygdala Volume in Adolescents Over a 2-Year Interval: An Exploratory Study.

BACKGROUND: Research has demonstrated an association between elevated systemic inflammation and changes in brain function. Affective areas of the brain involved in processing threat (e.g., amygdala) and reward (e.g., nucleus accumbens) appear to be sensitive to inflammation. Early-life stress, such as experiencing low socioeconomic status (SES), may also potentiate this association, but relevant evidence has come primarily from cross-sectional studies of brain function. It is unclear whether similar associations are present between early-life stress, inflammation, and brain structure, particularly in typically developing populations. METHODS: We recruited and assessed 50 adolescents (31 females/19 males) from the community (mean [SD] age = 15.5 [1.1] years, range = 13.1-17.5 years) and examined in exploratory analyses whether changes in C-reactive protein (ΔCRP) from blood spots predict changes in gray matter volume (ΔGMV) in the bilateral amygdala and nucleus accumbens over a 2-year period. We also investigated whether experiencing early-life stress, operationalized using a comprehensive composite score of SES disadvantage at the family and neighborhood levels, significantly moderated the association between ΔCRP and ΔGMV. RESULTS: We found that ΔCRP was negatively associated with Δamygdala GMV (i.e., increasing CRP levels were associated with decreasing amygdala volume; ß = -0.84, p = .012). This effect was stronger in youths who experienced greater SES disadvantage (ß = -0.56, p = .025). CONCLUSIONS: These findings suggest that increases in systemic inflammation are associated with reductions in amygdala GMV in adolescents, potentially signaling accelerated maturation, and that these neuroimmune processes are compounded in adolescents who experienced greater SES disadvantage. Our findings are consistent with theoretical frameworks of neuroimmune associations and suggest that they may influence adolescent neurodevelopment.

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents.

Adolescent-onset depression is a prevalent and debilitating condition commonly associated with treatment refractory depression and non-response to first-line antidepressants. There are, however, no objective tests to determine who may or may not respond to antidepressants. As depressed adolescents are especially vulnerable to the lifelong consequences of ineffectively-treated depression, it is critical to identify neurobiological predictors of treatment non-response in this population. Here, we describe the scientific rationale and protocol for the Teen Inflammation Glutamate Emotion Research (TIGER) study, a prospective 18-month investigation of 160 depressed adolescents who will be assessed before and after treatment with selective serotonin reuptake inhibitors. TIGER will be using ultra-high field imaging to test the effects of acute stress and antidepressant treatment on inflammatory and glutamatergic processes hypothesized to underlie depression maintenance. Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression. ClinicalTrials.gov Identifier: NCT05329441.

Exploring sex differences in trajectories of pubertal development and mental health following early adversity.

Despite evidence that early life adversity (ELA) affects mental health in adolescence, we know little about sex differences in how distinct dimensions of adversity affect development and their corresponding effects on mental health. In this three-wave longitudinal study, 209 participants (118 females; ages 9-13 years at baseline) provided objective (salivary hormones, BMI, age of menarche) and subjective (perceived gonadal and adrenal status) measures of puberty and physical development, and reported on levels of internalizing and externalizing symptoms at all timepoints. Participants also reported lifetime exposure to three distinct types of ELA: deprivation, threat, and unpredictability. Using generalized additive mixed models, we tested within each sex whether dimensions of adversity were associated with longitudinal changes in measures of pubertal and physical development, and whether these indices of development were associated with trajectories of internalizing and externalizing symptoms. In females, experiences of threat and unpredictability were significantly associated with earlier pubertal timing (e.g., age of menarche) whereas experiences of deprivation were associated with steeper increases in BMI; further, faster pubertal tempo (i.e., steeper increases in pubertal stage) was associated with increases in internalizing and externalizing symptoms. In males, however, ELA was not associated with any measures of pubertal or physical development or with symptoms. Together, our results suggest that adverse experiences during early life have sex-selective consequences for pubertal and physical maturation and mental health trajectories in ways that may elucidate why females are at higher risk for mental health difficulties during puberty, particularly following exposure to unpredictable and threatening experiences of adversity.

Early life stress moderates the relation between systemic inflammation and neural activation to reward in adolescents both cross-sectionally and longitudinally.

