28 results on '"Westlund Schreiner M"'
Search Results
2. Rumination induction task in fMRI: Effects of rumination focused cognitive behavioral therapy and stability in youth.
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Westlund Schreiner M, Jacobsen AM, Farstead BW, Miller RH, Jacobs RH, Thomas LR, Bessette KL, Pazdera M, Crowell SE, Kaufman EA, Feldman DA, Roberts H, Welsh RC, Watkins ER, and Langenecker SA
- Abstract
Background: Rumination is implicated in the onset and maintenance of major depressive disorder (MDD). Rumination-Focused Cognitive Behavioral Therapy (RF-CBT) effectively targets rumination and may change resting-state brain connectivity and change in activation during a rumination induction task (RIT) post-intervention predicts depressive symptoms two years later. We examined brain activation changes during an RIT in adolescents with remitted MDD following RF-CBT and evaluated RIT reliability (or stability) during treatment as usual (TAU)., Method: Fifty-five adolescents ages 14-17 completed an RIT at baseline, were randomized to 10-14 sessions of RF-CBT (n = 30) or treatment as usual (n = 25) and completed an RIT at post-treatment or equivalent time delay. The RIT includes recalling negative memories (Rumination Instruction), dwelling on their meaning/consequences (Rumination Prompt), and imagining unrelated scenes and objects (Distraction). We assessed activation change in the RF-CBT group using paired-samples t-tests. We assessed reliability (or stability) via intraclass correlation coefficients (ICCs) of five rumination-related ROIs for TAU and RF-CBT separately across task blocks., Results: Following treatment, participants receiving RF-CBT demonstrated increased activation of left precuneus during Rumination Instruction and of left angular and superior temporal gyri during Rumination Prompt blocks (p < .01). From baseline to post-treatment, across most ROIs and task blocks, the RF-CBT group demonstrated poor stability (M = 0.21, range = -0.19-0.69), while the TAU group demonstrated fair-to-excellent stability (M = 0.52, range = 0.27-0.86)., Conclusion: RF-CBT changes activation of rumination-related circuitry during state-induced rumination, offering exciting avenues for future interventions. The RIT has fair-to-excellent stability among individuals not explicitly treated for rumination, and as expected, RIT stability is disrupted by RF-CBT., Competing Interests: Declaration of competing interest This research was funded by the National Institutes of Mental Health (NIMH; R61MH118060/R33MH118060) awarded to Drs. Scott Langenecker and Edward Watkins. The authors have no financial conflicts of interest. This study was approved by the Institutional Review Board at the University of Utah., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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3. Early Emergence of Rumination has no Association with Performance on a Non-affective Inhibitory Control Task.
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Thomas LR, Bessette KL, Westlund Schreiner M, Dillahunt AK, Frandsen SB, Pocius SL, Schubert BL, Farstead BW, Roberts H, Watkins ER, Kerig PK, Crowell SE, and Langenecker SA
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- Humans, Female, Male, Adolescent, Child, Child Abuse psychology, Executive Function physiology, Rumination, Cognitive physiology, Inhibition, Psychological, Depression psychology
- Abstract
Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.6, SD = 1.8) completed self-report scales of rumination, maltreatment, and family cohesion, and performed a task assessing inhibitory control. Hierarchical regression models showed no significant relation between inhibitory control and moderator variables on rumination. However, adolescents who reported higher levels of maltreatment and who perceived lower family cohesion tended to indicate higher levels of rumination (B
Chilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], BFamily Cohesion = -0.40, 95% CIs [-0.65, -0.15]). These findings demonstrate an alternative understanding of factors that increase depression onset risk and recurrence in adolescents., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...- Published
- 2024
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4. A multi-modal assessment of self-knowledge in adolescents with non-suicidal self-injury: a research domains criteria (RDoC) study.
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Thai M, Başgöze Z, Westlund Schreiner M, Roediger DJ, Falke CA, Mueller BA, Fiecas MB, Quevedo K, Pfeifer JH, Klimes-Dougan B, and Cullen KR
- Abstract
Background: Adolescence is a critical period for brain development, consolidation of self-understanding, and onset of non-suicidal self-injury (NSSI). This study evaluated the RDoC (Research Domain Criteria) sub-construct of Self-Knowledge in relation to adolescent NSSI using multiple units of analysis., Methods: One hundred and sixty-four adolescents assigned female at birth (AFAB), ages 12-16 years with and without a history of NSSI entered a study involving clinical assessment and magnetic resonance imaging (MRI), including structural, resting-state functional MRI (fMRI), and fMRI during a self-evaluation task. For imaging analyses, we used an a priori defined Self Network (anterior cingulate, orbitofrontal, and posterior cingulate cortices; precuneus). We first examined interrelationships among multi-level Self variables. We then evaluated the individual relationships between NSSI severity and multi-level Self variables (self-report, behavior, multi-modal brain Self Network measures), then conducted model testing and multiple regression to test how Self variables (together) predicted NSSI severity., Results: Cross-correlations revealed key links between self-reported global self-worth and self-evaluation task behavior. Individually, greater NSSI severity correlated with lower global self-worth, more frequent and faster negative self-evaluations, lower anterior Self Network activation during self-evaluation, and lower anterior and posterior Self Network resting-state connectivity. Multiple regression analysis revealed the model including multi-level Self variables explained NSSI better than a covariate-only model; the strongest predictive variables included self-worth, self-evaluation task behavior, and resting-state connectivity., Conclusions: Disruptions in Self-Knowledge across multiple levels of analysis relate to NSSI in adolescents. Findings suggest potential neurobiological treatment targets, potentially enhancing neuroplasticity in Self systems to facilitate greater flexibility (more frequently positive) of self-views in AFAB adolescents. more...
