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115. Variation in rostral anterior cingulate functional connectivity with amygdala and caudate during first manic episode distinguish bipolar young adults who do not remit following treatment.

Author

Lippard, Elizabeth T. C., Weber, Wade, Welge, Jeffrey, Adler, Caleb M., Fleck, David E., Almeida, Jorge, DelBello, Melissa P., and Strakowski, Stephen M.

Subjects
FUNCTIONAL connectivity, AMYGDALOID body, YOUNG adults, CINGULATE cortex, BIPOLAR disorder, PREFRONTAL cortex, HYPOMANIA
Abstract

Objectives: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, was previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first‐episode manic participants who remitted after 8 weeks of treatment compared to those who did not. Methods: Forty‐two participants with bipolar disorder (60% female) during their first manic episode were recruited and received 8 weeks of treatment. Twenty‐one remitted following treatment. Participants completed fMRI scans, at baseline and following 8 weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n = 41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups. Results: At baseline, non‐remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate 8 weeks following treatment. Conclusions: Results provide evidence of alterations in anterior cingulate amygdala and caudate functional connectivity in bipolar disorder non‐remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First‐episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowskirank=1. [ABSTRACT FROM AUTHOR]

Published
2021
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116. 5.12 RATES AND PREDICTORS OF METABOLIC LABORATORY TEST MONITORING IN MOBILITY: A LARGE PRAGMATIC TRIAL OF YOUTH PRESCRIBED SECOND-GENERATION ANTIPSYCHOTICS

Author

Delbello, Melissa P., primary, Welge, Jeffrey, additional, Blom, Thomas, additional, Klein, Christina, additional, KLEIN, CHRISTINA, additional, Dyce, Brittany, additional, Higdon, Claudine, additional, Crystal, Stephen, additional, Patel, Nikesh, additional, Fornari, Victor, additional, and Correll, Christoph U., additional

Published
2019
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119. Mindfulness‐based cognitive therapy for children and adolescents with anxiety disorders at‐risk for bipolar disorder: A psychoeducation waitlist controlled pilot trial

Author

Cotton, Sian, primary, Kraemer, Kristen M., additional, Sears, Richard W., additional, Strawn, Jeffrey R., additional, Wasson, Rachel S., additional, McCune, Nina, additional, Welge, Jeffrey, additional, Blom, Thomas J., additional, Durling, Michelle, additional, and Delbello, Melissa P., additional

Published
2019
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120. Neurophysiological effects of multiple mood episodes in bipolar disorder

Author

Borgelt, Logan, primary, Strakowski, Stephen M., additional, DelBello, Melissa P., additional, Weber, Wade, additional, Eliassen, James C., additional, Komoroski, Richard A., additional, Chu, Wen‐Jang, additional, Welge, Jeffrey A., additional, Blom, Thomas J., additional, Rummelhoff, Emily, additional, Tallman, Maxwell, additional, Lee, Jing‐Huei, additional, and Adler, Caleb M., additional

Published
2019
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122. Longitudinal proton spectroscopy study of the prefrontal cortex in youth at risk for bipolar disorder before and after their first mood episode

Author

Nery, Fabiano G., primary, Weber, Wade A., additional, Blom, Thomas J., additional, Welge, Jeffrey, additional, Patino, Luis R., additional, Strawn, Jeffrey R., additional, Chu, Wen‐Jang, additional, Adler, Caleb M., additional, Komoroski, Richard A., additional, Strakowski, Stephen M., additional, and DelBello, Melissa P., additional

Published
2019
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128. Maternal plasma cholesterol concentration and preterm birth: a meta-analysis and systematic review of literature.

Author

Welge, Jeffrey A., Warshak, Carri R., and Woollett, Laura A.

Subjects
*PREMATURE labor, *CHOLESTEROL, *META-analysis, *METABOLIC syndrome, *HDL cholesterol, *RESEARCH, *PREMATURE infants, *RESEARCH methodology, *SYSTEMATIC reviews, *LDL cholesterol, *MEDICAL cooperation, *EVALUATION research, *COMPARATIVE studies
Abstract

Background: Women that previously had preterm labor are at an increased risk for heart disease. Because spontaneous preterm birth is an adverse pregnancy outcome that affects millions of children worldwide, our objective was to review and analyze studies that have examined associations between maternal total cholesterol (TC), LDL-C, and HDL-C concentrations during pregnancy and the risk of preterm birth to potentially define biomarkers or targets for treatment.Method: A search was performed and 22 articles were found that examined the association of maternal plasma cholesterol concentrations and preterm birth. A meta-analysis was performed on 10 of the articles, those that used maternal lipid concentrations as the outcome and presented results as means plus variables, and a qualitative review was performed on all 22 articles.Results: The meta-analysis showed no relationship between maternal TC, LDL-C, or HDL-C and increased risk of preterm birth, although, a near significant relationship between low maternal HDL-C concentration and preterm birth (p = .055). Importantly, associations increased when cholesterol concentrations were combined with inflammatory markers or metabolic syndrome factors.Conclusions: The relationship between maternal cholesterol levels and preterm birth is heterogeneous. Associations are strengthened when maternal cholesterol concentrations are combined with other factors that may be related to more recently defined lipoprotein functions. [ABSTRACT FROM AUTHOR]

Published
2020
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129. Mindfulness‐based cognitive therapy for children and adolescents with anxiety disorders at‐risk for bipolar disorder: A psychoeducation waitlist controlled pilot trial.

