Kathryn Regan Cullen

College students experience many unique stressors that can negatively impact their emotional health and well-being. In addition to the burden of academic expectations and responsibilities, students...

Adolescence is a life period marked by increased emotionality and, for some, volatile friendships and emotion dysregulation. Yet little research has examined peer processes in relation to adolescent emotion dysregulation from a dynamic perspective. This three‐wave longitudinal study examined two peer‐related processes—loneliness and friend support—in association with emotion dysregulation with data collected during the COVID‐19 pandemic. Further, we examined if these associations differed in those who had histories of non‐suicidal self‐injury (NSSI), a behavior known to be associated with emotion dysregulation. The sample included U.S. adolescents assigned female at birth ( N = 91; M _age = 15.93) who were oversampled for a history of NSSI (62%). Results from multilevel regression models indicated that loneliness and emotion dysregulation were positively associated, both on average across timepoints (between‐person) and in terms of deviations from adolescents’ average levels of loneliness at each timepoint (within‐person). At the within‐person level, friend support and emotion dysregulation were negatively associated. At the between‐person level, higher average levels of friend support were only associated with less emotion dysregulation in adolescents with no history of NSSI. When both processes were included in the model, loneliness remained significantly associated with emotion dysregulation. Results indicate that feeling lonely is strongly related to emotion dysregulation in adolescent females. The lack of negative association between emotion dysregulation and support from friends in adolescents with NSSI underscores the need for additional clinical attention for this group of youth to better understand interpersonal risk and protective processes.

The clinical and biological heterogeneity of major depressive disorder (MDD) may reflect the aggregation of different conditions with distinct pathologies under a single diagnostic label. Neuroanatomical heterogeneity in MDD was examined using a harmonized, age- and sex-matched sample from the ENIGMA MDD consortium (N = 5146; age range: 9–82 years; 64% female). Analyses of global neurostrucutral variability revealed greater cortical thickness heterogeneity in MDD compared with healthy controls (Cohen’s d = –0.26). Regionally, increased variability in cortical thickness was most prominent in the cingulate (+6.1 to +6.6% more variation in MDD) and insular (+5.8%) cortices, as well as in the frontal (+5.7 to +6.8%) and temporal (+6.1 to +6.8%) lobes. Heterogeneity in cortical thickness was more pronounced among patients using antidepressant medication (Cohen’s d = –0.39). Patient-specific analyses further showed that individuals with markedly increased cortical thickness variability (th percentile relative to the normative range) exhibited greater depressive symptom severity than those within the normative range (5 ^th –95 ^th percentile; Cohen’s d = 0.19–0.36). Overall, the results indicate that neuroanatomical heterogeneity in MDD is primarily expressed in cortical thickness, offering refined insights into the neurobiological complexity of structural alterations associated with depression. These findings could guide future stratification efforts examining whether regionally confined changes in cortical thickness within areas of pronounced variability reflect clinically meaningful patient subgroups.

Non-suicidal self-injury (NSSI) typically begins in adolescence and is associated with higher impulsivity and compromised white matter microstructure in the brain. Identifying early predictors of NSSI is a high priority. We used data from the Adolescent Brain Cognitive Development Study to examine whether baseline white matter, specifically generalized fractional anisotropy (GFA), and different facets of impulsivity were prospectively associated with NSSI onset two years later (Y ₂ ). We also examined interactions with sex. We identified 209 youth aged 8–11 years who reported NSSI at Y ₂ , but not at baseline (incident NSSI; iNSSI) and 209 controls matched by demographic and clinical characteristics. We conducted a Least Absolute Shrinkage and Selection Operator (LASSO) regularization, which yielded an AUC of .60, to narrow down predictors for logistic regression. Significant main effects indicated that lower GFA of the left parolfactory section of the cingulum (OR = 0.63) and higher negative urgency (OR = 1.54) were prospectively associated with Y ₂ NSSI. Sex interactions indicated that the relations between Y ₂ NSSI and lower GFA of the left parolfactory section of the cingulum (OR = 1.75) and higher negative urgency (OR = 0.60) were driven by males. Higher sensation seeking (OR = 1.36) and lack of perseverance (OR = 1.46) were more strongly associated with Y ₂ NSSI among females than males. Future work is needed to better understand the course of development of white matter microstructure and impulsivity as it relates to NSSI.