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- 2024
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5. Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial.
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Langenecker SA, Westlund Schreiner M, Bessette KL, Roberts H, Thomas L, Dillahunt A, Pocius SL, Feldman DA, Jago D, Farstead B, Pazdera M, Kaufman E, Galloway JA, Kerig PK, Bakian A, Welsh RC, Jacobs RH, Crowell SE, and Watkins ER more...
- Abstract
Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri., Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT ( n = 39; 34 completers) or treatment as usual ( n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging., Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large ( z change = 0.84; 0.73, respectively [ p s < .05])., Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy., (© 2023 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.) more...
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- 2023
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6. Negative association between non-suicidal self-injury in adolescents and default mode network activation during the distraction blocks of a rumination task.
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Westlund Schreiner M, Roberts H, Dillahunt AK, Farstead B, Feldman D, Thomas L, Jacobs RH, Bessette KL, Welsh RC, Watkins ER, Langenecker SA, and Crowell SE
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- Humans, Adolescent, Default Mode Network, Gyrus Cinguli diagnostic imaging, Self Report, Self-Injurious Behavior psychology, Depressive Disorder, Major diagnostic imaging
- Abstract
Introduction: Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI., Method: We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast., Results: Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum., Conclusion: Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change., (© 2023 American Association of Suicidology.) more...
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- 2023
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7. Relations of gray matter volume to dimensional measures of cognition and affect in mood disorders.
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Kim JU, Bessette KL, Westlund-Schreiner M, Pocius S, Dillahunt AK, Frandsen S, Thomas L, Easter R, Skerrett K, Stange JP, Welsh RC, Langenecker SA, and Koppelmans V
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- Humans, Adult, Adolescent, Young Adult, Mood Disorders diagnostic imaging, Cross-Sectional Studies, Cognition physiology, Magnetic Resonance Imaging methods, Brain diagnostic imaging, Brain pathology, Gray Matter diagnostic imaging, Gray Matter pathology, Depressive Disorder, Major diagnostic imaging
- Abstract
Understanding the relationship between brain measurements and behavioral performance is an important step in developing approaches for early identification of any psychiatric difficulties and interventions to modify these challenges. Conventional methods to identify associations between regional brain volume and behavioral measures are not optimized, either in scale, scope, or specificity. To find meaningful associations between brain and behavior with greater sensitivity and precision, we applied data-driven factor analytic models to identify and extract individual differences in latent cognitive functions embedded across several computerized cognitive tasks. Furthermore, we simultaneously utilized a keyword-based neuroimaging meta-analytic tool (i.e., NeuroSynth), restricted atlas-parcel matching, and factor-analytic models to narrow down the scope of search and to further aggregate gray matter volume (GMV) data into empirical clusters. We recruited an early adult community cross-sectional sample (Total n = 177, age 18-30) that consisted of individuals with no history of any mood disorder (healthy controls, n = 44), those with remitted major depressive disorder (rMDD, n = 104), and those with a diagnosis of bipolar disorder currently in euthymic state (eBP, n = 29). Study participants underwent structural magnetic resonance imaging (MRI) scans and separately completed behavioral testing using computerized measures. Factor-analyzing five computerized tasks used to assess aspects of cognitive and affective processing resulted in seven latent dimensions: (a) Emotional Memory, (b) Interference Resolution, (c) Reward Sensitivity, (d) Complex Inhibitory Control, (e) Facial Emotion Sensitivity, (f) Sustained attention, and (g)Simple Impulsivity/Response Style. These seven dimensions were then labeled with specific keywords which were used to create neuroanatomical maps using NeuroSynth. These masks were further subdivided into GMV clusters. Using regression, we identified GMV clusters that were predictive of individual differences across each of the aforementioned seven cognitive dimensions. We demonstrate that a dimensional approach consistent with core principles of RDoC can be utilized to identify structural variability predictive of critical dimensions of human behavior., Competing Interests: Declaration of competing interest PGNGS modified and developed by Langenecker, FEPT modified and developed by Langenecker, titrated MID modified and develop by Langenecker; all are free for use., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...
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- 2022
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8. Increased sensitivity of insula to supraliminal faces in adults with histories of mood disorders and self-injury.
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Westlund Schreiner M, Dillahunt AK, Frandsen SB, DelDonno SR, Schubert BL, Pocius SL, Jenkins LM, Kassel MT, Bessette KL, Thomas L, Stange JP, Crowell SE, and Langenecker SA
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- Adult, Amygdala diagnostic imaging, Emotions physiology, Facial Expression, Female, Humans, Magnetic Resonance Imaging, Male, Subliminal Stimulation, Mood Disorders diagnostic imaging, Mood Disorders etiology, Self-Injurious Behavior diagnostic imaging
- Abstract
Background: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs., Methods: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task., Results: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials., Conclusions: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...