Author

Cotton, Sian, Kraemer, Kristen M., Sears, Richard W., Strawn, Jeffrey R., Wasson, Rachel S., McCune, Nina, Welge, Jeffrey, Blom, Thomas J., Durling, Michelle, and Delbello, Melissa P.

Subjects
PSYCHOEDUCATION, MINDFULNESS-based cognitive therapy, ANXIETY disorders, BIPOLAR disorder, PERINATAL mood & anxiety disorders, TEENAGERS
Abstract

Aim: Previous studies suggest that Mindfulness‐Based Cognitive Therapy for Children (MBCT‐C) is feasible and may improve anxiety and emotion regulation in youth with anxiety disorders at‐risk for bipolar disorder. However, controlled studies are warranted to replicate and extend these findings. Methods: In the current study, 24 youth with anxiety disorders who have at least one parent with bipolar disorder participated in a MBCT‐C treatment period (n = 24; Mage = 13.6, 75% girls, 79% White) with a subset also participating in a prior psychoeducation waitlist control period (n = 19 Mage = 13.8, 68% girls, 84% White). Participants in both the waitlist and MBCT‐C periods completed independently‐rated symptom scales at each time point. Participants in the waitlist period received educational materials 12 weeks prior to the beginning of MBCT‐C. Results: There were significantly greater improvements in overall clinical severity in the MBCT‐C period compared to the waitlist period, but not in clinician‐ and child‐rated anxiety, emotion regulation or mindfulness. However, increases in mindfulness were associated with improvements in anxiety and emotion regulation in the MBCT‐C period, but not the waitlist period. Conclusions: Findings suggest that MBCT‐C may be effective for improving overall clinical severity in youth with anxiety disorders who are at‐risk for bipolar disorder. However, waitlist controlled designs may inflate effect sizes so interpret with caution. Larger studies utilizing prospective randomized controlled designs are warranted. [ABSTRACT FROM AUTHOR]

Published
2020
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131. 6.25 Risk of Metabolic Syndrome in a Community-Based Pragmatic Research Trial

Author

Higdon, Claudine, primary, Harper, Kari S., additional, Klein, Christina C., additional, Pirtle, Megan E., additional, Welge, Jeffrey, additional, Sheridan, Eva-Maria, additional, Patel, Nick, additional, Fornari, Victor, additional, Correll, Christoph U., additional, Duran, Luis Patino, additional, Blom, Thomas, additional, Sorter, Michael T., additional, Kurtz, Brian Perry, additional, DelBello, Melissa P., additional, and Dyce, Brittany, additional

Published
2018
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137. 5.39 Second-Generation Antipsychotics in Youth With Bipolar Disorder: Patient-Parent and Clinician-Reported Perspectives About Adherence and Adverse Effects

Author

Topalian, Alique G., primary, Klein, Christina, additional, DelBello, Melissa P., additional, Starr, Brian, additional, Welge, Jeffrey, additional, Blom, Thomas, additional, Duran, Luis Patino, additional, Turner, Heather, additional, Sorter, Michael T., additional, Day, Angie, additional, Nott, Jenna, additional, Fornari, Victor, additional, Sheridan, Eva, additional, Higdon, Claudine, additional, Correll, Christoph, additional, Deetz, Ingrid, additional, Starr, Cynthia, additional, and Sage, Jessica, additional

Published
2017
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138. 5.42 Conducting a Multi-Site, Community-Based, Pragmatic Research Trial: Study Design, Recruitment Barriers, and Initial Sample Characteristics of Mobility

Author

Higdon, Claudine, primary, Fornari, Victor, additional, Sheridan, Eva, additional, Klein, Christina, additional, Welge, Jeffrey, additional, Blom, Thomas, additional, Nott, Jenna, additional, Carmel, Arielle, additional, Duran, Luis Patino, additional, Sorter, Michael T., additional, Kurtz, Brian Perry, additional, Day, Angie, additional, Turner, Heather, additional, Modi, Avani, additional, Dyce, Brittany, additional, Snead, Norman, additional, Correll, Christoph U., additional, and DelBello, Melissa P., additional

Published
2017
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140. Prediction of lithium response in first-episode mania using the LITHium Intelligent Agent (LITHIA): Pilot data and proof-of-concept

Author

Fleck, David E, primary, Ernest, Nicholas, additional, Adler, Caleb M, additional, Cohen, Kelly, additional, Eliassen, James C, additional, Norris, Matthew, additional, Komoroski, Richard A, additional, Chu, Wen-Jang, additional, Welge, Jeffrey A, additional, Blom, Thomas J, additional, DelBello, Melissa P, additional, and Strakowski, Stephen M, additional

Published
2017
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142. Adolescents with or at ultra-high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker

Author

McNamara, Robert K., Jandacek, Ronald, Tso, Patrick, Blom, Thomas J., Welge, Jeffrey A., Strawn, Jeffrey R., Adler, Caleb M., Strakowski, Stephen M., and DelBello, Melissa P.

