Person: Spencer, Thomas
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Spencer
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Thomas
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Spencer, Thomas
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Publication Attention and working memory deficits in a perinatal nicotine exposure mouse model(Public Library of Science, 2018) Zhang, Lin; Spencer, Thomas; Biederman, Joseph; Bhide, Pradeep G.Background: Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure. Methodology/Principal findings Female C57Bl/6 mice received drinking water containing nicotine (100μg/ml) + saccharin (2%) starting 3 weeks prior to breeding and continuing throughout pregnancy, and until 3 weeks postpartum. Over the same period, female mice in two control groups received drinking water containing saccharin (2%) or plain drinking water. Offspring from each group were weaned at 3-weeks of age and subjected to behavioral analyses at 3 months of age. We examined spontaneous locomotor activity, anxiety-like behavior, spatial working memory, object based attention, recognition memory and impulsive-like behavior. We found significant deficits in attention and working memory only in male mice, and no significant changes in the other behavioral phenotypes in male or female mice. Exposure to saccharin alone did not produce significant changes in either sex. Conclusion/Significance The perinatal nicotine exposure produced significant deficits in attention and working memory in a sex-dependent manner in that the male but not female offspring displayed these behaviors. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and have been reported in other studies that used pre- or perinatal nicotine exposure. Therefore, we suggest that preclinical models of developmental nicotine exposure could be useful tools for modeling ADHD and related disorders.Publication Does the Mixed Opioid Receptor Antagonist Naltrexone Mitigate Stimulant-Induced Euphoria?: A Double-Blind, Placebo Controlled Trial of NaltrexoneSpencer, Thomas; Bhide, Pradeep; Zhu, Jinmin; Faraone, Stephen; Fitzgerald, Maura; Yule, Amy; Uchida, Mai; Spencer, Andrea; Hall, Anna M.; Koster, Ariana J.; Feinberg, Leah; Kassabian, Sarah; Storch, Barbara; Biederman, JosephPublication Longitudinal Course of Deficient Emotional Self-Regulation CBCL Profile in Youth with ADHD: Prospective Controlled Study(Dove Medical Press, 2012) Biederman, Joseph; Spencer, Thomas; Petty, Carter; Hyder, Laran L; O’Connor, Katherine B; Surman, Craig; Faraone, StephenBackground: While symptoms of deficient emotional self-regulation (DESR) have been long associated with attention-deficit/hyperactivity disorder (ADHD), there has been limited investigation of this aspect of the clinical picture of the disorder. The main aim of this study was to examine the predictive utility of DESR in moderating the course of ADHD children into adolescence. Methods: Subjects comprised 177 children with and 204 children without ADHD followed for an average of 4 years (aged 6–18 years at baseline, 54% male). Subjects were assessed with structured diagnostic interviews and measures of psychosocial functioning. DESR was defined by the presence (n = 79) or absence (n = 98) of Child Behavior Checklist (CBCL)-DESR profile (score ≥ 180 < 210 total of Attention, Aggression, and Anxious/Depressed subscales) at the baseline assessment. Results: Of subjects with DESR at baseline, 57% had DESR at follow-up. Persistent ADHD was significantly associated with DESR at follow-up (x\(^{2}\)\(_{(1)}\) = 15.37, P < 0.001). At follow-up, ADHD + DESR subjects had significantly more comorbidities (z = 2.55, P = 0.01), a higher prevalence of oppositional defiant disorder (z = 3.01, P = 0.003), and more impaired CBCL social problems t-score (t\(_{(227)}\) = 2.41, P = 0.02) versus ADHD subjects. Conclusion: This work suggests that a positive CBCL-DESR profile predicts subsequent psychopathology and functional impairments in children with ADHD suggesting that it has the potential to help identify children with ADHD at high risk for compromised outcomes.Publication A Laboratory Driving Simulation for Assessment of Driving Behavior in Adults with ADHD: A Controlled Study(BioMed Central, 2007) Monuteaux, Michael C; Reimer, Bryan; Coughlin, Joseph F; Aleardi, Megan; Dougherty, Meghan; Schoenfeld, Steven; Biederman, Joseph; Fried, Ronna; Surman, Craig; Spencer, Thomas; Faraone, StephenBackground: It is now estimated that attention deficit-hyperactivity disorder (ADHD) afflicts at least 4% of adults in the United States and is associated with high levels of morbidity and functional impairment. One key area of dysfunction associated with ADHD is impaired motor vehicle operation. Our goal was to examine the association between ADHD and specific driving outcomes in a sample of adults using a driving simulator. Methods: Subjects were 20 adults with full DSM-IV ADHD and 21 controls without ADHD of equal gender distribution. However, the mean age of subjects with ADHD was somewhat older. All analyses were adjusted for age and gender. All subjects participated in a driving simulation that lasted for one hour and consisted of a short training period, a high stimulus segment and a low stimulus segment with two distinct monotonous periods. Results: In the second monotonous period within the low stimulus environment, ADHD subjects were significantly more likely than controls to collide with an obstacle suddenly appearing from the periphery, adjusting for age and gender. Conclusion: Adults with ADHD were more likely than controls to collide with an obstacle during a driving simulation suggesting that deficits in directed attention may underlie driving impairments in this population.Publication Comparative Acute Efficacy and Tolerability of OROS and Immediate Release Formulations of Methylphenidate in the Treatment of Adults with Attention-Deficit/Hyperactivity Disorder(BioMed Central, 2007) Biederman, Joseph; Mick, Eric Owen; Surman, Craig; Doyle, Robert; Hammerness, Paul; Michel, Evan; Martin, Jessica; Spencer, ThomasBackground: The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH. Methods: Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67). Results: Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 ± 31.9 mg, 74.8 ± 26.2 mg, and 95.4 ± 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N = 36) on placebo. Conclusion: Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH. Trial Registration: The trial of OROS-MPH was registered at clinicaltrials.gov, number NCT00181571.Publication Efficacy of Atomoxetine in Adult Attention-Deficit/Hyperactivity Disorder: A Drug-placebo Response Curve Analysis(BioMed Central, 2005) Faraone, Stephen; Biederman, Joseph; Spencer, Thomas; Michelson, David; Adler, Lenard; Reimherr, Fred; Glatt, Stephen JBackground: The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) among adults by using drug-placebo response curve methods. Methods: We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. Results: Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. Conclusion: From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria.