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Browsing by Author "Hulvershorn, Leslie A."
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Item Abnormal Amygdala Functional Connectivity Associated With Emotional Lability in Children With Attention-Deficit/Hyperactivity Disorder(Elsevier, 2014-03) Hulvershorn, Leslie A.; Mennes, Maarten; Castellanos, F. Xavier; Di Martino, Adriana; Milham, Michael P.; Hummer, Tom A.; Roy, Amy Krain; Department of Psychiatry, IU School of MedicineObjective A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. Method Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). Results Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. Conclusions In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala–cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.Item Atypical Cortical Activation during Risky Decision-making in Disruptive Behavior Disordered Youth with Histories of Suicidal Ideation(Elsevier, 2020) Dir, Allyson L.; Allebach, Christian L.; Hummer, Tom A.; Adams, Zachary; Aalsma, Matthew C.; Finn, Peter R.; Nurnberger, John I.; Hulvershorn, Leslie A.; Psychiatry, School of MedicineBackground: Suicidality is a leading cause of death among adolescents. In addition to other psychiatric conditions, youths with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) are at heightened risk for suicide. Decision-making deficits are a hallmark symptom of ADHD and DBDs and are also implicated in suicidal behavior. We examined behavioral and neural differences in decision making among youths with ADHD and DBDs with (SI+) and without (SI-) histories of suicidal ideation. Methods: The Balloon Analog Risk Task, a risky decision-making task, was completed by 57 youths with ADHD and DBDs (38% SI+) during functional magnetic resonance imaging. Mean stop wager (mean wager at which youths bank money) was the primary measure of risk taking. We conducted whole-brain and region-of-interest analyses in the anterior cingulate cortex and orbitofrontal cortex (OFC) during choice (win vs. inflate) and outcome (inflate vs. explode) contrasts using parametric modulators accounting for probability of balloon explosion. Results: There were no differences between SI+ and SI- youths in Balloon Analog Risk Task performance. SI+ youths showed decreasing activation in the right medial frontal gyrus when choosing inflate as explosion probability increased compared with SI- youths. During explosions, SI- youths showed increasing activation in the left OFC as explosions became more likely. SI+ showed increasing left medial OFC activity in response to inflations as explosion probability increased. Conclusions: SI+ youths may show heightened sensitivity to immediate reward and decreased sensitivity to potential loss as evidenced by medial frontal gyrus activity. OFC findings suggest that SI+ youths may be drawn to reward even when there is high probability of loss.Item Brain responses during delay discounting in youth at high-risk for substance use disorders(Elsevier, 2021) Butcher, Tarah J.; Dzemidzic, Mario; Harezlak, Jaroslaw; Hulvershorn, Leslie A.; Oberlin, Brandon G.; Psychiatry, School of MedicineOffspring of parents with substance use disorders (SUD) discount future rewards at a steeper rate on the monetary delay discounting task (DD) than typically developing youth. However, brain activation during DD has yet to be studied in drug naïve youth with a family history (FH) of SUD. Here, we investigate brain activation differences in high-risk youth during DD. We recruited substance naïve youth, aged 11–12, into three groups to compare brain activation during DD: (1) High-risk youth (n = 35) with a FH of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n = 25) who had no FH of SUD, but with equivalent externalizing psychiatric disorders as high-risk youth, and (3) a healthy control group (n = 24) with no FH of SUD and minimal psychopathology. A whole-brain voxel wise analysis of the [Delay > Baseline], [Immediate > Baseline], and [Control > Baseline] contrasts identified functional regions of interest, from which extracted parameter estimates were tested for significant group differences. Relative to control youth, high-risk youth showed stronger activation in the left posterior insula and thalamus when making delayed choices, and stronger activation of the parahippocampal gyrus when making both delayed and control choices (ps < 0.05). Activation in the left posterior insula negatively correlated with both subscales of the Emotion Regulation Checklist, and positively correlated with the Stroop interference effect (ps < 0.05). Our findings suggest possible heritable SUD risk neural markers that distinguish drug naïve high-risk youth from psychiatric and healthy controls.Item Cannabis Use and the Developing Brain: Highs and Lows(Frontiers Media, 2023) Hurd, Yasmin L.; Ferland, Jacqueline-Marie N.; Nomura, Yoko; Hulvershorn, Leslie A.; Gray, Kevin M.; Thurstone, Christian; Psychiatry, School of MedicineAlthough cannabis is a naturally occurring plant with a long history of use by humans, the chemicals it contains, called cannabinoids, can act on the human body in many ways. Use of cannabis during important periods of development, such as during pregnancy and adolescence, can have a long-lasting impact on the way the brain forms and develops its systems to control emotions and other functions. This article gives an overview of some of the effects of cannabinoids on the developing brain, before birth and as teenagers, and provides information about how young people can prevent or minimize the negative effects of cannabis on their brains.Item Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial(Wiley, 