Summary: The BJPsych Open thematic series is devoted to recent advances in the study of non-suicidal self-injury (NSSI) in youth. Together, this body of work reveals new insights that, if replicated, could be translated into clinical practice, enhancing our abilities to understand and treat young people presenting with NSSI.

Fatigue is a pervasive and difficult-to-treat symptom of major depressive disorder (MDD) that contributes to disability. Understanding this problem in its earlier stages will be critical for averting long-term negative outcomes. To investigate the molecular roots of fatigue in early-stage depression, the current work measured bioenergetic mechanisms, with a focus on adenosine triphosphate (ATP), in brain and blood cells in young adults with MDD versus healthy controls (HC). To measure ATP concentration and ATP production rate in the visual cortex, we utilized ³¹P magnetic resonance spectroscopy imaging with magnetization transfer (³¹P MRSI-MT) at 7 Tesla, with and without gamma-ATP resonance saturation. ATP level was also measured in peripheral blood mononuclear cells (PBMCs) at rest and after serial addition of mitochondrial inhibitors. Out of 25 participants (mean age 21.8 years), usable data were available for 18 participants for imaging (9 per group); 24 for PBMCs (13 HC; 11 MDD). The MDD group demonstrated higher ATP production rate in the visual cortex than HC, which correlated positively with Fatigue Severity Scale (FSS) scores. ATP concentrations in PBMCs were higher in MDD than HC, and also correlated with FSS scores. After mitochondrial uncoupling, PBMCs in the MDD group had a lower capacity for ATP production than HC. For the first time, we demonstrate an ATP biosignature of fatigue in young adults with MDD that is visible in both brain and peripheral blood. The findings suggest a compensatory mechanism that occurs early in the disease stage.

There is an urgent need to advance understanding of the neural underpinnings of depression, especially early in the life span. Examination of neural dynamics using resting-state functional magnetic resonance imaging (fMRI) data can provide indices of neural flexibility, which may provide important new insights for the neurobiology of pediatric depression. Here we applied Hidden Markov Modeling (HMM) to resting-state fMRI data to investigate neural flexibility in relation to depression and suicidal thinking in children. We utilized data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study), and included data from 10,763 children (9-10 years) who completed two 5-min resting state fMRI scans at the baseline visit. After applying the NeuroMark framework to the data, HMM was applied with a varying number of states; a six-state model was selected from candidate models based on between-scan reliability. We applied linear mixed-effect modeling to test the relationship between two clinical predictors: current major depressive disorder (MDD) diagnosis and presence of suicidal ideation (SI) with our primary outcome for neural flexibility: the frequency of transitions between HMM-derived states ("state-switching"), while including sex, age, and other socio-demographic variables as covariates. Analyses were conducted both with and without correction for head motion. We also explored relationships with total time and dwell time in each state of the six states. Lower state-switching during rest was associated with both MDD and SI, although these findings were no longer significant after correcting for head motion. Notably, state-switching was inversely related to head motion and was higher in females than males. Exploratory analysis showed that MDD was associated with shorter dwell time in one state and longer dwell time in another, suggesting altered temporal persistence of specific neural configurations. Tentative evidence supported our hypothesis that lower state-switching in children with MDD and SI may reflect a reduction in brain flexibility, potentially contributing to a tendency to become "stuck" in negative patterns of thinking and feeling. However, the relatively low frequency of these problems in late childhood reduced statistical power after correcting for motion. Future research is needed to assess these relationships at later adolescent time points, when higher prevalence of depression and SI and lower prevalence of head motion will allow more powerful tests of these associations.