APNA 26th Annual Conference Session 2012: November 8, 2012

Transcription

1 From Circuits to Solutions: Brain Function in Pediatric Bipolar and Attention Deficit Disorders Julie A Carbray PhD, APN, BC Clinical Professor Pediatric Brain Research and Intervention Center Institiute for Juvenile Research University of Illinois at Chicago Disclosure Financial Disclosure Shionogi Inc, This speaker has not other conflict of interest to disclose. Objectives Identify both common and differing brain circuitry dysfunction patterns implicated in Pediatric Bipolar Disorder and Attention Deficit Hyperactivity Disorder Discuss how brain circuitry dysfunction relates to symptoms and the clinical presentation of illness in children and adolescents affected by these disorders Integrate theoretical underpinnings of brain circuitry dysfunction into neurobiologically informed nursing care of children and adolescents affected by Pediatric Bipolar Disorder and Attention Deficit Hyperactivity Disorder _ Carbray 1

2 Research Domain Criteria (RDoC) Strategies Improving classification of psychopathology based on dimensions of behavior and neurobiological measures Study basic dimensions of functioning (e.g., affect, cognition) across multiple levels of analysis (e.g., genetic, circuits, behavior) Insel and Cuthbert, NIMH BIOSIGNATURE OF ACTIVITY STUDIES: HOW I USE THE MODEL TO EDUCATE FAMILIES Pavuluri and Sweeney, JAACAP, 2008 BRAIN FUNCTION: SIX DYNAMIC CIRCUITS Probing the Brain Functional Domains Feeling Circuit (Fronto-limbic circuit) Understanding Facial Emotions circuit (Face response circuit) Reactive Circuit (Occipito-limbic associative circuit) (Face response circuit) Inhibiting impulsive behavior circuit (Response Inhibition circuit) Thinking circuit (Cognitive Circuit) Interface of thinking and feeling circuit Carbray 2

3 Impulsivity, Executive Functions and Reward Systems Differentiate PBD and ADHD EXECUTIVE SYSTEMS REWARD/ AFFECTIVE SYSTEMS IMPULSIVITY Interface of Impulse Regulation, Affect And Reward Systems VENTRAL FRONTO- STRIATAL SYSTEM DORSAL FRONTO- STRIATAL SYSTEM +VLPFC has Dual Role Passarotti and Pavuluri, 2011 Cognitive and Emotional Impulsivity ADHD Fronto-striatal PBD Fronto-striatal DORSAL SYSTEM VENTRAL SYSTEM Affective/Motivation Systems Cognitively-Driven Impulsivity Affective/Motivation Systems Emotionally-Driven Impulsivity Carbray 3

4 Neurobiologically-informed Treatment vity Impulsi? Passarotti and Pavuluri, 2011 Different Response Inhibition Phenotypes in PBD and ADHD PBD - ADHD PBD - HC ADHD - HC Y=19 Y=45 Y=20 Correct Stop minus correct Go Trials Red indicates greater activation in the first group of the comparison than in the second group Blue indicates the opposite. R=right; L=left. Passarotti et al. 2010; Psychiatry Research Conclusions During response inhibition both PBD and ADHD patients show PFC dysfunction relative to HC This dysfunction is more focal in PBD (i.e., VLPFC) and more generalized (i.e., both VPFC and DLPFC) in ADHD When comparing the two patient groups, ADHD has more compromised inhibition function, with reduced activation both in DLPFC and VLPFC, relative to PBD Carbray 4

5 Angry vs. Neutral Faces PBD - ADHD PBD - HC ADHD - HC Y=20 Y=5 Y=32 15 PBD 19 HC Mean Age =13.36±2.65 Passarotti et al., 2010; JAACAP Conclusions PBD and ADHD patients, relative to HC, show corticosub-cortical activity that is reduced under negative emotional challenge PBD relative to ADHD exhibits greater deployment of the emotion processing circuitry and reduced deployment of cognitive/working memory circuit under negative emotional challenge. Reduced Functional Connectivity in Amygdala and VLPFC In the Affect Regulation and Evaluation Network in PBD VMPFC AMYDALA VLPFC 41 PBD 16 HC Mean Age =14.32±2.76 [AACAP POSTER # 5.31] Passarotti et al., under review Carbray 5