2022) Wang, Yun; Kessel, Ellen; Lee, Seonjoo; Hong, Susie; Raffanello, Elizabeth; Hulvershorn, Leslie A.; Margolis, Amy; Peterson, Bradley S.; Posner, Jonathan; Psychiatry, School of MedicineBackground: Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics. Methods: We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213). Results: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples. Conclusions: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.Item Clinical Perspective: Treatment of adolescent e-cigarette use – limitations of existing nicotine use disorder treatment and future directions for e-cigarette use cessation(Elsevier, 2021) Adams, Zachary W.; Kwon, Elizabeth; Aalsma, Matthew C.; Zapolski, Tamika C.B.; Dir, Allyson; Hulvershorn, Leslie A.; Psychiatry, School of MedicineElectronic cigarette use ("vaping") has surged in the United States since the mid-2010s. From 2011 to 2018, current e-cigarette use among high school students escalated from 1.5% to 20.8% (∼3.05 million youths),1 countering downward trends in combustible nicotine product use (21.8% in 2011 to 13.9% in 2018).1 Although preventing the initial uptake of vaping is crucial, for the millions of adolescents who have taken up this behavior-many of whom express interest in quitting (eg, 44.5% of current, adolescent non-light e-cigarette users in one US national representative sample)2-it is critically important to help them quit vaping so as to curtail future substance use disorders and other health consequences. Here, we discuss several challenges around adolescent vaping treatment, and highlight research areas in urgent need of attention.Item Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric comorbidity(Cambridge, 2015-07) Monahan, Patrick O.; Stump, Timothy; Coryell, William H.; Harezlak, Jaroslaw; Marcoulides, George A.; Liu, Hai; Steeger, Christine M.; Mitchell, Philip B.; Wilcox, Holly C.; Hulvershorn, Leslie A.; Glowinski, Anne L.; Iyer-Eimerbrink, Priya Anapurna; McInnis, Melvin; Nurnberger, John I. Jr.; Department of Biostatistics, IU School of MedicineBackground The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders. Method A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998–2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA. Results The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives. Conclusions The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.Item Development of a computerized adaptive substance use disorder scale for screening, measurement and diagnosis - The CAT-SUD-E(Elsevier, 2022-03-23) Hulvershorn, Leslie A.; Adams, Zachary W.; Smoker, Michael P.; Aalsma, Matthew C.; Gibbons, Robert D.; Psychiatry, School of MedicineIntroduction: The Computerized Adaptive Test for Substance Use Disorder (CAT-SUD), an adaptive test based on multidimensional item response theory, has been expanded to include 7 specific Diagnostic and Statistical Manual, 5th edition (DSM-5) defined SUDs. Initial testing of the new measure, the CAT-SUD expanded (CAT-SUD-E) is reported here. Methods: 275 Community-dwelling adults (ages 18-68) responded to public and social-media advertisements. Participants virtually completed both the CAT-SUD-E and the Structured Clinical Interview for DSM-5, Research Version (SCID) to assess the validity of the CAT-SUD-E in determining whether participants met criteria for specific DSM-5 SUDs. Diagnostic classifications were based on 7 SUDs, each with 5 items, for current and lifetime SUDs. Results: For SCID-based presence of any lifetime SUD, predictions based on the overall CAT-SUD-E diagnosis and severity score were AUC=0.92, 95% CI = 0.88, 0.95 for current and AUC=0.94, 95% CI = 0.91, 0.97 for lifetime. For individual diagnoses, classification accuracy for current SUDs ranged from an AUC=0.76 for alcohol to AUC=0.92 for nicotine/tobacco. Classification accuracy for lifetime SUDs ranged from an AUC=0.81 for hallucinogens to AUC=0.96 for stimulants. Median CAT-SUD-E completion time was under 4 min. Conclusions: The CAT-SUD-E quickly produces similar results as lengthy structured clinical interviews for overall SUD and substance-specific SUDs, with high precision and accuracy, through a combination of fixed-item responses for diagnostic classification and adaptive SUD severity measurement. The CAT-SUD-E harmonizes information from mental health, trauma, social support and traditional SUD items to provide a more complete characterization of SUD and provides both diagnostic classification and severity measurement.Item Developmental Resting State Functional Connectivity for Clinicians(Springer International Publishing, 2014-09-01) Hulvershorn, Leslie A.; Cullen, Kathryn R.; Francis, Michael; Westlund, Mindy; Department of Psychiatry, IU School of MedicineResting state functional magnetic imaging (fMRI) is a novel means to examine functional brain networks. It allows investigators to identify functional networks defined by distinct, spontaneous signal fluctuations. Resting state functional connectivity (RSFC) studies examining child and adolescent psychiatric disorders are being published with increasing frequency, despite concerns about the impact of motion on findings. Here we review important RSFC findings on typical brain development and recent publications of child and adolescent psychiatric disorders. We close with a summary of the major findings and current strengths and limitations of RSFC studies.Item Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania(Mary Ann Liebert, 2016-04) Altinay, Murat I.; Hulvershorn, Leslie A.; Karne, Harish; Beall, Erik B.; Anand, Amit; Department of Psychiatry, School of MedicineBipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related.