Elevated levels of systemic inflammation are associated with altered reward-related brain function in ventral striatal areas of the brain like the nucleus accumbens (NAcc). In adolescents, cross-sectional research indicates that exposure to early life stress (ELS) can moderate the relation between inflammation and neural activation, which may contribute to atypical reward function; however, no studies have tested whether this moderation by ELS of neuroimmune associations persists over time. Here, we conducted a cross-sectional analysis and the first exploratory longitudinal analysis testing whether cumulative severity of ELS moderates the association of systemic inflammation with reward-related processing in the NAcc in adolescents (n = 104; 58F/46M; M[SD] age = 16.00[1.45] years; range = 13.07-19.86 years). For the cross-sectional analysis, we modeled a statistical interaction between ELS and levels of C-reactive protein (CRP) predicting NAcc activation during the anticipation and outcome phases of a monetary reward task. We found that higher CRP was associated with blunted NAcc activation during the outcome of reward in youth who experienced higher levels of ELS (ß = -0.31; p = 0.006). For the longitudinal analysis, we modeled an interaction between ELS and change in CRP predicting change in NAcc activation across 2 years. This analysis similarly showed that increasing CRP over time was associated with decreasing NAcc during reward outcomes in youth who experienced higher levels of ELS (ß = -0.47; p = 0.022). Both findings support contemporary theoretical frameworks involving associations among inflammation, reward-related brain function, and ELS exposure, and suggest that experiencing ELS can have significant and enduring effects on neuroimmune function and adolescent neurodevelopment.

Integrating Biobehavioral and Environmental Components of Developmental Psychopathology via Interpersonal Dynamics: An RDoC-Advancing Model.

Although the Research Diagnostic Criteria (RDoC) framework proposes biological and environmental mechanisms intersect in the etiology of psychopathology, there is no guidance on how to define or measure experiences in the environment within the RDoC matrix. Interpersonal dynamics during caregiver-child interactions involve temporal coordination of interacting partners' biobehavioral functioning; repeated experiences of signaling to caregivers and responding to caregivers' signals shape children's subsequent socioemotional and brain development. We begin with a review of the extant literature on caregiver-child dynamics, which reveals that RDoC's units of analysis (brain circuits, physiology, behavior, and self-report) are inextricably linked with moment-to-moment changes in the caregiving environment. We then offer a proof-of-concept for integrating biobehavioral RDoC units and environmental components via caregiver-child dynamics. Our approach uses dynamic structural equation models to estimate within-dyad dynamics involving arousal, social, cognitive, and negative or positive affective processes based on second-by-second changes in parasympathetic activity (RSA) during a conflict discussion and a positive event-planning task. Our results illustrate variation in parent-child RSA synchrony, suggesting differences depending on the driver (i.e., child- or parent-led) and on the unique and intersecting domains involved (e.g., positive or negative affect valence systems). We conclude with recommendations for conducting robust, methodologically rigorous studies of interpersonal dynamics that advance the RDoC framework and provide a summary of the clinical implications of this research. Examining caregiver-child dynamics during and across multiple dyadic interaction paradigms that differentially elicit key domains of functioning can deepen understanding of how caregiver- and child-led interpersonal dynamics contribute to child psychopathology risk.

Neighborhood Socioeconomic Disadvantage and White Matter Microstructure of the Arcuate Fasciculus and Uncinate Fasciculus in Adolescents.

Background: Neighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology. Methods: In 200 adolescents (ages 13-20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations. Results: Greater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (ß = -0.24, false discovery rate [FDR]-corrected p = .035) and right uncinate fasciculus (ß = -0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (ß = 0.17, FDR-corrected p = .026) and unemployment (ß = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts. Conclusions: Greater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.

Preparation and processing of dried blood spots for microRNA sequencing.

Dried blood spots (DBS) are biological samples commonly collected from newborns and in geographic areas distanced from laboratory settings for the purposes of disease testing and identification. MicroRNAs (miRNAs)-small non-coding RNAs that regulate gene activity at the post-transcriptional level-are emerging as critical markers and mediators of disease, including cancer, infectious diseases, and mental disorders. This protocol describes optimized procedural steps for utilizing DBS as a reliable source of biological material for obtaining peripheral miRNA expression profiles. We outline key practices, such as the method of DBS rehydration that maximizes RNA extraction yield, and the use of degenerate oligonucleotide adapters to mitigate ligase-dependent biases that are associated with small RNA sequencing. The standardization of miRNA readout from DBS offers numerous benefits: cost-effectiveness in sample collection and processing, enhanced reliability and consistency of miRNA profiling, and minimal invasiveness that facilitates repeated testing and retention of participants. The use of DBS-based miRNA sequencing is a promising method to investigate disease mechanisms and to advance personalized medicine.