Subjects
Male, Bipolar Disorder, Erythrocytes, Adolescent, Docosahexaenoic Acids, Prodromal Symptoms, Article, Young Adult, Eicosapentaenoic Acid, Risk Factors, Case-Control Studies, Fatty Acids, Omega-3, Humans, Female, Child, Biomarkers
Abstract

Mood disorders are associated with low levels of the long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker.Erythrocyte fatty acid composition was determined in healthy adolescents (n = 28, HC), asymptomatic adolescents with a biological parent with bipolar I disorder (n = 30; 'high risk', HR), adolescents with a biological parent with bipolar I disorder and major depressive disorder, or depressive disorder not otherwise specified (n = 36; 'ultra-high risk', UHR), and first-episode adolescent bipolar manic patients (n = 35, BP).Group differences were observed for DHA (P ≤ 0.0001) and EPA (P = 0.03). Compared with HC, erythrocyte EPA + DHA ('omega-3 index') was significantly lower in BP (-24%, P ≤ 0.0001) and UHR (-19%, P = 0.0006) groups, and there was a trend in the HR group (-11%, P = 0.06). Compared with HC (61%), a greater percentage of HR (77%, P = 0.02), UHR (80%, P = 0.005) and BP (97%, P = 0.001) subjects exhibited EPA + DHA levels of ≤4.0%. Among all subjects (n = 130), EPA + DHA was inversely correlated with manic (r = -0.29, P = 0.0008) and depressive (r = -0.28, P = 0.003) symptom severity. The AA/EPA + DHA ratio was significantly greater in BP (+22%, P = 0.0002) and UHR (+16%, P = 0.001) groups.Low EPA + DHA levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA + DHA deficits. Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.

Published
2015

143. Efficacy and Tolerability of Antidepressants in Pediatric Anxiety Disorders: a Systematic Review and Meta-Analysis

Author

Strawn, Jeffrey R., Welge, Jeffrey A., Wehry, Anna M., Keeshin, Brooks R., and Rynn, Moira A.

Subjects
Psychiatric Status Rating Scales, Adolescent, Humans, Prospective Studies, Anxiety, Serotonin and Noradrenaline Reuptake Inhibitors, Child, Anxiety Disorders, Article, Antidepressive Agents, Selective Serotonin Reuptake Inhibitors, Randomized Controlled Trials as Topic, Suicidal Ideation
Abstract

Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders.A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships.Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021).Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size.

Published
2014

144. Reduced Short Interval Cortical Inhibition Correlates with Atomoxetine Response in Children with ADHD

Author

Chen, Tina H., Wu, Steve W., Welge, Jeffrey A., Dixon, Stephan, Shahana, Nasrin, Huddleston, David A., Sarvis, Adam R., Sallee, Floyd R., and Gilbert, Donald L.

Subjects
Male, Time Factors, Adrenergic Uptake Inhibitors, Propylamines, Motor Cortex, Neural Inhibition, Atomoxetine Hydrochloride, Transcranial Direct Current Stimulation, behavioral disciplines and activities, Article, Inhibition, Psychological, Attention Deficit Disorder with Hyperactivity, Humans, Female, Child
Abstract

Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation-evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition.

Published
2014

145. Neurofunctional Differences Among Youth With and at Varying Risk for Developing Mania

Author

Welge, Jeffrey A., primary, Saliba, Lawrence J., additional, Strawn, Jeffrey R., additional, Eliassen, James C., additional, Patino, L. Rodrigo, additional, Adler, Caleb M., additional, Weber, Wade, additional, Schneider, Marguerite Reid, additional, Barzman, Drew H., additional, Strakowski, Stephen M., additional, DelBello, Melissa P., additional, and McNamara, Robert K., additional

Published
2016
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149. fMRI brain activation changes following treatment of a first bipolar manic episode

Author

Strakowski, Stephen M, primary, Fleck, David E, additional, Welge, Jeffrey, additional, Eliassen, James C, additional, Norris, Matthew, additional, Durling, Michelle, additional, Komoroski, Richard A, additional, Chu, Wen-Jang, additional, Weber, Wade, additional, Dudley, Jonathan A, additional, Blom, Thomas J, additional, Stover, Amanda, additional, Klein, Christina, additional, Strawn, Jeffrey R, additional, DelBello, Melissa P, additional, Lee, Jing-Huei, additional, and Adler, Caleb M, additional

Published
2016
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