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- 2022
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9. Structural and Functional Neural Correlates of Treatment Response for Interpersonal Psychotherapy for Depressed Adolescents.
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Klimes-Dougan B, Başgöze Z, Mueller B, Wiglesworth A, Carosella KA, Westlund Schreiner M, Bortnova A, Reigstad K, Cullen KR, and Gunlicks-Stoessel M
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Precision medicine approaches hold tremendous promise to advance current clinical practice by providing information about which individuals will benefit from which treatments. This pilot study evaluated if baseline structure and function of the salience and emotion brain regions implicated in adolescent depression, specifically the amygdala and anterior cingulate cortex (ACC), predict response to Interpersonal Psychotherapy for Depressed Adolescents (IPT-A). Adolescents ( n = 15; mean age = 14.5 (1.6); 80.0% female) diagnosed with a depressive disorder completed brain scans before the start of a 16 week trial of IPT-A. Clinical measures assessing depressive symptoms were completed before, during, and after a trial of therapy. Results show that at baseline, greater ACC activation in the context of an emotion-matching task and greater amygdala-ACC resting-state functional connectivity was related to greater improvement in depression symptoms. There was minimal evidence that brain structure predicted changes in depressive symptoms. The present study is the first to evaluate neural predictors of IPT-A response. While the results are preliminary, these findings suggest some avenues for future research to pursue in the hopes that more will benefit from treatment. more...
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- 2022
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10. Self-Injury in Adolescence Is Associated with Greater Behavioral Risk Avoidance, Not Risk-Taking.
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Dillahunt AK, Feldman DA, Thomas LR, Farstead BW, Frandsen SB, Lee S, Pazdera M, Galloway J, Bessette KL, Roberts H, Crowell SE, Watkins ER, Langenecker SA, and Westlund Schreiner M
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Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have ( n = 31) and who do not have ( n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state. more...
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- 2022
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11. Using Network Parcels and Resting-State Networks to Estimate Correlates of Mood Disorder and Related Research Domain Criteria Constructs of Reward Responsiveness and Inhibitory Control.
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Langenecker SA, Westlund Schreiner M, Thomas LR, Bessette KL, DelDonno SR, Jenkins LM, Easter RE, Stange JP, Pocius SL, Dillahunt A, Love TM, Phan KL, Koppelmans V, Paulus M, Lindquist MA, Caffo B, Mickey BJ, and Welsh RC more...
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- Adolescent, Adult, Humans, Reward, Young Adult, Magnetic Resonance Imaging, Mood Disorders
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Background: Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with Research Domain Criteria (RDoC) constructs for accurate identification of mood disorder-related markers, while minimizing active symptoms of disease., Methods: We compared 132 individuals with currently remitted or euthymic mood disorder with 65 healthy comparison participants, ages 18-30 years. Subsets of smaller brain parcels, combined into three prominent networks and one network of parcels overlapping across these networks, were used to compare edge differences between groups. Consistent with the RDoC framework, we evaluated individual differences with performance measure regressors of inhibitory control and reward responsivity. Within an omnibus regression model, we predicted edges related to diagnostic group membership, performance within both RDoC domains, and relevant interactions., Results: There were several edges of mood disorder group, predominantly of greater connectivity across networks, different than those related to individual differences in inhibitory control and reward responsivity. Edges related to diagnosis and inhibitory control did not align well with prior literature, whereas edges in relation to reward responsivity constructs showed greater alignment with prior literature. Those edges in interaction between RDoC constructs and diagnosis showed a divergence for inhibitory control (negative interactions in default mode) relative to reward (positive interactions with salience and emotion network)., Conclusions: In conclusion, there is evidence that prior simple network models of mood disorders are currently of insufficient biological or diagnostic clarity or that parcel-based edges may be insufficiently sensitive for these purposes., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) more...
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- 2022
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12. Multimodal assessment of sustained threat in adolescents with nonsuicidal self-injury.
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Başgöze Z, Mirza SA, Silamongkol T, Hill D, Falke C, Thai M, Westlund Schreiner M, Parenteau AM, Roediger DJ, Hendrickson TJ, Mueller BA, Fiecas MB, Klimes-Dougan B, and Cullen KR
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- Adolescent, Humans, Female, Cross-Sectional Studies, Suicide, Attempted, Amygdala diagnostic imaging, Hydrocortisone, Self-Injurious Behavior
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Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity ( N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala-mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala-mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI. more...
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- 2021
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13. Advancing a temporal framework for understanding the biology of nonsuicidal self- injury: An expert review.