6 Pharmacotherapy Effects on VLPFC and Amygdala Function in PBD A B C PBD vs HC A) Angry Face condition at Baseline B) Happy Face condition at Baseline C) Angry Face condition at Follow-up vs. Baseline Amydala Passarotti et al., 2011 Reward Circuits in interaction with Affect and Impulse Regulation Circuits *Reward Related Functions Ventral Fronto-insularamygdalar Circuit *Affect Regulation Dimension Fronto-dorsal-striatal Ciruit *Impulse Regulation Dimension Delay Discounting Task 85 PBD 65 ADHD 100 HC Mean Age ± 2.2 Passarotti et al., (in preparation) Carbray 6

7 Response to Monetary Reward and Loss in PBD vs. ADHD PBD vs ADHD The ventral fronto-striatal circuit is differentially modulated by positive and negative contingencies in PBD and ADHD. PBD shows greater ventral striatum activity than ADHD and HC for losses Monetary Reward and Loss Task ADHD shows similar response for reward and loss. Stop Signal Task with Monetary Feedback We tested the ability to adjust performance on Stop signal task based on feedback contingencies PBD exhibited decreased dorsal fronto-striatal regulation relative to ADHD on incorrect stop trials with negative feedback PBD vs ADHD Affective Impulsivity: Frustration and affective over-reactivity lead to decreased dorsal frontostriatal engagement in PBD relative to ADHD Implications for Neurobiologically-informed informed Treatment Mood stabilizers to aid ventral frontostriatal and limbic system Stimulants to aid dorsal fronto striatal system Contingencybased Intervention: - Rainbow CFF-CBT -Working Memory Enhancement Carbray 7

8 Mood Stabilization Medication* Mood stabilizer Second Generation Antipsychotic First Choice Lithium Risperidone, Aripiprazole Sequence of Choices DVPX, CBZ, Lamotrigine, Topiramate Oxcarbazepine Quetiapine, Ziprasidone,, Olanzapine, *Any history of a drug that had negative or no effect was not prescribed; Combination of MS+SGA if severe Working Memory Enhancement Program Cogmed Computer-based Working Memory Training (Klingberg et al., 2005) Few of many books out there; We wrote with the mission of reaching out to parents and clinicians training in this field Carbray 8

9 Current Funding Sources NARSAD Young Investigator (AP) Colbeth Endowment Funds (MP) Marshall Reynolds (MP) NIH/NIMH (MP) 1R01MH081019A 1R01MH A1 RC1MH HHSN C The Pediatric Brain Research And Intervention Center Phone: (312) www/psych.uic.edu/brain-center The Pediatric Brain Research and Intervention Center Institute for Juvenile Research University of Illinois at Chicago Department of Psychiatry 1747 West Roosevelt Road Chicago, Illinois Pediatric BRAIN Center Mani N Pavuluri, MD, PhD Alessandra Passeroti PhD Minjie Wu PhD Lisa Lu PhD Jacklynn Fitzgerald BA James Ellis BA Hongyu Yang PhD Binu Varghese MA Richard Whitley MA Jon O Neil BA Allison Lowes BA Meredith Wong BA Stephanie Monroe BA Bryn Levitan BA Nicole Witowski BA Nathan Carley BA Noah Yulish MA Gail Schuck BA Jean Madigan BA Our Team MRI Methodology Joe Zhou PhD Deb Little PhD Genomics and Neurochemistry Jeff Bishop Pharm D Christian Gossett BA Ghan Shyam Pandey PhD Yogesh Dwivedi PhD Clinical Julie Carbray PhD Sonali Nanayakkara MD Amy West PhD Sally Weinstein PhD Collaborators Mike Stevens PhD John Sweeney PhD Mark Stein PhD Carbray 9

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