Early life stress, sleep disturbances, and depressive symptoms during adolescence: The role of the cingulum bundle.

Adolescence is often characterized by sleep disturbances that can affect the development of white matter tracts implicated in affective and cognitive regulation, including the cingulate portion of the cingulum bundle (CGC) and the uncinate fasciculus (UF). These effects may be exacerbated in adolescents exposed to early life adversity (ELA). We examined the longitudinal relations between sleep problems and CGC and UF microstructure during adolescence and their relation to depressive symptoms as a function of exposure to ELA. We assessed self-reported sleep disturbances and depressive symptoms and acquired diffusion-weighted MRI scans twice: in early adolescence (9-13 years) and four years later (13-17 years) (N = 72 complete cases). Independent of ELA, higher initial levels and increases in sleep problems were related to increases in depressive symptoms. Further, increases in right CGC fractional anisotropy (FA) mediated the association between sleep problems and depressive symptoms for youth who experienced lower, but not higher, levels of ELA. In youth with higher ELA, higher initial levels of and steeper decreases in sleep problems were associated with greater decreases in right UF FA, but were unrelated to depressive symptoms. Our findings highlight the importance of sleep quality in shaping fronto-cingulate-limbic tract development and depressive symptoms during adolescence.

Subcortical Brain Alterations in Carriers of Genomic Copy Number Variants.

OBJECTIVE: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs. METHODS: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression. RESULTS: All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia. CONCLUSIONS: The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effects of puberty and sex on adolescent white matter development: A systematic review.

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to rising levels in adrenal and gonadal hormones. The extent to which pubertal hormones and related neuroendocrine processes explain sex differences in WM during this period is unclear. In this systematic review, we sought to examine whether there are consistent associations between hormonal changes and morphological and microstructural properties of WM across species and whether these effects are sex-specific. We identified 90 (75 human, 15 non-human) studies that met inclusion criteria for our analyses. While studies in human adolescents show notable heterogeneity, results broadly demonstrate that increases in gonadal hormones across pubertal development are associated with macro- and microstructural changes in WM tracts that are consistent with the sex differences found in non-human animals, particularly in the corpus callosum. We discuss limitations of the current state of the science and recommend important future directions for investigators in the field to consider in order to advance our understanding of the neuroscience of puberty and to promote forward and backward translation across model organisms.

Subcortical brain alterations in carriers of genomic copy number variants.

Objectives: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs) including autism (ASD) and schizophrenia (SZ). Overall, little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, we investigated gross volume, and vertex level thickness and surface maps of subcortical structures in 11 different CNVs and 6 different NPDs. Methods: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (at the following loci: 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2) and 782 controls (Male/Female: 727/730; age-range: 6-80 years) as well as ENIGMA summary-statistics for ASD, SZ, ADHD, Obsessive-Compulsive-Disorder, Bipolar-Disorder, and Major-Depression. Results: Nine of the 11 CNVs affected volume of at least one subcortical structure. The hippocampus and amygdala were affected by five CNVs. Effect sizes of CNVs on subcortical volume, thickness and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and SZ. Shape analyses were able to identify subregional alterations that were averaged out in volume analyses. We identified a common latent dimension - characterized by opposing effects on basal ganglia and limbic structures - across CNVs and across NPDs. Conclusion: Our findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions. We also observed distinct effects with some CNVs clustering with adult conditions while others clustered with ASD. This large cross-CNV and NPDs analysis provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD, as well as why a single CNV increases the risk for a diverse set of NPDs.

How Obstructed Action Efficacy Impacts Reward-Based Decision Making in Adolescent Depression: An fMRI Study.