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Kaess M, Hooley JM, Klimes-Dougan B, Koenig J, Plener PL, Reichl C, Robinson K, Schmahl C, Sicorello M, Westlund Schreiner M, and Cullen KR
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- Adolescent, Humans, Neurobiology, Phenotype, Risk Factors, Young Adult, Self-Injurious Behavior
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Nonsuicidal self-injury (NSSI) is a serious clinical problem, particularly for adolescents and young adults. NSSI is a complex behavior that emerges through the intersecting effects of social, psychological, and biological mechanisms. Although the social and psychological contributions to risk for developing NSSI are relatively well understood and have guided the development of effective psychosocial treatments for self-injury, the biological mechanisms underlying NSSI have just begun to come to light. To evaluate and categorize the biological research conducted on the topic of NSSI, we propose a model that distinguishes between trait and state markers. According to this model, risk factors and mechanisms involved in NSSI can be distinguished into both trait and state factors. We review the existing evidence on distal biological traits (predictors) of NSSI, proximal biological traits (correlates) of NSSI, and biological states directly preceding or following NSSI. We conclude by providing recommendations for future research on the neurobiology of NSSI., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2021
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14. Effect of SSRIs on Resting-State Functional Brain Networks in Adolescents with Major Depressive Disorder.
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Chu SH, Parhi KK, Westlund Schreiner M, Lenglet C, Mueller BA, Klimes-Dougan B, and Cullen KR
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Investigation of brain changes in functional connectivity and functional network topology from receiving 8-week selective serotonin reuptake inhibitor (SSRI) treatments is conducted in 12 unmedicated adolescents with major depressive disorder (MDD) by using wavelet-filtered resting-state functional magnetic resonance imaging (fMRI). Changes are observed in frontal-limbic, temporal, and default mode networks. In particular, topological analysis shows, at the global scale and in the 0.12-0.25 Hz band, that the normalized clustering coefficient and smallworldness of brain networks decreased after treatment. Regional changes in clustering coefficient and efficiency were observed in the bilateral caudal middle frontal gyrus, rostral middle frontal gyrus, superior temporal gyrus, left pars triangularis, putamen, and right superior frontal gyrus. Furthermore, changes of nodal centrality and changes of connectivity associated with these frontal and temporal regions confirm the global topological alternations. Moreover, frequency dependence is observed from FDR-controlled subnetworks for the limbic-cortical connectivity change. In the high-frequency band, the altered connections involve mostly frontal regions, while the altered connections in the low-frequency bands spread to parietal and temporal areas. Due to the limitation of small sample sizes and lack of placebo control, these preliminary findings require confirmation with future work using larger samples. Confirmation of biomarkers associated with treatment could suggest potential avenues for clinical applications such as tracking treatment response and neurobiologically informed treatment optimization. more...
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- 2021
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15. Mechanisms of rumination change in adolescent depression (RuMeChange): study protocol for a randomised controlled trial of rumination-focused cognitive behavioural therapy to reduce ruminative habit and risk of depressive relapse in high-ruminating adolescents.
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Roberts H, Jacobs RH, Bessette KL, Crowell SE, Westlund-Schreiner M, Thomas L, Easter RE, Pocius SL, Dillahunt A, Frandsen S, Schubert B, Farstead B, Kerig P, Welsh RC, Jago D, Langenecker SA, and Watkins ER more...
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- Adolescent, Gyrus Cinguli, Habits, Humans, Randomized Controlled Trials as Topic, Recurrence, Young Adult, Cognitive Behavioral Therapy, Depression therapy
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Background: Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression. Targeting habitual depressive rumination, a specific known risk factor for relapse, may improve clinical outcomes for adolescents who have experienced a depressive episode. Randomized controlled trials (RCTs) thus far have demonstrated that rumination-focused cognitive behavioral therapy (RFCBT) reduces depressive symptoms and relapse rates in patients with residual depression and adolescents and young adults with elevated rumination. This was also observed in a pilot RCT of adolescents at risk for depressive relapse. Rumination can be measured at the self-report, behavioral, and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity is a putative important mechanism for understanding reduced rumination via RFCBT. A feasibility trial in adolescents found that reductions in connectivity between DMN and CCN regions following RFCBT were correlated with change in rumination and depressive symptoms., Method: This is a phase III two-arm, two-stage, RCT of depression prevention. The trial tests whether RFCBT reduces identified risk factors for depressive relapse (rumination, patterns of neural connectivity, and depressive symptoms) in adolescents with partially or fully remitted depression and elevated rumination. In the first stage, RFCBT is compared to treatment as usual within the community. In the second stage, the comparator condition is relaxation therapy. Primary outcomes will be (a) reductions in depressive rumination, assessed using the Rumination Response Scale, and (b) reductions in resting state functional magnetic resonance imaging connectivity of DMN (posterior cingulate cortex) to CCN (inferior frontal gyrus), at 16 weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12 months post-intervention period, and whether engagement with therapy homework (as a dose measure) is related to changes in the primary outcomes., Discussion: RFCBT will be evaluated as a putative preventive therapy to reduce the risk of depressive relapse in adolescents, and influence the identified self-report, behavioral, and neural mechanisms of change. Understanding mechanisms that underlie change in rumination is necessary to improve and further disseminate preventive interventions., Trial Registration: ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019. more...
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- 2021
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16. Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression.
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Roy AV, Thai M, Klimes-Dougan B, Westlund Schreiner M, Mueller BA, Albott CS, Lim KO, Fiecas M, Tye SJ, and Cullen KR
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- Adolescent, Entropy, Excitatory Amino Acid Antagonists therapeutic use, Female, Humans, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Magnetic Resonance Imaging methods, Male, Nucleus Accumbens drug effects, Nucleus Accumbens metabolism, Antidepressive Agents therapeutic use, Biomarkers metabolism, Brain metabolism, Depressive Disorder, Treatment-Resistant drug therapy, Depressive Disorder, Treatment-Resistant metabolism, Ketamine therapeutic use, Nerve Growth Factors metabolism
- Abstract
Background: Current theory suggests that treatment-resistant depression (TRD) involves impaired neuroplasticity resulting in cognitive and neural rigidity, and that clinical improvement may require increasing brain flexibility and adaptability., Aims: In this hypothesis-generating study, we sought to identify preliminary evidence of brain flexibility correlates of clinical change within the context of an open-label ketamine trial in adolescents with TRD, focusing on two promising candidate markers of neural flexibility: (a) entropy of resting-state functional magnetic resonance imaging (fMRI) signals; and (b) insulin-stimulated phosphorylation of mammalian target of rapamycin (mTOR) and glycogen synthase-3-beta (GSK3β) in peripheral blood mononuclear cells., Methods: We collected resting-state functional magnetic resonance imaging data and blood samples from 13 adolescents with TRD before and after a series of six ketamine infusions over 2 weeks. Usable pre/post ketamine data were available from 11 adolescents for imaging and from 10 adolescents for molecular signaling. We examined correlations between treatment response and changes in the central and peripheral flexibility markers., Results: Depression reduction correlated with increased nucleus accumbens entropy. Follow-up analyses suggested that physiological changes were associated with treatment response. In contrast to treatment non-responders ( n =6), responders ( n =5) showed greater increase in nucleus accumbens entropy after ketamine, together with greater post-treatment insulin/mTOR/GSK3β signaling., Conclusions: These data provide preliminary evidence that changes in neural flexibility may underlie symptom relief in adolescents with TRD following ketamine. Future research with adequately powered samples is needed to confirm resting-state entropy and insulin-stimulated mTOR and GSK3β as brain flexibility markers and candidate targets for future clinical trials., Clinical Trial Name: Ketamine in adolescents with treatment-resistant depression URL: https://clinicaltrials.gov/ct2/show/NCT02078817 Registration number: NCT02078817. more...
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- 2021
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17. Corrigendum: White Matter Microstructure in Adolescents and Young Adults With Non-Suicidal Self-Injury.
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Westlund Schreiner M, Mueller BA, Klimes-Dougan B, Begnel ED, Fiecas M, Hill D, Lim KO, and Cullen KR
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[This corrects the article DOI: 10.3389/fpsyt.2019.01019.]., (Copyright © 2020 Westlund Schreiner, Mueller, Klimes-Dougan, Begnel, Fiecas, Hill, Lim and Cullen.)
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- 2020
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18. White Matter Microstructure in Adolescents and Young Adults With Non-Suicidal Self-Injury.
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Westlund Schreiner M, Mueller BA, Klimes-Dougan B, Begnel ED, Fiecas M, Hill D, Lim KO, and Cullen KR
- Abstract
Background: Non-suicidal self-injury (NSSI) is a growing public health concern that commonly begins in adolescence, and can persist into young adulthood. A promising approach for advancing our understanding of NSSI in youth is to examine white matter microstructure using diffusion magnetic resonance imaging (dMRI)., Method: The present study examined whole-brain group differences in structural connectivity (as measured by generalized fractional anisotropy [GFA]) between 28 female adolescents and young adults ages 13-21 years with NSSI and 22 age-matched healthy controls (HC). We also explored the association between clinical characteristics including NSSI severity and duration, impulsivity, emotion regulation and personality traits within the NSSI group and GFA of the uncinate fasciculus and cingulum., Results: Compared to the HC group, participants with NSSI had lower GFA in several white matter tracts, including the uncinate fasciculus, cingulum, bilateral superior and inferior longitudinal fasciculi, anterior thalamic radiation, callosal body, and corticospinal tract. When controlling for depressive symptoms, the NSSI group showed an association between NSSI duration (time since initiating NSSI behavior) and lower GFA in the left cingulum. Higher levels of attentional impulsivity were related to lower GFA in the left uncinate fasciculus within the NSSI group., Conclusions: We found evidence suggesting widespread white matter microstructure deficits in adolescents and young adults with NSSI versus HC. We also report inverse associations between white matter integrity and clinical characteristics (duration of NSSI and attentional impulsivity). These white matter microstructural deficits may represent a possible neurobiologically-based vulnerability to developing maladaptive coping mechanisms, such as NSSI. Additionally, results suggest that this white matter disorganization may either worsen with prolonged engagement in NSSI or predict persistent NSSI; thereby highlighting the importance of early intervention targeting this behavior., (Copyright © 2020 Westlund Schreiner, Mueller, Klimes-Dougan, Begnel, Fiecus, Hill, Lim and Cullen.) more...
- Published
- 2020
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19. Neurocircuitry associated with symptom dimensions at baseline and with change in borderline personality disorder.
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Westlund Schreiner M, Klimes-Dougan B, Mueller BA, Nelson KJ, Lim KO, and Cullen KR
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- Adult, Amygdala diagnostic imaging, Amygdala physiopathology, Borderline Personality Disorder diagnostic imaging, Female, Hippocampus diagnostic imaging, Hippocampus physiopathology, Humans, Impulsive Behavior physiology, Magnetic Resonance Imaging methods, Male, Middle Aged, Rest psychology, Young Adult, Antipsychotic Agents therapeutic use, Borderline Personality Disorder drug therapy, Borderline Personality Disorder psychology, Quetiapine Fumarate therapeutic use
- Abstract
Borderline personality disorder (BPD) is a serious illness associated with chronic suffering and self-injurious behavior. Parsing the relationships between specific symptom domains and their underlying biological mechanisms may help us further understand the neural circuits implicated in these symptoms and how they might be amenable to change with treatment. This study examines the association between symptom dimensions (Affective Disturbance, Cognitive Disturbance, Disturbed Relationships, and Impulsivity) and amygdala resting-state functional connectivity (RSFC) in a sample of adults with BPD (n = 18). We also explored the relationships between change in symptom dimensions and change in amygdala RSFC in a subset of this sample (n = 13) following 8 weeks of quetiapine or placebo. At baseline, higher impulsivity was associated with increased positive RSFC between right amygdala and left hippocampus. There were no significant differences in neural change between treatment groups. Improvement in cognitive disturbance was associated with increased positive RSFC between left amygdala and temporal fusiform and parahippocampal gyri. Improvement in disturbed relationships was associated with increased negative RSFC between right amygdala and frontal pole. These results support that specific dimensions of BPD are associated with specific neural connectivity patterns at baseline and with change, which may represent neural treatment targets., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...
- Published
- 2019
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20. Increases in orbitofrontal cortex thickness following antidepressant treatment are associated with changes in resting state autonomic function in adolescents with major depression - Preliminary findings from a pilot study.
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Koenig J, Westlund Schreiner M, Klimes-Dougan B, Ubani B, Mueller BA, Lim KO, Kaess M, and Cullen KR
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- Adolescent, Depressive Disorder, Major drug therapy, Female, Heart Rate drug effects, Heart Rate physiology, Humans, Male, Organ Size drug effects, Pilot Projects, Prefrontal Cortex drug effects, Rest physiology, Treatment Outcome, Antidepressive Agents pharmacology, Autonomic Nervous System physiopathology, Depressive Disorder, Major pathology, Depressive Disorder, Major physiopathology, Prefrontal Cortex pathology, Selective Serotonin Reuptake Inhibitors pharmacology
- Abstract
In adults with major depressive disorder (MDD), effective treatment has been associated with increases in both heart rate variability (HRV) and cortical thickness. However, the impact of treatment on these indices has not yet been examined in adolescents. Cortical thickness and HRV were measured in twelve adolescents with MDD before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). We examined treatment-related changes in depression symptoms, HRV, heart rate (HR), and cortical thickness, and analyzed correlations among these change indices. At follow-up, patients showed significantly decreased depression severity, increased HRV and increased thickness of the left medial orbitofrontal cortex (OFC). Clinical improvement was associated with increased HRV and decreased HR. Increased HRV was associated with increased cortical thickness of left lateral OFC and superior frontal cortex. Due to the small sample size, results represent preliminary findings that need replication. Further, in the absence of a placebo arm, we cannot confirm that the observed effects are due solely to medication. These preliminary findings suggest that SSRI treatment in adolescents impacts both cortical thickness and autonomic functioning. Confirmation of these findings would support OFC thickness and HRV as neurobiological mediators of treatment outcome., (Copyright © 2018. Published by Elsevier B.V.) more...
- Published
- 2018
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21. Brain structural thickness and resting state autonomic function in adolescents with major depression.
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Koenig J, Westlund Schreiner M, Klimes-Dougan B, Ubani B, Mueller B, Kaess M, and Cullen KR
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- Adolescent, Case-Control Studies, Child, Depressive Disorder, Major psychology, Female, Heart Rate, Humans, Limbic System diagnostic imaging, Limbic System physiopathology, Magnetic Resonance Imaging, Male, Neuroimaging, Psychiatric Status Rating Scales, Rest, Vagus Nerve physiopathology, Young Adult, Autonomic Nervous System physiopathology, Brain diagnostic imaging, Brain physiopathology, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major physiopathology
- Abstract
Major depressive disorder (MDD) has been associated with abnormalities in cortical thickness and autonomic function. Adolescence is a time notable for brain development and MDD onset. In healthy adolescents, greater resting state vagal activity (RVA) is associated with lower cortical thickness. The relationship between brain structural thickness and RVA in adolescents with MDD has not previously been studied. This secondary analysis drew on a sample of 37 non-depressed controls and 53 adolescents with MDD. Resting state heart rate and two indices of RVA (HF-HRV and RMSSD) were recorded during a neuroimaging session. Cortical thickness within fronto-limbic regions of interest was measured using Freesurfer analysis of T1-weighted high-resolution structural images. Self-reports of depression severity showed a significant interaction with cortical thickness of the right insula in predicting RMSSD [t = 2.22, P=0.030, β = 5.44; model fit of the interaction term as indicated by the 'Bayes Factor' (BF): 7.58] and HF-HRV (t = 2.09, P=0.041, β = 4.72; BF: 7.94). Clinician ratings of depression severity showed further interactions. Findings underscore the important relationships between RVA and cortical development, suggesting two possible explanations: (i) in adolescent MDD, greater fronto-limbic thickness is compensatory for deficits in autonomic regulation or (ii) increased autonomic arousal results in delayed fronto-limbic maturation. Longitudinal research is necessary to further clarify the nature of the relationship between autonomic functioning and cortical development. more...