OBJECTIVE: Disruption of reward seeking behavior by unforeseen obstacles can promote negative affect, including frustration and irritability, in adolescents. Repeated experiences of obstructed reward may in fact contribute to the development of depression in adolescents. However, the neurocognitive mechanisms whereby goal disruption impacts reward processing in adolescent depression have not yet been characterized. The present study addresses this gap by using neuroimaging and a novel paradigm to assess how incidental action obstruction impacts reward-based decision making. METHOD: We assessed 62 unmedicated adolescents with major depressive disorder (MDD; mean age = 15.6 years, SD = 1.4 years, 67% female participants) and 68 matched healthy control participants (mean age = 15.3 years, SD = 1.4 years, 50% female participants) using functional magnetic resonance imaging (fMRI) while they played a card game in which they had to guess between 2 options to earn points, in low- and high-stake conditions. Functioning of button presses through which they made decisions was intermittently blocked, thereby blocking action efficacy. RESULTS: Participants with MDD made fewer button press repetitions in response to action efficacy obstruction, which was more apparent in the low-stake condition (rate ratio =0.85, p = .034). During response repetition across stake conditions, MDDs exhibited higher activation in regions in the ventromedial prefrontal cortex, caudate, and putamen (F1,125 = 16.4-25.6, df=1,125; p values <.001; Hedges g = 0.85-0.98). CONCLUSION: Adolescents with depression tend to exhibit less flexible behavioral orientation in the face of blocked action efficacy, and abnormalities in neural systems critical to regulating negative affect during reward-based decision making. This research highlights possible mechanisms relevant to understanding and treating affective dysregulation in adolescent depression.

Lower eyelid margin reconstruction: results of five different techniques.

PURPOSE: This retrospective study was performed to examine surgical results of five different techniques for lower eyelid margin reconstruction after Mohs surgery: primary closure, semicircular flap, dermal matrix graft, sliding tarsal flap, and tarsoconjunctival flap. METHODS: Medical records were reviewed in 178 patients undergoing surgery between 2005 and 2020. Outcomes were evaluated (photographic review) by three oculoplastic observers masked to procedure type, both with and without knowledge of the eyelid defect. RESULTS: All patients achieved a good-excellent functional result and 90.4% were asymptomatic after surgery. Tarsoconjunctival flaps were associated with greater need for subsequent interventions (p < .001) and anterior lamellar deformities (p < .001). Semicircular flaps had a higher incidence of lateral canthal deformity (p < .001), but less eyelash disruption than other flap/graft techniques (p < .001). Mean cosmetic ratings (defect masked) were similar for dermal matrix grafts, semicircular, and sliding tarsal flaps; with each grading higher than tarsoconjunctival flaps (p ≤ .05). Among patients with 9-15 mm wide defects, results were better for semicircular and sliding tarsalflaps, than dermal matrix grafts (p ≤ .005) and tarsoconjunctival flaps (p ≤ .02). CONCLUSIONS: All patients achieved a good-excellent functional result and 87.1% a good-excellent cosmetic result. The semicircular flap was effective for repairing medium sized wounds that could not be closed primarily, creating a continuous lash line, although with a higher incidence of lateral canthal deformities. The sliding tarsal flap was effective for shallow wounds of varying widths. The single-staged dermal matrix graft provided similar results as the tarsoconjunctival flap. Subsequent interventions were more frequent after the tarsoconjunctival flap than other methods.

Disorders of the Angular Vein.

PURPOSE: The angular vein extends between the supraorbital and supratrochlear veins superiorly and the facial vein inferiorly. Rarely, this vessel can be involved by infections, vascular malformations, or benign tumors. In this study, we report both our experience and the published literature on angular vein disorders. METHODS: A retrospective study was performed on patients seen between 2008 and 2022. The medical literature was searched for reports of conditions affecting the angular vein. RESULTS: During the study period, we encountered 5 patients with angular vein disorders. Information from these patients was combined with 18 published cases. Among the 23 patients, the diagnosis was confused with lacrimal drainage abnormalities in 52%, and 57% underwent imaging. "Swelling" or a palpable, moveable mass were frequent findings. Pain or tenderness was experienced by 43.5% of patients. Five patients were observed, and 2 infections were treated with antibiotics. The remaining 16 lesions were successfully treated with excision (n = 15) or cauterization (n = 1), without complications. Final diagnosis included 14 vascular malformations (isolated varix: 7, thrombosis: 6, cavernous venous malformation: 1), 7 vascular tumors (intravenous pyogenic granulomas: 6, intravascular papillary endothelial hyperplasia: 1) and thrombophlebitis (n = 2). CONCLUSIONS: Disorders of the angular vein are uncommon and frequently misdiagnosed as lacrimal abnormalities. While these lesions can frequently be identified on clinical findings, imaging can be helpful in some cases. Patients with suspected thrombophlebitis require urgent antibiotic therapy. Minimally symptomatic angular vein lesions can be observed. Surgical excision is effective in treating the different vascular malformations and tumors affecting this structure.