- Published
- 2018
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22. Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study.
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Cullen KR, Amatya P, Roback MG, Albott CS, Westlund Schreiner M, Ren Y, Eberly LE, Carstedt P, Samikoglu A, Gunlicks-Stoessel M, Reigstad K, Horek N, Tye S, Lim KO, and Klimes-Dougan B
- Subjects
- Administration, Intravenous, Adolescent, Child, Dose-Response Relationship, Drug, Female, Humans, Male, Psychiatric Status Rating Scales, Depressive Disorder, Treatment-Resistant drug therapy, Excitatory Amino Acid Antagonists therapeutic use, Ketamine therapeutic use
- Abstract
Background: Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors., Methods: Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children's Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS)., Results: Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response., Conclusions: These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use. more...
- Published
- 2018
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23. N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.
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Cullen KR, Klimes-Dougan B, Westlund Schreiner M, Carstedt P, Marka N, Nelson K, Miller MJ, Reigstad K, Westervelt A, Gunlicks-Stoessel M, and Eberly LE
- Subjects
- Acetylcysteine adverse effects, Administration, Oral, Adolescent, Depression epidemiology, Dose-Response Relationship, Drug, Female, Free Radical Scavengers administration & dosage, Free Radical Scavengers adverse effects, Humans, Pilot Projects, Psychiatric Status Rating Scales, Treatment Outcome, Young Adult, Acetylcysteine administration & dosage, Depression drug therapy, Impulsive Behavior drug effects, Self-Injurious Behavior drug therapy
- Abstract
Background: Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth., Methods: Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90)., Results: About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects., Conclusion: We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy. more...
- Published
- 2018
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24. Neural and neuroendocrine predictors of pharmacological treatment response in adolescents with depression: A preliminary study.
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Klimes-Dougan B, Westlund Schreiner M, Thai M, Gunlicks-Stoessel M, Reigstad K, and Cullen KR
- Subjects
- Adolescent, Biomarkers metabolism, Brain drug effects, Brain physiopathology, Brain Mapping, Child, Cross-Sectional Studies, Depressive Disorder, Major physiopathology, Emotions drug effects, Emotions physiology, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Pilot Projects, Prognosis, Rest, Saliva metabolism, Antidepressive Agents therapeutic use, Brain diagnostic imaging, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy, Hydrocortisone metabolism
- Abstract
Objective: Typically, about 30 to 50% of adolescents with depression fail to respond to evidence-based treatments, including antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). Efforts for identifying predictors and moderators of treatment response are needed to begin to address critical questions relevant to personalized care in adolescent depression. In this pilot study, we aim to identify biological predictors of response to antidepressant treatment., Method: We used a multiple levels of analysis approach to evaluate threat system functioning (fronto-limbic system and the associated hormonal cascade) to determine if key biological indexes at baseline could predict improvement in depressive symptoms after eight weeks of antidepressant treatment in adolescents with depression., Results: Neural predictors of favorable treatment response included lower amygdala connectivity with left supplementary motor area and with right precentral gyrus, and greater amygdala connectivity with right central opercular cortex and Heschl's gyrus connectivity during rest. During an emotion task, neural predictors of treatment response were greater activation of the bilateral anterior cingulate cortex and left medial frontal gyrus. Additionally, different patterns of salivary cortisol obtained in the context of a modified Trier Social Stress Test were associated with those whose depressive symptoms remitted as compared to those whose symptoms persisted., Conclusions: This approach shows significant promise for identifying predictors of treatment response in adolescents with depression. Future work is needed that incorporates sufficiently powered, randomized control trials to provide the basis by which both predictors and moderators of treatment response are identified. The hope is that this work will inform the development of methods that can guide clinician decision-making in assigning beneficial treatments for adolescents who are suffering from depression., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...
- Published
- 2018
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25. Multi-modal neuroimaging of adolescents with non-suicidal self-injury: Amygdala functional connectivity.
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Westlund Schreiner M, Klimes-Dougan B, Mueller BA, Eberly LE, Reigstad KM, Carstedt PA, Thomas KM, Hunt RH, Lim KO, and Cullen KR
- Subjects
- Adolescent, Amygdala physiopathology, Brain Mapping methods, Cerebral Cortex diagnostic imaging, Cerebral Cortex physiopathology, Cross-Sectional Studies, Emotions physiology, Facial Recognition, Female, Gyrus Cinguli diagnostic imaging, Gyrus Cinguli physiopathology, Humans, Magnetic Resonance Imaging, Male, Rest physiology, Self-Injurious Behavior physiopathology, Amygdala diagnostic imaging, Functional Neuroimaging methods, Self-Injurious Behavior diagnostic imaging
- Abstract
Background: Non-suicidal self-injury (NSSI) is a significant mental health problem among adolescents. Research is needed to clarify the neurobiology of NSSI and identify candidate neurobiological targets for interventions. Based on prior research implicating heightened negative affect and amygdala hyperactivity in NSSI, we pursued a systems approach to characterize amygdala functional connectivity networks during rest (resting-state functional connectivity [RSFC)]) and a task (task functional connectivity [TFC]) in adolescents with NSSI., Method: We examined amygdala networks in female adolescents with NSSI and healthy controls (n = 45) using resting-state fMRI and a negative emotion face-matching fMRI task designed to activate the amygdala. Connectivity analyses included amygdala RSFC, amygdala TFC, and psychophysiological interactions (PPI) between amygdala connectivity and task conditions., Results: Compared to healthy controls, adolescents with NSSI showed atypical amygdala-frontal connectivity during rest and task; greater amygdala RSFC in supplementary motor area (SMA) and dorsal anterior cingulate; and differential amygdala-occipital connectivity between rest and task. After correcting for depression symptoms, amygdala-SMA RSFC abnormalities, among others, remained significant., Limitations: This study's limitations include its cross-sectional design and its absence of a psychiatric control group., Conclusions: Using a multi-modal approach, we identified widespread amygdala circuitry anomalies in adolescents with NSSI. While deficits in amygdala-frontal connectivity (driven by depression symptoms) replicates prior work in depression, hyperconnectivity between amygdala and SMA (independent of depression symptoms) has not been previously reported. This circuit may represent an important mechanism underlying the link between negative affect and habitual behaviors. These abnormalities may represent intervention targets for adolescents with NSSI., (Copyright © 2017 Elsevier B.V. All rights reserved.) more...
- Published
- 2017
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26. Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder.
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Cullen KR, Klimes-Dougan B, Vu DP, Westlund Schreiner M, Mueller BA, Eberly LE, Camchong J, Westervelt A, and Lim KO
- Subjects
- Adolescent, Amygdala diagnostic imaging, Brain diagnostic imaging, Depressive Disorder, Major physiopathology, Depressive Disorder, Major psychology, Emotions physiology, Female, Humans, Male, Nerve Net diagnostic imaging, Depressive Disorder, Major drug therapy, Magnetic Resonance Imaging, Selective Serotonin Reuptake Inhibitors therapeutic use
- Abstract
Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research., Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC., Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex., Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments. more...
- Published
- 2016
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27. Conceptualizing the neurobiology of non-suicidal self-injury from the perspective of the Research Domain Criteria Project.
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Westlund Schreiner M, Klimes-Dougan B, Begnel ED, and Cullen KR
- Subjects
- Humans, Self-Injurious Behavior classification, Human Development, Self-Injurious Behavior diagnosis
- Abstract
Non-suicidal self-injury (NSSI) commonly starts in adolescence and is associated with an array of negative outcomes. Neurobiological research investigating NSSI is in its early stages and most studies have examined this behavior within the context of specific diagnoses. However, the Research Domain Criteria (RDoC) initiative encourages researchers to examine brain-behavior relationships across diagnoses. This review on the neurobiology associated with NSSI is organized using the domains proposed by RDoC: Negative Valence, Positive Valence, Cognitive, Social Processes, and Arousal/Regulatory Systems. Evidence of neurobiological anomalies is found in each of these domains. We also propose future research directions, especially in regard to human development. Future NSSI studies should address this behavior independent of diagnosis, examine relevant constructs across multiple units of analysis, and assess how systems change across development and course of illness. These advances will be essential for guiding neurobiologically informed intervention and prevention strategies to target NSSI. In doing so, we may prevent the associated negative outcomes across the lifespan., (Copyright © 2015 Elsevier Ltd. All rights reserved.) more...
- Published
- 2015
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28. Multilevel assessment of the neurobiological threat system in depressed adolescents: interplay between the limbic system and hypothalamic-pituitary-adrenal axis.
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Klimes-Dougan B, Eberly LE, Westlund Schreiner M, Kurkiewicz P, Houri A, Schlesinger A, Thomas KM, Mueller BA, Lim KO, and Cullen KR
- Subjects
- Adolescent, Adult, Brain Mapping, Child, Female, Humans, Magnetic Resonance Imaging, Male, Social Perception, Young Adult, Amygdala metabolism, Amygdala pathology, Amygdala physiopathology, Depressive Disorder, Major metabolism, Depressive Disorder, Major pathology, Depressive Disorder, Major physiopathology, Hydrocortisone metabolism, Hypothalamo-Hypophyseal System metabolism, Pituitary-Adrenal System metabolism, Stress, Psychological metabolism, Stress, Psychological physiopathology
- Abstract
Integrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12-19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts. more...
- Published
- 2014
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